UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Baroreceptor and chemoreceptor activity during nasal stimulation in the muskrat (Ondatra zibethica) Douse, Mark Alan 1985

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata

Download

Media
831-UBC_1985_A6_7 D69.pdf [ 2.93MB ]
Metadata
JSON: 831-1.0096075.json
JSON-LD: 831-1.0096075-ld.json
RDF/XML (Pretty): 831-1.0096075-rdf.xml
RDF/JSON: 831-1.0096075-rdf.json
Turtle: 831-1.0096075-turtle.txt
N-Triples: 831-1.0096075-rdf-ntriples.txt
Original Record: 831-1.0096075-source.json
Full Text
831-1.0096075-fulltext.txt
Citation
831-1.0096075.ris

Full Text

BARORECEPTOR AND CHEMORECEPTOR ACTIVITY DURING NASAL STIMULATION IN THE MUSKRAT (ONDATRA ZIBETHICA) by MARK ALAN DOUSE B.Sc. U n i v e r s i t y Of B r i t i s h Columbia 1981 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE STUDIES (Department of Zoology) We accerjt t h i s t h e s i s as conforming to the TScwired, standard THE UNIVERSITY OF BRITISH COLUMBIA J u l y 1985 © Mark Alan Douse, 1985 In presenting t h i s thesis i n p a r t i a l f u l f i l m e n t of the requirements for an advanced degree at the University of B r i t i s h Columbia, I agree that the Library s h a l l make i t f r e e l y available for reference and study. I further agree that permission for extensive copying of t h i s thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. I t i s understood that copying or publication of t h i s thesis for f i n a n c i a l gain s h a l l not be allowed without my written permission. Department of '<OQ 1<S>C^  ^ The University of B r i t i s h Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3 Date Any i/juf DE-6 (3/81) i i ABSTRACT D i v i n g muskrats (Ondatra z i b e t h i c a ) invoke a s e r i e s of c a r d i o v a s c u l a r and r e s p i r a t o r y adjustments i n response to s t i m u l a t i o n of the nares with water. .This dive response i s c h a r a c t e r i z e d by apnoea, a decrease in c a r d i a c output and an i n c r e a s e i n p e r i p h e r a l r e s i s t a n c e . The r e s u l t i s that blood flow i s maintained to those organs most s u s c e p t i b l e to oxygen d e p r i v a t i o n , the h e a r t and the b r a i n . The i n i t i a t i o n of the dive response in mammals i s p r i m a r i l y the r e s u l t of n a s a l s t i m u l a t i o n with water. In a d d i t i o n , the b a r o r e c e p t o r s a c t i n g v i a the b a r o r e f l e x have been suggested to be i n v o l v e d i n e i t h e r the i n i t i a t i o n or the maintenance of t h i s response. The chemoreceptors, a c t i n g v i a the chemoreflex, have a l s o been i m p l i c a t e d i n the maintenance of the d i v e response, although the importance of t h i s c o n t r i b u t i o n i s c o n t r o v e r s i a l . . The purpose of t h i s t h e s i s was to examine the r o l e of the b a r o r e c e p t o r s and chemoreceptors i n the d i v i n g response of the muskrat. Changes i n input from these r e c e p t o r s recorded from the cut c a r o t i d s i n u s nerve and t h e i r modulation by the c a r o t i d s i n u s e f f e r e n t a c t i v i t y d u r i n g n a s a l s t i m u l a t i o n may have important i m p l i c a t i o n s f o r the r o l e of the b a r o r e c e p t o r s and chemoreceptors i n the d i v i n g response. In the i n i t i a l p a r t of the d i v e , b a r o r e c e p t o r a c t i v i t y decreased, while chemoreceptor a c t i v i t y d i d not change. Subsequently, baroreceptor and chemoreceptor a c t i v i t y i n c r e a s e d , exceeding pr e - d i v e l e v e l s . T h i s i n c r e a s e was not due to a change in r e c e p t o r t h r e s h o l d or s e n s i t i v i t y induced by the n a s a l s t i m u l a t i o n , but was a r e f l e c t i o n of the i n c r e a s e i n the u s u a l stimulus modality of both receptor groups. The e f f e r e n t a c t i v i t y recorded from the c e n t r a l end of the cut c a r o t i d sinus nerve was of two types, both of which responded to n a s a l s t i m u l a t i o n . T h i s change in the e f f e r e n t d i s c h a r g e has the p o t e n t i a l to modify a f f e r e n t a c t i v i t y . Nasal s t i m u l a t i o n caused one type of e f f e r e n t a c t i v i t y (type A) to stop. The second type of e f f e r e n t a c t i v i t y (type B) responded with an i n i t i a l i n c r e a s e i n d i s c h a r g e , r e t u r n i n g to pre-dive l e v e l s a f t e r 6 . 6 seconds. Based-on the s i m i l a r c h a r a c t e r i s t i c s of these e f f e r e n t s to those of p r e v i o u s work i t i s p o s t u l a t e d that the a c t i o n s of the e f f e r e n t s would be to i n h i b i t the b a r o r e c e p t o r s and chemoreceptors d u r i n g the i n i t i a t i o n of the n a s a l s t i m u l a t i o n , but to be l e s s e f f e c t i v e as the dive progressed. It i s concluded that there i s no c o n t r i b u t i o n from the b a r o r e c e p t o r s to the i n i t i a t i o n of the d i v i n g b r a d y c a r d i a , although the l a c k of b a r o r e c e p t o r a c t i v i t y may c o n t r i b u t e to the i n c r e a s e i n p e r i p h e r a l r e s i s t a n c e . L a t e r i n the d i v e , both heart r a t e and a r t e r i a l blood p r e s s u r e i n c r e a s e , d e s p i t e a concomitant e l e v a t i o n i n baroreceptor a c t i v i t y . The b a r o r e c e p t o r s t h e r e f o r e have no r o l e i n the maintenance of the d i v i n g response. The i n i t i a l i n h i b i t i o n of the chemoreceptors may be important to permit the f u l l e x p r e s s i o n of the dive response, i n c l u d i n g a decrease i n c e n t r a l r e s p i r a t o r y output. L a t e r i n the dive the chemoreceptors may c o n t r i b u t e to the maintenance and t e r m i n a t i o n of the d i v i n g response. i v TABLE OF CONTENTS ABSTRACT i i LIST OF TABLES v LIST OF FIGURES v i ACKNOWLEDGEMENTS v i i INTRODUCTION 1 METHODS 8 Experimental P r o t o c o l . .. 10 Measurements and A n a l y s i s 12 RESULTS 14 I. Cardiac and Blood Pressure Responses t o Nasal S t i m u l a t i o n 14 I I . Baroreceptor A c t i v i t y d u r i n g a Pressor Test and during Nasal S t i m u l a t i o n 17 I I I . Chemoreceptor A c t i v i t y d u r i n g a Nitrogen Test and during Nasal S t i m u l a t i o n 29 IV. E f f e r e n t C h a r a c t e r i z a t i o n and Modulation by Nasal S t i m u l a t i o n 38 DISCUSSION 55 REFERENECES CITED 66 V LIST OF TABLES E f f e c t of Nasal S t i m u l a t i o n 15 E f f e c t of Pressor t e s t on Baroreceptor A c t i v i t y 20 E f f e c t of Nasal S t i m u l a t i o n on Baroreceptor A c t i v i t y 25 E f f e c t of Nasal S t i m u l a t i o n on Chemoreceptor A c t i v i t y 34 E f f e c t of Nasal S t i m u l a t i o n on E f f e r e n t A c t i v i t y 48 LIST OF FIGURES v i . E f f e c t of Mean A r t e r i a l Blood Pressure on Baroreceptor A c t i v i t y 18 E f f e c t of Pressor t e s t on Baroreceptor A c t i v i t y 22 E f f e c t of Nasal S t i m u l a t i o n on Baroreceptor A c t i v i t y 27 E f f e c t of F i o 2 on Chemoreceptor A c t i v i t y 30 E f f e c t of Nitrogen t e s t on Chemoreceptor A c t i v i t y 32 E f f e c t of Nasal S t i m u l a t i o n on Chemoreceptor A c t i v i t y ..... 36 Type A and Type B E f f e r e n t A c t i v i t y 39 E f f e c t of V e n t i l a t i o n Frequency on Type A A c t i v i t y 42 E f f e c t of V e n t i l a t i o n on Type A A c t i v i t y 44 E f f e c t of Pressor t e s t on Type B A c t i v i t y 46 E f f e c t of Nasal S t i m u l a t i o n on Type A A c t i v i t y 51 E f f e c t of Nasal S t i m u l a t i o n on Type B A c t i v i t y 53 v i i ACKNOWLEDGEMENTS I thank Dr. David R. Jones f o r h i s h e l p and guidance and Dr. W i l l i a m K. Milsom f o r h i s encouragement. I a l s o thank my c o l l e a g u e s i n - the l a b of Dr. Jones for t h e i r i n v a l u a b l e h e l p and c r i t i c i s m s throughout the y e a r s . I am g r a t e f u l f o r the s c h o l a r s h i p s I have r e c e i v e d from the B r i t i s h Columbia Heart Foundation. B r i t i s h Columbia Heart Foundat i o n . 1 INTRODUCTION During submersion, d i v i n g animals invoke a s e r i e s of r e s p i r a t o r y and c a r d i o v a s c u l a r r e f l e x e s , c o l l e c t i v e l y c a l l e d the d i v i n g response. T h i s response i s c h a r a c t e r i z e d by apnoea, a decrease i n c a r d i a c output, and an i n c r e a s e i n p e r i p h e r a l r e s i s t a n c e ( I r v i n g et a l . 1942; E i s n e r et a l . 1966). The r e s u l t i s a r e d i s t r i b u t i o n of blood flow from the muscles and spla n c h n i c beds to the heart and the b r a i n (Zapol e_t a l . 1979; Jones et a l . 1982; McKean 1982). The d i v i n g response i s thus viewed as an oxygen c o n s e r v i n g mechanism which preserves, the i n t e g r i t y of the o b l i g a t e a e r o b i c t i s s u e s d u r i n g the prolonged p e r i o d s of apnoea accompaning submersion ( I r v i n g et a l . 1942; E i s n e r et a l . 1966). I t i s g e n e r a l l y accepted that the i n i t i a t i o n of the d i v i n g response, at l e a s t i n mammals, i s p r i m a r i l y the r e s u l t of s t i m u l a t i o n of na s a l r e c e p t o r s by water ( A n g e l l James and Daly 1972; Dykes 1974; Drummond and Jones 1979). D i v i n g b r a d y c a r d i a i s maintained dur i n g a r t i f i c i a l v e n t i l a t i o n i n s e a l s and muskrats ( T a n j i et a l . 1975; Drummond and Jones 1979), although the response i s attenuated (Dykes 1974; Drummond and Jones 1979). In a d d i t i o n , there i s a decrease i n c e n t r a l r e s p i r a t o r y output d u r i n g a d i v e , as shown i n the muskrat by a lack of phrenic nerve a c t i v i t y d u r i n g n a s a l s t i m u l a t i o n (Drummond and Jones, unpublished o b s e r v a t i o n s ) . Lung d e f l a t i o n and apnoea, without s t i m u l a t i o n of the nares, a l s o r e s u l t s i n an immediate b r a d y c a r d i a (Jones et a l . 1973; T a n j i et a_l. 1975; Drummond and Jones 1979; Pasche and Krog 1980), which suggests that 1) 2 the decrease in c e n t r a l r e s p i r a t o r y output, and 2) the lack of pulmonary receptor input i n d i v e s , c o n t r i b u t e s to the d i v i n g response. C e n t r a l r e s p i r a t o r y output and pulmonary s t r e t c h r e c e p t o r s are j u s t two of s e v e r a l groups of modulators that a f f e c t the e x p r e s s i o n of the d i v e response. C e n t r a l to t h i s t h e s i s are the r o l e s of the b a r o r e c e p t o r s and chemoreceptors i n the d i v i n g response of the muskrat, Ondatra z i b e t h i c a . The r a p i d onset of the d i v i n g b r a d y c a r d i a i n these animals i s accompanied by a v a s o c o n s t r i c t i o n of the p e r i p h e r a l v a s c u l a t u r e so that mean a r t e r i a l pressure i s maintained (Drummond and Jones 1979; Drummond 1980), or r i s e s (Jones et a l . 1982). T h i s s t a b i l i t y of blood pressure i n d i c a t e s that the b a r o r e c e p t o r s have a r o l e i n these r e f l e x adjustments. Baroreceptors respond to an i n c r e a s e i n blood p r e s s u r e with an i n c r e a s e in n e u r a l discharge (Bronk and S t e l l a -1932). Under normal r e s t i n g c o n d i t i o n s baroreceptor input h e l p s to maintain the blood p r e s s u r e v i a the b a r o r e f l e x a d j u s t i n g c a r d i a c output and p e r i p h e r a l r e s i s t a n c e (Heymans and N e i l 1958). The i n i t i a t i o n of d i v i n g b r a d y c a r d i a has t h e r e f o r e been suggested to r e s u l t from the i n t e r a c t i o n of nasal s t i m u l a t i o n with input from the b a r o r e c e p t o r s (Daly and A n g e l l James 1975; A n g e l l James et a l . 1978; Daly 1984). In c o n t r a s t , other workers suggest that the decrease i n heart r a t e i s l a r g e l y baroreceptor independent, and the b a r o r e f l e x helps to maintain blood pressure once the response i s f u l l y e s t a b l i s h e d (Drummond and Jones 1979; Drummond 1980; B u t l e r and Jones 1982; Folkow and B l i x 1984). The b a r o r e c e p t o r s have t h e r e f o r e been 3 i m p l i c a t e d i n both the i n i t i a t i o n and maintenance o.f the di v e response. P e r i p h e r a l chemoreceptors respond to decreases i n blood oxygen ten s i o n with an i n c r e a s e i n n e u r a l a c t i v i t y . Although p r i m a r i l y responsive to a r t e r i a l Po 2, they are a l s o s e n s i t i v e to f l u c t u a t i o n s i n blood Pco 2 and pH (Biscoe et a l . 1967,1970b; L a h i r i and DeLaney 1975). An i n c r e a s e i n chemoreceptor a c t i v i t y under normal r e s t i n g c o n d i t i o n s produces an i n c r e a s e i n r e s p i r a t i o n , heart r a t e , and p e r i p h e r a l a r t e r i a l d i l a t i o n (Daly and S c o t t 1958,1962,1963; L a h i r i et a l . 1978). The t a c h y c a r d i a and v a s o d i l a t i o n i s a secondary r e f l e x due to the i n c r e a s e i n v e n t i l a t i o n (Daly and Scott 1958,1963). The primary chemoreflex i s manifested d u r i n g an apneoic p e r i o d , when b r i e f chemoreceptor s t i m u l a t i o n r e s u l t s i n b r a d y c a r d i a and an i n c r e a s e i n p e r i p h e r a l v a s c u l a r c o n s t r i c t i o n (Scott and Daly 1958,1962,1963). The chemoreceptors have t h e r e f o r e been p o s t u l a t e d to have a r o l e i n the maintenance of the d i v i n g response, as the blood oxygen f a l l s and carbon d i o x i d e i n c r e a s e s d u r i n g the dive (Daly and A n g e l l James 1975; Daly et a l . 1977; Daly 1984). The extent of chemoreceptor c o n t r i b u t i o n , however, i s open to q u e s t i o n , but suggestions have ranged from an important (Daly et a l . 1977), to a minor r o l e i n the maintenance of the di v e response ( T a n j i et a l . 1975; Drummond 1979). The mechanism by which b a r o r e c e p t o r s or chemoreceptors may c o n t r i b u t e to the d i v e response are 1) an increase i n the a f f e r e n t a c t i v i t y from these p e r i p h e r a l r e c e p t o r s , evoking the b a r o r e f l e x or the chemoreflex; or 2) a change i n c e n t r a l b r a i n 4 stem s e n s i t i v i t y c o u l d occur, so that the same a f f e r e n t input has a l a r g e r a f f e c t on the c a r d i a c slowing and p e r i p h e r a l v a s o c o n s t r i c t i o n i n a d i v e . Previous s t u d i e s have not c o n c l u s i v e l y shown a change i n c e n t r a l s e n s i t i v i t y f o r the b a r o r e f l e x d u r i n g a dive ( A n g e l l James et a l . 1978), and there i s no change i n the c e n t r a l chemoreflex s e n s i t i v i t y ( E i s n e r et a l . 1977; c f B u t l e r and Jones 1982). The a f f e r e n t a c t i v i t y of the b a r o r e c e p t o r s and chemoreceptors, on the other hand, may be m o d i f i e d i n s e v e r a l ways d u r i n g a d i v e . B a r o r e c e p t o r s w i l l respond to the increase i n blood p r e s s u r e , which, may occur d u r i n g the l a t t e r stages of a d i v e (Jones et a_l. 1982), although the t o t a l number of r e c e p t o r impulses, per u n i t time, c o u l d f a l l due to the d i v i n g b r a d y c a r d i a (Bronk and S t e l l a 1932; A n g e l l James 1971). The chemoreceptors w i l l i n c r e a s e t h e i r a c t i v i t y as the blood oxygen decreases, but they a l s o respond to r a p i d f l u c t u a t i o n s i n blood p r e s s u r e with a change i n discharge i n the o p p o s i t e d i r e c t i o n . An i n c r e a s e i n blood pressure i n c r e a s e s the blood flow to the c a r o t i d bodies, d e l i v e r i n g more oxygen to the r e c e p t o r s and r e d u c i n g the d i s c h a r g e (Biscoe et a l . 1970a). L e v e l s of c i r c u l a t i n g catecholamines a l s o i n c r e a s e d u r i n g n a s a l s t i m u l a t i o n ( A l l i s o n and Powes 1971; Hance e_t a l . 1982; Mangalam and Jones, unpublished o b s e r v a t i o n s ) , and may modulate r e c e p t o r discharge through t h e i r e f f e c t on v e s s e l s t i f f n e s s , c a r o t i d body blood flow, or through d i r e c t a c t i o n s on the r e c e p t o r s themselves (Aars 1971; McDonald 1981; Tomomatsu and N i s h i 1981; Holmes and Ledsome 1984). The t h r e s h o l d and s e n s i t i v i t y of the b a r o r e c e p t o r s and 5 chemoreceptors may be f u r t h e r m o d i f i e d , d u r i n g a d i v e , by any e f f e r e n t i n n e r v a t i o n which may be present i n these animals. These e f f e r e n t s may a f f e c t a f f e r e n t a c t i v i t y through t h e i r a c t i o n s on v e s s e l s t i f f n e s s , c a r o t i d body blood flow, or through d i r e c t a c t i o n s on the r e c e p t o r s themselves (Koizumi and Sato 1969; Majcherczyk et a l . 1980; Acker and O'Regan 1981; McDonald 1981; O'Regan 1981; Tomomatsu and N i s h i 1981). Although the exact mechanism of e f f e r e n t a c t i o n on a f f e r e n t discharge i s unc l e a r , they do have the c a p a c i t y to modulate receptor d i scharge independant of changes i n blood p r e s s u r e or blood oxygen t e n s i o n . Sympathetic i n n e r v a t i o n from the s u p e r i o r c e r v i c a l g a n g l i o n appears to be predominantly f a c i l i t a t o r y to both r e c e p t o r groups i n ca t s and dogs ( F l o y d and N e i l 1952; E y z a g u i r r e and Lewin 1961b; Koizumi and Sato 1969; O'Regan 1981; Tomomatsu and N i s h i 1981), although a number of i n h i b i t o r y e f f e r e n t s have been found ( K e i t h et a l . 1974; O'Regan 1981). Sympathetic outflow i n c r e a s e s to many areas of the p e r i p h e r y during n a s a l s t i m u l a t i o n (White and McRitchie 1973; White et a l . 1974), and may s i m i l a r l y i n c r e a s e to c a r o t i d b i f u r c a t i o n receptor a r e a s . In a d d i t i o n , there may be i n h i b i t o r y f i b r e s which run i n the c a r o t i d sinus nerve to the chemoreceptors (Sampson and Biscoe 1970; N e i l and O'Regan 1971), and p o s s i b l y a l s o to the bar o r e c e p t o r s (Koushanpour and Behnia 1982). These e f f e r e n t f i b r e s d i s p l a y a random or non-rhythmical discharge i n c a t s (Biscoe and Sampson 1968), and have been p o s t u l a t e d to be of parasympathetic o r i g i n (see Majcherczyk e_t a_l. 1980). The sinus nerve a l s o c o n t a i n s e f f e r e n t s which d i s p l a y a r h y t h m i c a l , 6 r e s p i r a t o r y modulated d i s c h a r g e , probably of sympathetic o r i g i n (Biscoe and Sampson 1968). The i n h i b i t o r y e f f e c t of the non-rhythmic c a r o t i d sinus e f f e r e n t s on chemoreceptors and b a r o r e c e p t o r s i s c o n t r o v e r s i a l . These e f f e r e n t s , however, respond to an i n c r e a s e i n blood pressure with a delayed burst of a c t i v i t y ; and to apnoea with a slow i n c r e a s e i n a c t i v i t y (Biscoe and Sampson 1968; N e i l and 0"Regan 1971; Majcherczyk et al. 1980). T h i s i n c r e a s e in e f f e r e n t a c t i v i t y may then be important i n modulating the a f f e r e n t r e c e p t o r d i s c h a r g e d u r i n g n a s a l s t i m u l a t i o n . The c a r o t i d sinus r h y t h m i c a l e f f e r e n t s respond to an i n c r e a s e in blood p r e s s u r e , which may occur during a d i v e , with a decrease in a c t i v i t y (Biscoe and Sampson 1968). There i s a l s o an i n c r e a s e i n the sympathetic outflow to the p e r i p h e r y during n a s a l s t i m u l a t i o n (White and McRitchie 1973; White et a l . 1974). The r e s u l t a n t a c t i v i t y of the r h y t h m i c a l c a r o t i d sinus e f f e r e n t s may then be a combination of these two e f f e c t s . In a d d i t i o n , the l a c k of c e n t r a l r e s p i r a t o r y output d u r i n g a dive (Drummond and Jones, unpublished o b s e r v a t i o n s ) , may a l l o w the n a t u r a l 2-6, and 10 c y c l e s / s rhythym of sympathetic d i s c h a r g e to emerge (Gebber 1980; Gebber and Barman 1982). The d i v e r s e c a r d i o v a s c u l a r and r e s p i r a t o r y changes that comprise the d i v i n g response may have the c a p a c i t y to modify the a f f e r e n t and e f f e r e n t d i s c h a r g e i n the c a r o t i d sinus nerve. The r e s u l t a n t a f f e r e n t input may then have important i m p l i c a t i o n s f o r the r o l e of the b a r o r e c e p t o r s i n the i n i t i a t i o n and maintenance of the d i v i n g response, and f o r the r o l e of the 7 chemoreceptors in the maintenance of the d i v i n g response. Consequently, the purpose of t h i s t h e s i s i s to examine the d i s c h a r g e c h a r a c t e r i s t i c s of the b a r o r e c e p t o r and chemoreceptor f i b r e s from the cut c a r o t i d sinus nerve i n the a n a e s t h e t i z e d muskrat, Ondatra z i b e t h i c a . The b a r o r e c e p t o r s w i l l be c h a r a c t e r i z e d , and t h e i r modulation d u r i n g simulated d i v i n g by n a s a l s t i m u l a t i o n w i l l be compared to t h e i r response dur i n g a s i m i l a r i n c r e a s e i n blood pressure i n a p r e s s o r t e s t . In a s i m i l a r f a s h i o n , the chemoreceptors w i l l a l s o be c h a r a c t e r i z e d , and t h e i r modulation d u r i n g n a s a l s t i m u l a t i o n w i l l be compared to t h e i r response dur i n g a s i m i l a r time p e r i o d of n i t r o g e n v e n t i l a t i o n i n a n i t r o g e n t e s t . As both types of a f f e r e n t d i s c h a r g e i n the c a r o t i d s i n u s nerve may be modulated by the e f f e r e n t a c t i v i t y which i s a l s o present i n the c a r o t i d sinus nerve, n e u r a l a c t i v i t y w i l l be recorded from the c e n t r a l end of the cut s i n u s nerve. The e f f e r e n t d i s c h a r g e s w i l l be c h a r a c t e r i z e d , and t h e i r response to s t i m u l a t i o n of the nares of the muskrat w i l l be recorded. 8 METHODS Experiments were done on 16 muskrats of both sexes, v a r y i n g i n weight from 0.548 to 1.124 kg (mean ± SD = 0.588 ± 0.158). The animals were a n a e s t h e t i z e d with urethane ( D i a l u r e t h a n e , 1000 mg/kg) or f e n t a n y l and d r o p e r i d o l (Innovar, 0.2 mL/kg) and t h i o p e n t a l sodium ( P e n t o t h a l , 0.25 mg/kg) i n j e c t e d i n t r a -p e r i t o n e a l l y , a f t e r p r i o r i n d u c t i o n with e t h y l ether. The l a t t e r combination of drugs r e s u l t e d i n a l i g h t a n aesthesia l e v e l and t h e r e f o r e i n i t i a l l y , and p e r i o d i c a l l y throughout the experiment, a l l i n c i s i o n s were i n f i l t r a t e d with- l o c a l a n a e s t h e t i c ( X y l o c a i n e , 2%). If the a n a e s t h e s i a l e v e l became to l i g h t , more drugs were i n j e c t e d u n t i l a s a t i s f a c t o r y plane of anaes t h e s i a was achieved. A f t e r p l a c i n g the animal on i t s back, the trachea was cannulated low i n the neck, and the muskrats were then p a r a l y z e d with d-tubocurare (Tubarine, 0.2 mg/kg). V e n t i l a t i o n with h u m i d i f i e d room a i r , supplemented with oxygen when necessary, was c a r r i e d out with a p o s i t i v e p r essure pump at a frequency of .70 breaths per minute. End i n s p i r a t o r y p r essure was set at approximately 5 cm H 20 and maximum i n s p i r a t o r y p ressure d i d not exceed 15 cm H 20. I n t r a t r a c h e a l r e s p i r a t o r y p r e s s u r e s were monitored with a Statham P23V pressure t r a n s d u c e r . R e c t a l temperature was monitored and maintained at 37°C by means of a h e a t i n g pad, with a d d i t i o n a l r a d i a n t heat when necessary. In a l l animals, both femoral a r t e r i e s were cannulated with p o l y e t h y l e n e tubing (i.d.=0.58 mm, o.d.=0.965 mm). , One cannula was att a c h e d to a B i o t e c BT70 pr e s s u r e transducer f o r continuous 9 measurement of blood p r e s s u r e . The other cannula was attached to a s a l i n e - p h e n y l e p h r i n e r e s e r v o i r (Neo-synephrine, 0.04 mg/ml) with a pressure head of 67 cm H 20. If a r t e r i a l pressure dropped below 67 cm H 20 then the r e s e r v o i r system d r a i n e d i n t o the a r t e r y , i n c r e a s i n g the a r t e r i a l c o n s t r i c t i o n , and t h e r e f o r e m a i n t a i n i n g blood p r e s s u r e . During a p r o t o c o l , the r e s e r v o i r system was c l o s e d and the cannula used f o r the. i n t r a - a r t e r i a l i n j e c t i o n of drugs. The l e f t c a r o t i d b i f u r c a t i o n was exposed by c u t t i n g the trachea and the esophagus and r e t r a c t i n g them i n the m i d l i n e . The l e f t c a r o t i d sinus nerve was i d e n t i f i e d , i s o l a t e d and cut at i t s j u n c t i o n with the glossopharyngeal nerve when r e c o r d i n g the a f f e r e n t a c t i v i t y , or cut as i t j o i n e d the c a r o t i d b i f u r c a t i o n when r e c o r d i n g e f f e r e n t a c t i v i t y . The r i g h t c a r o t i d sinus nerve, and both a o r t i c nerves were l e f t i n t a c t . The cut nerve was l a i d on a small metal p l a t e and d i s s e c t e d i n a pool of warm l i q u i d p a r a f f i n (37°C). A c t i v i t y from s m a l l f i l a m e n t s was recorded with b i p o l a r s i l v e r e l e c t r o d e s , a m p l i f i e d (Framp Pra-1), and monitored on a o s c i l l o s c o p e ( T e k t r o n i x 5113). The a c t i v i t y from s i n g l e or f e w - f i b r e p r e p a r a t i o n s was used to t r i g g e r a window d i s c r i m i n a t o r (WPI). P u l s e s from the window d i s c r i m i n a t o r were then counted by a rate meter and d i s p l a y e d as pu l s e s per second (pps). Blood pressure and r e s p i r a t o r y p r e s s u r e , or blood pressure and the nerve frequency response were d i s p l a y e d on a Gould 220 c h a r t recorder. Blood p r e s s u r e , r e s p i r a t o r y pressure and the u n f i l t e r e d nerve a c t i v i t y were a l s o recorded on magnetic tape (Tanberg). 10 Experimental P r o t o c o l The c a r o t i d b a r o r e c e p t o r s were" i d e n t i f i e d by t h e * r e l a t i o n of t h e i r d i s c h a r g e with blood pressure p u l s e s and the c e s s a t i o n of a c t i v i t y upon o c c l u s i o n of the l e f t common c a r o t i d a r t e r y . The response of c a r o t i d baroreceptors to changes i n a r t e r i a l blood pressure was determined by the slow i n f u s i o n of phenylephrine (Neo-Synephrine h y d r o c h l o r i d e , Winthrop, 0.35 mls/kg) or papaverine (Papaverine h y d r o c h l o r i d e , F r o s s t , 4.0 mls/kg). Mean a r t e r i a l blood pressure versus baroreceptor a c t i v i t y response curves were then c o n s t r u c t e d . Mean a r t e r i a l p r e s sure was used as the independant v a r i a b l e , as i t has the best c o r r e l a t i o n with baroreceptor a c t i v i t y and f u n c t i o n (Landgren 1952; Arndt et a l . 1977). Baroreceptor a c t i v i t y was a l s o monitored d u r i n g a pres s o r t e s t , where an i n c r e a s e i n blood pressure was induced by a r a p i d i n j e c t i o n of phenylephrine (0.35 mls/kg i . a . ). Phenylephrine i n c r e a s e s blood pressure through i t s a f f e c t s on the p e r i p h e r a l v a s c u l a t u r e and has minimal d i r e c t c a r d i a c e f f e c t s , as w e l l as minimal e f f e c t s on the b a r o r e c e p t o r s themselves ( F a r i s et a l . 1980; Peveler et a l . 1983). The c a r o t i d body chemoreceptors were i d e n t i f i e d by t h e i r s p o r a d i c random d i s c h a r g e , and the prompt i n c r e a s e i n a c t i v i t y i n response to apnoea. The response of the chemoreceptors to changes i n blood oxygen t e n s i o n s was determined by v e n t i l a t i o n of the muskrat with d i f f e r e n t gas mixtures. F r a c t i o n of i n s p i r e d oxygen versus chemoreceptor a c t i v i t y response curves were then c o n s t r u c t e d . Chemoreceptor a c t i v i t y was a l s o monitored d u r i n g a n i t r o g e n t e s t , when the muskrat was 11 v e n t i l a t e d with n i t r o g e n . Both baroreceptor and chemoreceptor d i s c h a r g e s were monitored before and d u r i n g simulated d i v i n g induced by n a s a l s t i m u l a t i o n while s i m u l t a n e o u s l y stopping the v e n t i l a t i o n pump with the lungs d e f l a t e d . S t i m u l a t i o n of the r e c e p t o r s in the nares was achieved by p a s s i n g water through an o r a l l y f a c i n g t r a c h e a l tube and out of the nares, at a flow r a t e of 150 mis per minute. In t h i s t h e s i s the terms nasal s t i m u l a t i o n and flowing water through the nares are used synonymously. The terms d i v e and dive response are a l s o used and- encompass a l l n a r i a l s t i m u l a t i o n r e s u l t i n g i n a response t y p i f i e d by d i v i n g b r a d y c a r d i a . Two types of e f f e r e n t a c t i v i t y from the c e n t r a l side of the c u t sinus nerve was recorded from four muskrats. A c t i v i t y with a r h y t h m i c a l d i s c h a r g e was recorded from three muskrats (type A e f f e r e n t ) and random or non-rhythmical a c t i v i t y was recorded from one muskrat (type B e f f e r e n t ) . The response of both types of e f f e r e n t a c t i v i t y to i n c r e a s e s (1.0 mls/kg phenylephrine) and decreases (5.0 mls/kg papaverine) i n blood pressure was monitored. The response to changes in the frequency of the a r t i f i c i a l v e n t i l a t i o n was a l s o recorded f o r both types of e f f e r e n t a c t i v i t y . As the a c t i v i t y of the type A e f f e r e n t s appeared to be r e l a t e d to r e s p i r a t o r y frequency, the response of these f i b r e s to a two minute p e r i o d of apnoea was a l s o recorded. In a d d i t i o n , the response of both types of e f f e r e n t a c t i v i t y was monitored before and d u r i n g n a s a l s t i m u l a t i o n . 1 2 Measurements and A n a l y s i s Mean bloo d pressure" was- c a l c u l a t e d - from the blood pressure" t r a c e using the formulae MAP = (2D+S)/3, where D = d i a s t o l i c blood p r e s s u r e and S = s y s t o l i c blood p r e s s u r e . C a r d i a c i n t e r v a l s were a l s o measured from the blood pressure t r a c e , and were taken as the mean of three c o n s e c u t i v e i n t e r v a l s i n a l l p r e - t e s t , t e s t , p r e - d i v e and d i v e s i t u a t i o n s . When stu d y i n g the bar o r e c e p t o r response to d i v i n g , however, the d i v e c a r d i a c i n t e r v a l was the f i r s t c a r d i a c i n t e r v a l a f t e r the commencement of n a s a l s t i m u l a t i o n , and not the means of the f i r s t three i n t e r v a l s . V e n t i l a t i o n frequency was measured from the r e s p i r a t o r y p ressure t r a c e and c a l c u l a t e d as the mean of three c o n s e c u t i v e i n t e r v a l s , then converted to breaths per minute. Neural a c t i v i t y was measured i n three ways. In most cases the a c t i v i t y l e v e l s were measured as p u l s e s per second (pps). The type A e f f e r e n t s were a l s o measured i n t h i s way, but i n a d d i t i o n they were q u a n t i f i e d as the mean of the i n t e r v a l s between three c o n s e c u t i v e b u r s t s of c y c l i c a c t i v i t y , converted to c y c l e s per minute. F i n a l l y , c o n s t r u c t i o n of chemoreceptor response curves was f a c i l i t a t e d by co u n t i n g the number of a c t i o n p o t e n t i a l s over a 60 second time p e r i o d , f o r any given gas mixture, which was then expressed as pulses per second. Values i n the tex t are given as means ± standard e r r o r of N animals, u n l e s s otherwise noted. T e s t s f o r s i g n i f i c a n c e were c a r r i e d out u s i n g a m o d i f i e d a n a l y s i s of v a r i a n c e (Anvart) f o r repeated measures over time i n the case of the a r t e r i a l p r e s s u r e and c a r d i a c i n t e r v a l responses to n a s a l s t i m u l a t i o n . A two way 13 anova was used when comparing the mean a r t e r i a l p r e ssure and c a r d i a c i n t e r v a l response to the p r e s s o r t e s t with t h e i r response to n a s a l s t i m u l a t i o n . In the case of a s i g n i f i c a n t F value (P < 0.05), p a i r e d comparisons of means was done with Scheffe's t e s t . 14 RESULTS I_. C a r d i a c and Blood P r e s s u r e Responses to Nasal S t i m u l a t i o n The c a r d i a c i n t e r v a l s and blood p r e s s u r e s from s i x t e e n experiments are presented i n Table I. There was c o n s i d e r a b l y more v a r i a t i o n i n the p r e - d i v e blood pressure (80.5 ± 26.6 mmHg X ± SD) on a percentage b a s i s , than in the c a r d i a c i n t e r v a l (219 ± 31 msec = X ± SD). Running water through the nares at the same time as stopping the v e n t i l a t i o n pump, r e s u l t e d i n an immediate and s i g n i f i c a n t l e n g t h e n i n g of the subsequent c a r d i a c i n t e r v a l s , from 219 ± 7.7 msec to 1,474 ± 234 msec (Table I ) , an incr e a s e of over s i x - f o l d . As the di v e progressed, the c a r d i a c i n t e r v a l g r a d u a l l y shortened. A di v e was terminated when the c a r d i a c i n t e r v a l had decreased to a value of approximately twice the p r e - d i v e i n t e r v a l , or a time p e r i o d of two minutes had elapsed, whichever came f i r s t . T h i s r e s u l t e d i n an mean d i v e l e n g t h of 52.7 ± 31.7 seconds (X ± SD), and a mean end div e c a r d i a c i n t e r v a l of 640 ± 74 msec (Table I ) . In el e v e n of the d i v e s there was an i n i t i a l s l i g h t f a l l i n mean a r t e r i a l p r e s s u r e , w h i l e i n the remaining f i v e d i v e s there was a small i n c r e a s e . The net r e s u l t was a s i g n i f i c a n t decrease i n mean bloo d pressure (Table I ) . As the dive progressed, mean pressures i n c r e a s e d , as both d i a s t o l i c and s y s t o l i c pressures rose. At the te r m i n a t i o n of the d i v e , a mean bloo d pressure of 108.8 ± 7.9 mmHg was reached. T h i s was s i g n i f i c a n t l y above the pre - d i v e p r e s s u r e s (Table I ) , r e p r e s e n t i n g an i n c r e a s e of over 40%. 1 5 Table I. E f f e c t of nasal s t i m u l a t i o n with water on mean a r t e r i a l blood pressure and c a r d i a c i n t e r v a l i n the muskrat. Values are means ± SE of N animals. Pre-dive values were obtained 10 seconds before n a s a l s t i m u l a t i o n . Dive va l u e s were obtained from the f i r s t three pressure p u l s e s a f t e r n a s a l s t i m u l a t i o n and end-dive va l u e s were obt a i n e d from the three pressure p u l s e s before the t e r m i n a t i o n of n a s a l s t i m u l a t i o n . MAP = mean a r t e r i a l blood p r e s s u r e (mmHg); CI = c a r d i a c i n t e r v a l (msecs). Table I. - Ef f e c t of nasal stimulation with water on mean a r t e r i a l blood pressure and cardiac Interval in the muskrat. pre-dlve dive end-dive MAP 80.5±6.6 68.3±5.9 * 108.8+7.9 * (N=16) 41 CI 219±7.7 1474±234 * 640174 (N=16) * s i g n i f i c a n t at p<0.05 from pre-dlve. 17 I I . B a r o r e c e p t o r A c t i v i t y d u r i n g a P r e s s o r T e s t and d u r i n g N a s a l S t i m u l a t i o n A t o t a l of t e n s i n g l e f i b r e b a r o r e c e p t o r s were r e c o r d e d from t e n muskr a t s . I n f u s i o n of p h e n y l e p h r i n e (0.35 mls/kg) or pa p a v e r i n e (4.0 mls/kg) produced changes i n mean a r t e r i a l b l o o d p r e s s u r e , as w e l l as changes i n peak r e c e p t o r a c t i v i t y ( F i g u r e 1). The f i b r e on the l e f t i n F i g u r e 1 had a t h r e s h o l d a t a p r e s s u r e of 58.0 mmHg, and a fr e q u e n c y response of 95 p u l s e s per second (pps) a t the maximum p r e s s u r e a t t a i n e d of 130.0 mmHg. The f i b r e on the r i g h t had a h i g h e r t h r e s h o l d , a t a p r e s s u r e of 83.0 mmHg, and a lower d i s c h a r g e frequency of 20 pps a t a maximum p r e s s u r e of 135.0 mmHg. The fr e q u e n c y response c u r v e s of the o t h e r b a r o r e c e p t o r s were s i m i l a r t o t h e s e r e p r e s e n t a t i v e c u r v e s , a l t h o u g h i n d i v i d u a l r e c e p t o r t h r e s h o l d s and d i s c h a r g e f r e q u e n c i e s a t maximum b l o o d p r e s s u r e s v a r i e d . The b a r o r e c e p t o r response i n the p r e s s o r t e s t was m o n i t o r e d by t r a n s i e n t l y i n c r e a s i n g mean a r t e r i a l b l o o d p r e s s u r e by i n t r a -a r t e r i a l i n j e c t i o n of p h e n y l e p h r i n e . R e c o r d i n g s were o b t a i n e d from f i v e b a r o r e c e p t o r s d u r i n g a p r e s s o r t e s t . I n j e c t i o n of 0.35 mls/kg p h e n y l e p h r i n e r e s u l t e d i n a s i g n i f i c a n t i n c r e a s e i n mean b l o o d p r e s s u r e , from 84.6 ± 13.7 mmHg t o 149.0 ± 8.0 mmHg. As the b l o o d p r e s s u r e r o s e , the c a r d i a c i n t e r v a l a l s o i n c r e a s e d s i g n i f i c a n t l y ( T a ble I I ) . C o n c u r r e n t w i t h t h e i n c r e a s e i n mean a r t e r i a l p r e s s u r e , b a r o r e c e p t o r a c t i v i t y i n c r e a s e d , from 2.25X to 6.7X t h a t of. the p r e - t e s t d i s c h a r g e r a t e s (Table I I ) . A t y p i c a l r e c o r d i n g o b t a i n e d d u r i n g a p r e s s o r t e s t i s shown i n F i g u r e 2. 18 F i g u r e 1. E f f e c t of changing mean a r t e r i a l blood pressure (MAP) on the n e u r a l a c t i v i t y (NA) of two s i n g l e f i b r e b a r o r e c e p t o r s . 19 20 Table I I . E f f e c t of the p r e s s o r t e s t on mean a r t e r i a l p r e s s u r e , c a r d i a c i n t e r v a l and the n e u r a l a c t i v i t y of f i v e s i n g l e f i b r e b a r o r e c e p t o r s from f i v e muskrats. P r e - t e s t values were obtained 10 seconds before the t e s t and t e s t values were obtained at the peak of the blood pressure response. BP = a r t e r i a l blood pressure (mmHg); CI = c a r d i a c i n t e r v a l (msecs); NA = neural a c t i v i t y (pps). 21 Table II. - Ef f e c t of the pressor test on mean a r t e r i a l blood pressure, cardiac interval and the neural a c t i v i t y of f i v e single f i b r e baroreceptors from f i v e muskrats. f i b r e a pre-test test 1ncrease MAP CI NA 72 .0 200 24 142.0 240 90 70.0 40 3.75X MAP CI NA 92 .0 200 10 167 .0 800 38 75.0 600 3 . 8X MAP CI NA 38.0 200 6 125.0 240 40 87.0 40 6.7X MAP CI NA 113. 240 4 167.0 600 16 54 360 4 .OX MAP CI NA 108 . 200 8 145.0 380 18 37 .0 180 2.25X Mean ±SE MAP CI 84.6±13.7 208±8.0 149.0+8.0 * 4521109.0 * * s i g n i f i c a n t at p<0.05 from pre-test. 22 F i g u r e 2 . E f f e c t of i n c r e a s i n g a r t e r i a l blood pressure (BP) by i n t r a - a r t e r i a l i n j e c t i o n of phenylephrine on the neu r a l a c t i v i t y (NA) of a s i n g l e f i b r e b a r o r e c e p t o r . 23 24 Running water through the nares r e s u l t e d i n an immediate lengthening of the c a r d i a c i n t e r v a l , a'- decrease' in mean blood" p r e s s u r e , and an abrupt h a l t to barore c e p t o r discharge i n a l l ten b a r o r e c e p t o r s recorded. Discharge remained absent f o r a p e r i o d of time equal to that of the g r e a t l y lengthened i n i t i a l c a r d i a c i n t e r v a l of the dive (Table I I I ) . With every subsequent pressure pulse there was a burst of baroreceptor a c t i v i t y . These b u r s t s became s u c c e s s i v e l y l a r g e r as the mean a r t e r i a l p r e s s u r e slowly i n c r e a s e d d u r i n g the d i v e ( F i g u r e 3). When, the d i v e was terminated, baroreceptor a c t i v i t y had r i s e n to l e v e l s 2.7X to 7.5X that of p r e - d i v e l e v e l s (Table I I I ) . T h i s increase i n a c t i v i t y was seen i n a l l the r e c e p t o r s , although i t was somewhat atte n u a t e d i n the high t h r e s h o l d , low frequency response f i b r e s ( f i b r e #4,#5,#7 and #9, Table I I I ) . One f i b r e ( f i b r e #6, Table I I I ) showed a l a r g e i n c r e a s e i n a c t i v i t y , even though the i n c r e a s e i n mean a r t e r i a l p r e s s u r e was s m a l l . A two way a n a l y s i s of v a r i a n c e f o r the c a r d i a c i n t e r v a l and _ the mean a r t e r i a l blood pressure changes of the f i v e muskrats t e s t e d i n the pr e s s o r t e s t and i n the d i v e , f o r the same ba r o r e c e p t o r s ( f i b r e s #1-5, Table II and I I I ) , was done. There was no s i g n i f i c a n t d i f f e r e n c e between the p r e - t e s t and pre-dive c a r d i a c i n t e r v a l s and mean blood p r e s s u r e s . As w e l l , there was no s i g n i f i c a n t d i f f e r e n c e between the pr e s s o r t e s t and the end-d i v e c a r d i a c i n t e r v a l s and mean a r t e r i a l blood p r e s s u r e s . However, i n both the pres s o r t e s t and the dive there was a s i g n i f i c a n t i n c r e a s e i n the c a r d i a c i n t e r v a l and mean blood p r e s s u r e . Baroreceptor a c t i v i t y i n c r e a s e d by a s i m i l a r r e l a t i v e 2 5 Table I I I . E f f e c t of nasal s t i m u l a t i o n with water on mean a r t e r i a l blood p r e s s u r e , c a r d i a c i n t e r v a l and the n e u r a l a c t i v i t y of ten s i n g l e f i b r e b a r o r e c e p t o r s from ten muskrats. Pr e - d i v e , d i v e and end-dive values were obtained as d e s c r i b e d i n Table I. A b b r e v i a t i o n s are the same as i n Table I I . Table I I I . - Effect of nasal stimulation with water on mean a r t e r i a l blood pressure, cardiac interval and the neural a c t i v i t y of ten s i n g l e f i b r e baroreceptors from ten muskrats. f i b r e H pre-dive dive end-dive increase MAP 58.0 45.0 85.0 27.0 1 CI 208 1000 1200 992 NA 15 12 54 3.6X MAP 102.0 78.0 132.0 30 2 CI 185 1200 600 415 NA 6 0 16 2.7X MAP 52.0 58.0 112.0 60 3 CI 204 3600 700 496 NA 4 18 30 7.5X MAP 98.0 73.0 137.0 39.0 4 CI 200 1200 1000 800 NA 4 0 16 4.OX MAP 118.0 108.0 168.0 50.0 5 CI 178 500 400 222 NA 8 4 22 2.75X MAP 73.0 47.0 77.0 40.0 6 CI 210 1600 1200 990 NA 20 0 60 3. OX MAP 47.0 50.0 82.0 35 7 CI 256 1100 800 544 NA 6 6 20 3.3X MAP 122.0 108.0 148.0 26.0 8 CI 196 600 300 104 NA 22 12 58 2.6X MAP 85.0 95.0 123.O 38.0 9 CI 250 2000 800 550 NA 4 4 28 7.OX MAP 105.0 95.0 117.O 12.0 10 CI 200 960 400 200 NA 30 28 72 2.4X Mean MAP 86.0±8.6 75.717.9 118.119.5 ±SE CI 20918.0 13701280 740+102 27 F i g u r e 3. E f f e c t of n a s a l s t i m u l a t i o n with water (dive) on a r t e r i a l blood pressure (BP) and baroreceptor a c t i v i t y . ENG = electroneurogram of a s i n g l e f i b r e b a r o r e c e p t o r ; NA = baroreceptor a c t i v i t y (pps). T h i s i s the same receptor as i n F i g u r e 2. 28 29 amount i n both cases (cf Table II and Table I I I ) , although the peak a c t i v i t i e s which were reached d i f f e r e d s l i g h t l y . I I I . Chemoreceptor A c t i v i t y d u r i n g a Nitrogen Test and during Nasal S t i m u l a t i o n Only two r e c o r d i n g s of chemoreceptor a c t i v i t y were obtained, one each from two muskrats. One r e c o r d i n g c o n s i s t e d of s i n g l e f i b r e a c t i v i t y , while the other r e c o r d i n g d i s p l a y e d a f e w - f i b r e output. Changing the l e v e l of i n s p i r e d oxygen caused changes i n receptor a c t i v i t y , r e s u l t i n g i n the response curve shown i n F i g u r e 4. The chemoreceptor response to the n i t r o g e n t e s t was obtained by v e n t i l a t i n g the muskrat with 100% n i t r o g e n f o r a p e r i o d of time equal to that of the n a s a l s t i m u l a t i o n (Figure 5). T h i s r e s u l t e d i n a i n c r e a s e i n chemoreceptor a c t i v i t y , 2.5X to 4.7X that of p r e - t e s t l e v e l s (Table IVa). C o n c u r r e n t l y , mean a r t e r i a l p r essure i n c r e a s e d by an average of 13.5 mmHg, while the c a r d i a c i n t e r v a l showed no change. Flowing water through the nares, although r e s u l t i n g i n an i n c r e a s e i n c a r d i a c i n t e r v a l and l a r g e f l u c t u a t i o n s i n beat to beat blood pressure, had no i n i t i a l e f f e c t on chemoreceptor a c t i v i t y . As the dive progressed, the chemoreceptor a c t i v i t y g r a d u a l l y i n c r e a s e d (Figure 6). At the end of the d i v e , peak a c t i v i t y l e v e l s were lower than those seen during a s i m i l a r time p e r i o d of n i t r o g e n v e n t i l a t i o n (Table IVb). In r e l a t i v e terms t h i s was an i n c r e a s e i n the f e w - f i b r e discharge of 2.5X during n i t r o g e n v e n t i l a t i o n and 2.OX d u r i n g n a s a l s t i m u l a t i o n . For the 30 Fig u r e 4 . E f f e c t of changing the f r a c t i o n of i n s p i r e d oxygen ( F i o 2 ) on the n e u r a l a c t i v i t y (NA) of a s i n g l e f i b r e chemoreceptor. 31 32 F i g u r e 5 . E f f e c t of n i t r o g e n t e s t on the a r t e r i a l blood pressure (BP) and on n e u r a l a c t i v i t y (NA) of a s i n g l e f i b r e chemoreceptor. 33 in i L. O O J o ID I I I O o o eg O) a CL 34 Table IV. Response of chemoreceptor a c t i v i t y ,to A. The n i t r o g e n t e s t and B. Nasal s t i m u l a t i o n with water. P r e - t e s t values were obtained 10 seconds before the t e s t , and t e s t v a l u e s were obtained a f t e r a time p e r i o d equal to that of the nasal s t i m u l a t i o n . Pre-dive and end-dive values were obtained as d e s c r i b e d i n Table I. A b b r e v i a t i o n s are the same as i n Table I I . Table IV. - Response of chemoreceptor a c t i v i t y to A. the nitrogen test and B. nasal stimulation. A. Nitrogen test B. Nasal stimulation f i b r e # pre-test test increase pre-dive end-dive increase MAP 65.0 87.0 22.0 80.0 110.0 30.0 CI 220 220 0 220 330 110 NA 40 100 2.5X 50 100 2. OX MAP 48.0 53.0 5.0 48.0 52.0 4.0 CI 260 260 0 270 680 410 NA . 6 28 4.7X 14 22 1.6X 36 F i g u r e 6. E f f e c t of nasa l s t i m u l a t i o n with water (dive) on a r t e r i a l blood pressure (BP) and chemoreceptor a c t i v i t y . ENG = electroneurogram of a s i n g l e f i b r e chemoreceptor; NA = chemoreceptor nerve (pps). T h i s i s the same receptor as in Figure 5. Pre-dive BP [mmHg] ENG NA [pps] 100r-50h ^ ^^^^^^\mLMm\ o 20 T 0 L Dive 40s H 1 5s 38 s i n g l e f i b r e , t h i s was an i n c r e a s e i n di s c h a r g e of 4.7X d u r i n g n i t r o g e n v e n t i l a t i o n and 1.6X d u r i n g the d i v e . In a d d i t i o n , d u r i n g n i t r o g e n v e n t i l a t i o n the a c t i v i t y was c o n s i s t e n t l y at a higher l e v e l than chemoreceptor a c t i v i t y observed d u r i n g n a s a l s t i m u l a t i o n ( c f Fi g u r e 5+6). IV. E f f e r e n t C h a r a c t e r i z a t i o n and Modulation by Nasal S t i m u l a t i o n Two types of e f f e r e n t a c t i v i t y were recorded from the cut c e n t r a l end of the c a r o t i d sinus nerve ( F i g u r e 7a+b). Few-fibre a c t i v i t y with a rhythmical d i s c h a r g e p a t t e r n was recorded from 3 muskrats (type A e f f e r e n t ) . The peak d i s c h a r g e r a t e ( p u l s e s per second) v a r i e d c o n s i d e r a b l y from p r e p a r a t i o n to p r e p a r a t i o n , but the r h y t h m i c a l a c t i v i t y ( c y c l e s per minute) was c o n s i s t e n t and c o i n c i d e n t with the r e s p i r a t o r y pump frequency of 70 breaths per minute ( F i g u r e 7a). E f f e r e n t a c t i v i t y was a l s o recorded from one muskrat that d i s p l a y e d a random, non-rhythmical d i s c h a r g e (type B e f f e r e n t ) . As t h i s a c t i v i t y was much smal l e r i n amplitude than the rh y t h m i c a l a c t i v i t y , the nerve was subdivi d e d , u n t i l s i n g l e f i b r e d i s c h a r g e was obtained ( F i g u r e 7b) . Changes i n the pump v e n t i l a t i o n frequency r e s u l t e d i n changes i n the type A a c t i v i t y , measured as c y c l e s per minute (Figure 8), but had no c o n s i s t e n t e f f e c t on peak d i s c h a r g e (pps). Over the mid-range of v e n t i l a t i o n , from 20 to 75 breaths per minute, t h e r e appeared to be a one to one r e l a t i o n s h i p with the c y c l i c d i s c h a r g e . These c y c l e s of a c t i v i t y were, however, gure 7. Trace showing the two types of e f f e r e n t a c t i v i t y recorded from the cut c e n t r a l end of the c a r o t i d sinus nerve. A = type A e f f e r e n t , B = type B e f f e r e n t . RP = i n t r a t r a c h e a l r e s p i r a t o r y p r e s s u r e . 40 41 not always i n exact synchrony with the a r t i f i c i a l v e n t i l a t i o n (see F i g u r e 7a). At higher v e n t i l a t i o n f r e q u e n c i e s , the c y c l i c d i s c h a r g e was below the r e s p i r a t o r y pump f r e q u e n c i e s . At very low v e n t i l a t i o n f r e q u e n c i e s (5-20 breaths per minute), a c t i v i t y c y c l e s were g r e a t e r in number than the v e n t i l a t i o n frequency (Figure 8). The slow r e s p i r a t o r y f r e q u e n c i e s r e s u l t e d i n l a r g e r r e s p i r a t o r y p r e s s u r e s and a lack of e f f e r e n t a c t i v i t y d u r i n g lung i n f l a t i o n ( F i gure 9). There was no obvious response of the type B f i b r e s to changes i n v e n t i l a t i o n frequency. The response to induced changes i n blood pressure d i f f e r e d between the two groups. An in c r e a s e (+33.8 ± 8.3 mmHg; 1.0 mls/kg phenylephrine, i . a . ) or decrease (-38.5 ± 7.3 mmHg; 5.0 mls/kg. papaverine, i.a.) i n blood p r e s s u r e had no e f f e c t on e i t h e r the peak discharge r a t e or the r a t e of c y c l i c a c t i v i t y of the type A d i s c h a r g e . Type B a c t i v i t y was not a f f e c t e d by a decrease i n blood pressure (-33.0 mmHg; 5.0 mls/kg papaverine, i . a . ) , but responded to an i n c r e a s e i n pr e s s u r e (+55.0 mmHg; 1.0 mls/kg phenylephrine, i .a.) with a burst of a c t i v i t y , a f t e r a l a t e n t p e r i o d of 22.5 seconds (Figure 10). T h i s burst reached a peak di s c h a r g e of 48 pps, and had a d u r a t i o n of 8.8 seconds. The response of the type A e f f e r e n t s to f o r c e d apnoea, with the lungs d e f l a t e d , of two minutes d u r a t i o n was a re d u c t i o n i n the ra t e of c y c l i c a c t i v i t y . The amount of re d u c t i o n ranged c o n s i d e r a b l y , from 1.2 c y c l e s per minute to 36.8 c y c l e s per minute (Table V ) . There was a s l i g h t i n c r e a s e i n the peak a c t i v i t y (pps) d u r i n g apnoea. Running water past the nares at the same time as stopping 42 F i g u r e 8. E f f e c t of changing the a r t i f i c i a l v e n t i l a t i o n frequency on the type A e f f e r e n t a c t i v i t y , . measured as c y c l e s per minute. (The l a r g e p o i n t at 72 breaths per minute r e p r e s e n t s a c o m p i l a t i o n of 4 data p o i n t s ) 100-• c ^ 80i U >s 60-•jl 40 u D 0) 20-/ 0 / % 0 20 40 6"o 80 100 120 ventilation frequency [breaths-01511''3 4 4 F i g u r e 9 . E f f e c t of a very low a r t i f i c i a l v e n t i l a t i o n frequency (8 breaths per minute) on a r t e r i a l blood pressure (BP), i n t r a t r a c h e a l r e s p i r a t o r y pressure (RP) and on the n e u r a l a c t i v i t y (NA) of a few f i b r e p r e p a r a t i o n of type A e f f e r e n t s . 45 46 F i g u r e 1 0 . E f f e c t of i n c r e a s i n g mean a r t e r i a l p r e ssure (MAP) by the i n t r a - a r t e r i a l i n j e c t i o n of phenylephrine on the neural a c t i v i t y (NA) of a s i n g l e f i b r e type B e f f e r e n t . 47 48 Table V. E f f e c t of A. A two minute apnoea and nasal s t i m u l a t i o n on the n e u r a l a c t i v i t y of the type A e f f e r e n t s , and B. Nasal s t i m u l a t i o n on the neural a c t i v i t y of a s i n g l e f i b r e type B e f f e r e n t . P r e - t e s t values were obtained 10 seconds before the apnoea. Test values were obtained from the f i r s t three pressure p u l s e s and b u r s t s of c y c l i c a c t i v i t y a f t e r apnoea. End-test values were obtained from the three pressure p u l s e s and b u r s t s of c y c l i c a c t i v i t y before the t e r m i n a t i o n of apnoea. P r e - d i v e , d i v e and end-dive v a l u e s were obtained as d e s c r i b e d i n Table I. CPM = c y c l e s per minute; a l l other a b b r e v i a t i o n s as i n Table I I . Table V. - Ef f e c t of A. a two minute apneoa and nasal stimulation on the neural a c t i v i t y of the type A efferents and B. nasal stimulation on the neural a c t i v i t y of the type B efferent. A. Type A Efferents Apneolc test Nasal stimulation f ibre ft pre-test test end-test pre-di ve dive end-dive MAP 58.0 53.0 48.0 90.0 70.0 95.0 1 CI 290 250 300 270 1000 500 NA 80 80 100 100 100 100 CPM 27 .0 26.5 25.8 31 2.4 25.8 MAP 53.0 50.0 40.0 48.0 37.0 60.0 2 CI 263 300 300 256 1700 430 NA 200 220 240 200 220 200 CPM 50.0 13.0 13.2 57 . 7 13.3 20.5 MAP 57.0 92.0 122 .0 55.0 47.0 120.0 3 CI 204 330 700 208 2800 600 NA 60 180 260 120 260 240 CPM 72 .0 56.3 22.8 69.0 1 .2 14.4 B. Type B Efferent Nasal stimulation f i b r e # pre-dive dive end-dive MAP 107.0 50.0 122.0 1 CI 196 3,000 300 NA 10 28 4 50 v e n t i l a t i o n with the lungs d e f l a t e d caused the rhythmical a c t i v i t y , to stop for a p e r i o d of time ranging from 4.5 to 51.6 seconds (Table Va). The a c t i v i t y then e i t h e r slowly s t a r t e d to i n c r e a s e , or continued at a much slower rhythm ( F i g u r e 11, Table Va). Note that "gasping" movements can be d i s c e r n e d as downward movements on the r e s p i r a t o r y t r a c e d u r i n g the d i v e (Figure 11). These r e s p i r a t o r y d e f l e c t i o n s are c o i n c i d e n t with a r e l a t i v e decrease i n the c a r d i a c i n t e r v a l , while immediately a f t e r a "gasp" there i s a r e l a t i v e increase i n the c a r d i a c i n t e r v a l . The "gasping" movements are a l s o c o i n c i d e n t with the type A d i scharge. Running water past the nares r e s u l t e d i n an immediate in c r e a s e i n a c t i v i t y of the type B e f f e r e n t . I n t e r e s t i n g l y , t h i s e f f e r e n t showed a response to n a s a l s t i m u l a t i o n before the c a r d i a c response was i n i t i a t e d ( F i g u r e 12). The burst of a c t i v i t y reached a peak discharge of 24 pps, and c o n t i n u e d for a d u r a t i o n of 6.6 seconds whereupon the a c t i v i t y l e v e l s returned to p r e - d i v e values and remained t h e r e f o r the d u r a t i o n of the d i v e (Table Vb). 51 Fig u r e 11. E f f e c t of nasal s t i m u l a t i o n with water (dive) and sto p p i n g the a r t i f i c i a l v e n t i l a t i o n i n d e f l a t i o n (RP) on a r t e r i a l blood pressure (BP) and the neural a c t i v i t y (NA) of a f e w - f i b r e p r e p a r a t i o n of type A e f f e r e n t s . Note the downward movements on the r e s p i r a t o r y t r a c e d u r i n g nasal s t i m u l a t i o n . 52 53 F i g u r e 12. E f f e c t of n a s a l a r t e r i a l blood pressure (NA) of a s i n g l e f i b r e s t i m u l a t i o n with water (dive) on (BP) and the n e u r a l a c t i v i t y type B e f f e r e n t . 54 5 5 DISCUSSION S t i m u l a t i o n of the nares i n muskrats with water r e s u l t e d i n a tremendous i n c r e a s e i n the c a r d i a c i n t e r v a l , as has been noted f o r most d i v i n g mammals (Bu t l e r and Jones 1982). In t h i s t h e s i s c a r d i a c i n t e r v a l r a t h e r than heart r a t e i s presented, s i n c e i t i s i n d i c a t i v e of the r a p i d c a r d i a c response to n a s a l s t i m u l a t i o n . The more c o n v e n t i a l l y used heart r a t e i s i n d i c a t i v e of a steady s t a t e s i t u a t i o n , but may not be an adequate r e f l e c t i o n of short term changes (Heslegrave et a l . 1979). Blood pressure* at the. s t a r t of. the dive- showed a s i g n i f i c a n t decrease, but by the end of the dive had s i g n i f i c a n t l y i n c r e a s e d over p r e - d i v e l e v e l s , as has been repor t e d p r e v i o u s l y f o r muskrats (Drummond and Jones 1979; Jones et a l . 1982). T h i s increase i n blood p r e s s u r e , i n the face of a decrease i n c a r d i a c output, has been assumed to be i n d i c a t i v e of a major sympathetic v a s o c o n s t r i c t i o n of the p e r i p h e r y ( I r v i n g et a l . 1942; E i s n e r et a l . 1966). The baroreceptor versus blood pressure response curves showed a trend f o r a dichotomy i n f i b r e types, such that e i t h e r a low t h r e s h o l d , high frequency d i s c h a r g e , or a h i g h t h r e s h o l d , low frequency discharge was observed. T h i s i s t y p i c a l of mammalian baroreceptors (Kircheim 1976). I n i t i a l l y , b a roreceptor a c t i v i t y i n the d i v e decreased to zero f o r a p e r i o d of time corresponding to the g r e a t l y lengthened i n i t i a l c a r d i a c i n t e r v a l . As the blood pressure rose d u r i n g the d i v e , the baroreceptor a c t i v i t y a l s o r o s e . By the end of the d i v e , the i n c r e a s e i n a c t i v i t y was comparable to that seen f o r a s i m i l a r 56 i n c r e a s e i n mean blood pressure i n the p r e s s o r t e s t . T h i s suggests that the baroreceptor a c t i v i t y i s not being m o d i f i e d by the e f f e c t s of the d i v i n g response on r e c e p t o r t h r e s h o l d or s e n s i t i v i t y , but that the a c t i v i t y i s being wholly modulated by the changes i n blood p r e s s u r e . The e x c e p t i o n may be f i b r e number 6 (Table I I I ) which had an i n c r e a s e i n a c t i v i t y even though the i n c r e a s e i n mean a r t e r i a l pressure was s m a l l . T h i s i n c r e a s e i s most l i k e l y due to a g r e a t e r amount of time the pressure wave was above the r e c e p t o r t h r e s h o l d (Landgren 1952), as the p u l s e pressure runoff a f t e r s y s t o l e i s slowed during a d i v e (see F i g u r e 3). Thus, as with the other b a r o r e c e p t o r s , i t i s probable that there i s no change i n the t h r e s h o l d or s e n s i t i v i t y of the baroreceptor due to the d i v i n g response. The chemoreceptors of the muskrat responded in t y p i c a l mammalian f a s h i o n to changes in i n s p i r e d oxygen l e v e l s . When these responses were p l o t t e d , a curve t y p i c a l of the p e r i p h e r a l chemoreceptors r e s u l t e d , with the base of the curve centered at normal oxygen l e v e l s ( E y z a g u i r r e and Lewis 1961a; Hornbein e_t a l . 1961; Biscoe et a_l. 1967,1970b). During n a s a l s t i m u l a t i o n the chemoreceptors showed a slow and e r r a t i c i n c r e a s e in a c t i v i t y , reaching l e v e l s below those seen d u r i n g a s i m i l a r time p e r i o d of n i t r o g e n v e n t i l a t i o n . T h i s i s probably due to wash out of oxygen from the lungs d u r i n g the n i t r o g e n v e n t i l a t i o n , as w e l l as a slower oxygen u t i l i z a t i o n d u r i n g the d i v e (Drummond 1980). Thus, from t h i s evidence i t appears that chemoreceptor a c t i v i t y i s not being d r a m a t i c a l l y a l t e r e d by the d i v i n g response, nor by the l a r g e blood pressure f l u c t u a t i o n s , which 57 under other c o n d i t i o n s a f f e c t s the chemoreceptor discharge (Biscoe et a l . 1970a). The response of the ba r o r e c e p t o r s and chemoreceptors to nas a l s t i m u l a t i o n suggests that nothing i s modulating t h e i r d i s c h a r g e beyond t h e i r usual stimulus m o d a l i t i e s . The sinus nerve was cut to r e c o r d the a f f e r e n t a c t i v i t y , t h e r e f o r e the e f f e r e n t f i b r e s running i n the c a r o t i d sinus nerve may a f f e c t the r e c e p t o r d i s c h a r g e recorded d u r i n g n a s a l s t i m u l a t i o n (Majcherczyk et. a l . 1980; Kousanpour and Behnia 1982). The e f f e r e n t s were t h e r e f o r e c h a r a c t e r i z e d and, t h e i r modulation by the d i v i n g response was monitored. The e f f e r e n t a c t i v i t y recorded from the c e n t r a l end of the cut c a r o t i d sinus nerve can be d i v i d e d i n t o two types by t h e i r d i f f e r e n t i a l response to 1) changes i n v e n t i l a t i o n frequency and 2) changes i n mean a r t e r i a l p r e s s u r e . The apparent time r e l a t i o n s h i p of the type A e f f e r e n t d i s c h a r g e to v e n t i l a t i o n and the i n h i b i t i o n of type A a c t i v i t y by a l a r g e lung i n f l a t i o n i s t y p i c a l of many types of sympathetic discharge (Adrian et a l . 1932; Koizumi et a l . 1971; Cohen et a l . 1980). A s i m i l a r type of r e s p i r a t o r y r e l a t e d a c t i v i t y has been recorded from the c e n t r a l end of the cut si n u s nerve i n the c a t . T h i s a c t i v i t y was a b o l i s h e d by c u t t i n g the nerve connection to the s u p e r i o r c e r v i c a l g a n g l i o n , showing that t h i s a c t i v i t y i s of sympathetic o r i g i n (Biscoe and Sampson 1968). S u r p r i s i n g l y , an in c r e a s e or decrease i n blood pressure had no e f f e c t on the peak discharge or c y c l i c a c t i v i t y of the type A e f f e r e n t s i n muskrats. In c a t s , i n j e c t i o n of a d r e n a l i n e i n c r e a s e s blood pressure and 58 decreases the rhy t h m i c a l a c t i v i t y recorded from the cut c e n t r a l end of the c a r o t i d sinus nerve (Biscoe and Sampson 1968). The e f f e c t of apnoea on the type A e f f e r e n t d i s c h a r g e suggests that the lack of pulmonary s t r e t c h receptor feedback, which reduces r e s p i r a t o r y , c y c l i c motor a c t i v i t y (Lumsden 1923/24), makes a major c o n t r i b u t i o n to the decrease i n d i s c h a r g e , while the prolonged asphyxia had minimal e f f e c t s (Okada and Fox 1976). During n a s a l s t i m u l a t i o n there was a h a l t in e f f e r e n t a c t i v i t y . The d i s c h a r g e then s t a r t e d a g a i n , c o n t i n u i n g at a much slower r a t e or slowly i n c r e a s i n g . Since blood pressure changes had no e f f e c t on a c t i v i t y l e v e l s , and the lack of pulmonary receptor feedback and asphyxia cannot f u l l y e x p l a i n t h i s lack of a c t i v i t y , some other f a c t o r inherent to the di v e must make a major c o n t r i b u t i o n to the d e f i c i t of d i s c h a r g e . Such a f a c t o r may be the lack of c e n t r a l r e s p i r a t o r y output d u r i n g a d i v e , as t h i s decreases or stops with n a s a l s t i m u l a t i o n in the a n a e s t h e t i z e d muskrat (Drummond and Jones, unpublished o b s e r v a t i o n s ) . T h i s i s f u r t h e r supported by the changes i n c a r d i a c i n t e r v a l c o i n c i d e n t with the "gasping" movements seen d u r i n g the dive i n F i g u r e 11. These r e s p i r a t o r y e f f o r t s would be maximal as the muskrats are c u r a r i z e d , a l b e i t l i g h t l y i n t h i s case, and are the r e s u l t of r e s p i r a t o r y d r i v e overcoming the di v e response. The type A a c t i v i t y i s a l s o c o i n c i d e n t with t h i s s i n u s arrythmia, again suggesting that the e f f e r e n t d i s charge i s being d r i v e n by c e n t r a l r e s p i r a t o r y output. Thus, the type A e f f e r e n t s are i n h i b i t e d by l a r g e lung i n f l a t i o n s and e x c i t e d by r e s p i r a t o r y i n s p i r a t o r y e f f o r t s . The lack of a c t i v i t y d u r i n g a 59 d i v e i s somewhat s u p r i s i n g , s i n c e i f these f i b r e s possess a r e s p i r a t o r y r e l a t e d sympathetic outflow, a b o l i t i o n of r e s p i r a t o r y output might have allowed the n a t u r a l 2-6 and 10 c y c l e s / s a c t i v i t y of the sympathetics to emerge, as has been suggested by Gebber and h i s co-workers (Gebber 1980; Gebber and Barnum 1982). These o b s e r v a t i o n s , and the lac k of response of the type A e f f e r e n t s to blood pressure changes, suggest that i n muskrats t h i s n e u r a l a c t i v i t y may be a r e s p i r a t o r y motor output which bypasses the c a r o t i d s i n u s area and i n n e r v a t e s the airway passages or the pharyngeal muscles. However, in other mammals some sympathetic outflows show a minimal response to blood p r e s s u r e changes (Ninomiya et a l . 1973; Ninomiya and Irisawa 1975), and the s i m i l a r i t y to p r e v i o u s l y recorded r h y t h m i c a l e f f e r e n t s i n the c a r o t i d s inus nerve (Biscoe and Sampson 1968), suggest that the type A e f f e r e n t d i s c h a r g e i s probably of sympathetic o r i g i n . The d i s c h a r g e of the type B e f f e r e n t had no obvious r e l a t i o n s h i p w i t h v e n t i l a t i o n , but responded to an i n c r e a s e i n b l o o d pressure w i t h a delayed burst of a c t i v i t y . In c a t s , an i n c r e a s e i n b l o o d pressure r e s u l t e d i n a b u r s t of a c t i v i t y from the non-rhythmical e f f e r e n t s recorded from the cut c e n t r a l end of the c a r o t i d s i n u s nerve, a f t e r a l a t e n t p e r i o d of 10-30 seconds (Biscoe and Sampson 1968). There was no response by the type B e f f e r e n t t o a decrease i n blood p r e s s u r e i n the muskrat, as has been r e p o r t e d p r e v i o u s l y f o r c a t s (Willshaw and Majcherczyk 1978 - i n Majcherczyk et a_l. 1980), probably because of the s m a l l decreases i n blood p r e s s u r e achieved i n the 60 present work. These c h a r a c t e r i s t i c s of the type B e f f e r e n t s are s i m i l a r to those e f f e r e n t s i n the c a r o t i d sinus nerve that have been proposed to be of parasympathetic o r i g i n (Majcherczyk et. a l . 1980). During n a s a l s t i m u l a t i o n , the type B f i b r e d i s p l a y e d an immediate i n c r e a s e in a c t i v i t y . T h i s increase was observed before any heart rate response, and can be accounted f o r by the time l a g between nasal s t i m u l a t i o n and stopping the a r t i f i c i a l v e n t i l a t i o n i n lung d e f l a t i o n (see F i g u r e 12), as lung i n f l a t i o n i n h i b i t s the d i v i n g b r a d y c a r d i a (Dykes 1974; Drummond and Jones 1979). The b u r s t of a c t i v i t y o c c u r r e d before an i n c r e a s e i n blood p r e s s u r e was r e a l i z e d , and before the apnoea c o u l d have had any e f f e c t s ( N e i l and O'Regan 1971). As the d i v e progressed, a c t i v i t y l e v e l s returned t o , and remained a t , pre-d i v e l e v e l s , d e s p i t e the i n c r e a s e i n blood p r e s s u r e and the p r o l o n g a t i o n of the apnoea. T h i s suggests that i n muskrats the i n c r e a s e i n the type B a c t i v i t y i s not due to an i n c r e a s e i n blood p r e s s u r e per se, as has been suggested fo r the i n c r e a s e i n non-rhythmical a c t i v i t y i n c a t s (Majcherczyck e_t a l . 1980), but to some oth e r f a c t o r s inherent i n the d i v i n g response. Such f a c t o r s may be lung d e f l a t i o n , or the decrease i n c e n t r a l r e s p i r a t o r y output d u r i n g a d i v e . S e c t i o n of the v a g i i n dogs r e s u l t s i n an increase i n a c t i v i t y of the non-rhythmical e f f e r e n t s recorded from the cut c a r o t i d sinus nerve (Kostreva et a l . 1984). However, v a g a l d e n e r v a t i o n removes the input of other a f f e r e n t r e c e p t o r s besides the pulmonary s t r e t c h r e c e p t o r s ( P a i n t a l 1973), while an apneoic p e r i o d r e s u l t s i n a slow, but 61 small i n crease i n non-rhythmical e f f e r e n t a c t i v i t y ( N e i l and O'Regan 1971). T h i s suggests t h a t i t i s the n a s a l l y induced h a l t i n r e s p i r a t o r y output that i s inst r u m e n t a l i n e l i c i t i n g the burst of a c t i v i t y from the type B e f f e r e n t . T h i s i s f u r t h e r supported by the i n c r e a s e in a c t i v i t y observed before the d i v i n g b r a d y c a r d i a was manifested, due to the time l a g between n a s a l s t i m u l a t i o n and lung d e f l a t i o n . Thus, any e f f e c t due to a p h a r m a c o l o g i c a l l y induced i n c r e a s e i n blood p r e s s u r e may be due to e f f e c t s of the drug a d m i n i s t e r e d on the c e n t r a l nervous system (see Biscoe and Sampson 1968), or to r e f l e x i n h i b i t i o n of r e s p i r a t i o n by i n c r e a s e d baroreceptor a c t i v i t y (Heymans and N e i l 1958; Brunner et a l . 1982). In c a t s , nasal s t i m u l a t i o n had no e f f e c t on the non-rhythmical e f f e r e n t a c t i v i t y recorded from the cut c e n t r a l end of the c a r o t i d sinus nerve (Purves 1975), however these animals are not noted f o r t h e i r d i v i n g a b i l i t y , and may lack a st r o n g n a s a l mechanism f o r i n i t i a t i n g and m a i n t a i n i n g a decrease i n c e n t r a l r e s p i r a t o r y output. N e i t h e r baroreceptor nor chemoreceptor d i s c h a r g e appears to be d i r e c t l y a f f e c t e d by the c a r d i o v a s c u l a r and r e s p i r a t o r y adjustments to d i v i n g , but these adjustments do a f f e c t the e f f e r e n t d i s c h a r g e i n the c a r o t i d s inus nerve. The e f f e r e n t a c t i v i t y may i n tu r n modulate the a f f e r e n t discharge of these r e c e p t o r s during a d i v e . The type A e f f e r e n t s are probably of sympathetic o r i g i n (Biscoe and Sampson 1968), and may t h e r e f o r e be expected to be predominantly e x c i t a t o r y to both r e c e p t o r types ( F l o y d and N e i l 1952; E y z a g u i r r e and Lewin 1961b; Koizumi and Sato 1969; O'Regan 1981; Tomomatsu and N i s h i 1981). Since 62 type A e f f e r e n t a c t i v i t y l e v e l s decrease to zero d u r i n g nasal s t i m u l a t i o n , any e f f e c t that they may have had on the r e c e p t o r s p r e - d i v e , would be absent. As the dive progresses, the a c t i v i t y r e t u r n s , but i s probably due to c e n t r a l r e s p i r a t o r y breakthrough (see above). The type B e f f e r e n t response to an in c r e a s e i n blood pressure i s c h a r a c t e r i s t i c of the type of e f f e r e n t that has been proposed to be i n h i b i t o r y to the chemoreceptors ( N e i l and 0'Regan 1971; Majcherczyk et a l . 1980), and the ba r o r e c e p t o r s (Koushanpour and Behnia 1982). The burst of type B a c t i v i t y seen at the i n i t i a t i o n - of nasal.- s t i m u l a t i o n may t h e r e f o r e 'tend to i n h i b i t both types of r e c e p t o r s . The combined e f f e c t of the decrease i n type A a c t i v i t y and the i n c r e a s e i n type B a c t i v i t y d u r i n g the i n i t i a t i o n of n a s a l s t i m u l a t i o n may t h e r e f o r e be to decrease both types of a f f e r e n t d i s c h a r g e . T h i s i n h i b i t o r y stimulus would have l e s s of an a f f e c t on receptor a c t i v i t y as the di v e progressed, s i n c e the type B e f f e r e n t a c t i v i t y has returned to p r e - d i v e a c t i v i t y l e v e l s and the type A e f f e r e n t a c t i v i t y i s the r e s u l t of r e s p i r a t o r y breakthrough. These p o s t u l a t e d a c t i o n s of e f f e r e n t a c t i v i t y on receptor d i s c h a r g e would be t e s t a b l e by r e c o r d i n g receptor a c t i v i t y i n a nerve s l i p prepared from an otherwise i n t a c t c a r o t i d s i n u s nerve (see N e i l and Q'Regan 1971). The input from the b a r o r e c e p t o r s would thus be an i n i t i a l decrease to zero, f o l l o w e d by a r i s e i n a c t i v i t y . There would t h e r e f o r e be no c o n t r i b u t i o n by the bar o r e c e p t o r s to the i n i t i a t i o n of the d i v i n g b r a d y c a r d i a . A change i n c e n t r a l s e n s i t i v i t y of the b a r o r e f l e x d u r i n g a d i v e ( E i s n e r et a l . 63 1977) would a l s o have no e f f e c t , as the b a r o r e f l e x r e l i e s on baroreceptor i n p u t . The lack of baror e c e p t o r a c t i v i t y may, however, f a c i l i t a t e the p e r i p h e r a l a r t e r i a l c o n s t r i c t i o n . As the dive p r o g r e s s e s , blood pressure and heart r a t e i n c r e a s e s , d e s p i t e an i n c r e a s e i n ba r o r e c e p t o r a c t i v i t y t r a v e l l i n g c e n t r a l l y v i a the i n t a c t c o n t r a l a t e r a l c a r o t i d s i n u s nerve and both a o r t i c nerves. No s i g n i f i c a n t d i f f e r e n c e was seen i n the c a r d i a c i n t e r v a l s and blood p r e s s u r e s between the pre s s o r t e s t and the end of the d i v e (Table I I I ) . T h i s does not imply that at t h i s time the b a r o r e c e p t o r s are c o n t r i b u t i n g to the c a r d i a c p o r t i o n of the dive response. In the p r e s s o r t e s t the blood pressure i n c r e a s e d , the baroreceptor a c t i v i t y i n c r e a s e d and the c a r d i a c i n t e r v a l i n c r e a s e d . During n a s a l s t i m u l a t i o n the blood pressure i n c r e a s e d , the baror e c e p t o r a c t i v i t y i n c r e a s e d , yet the c a r d i a c i n t e r v a l decreased. T h i s d e c o u p l i n g of baroreceptor a c t i v i t y must be o c c u r r i n g c e n t r a l l y , as normally the i n c r e a s e in d i s c h a r g e a c t s to i n c r e a s e c a r d i a c i n t e r v a l , decrease p e r i p h e r a l r e s i s t a n c e and t h e r e f o r e decrease blood pressure (Heymans and N e i l 1958). Thus, there would be a decrease i n the c e n t r a l b r a i n stem s e n s i t i v i t y of the b a r o r e f l e x d u r i n g a d i v e , and not an i n c r e a s e , as has been proposed f o r s e a l s ( E i s n e r e_t a l . 1977). T h i s decoupling has been noted p r e v i o u s l y i n the s e a l (Murdaugh et a_l. 1968), where a r t e r i a l c o n s t r i c t i o n continued i n the absence of the d i v i n g b r a d y c a r d i a . Such a decoupling of the baroreceptor input d u r i n g a d i v e would be important s i n c e i t may be expected that the p e r i p h e r a l a r t e r i a l c o n s t r i c t i o n would be the primary goal of the oxygen c o n s e r v i n g 64 response of the d i v e (Murdaugh et. a J . 1968). Thus, d e s p i t e an i n c r e a s e i n heart r a t e , blood pressure and baroreceptor a c t i v i t y l a t e r i n the d i v e i n the muskrat, the oxygen conserving mechanism of the v a s o c o n s t r i c t i o n ' i s maintained. The b a r o r e c e p t o r s t h e r e f o r e have no r o l e i n the maintenance of the d i v i n g response. The input from the chemoreceptors would most l i k e l y be a slow r i s e i n a c t i v i t y . The c o n t r i b u t i o n of the chemoreceptors to the d i v i n g response i s t h e r e f o r e probably delayed u n t i l the l a t e r stage of the d i v e . T h i s delay i s due to 1) the oxygen co n s e r v i n g mechanisms (Drummond 1980); 2) the i n c r e a s e i n the i n h i b i t o r y a c t i v i t y of the type B e f f e r e n t s (Majcherczyk e_t a l . 1980); and 3) no change i n c e n t r a l s e n s i t i v i t y of the chemoreflex ( E i s n e r et ajL. 1 977; cf B u t l e r and Jones 1982). Indeed, there may be a c e n t r a l i n h i b i t i o n of the chemoreflex due to the i n c r e a s e i n baroreceptor a c t i v i t y ( H e i s t a d et a l . 1974,1975) seen d u r i n g the l a t e r stages of n a s a l s t i m u l a t i o n i n the muskrat. T h i s delayed c o n t r i b u t i o n may a s s i s t i n the maintenance of the d i v i n g b r a d y c a r d i a and the p e r i p h e r a l a r t e r i a l c o n s t r i c t i o n (White e_t a l . 1974; Daly et a l . 1977), or, perhaps more importantly, may serve to terminate the response as the oxygen res e r v e s are d e p l e t e d to c r i t i c a l l e v e l s (White and M c R i t c h i e 1973; M c R i t c h i e and White 1974; B u t l e r and Woakes 1982). The i n i t i a l i n h i b i t i o n of the chemoreceptors may be important to permit the f u l l e x p r e s s i o n of the n a s a l l y d r i v e n d i v i n g response, i n c l u d i n g the shutdown of c e n t r a l r e s p i r a t o r y output. T h i s e f f e c t may be t r a n s i t o r y , l a t e r i n the d i v e the 65 chemoreceptor a c t i v i t y m i r r o r s the blood oxygen l e v e l s and thus c o n t r i b u t e s to the maintenance and t e r m i n a t i o n of the d i v i n g response. 66 REFERENECES CITED Aars, H. (1971) Diameter and e l a s t i c i t y of the ascending a o r t a during i n f u s i o n of n o r - a d r e n a l i n e . Acta P h y s i o l . Scand. 83, 133-138. Acker, H. and R.G. O'Regan (1981) The e f f e c t s of s t i m u l a t i o n of autonomic nerves on c a r o t i d body b l o o d flow i n the c a t . J . P h y s i o l . 315, 99-110. Ad r i a n , E.D., D.W. Bronk and G i l b e r t P h i l l i p s (1932) Discharges in mammalian sympathetic nerves. J . P h y s i o l . 74, 115-133. A l l i s o n , D,J, and D.A. Powis (1971) Adrenal catecholamine s e c r e t i o n during s t i m u l a t i o n of the n a s a l mucous membrane in the r a b b i t . J . P h y s i o l . 217, 327-339 A n g e l l James, J e n n i f e r E. and M. de B. Daly (1972) R e f l e x r e s p i r a t o r y and c a r d i o v a s c u l a r e f f e c t s of s t i m u l a t i o n of r e c e p t o r s i n the nose of the dog. J . P h y s i o l . 220, 673-696 A n g e l l James, J e n n i f e r E., M. de B. Daly and R. E i s n e r (1978) A r t e r i a l baroreceptor r e f l e x e s i n the s e a l and t h e i r m o d i f i c a t i o n during experimental d i v e s . Am. J . P h y s i o l . 234, H730-H739 A n g e l l James, J e n n i f e r E. (1971) The e f f e c t s of a l t e r i n g mean pressur e , pulse p r e s s u r e and p u l s e frequency on the impulse a c t i v i t y i n baro r e c e p t o r f i b r e s from the a o r t i c arch and r i g h t s u b c l a v i a n a r t e r y i n the r a b b i t . J . P h y s i o l . 214, 65-88 Arndt, T.O., J . Morgenstern and L. Samodelov (1977) The p h y s i o l o g i c a l l y r e l e v a n t i n f o r m a t i o n r e g a r d i n g systemic blood pressure encoded i n the c a r o t i d sinus baroreceptor discharge p a t t e r n . J . P h y s i o l . 268, 775-791. Biscoe, T . J . and S.R. Sampson (1968) Rhythmical and non-rhythmical spontaneous a c t i v i t y r e c o r d e d from the c e n t r a l cut end of the sinus nerve. J . P h y s i o l . 196, 327-338 67 Bis c o e , T.J., G.W. Bradley, and M.J. Purves (1970a) The r e l a t i o n between c a r o t i d body chemoreceptor d i s c h a r g e , c a r o t i d s i n u s pressure and c a r o t i d body venous flow. J . P h y s i o l . 208, 99-120 Bis c o e , T .J., M.J. Purves and S.R. Sampson (1970b) The frequency of nerve impulses i n s i n g l e c a r o t i d body chemoreceptor a f f e r e n t f i b r e s recorded in v i v o with i n t a c t c i r c u l a t i o n . J . P h y s i o l . 208, 121-131. Bis c o e , T.J., S.R. Sampson and M.J. Purves (1967) Stimulus response curves of s i n g l e c a r o t i d body chemoreceptor a f f e r e n t f i b r e s . Nature 215, 654-655. B l i x , A.S. and B. Folkow (1984) C a r d i o v a s c u l a r adjustments to diving- i n mammals and b i r d s . In-: Handbook of Physiology -The C a r d i o v a s c u l a r System I I I , ch. 25, 917-945. Bronk, D.W. and G. S t e l l a (1932) A f f e r e n t impulses i n the c a r o t i d sinus nerve. I. The r e l a t i o n of the discharge from s i n g l e end organs to a r t e r i a l blood p r e s s u r e . J . C e l l . Comp. P h y s i o l . 1, 113-130 Brunner, M.J.,.M.S. Sussman, A.S. Greene, C H . Kallman and A.A. Shoukas (1982) C a r o t i d s i n u s b a r o r e c e p t o r r e f l e x c o n t r o l of r e s p i r a t i o n . C i r c . Res. 51, 624-636. B u t l e r , P.J. and A.J. Woakes (1982) C o n t r o l of heart rate by c a r o t i d body chemoreceptors d u r i n g d i v i n g i n t u f t e d ducks. J . Appl. P h y s i o l . 53, 1405-1410. B u t l e r , P.J. and David R. Jones 0 982) The comparative p h y s i o l o g y of d i v i n g i n v e r t e b r a t e s . Advances i n Comp. P h y s i o l , and Biochem., V o l . 8, 179-364. Cohen, Morton I., P h y l l i s Gootman and Jack L. Feldman (1980) I n h i b i t i o n of sympathetic d i s c h a r g e by lung i n f l a t i o n . In: A r t e r i a l B a r oreceptors and Hypertension, ed. P. S l e i g h t , 161-166. Daly, M de B. and M.J. Scott (1958) The e f f e c t s of s t i m u l a t i o n of the c a r o t i d body chemoreceptors on heart rate in the dog. J . P h y s i o l . 144, 148-166. 68 Daly, M de B. and M.J. Scott (1963) The c a r d i o v a s c u l a r responses to s t i m u l a t i o n of the c a r o t i d body chemoreceptors i n the dog. J . P h y s i o l . 165, 179-197. Daly, M. de B. (1984) Breath-hold d i v i n g : mechanisms of c a r d i o v a s c u l a r adjustments i n the mammal. In: Recent Advances i n Physiology #10, ed. P.F. Baker, 201-245. Daly, M. de B. and J e n n i f e r E. A n g e l l James (1975) Role of the a r t e r i a l chemoreceptors i n the c o n t r o l of the c a r d i o v a s c u l a r responses to bre a t h - h o l d d i v i n g . In: The P e r i p h e r a l A r t e r i a l Chemoreceptors, ed. M.J. Purves, 387-403. Daly, M. de B. and M.J. Scott (1958) The e f f e c t s of s t i m u l a t i o n of the c a r o t i d body chemoreceptors on heart ra t e i n the-dog. J . P h y s i o l . 144, 148-166. Daly, M. de B. and Mary J . Sc o t t (1962) An a n a l y s i s of the primary c a r d i o v a s c u l a r r e f l e x e f f e c t s of s t i m u l a t i o n of the c a r o t i d body chemoreceptors i n the dog. J . P h y s i o l . 162, 555-573 Daly, M. de B., R. E i s n e r and J e n n i f e r E. A n g e l l James (1977) C a r d i o r e s p i r a t o r y c o n t r o l by c a r o t i d chemoreceptors during experimental d i v e s i n the s e a l . Am. J . P h y s i o l . 232, H508-H51 6 Drummond, P.C. and David R. Jones (1979) The i n i t i a t i o n and maintenance of br a d y c a r d i a i n a d i v i n g mammal, the muskrat, Ondatra z i b e t h i c a . J . P h y s i o l . 290, 253-271 Drummond, P.CP. (1980) The i n i t i a t i o n and recovery from d i v i n g b r a d y c a r d i a i n the muskrat. Ph.D T h e s i s Dykes, Robert W. (1974a) F a c t o r s r e l a t e d to the d i v e r e f l e x i n harbor s e a l s : r e s p i r a t i o n , immersion b r a d y c a r d i a , and l a b i l i t y of heart r a t e . Can. J . P h y s i o l . Pharmacol. 52, 248-258. Dykes, Robert W. (1974b) F a c t o r s r e l a t e d to the d i v e r e f l e x i n harbor s e a l s : sensory c o n t r i b u t i o n s from the t r i g e m i n a l nerve. Can. J . P h y s i o l . Pharmacol. 52, 259-265. 69 E i s n e r , R., J e n n i f e r E. A n g e l l James and M. de B. Daly (1977) C a r o t i d body chemoreceptor r e f l e x e s and t h e i r i n t e r a c t i o n s i n the s e a l . Am. J . P h y s i o l . 232, H517-H525 E i s n e r , Robert, Dean L. F r a n k l i n , Robert L. Van C i t t e r s and David W. Kenney (1966) C a r d i o v a s c u l a r defense a g a i n s t asphyxia. Science 153, 941-949. E y z a g u i r r e , C. and J . Lewin (1961a) Chemoreceptor a c t i v i t y of the c a r o t i d body of the c a t . J . P h y s i o l . 159, 222-237. E y z a g u i r r e , C. and J . Lewin (1961b) The e f f e c t of sympathetic s t i m u l a t i o n on c a r o t i d nerve a c t i v i t y . J . P h y s i o l . 159, 251-267 F a r i s , I.B., J . Iannos, G.G. Jamieson and J . Ludbrook (1980) Comparison of methods f o r e l i c i t i n g the b a r o r e c e p t o r - h e a r t rate r e f l e x i n c o n s c i o u s r a b b i t s . C l i n i c a l and Experimental Pharmacology and Physiology 7, 281-291 Floy d , W.F. and E. N e i l (1952) The i n f l u e n c e of the sympathetic i n n e r v a t i o n of the c a r o t i d b i f u r c a t i o n on chemoreceptor and baroreceptor a c t i v i t y i n the c a t . Arch. I n t . Pharmacodyn. 91, 230-239 Gebber, Gerard L. and Susan M. Barman (1982) B r a i n stem neurons governing the d i s c h a r g e s of sympathetic nerves. J . Auto. Nerv. Sys. 5, 55-61 Gebber, Gerard L. (1980) C e n t r a l o s c i l l a t o r s r e s p o n s i b l e f o r sympathetic nerve d i s c h a r g e . Am. J . P h y s i o l . 239, H143-H1 55 Gr u n s t e i n , M.M., J.P. Derenne and J . M i l i c - E m i l i (1975) C o n t r o l of depth and frequency of b r e a t h i n g d u r i n g baroreceptor s t i m u l a t i o n i n c a t s . J . Appl. P h y s i o l . 39, 395-404 Hance, A.J., E.D. Robin, J.B. H a l t e r , N. Lewiston, D.A. Robin, L. C o r n e l l , M. C a l i g i u r i and J . Theodore (1982) Hormonal changes and e n f o r c e d d i v i n g i n the harbor s e a l Phoca v i t u l i n a . I I . Plasma catecholamines. Am. J . P h y s i o l . 242, R528-R532. 70 H e i s t a d , D.D, F.M. Abboud, &.L. Mark and P.G. Schmid (1974) I n t e r a c t i o n of baro r e c e p t o r and chemoreceptor r e f l e x e s : modulation of the chemoreflex by changes i n baroreceptor a c t i v i t y . J . of C l i n i c a l I n v e s t i g a t i o n 53, 1226-1236. H e i s t a d , D.D, F.M. Abboud, A.L. Mark and P.G. Schmid (1975) E f f e c t of baroreceptor a c t i v i t y on v e n t i l a t o r y response to chemoreceptor s t i m u l a t i o n . J . Appl. P h y s i o l . 39, 411-416. Heslegrave,R.J., J.C. O g i l i v i e and J . J . Furedy (1979) Measuring b a s e l i n e - t r e a t m e n t d i f f e r e n c e s in heart r a t e v a r i a b i l i t y : v a r i a n c e versus s u c c e s s i v e d i f f e r e n c e mean square and beats per minute versus i n t e r b e a t i n t e r v a l s . Psychophysiology 16, 151-157. Heymans, C. and E. N e i l (1958) Re f l e x o g e n i c Areas of the C a r d i o v a s c u l a r System. J . and A. C h u r c h i l l L t d . , London. Holmes, A.E. and J.R. Ledsome (1984) E f f e c t of norepinephrine and v a s o p r e s s i n on c a r o t i d s i n u s b a r o r e c e p t o r a c t i v i t y i n the a n a e s t h e t i z e d r a b b i t . Experimentia 40, 825-827. Hornbein, T.F., Z.J. G r i f f o and A. Roos (1961) Q u a n t i t a t i o n of chemoreceptor a c t i v i t y : i n t e r r e l a t i o n of hypoxia and hypercapnia. J . N e u r o p h y s i o l . 24, 561-568. I r v i n g , Laurence, P.F. Scholander and S.W. G r i l l n e r (1942 ) The r e g u l a t i o n of a r t e r i a l blood pressure i n the s e a l d u r i n g d i v i n g . Am. J . P h y s i o l . 135, 557-566. Jones, D.R., H.D. F i s h e r , S. McTaggurt and N. West (1973) Heart r a t e d u r i n g b r e a t h - h o l d i n g and d i v i n g i n the u n r e s t r a i n e d harbour s e a l (Phoca v i t u l i n a r i c h a r d i ) . Can. J . P h y s i o l . 51, 671-680. Jones, David R., N i g e l H. West, Owen S. Bamford, Peter C. Drummond and Raymond A. Lord (1982) The e f f e c t of the s t r e s s of f o r c i b l e submergence on the d i v i n g response i n muskrats (Ondatra z i b e t h i c a ) . Can. J . Z o o l . 60, 187-193 K e i t h , I.C., C. Kidd, C M . Malpus and P.E. Penna (1974) Reduction of baroreceptor impulse a c t i v i t y by sympathetic nerve s t i m u l a t i o n . J . P h y s i o l . 238, 61P-62P. 71 Kirchheim, Hartmut R. (1976) Systemic a r t e r i a l b a r o r e c e p t o r r e f l e x e s . P h y s i o l . Rev. 56, 100-176. Koizumi, K. and A. Sato (1969) I n f l u e n c e of sympathetic i n n e r v a t i o n on c a r o t i d s i n u s baroreceptor a c t i v i t y . Am. J, P h y s i o l . 216, 321-329. Koizumi, K., H. S e l l e r , A. Kaufman and C. McC. Brooks (1971) Pat t e r n of sympathetic d i s c h a r g e s and t h e i r r e l a t i o n to baroreceptor and r e s p i r a t o r y a c t i v i t i e s . B r a i n Res. 27, 281-294. Kostreva, D.R., G.L. Pal o t a s and J.P. Kampine (1984) Vagal i n h i b i t i o n of r e s p i r a t o r y - l i n k e d e f f e r e n t a c t i v i t y i n the c a r o t i d s i n u s nerve. Am. J . P h y s i o l . 247, R681-R686. • Koushanpour, Esmail and Rahim Behnia (1982) Comparison of pressure-nerve r e l a t i o n s h i p between i n t a c t and cut c a r o t i d s i n u s nerve. F e d e r a t i o n Proc. 41, 1229 ( a b s t r a c t ) . L a h i r i , S. and R.G. DeLaney (1975) Stimulus i n t e r a c t i o n i n the responses of c a r o t i d body chemoreceptor s i n g l e a f f e r e n t f i b e r s . Resp. P h y s i o l . 24, 249-266. L a h i r i , S., A. Mokashi, R.G. Delaney and A.P. Fishman (1978) A r t e r i a l p o 2 and pco 2 s t i m u l u s t h r e s h o l d f o r c a r o t i d chemoreceptors and b r e a t h i n g . Resp. P h y s i o l . 34, 359-375 Landgren, S. (1952) On the e x c i t a t i o n mechanism of the c a r o t i d b a r o r e c e p t o r s . Acta P h y s i o l . Scand. 26, 1-34. Lumsden; T. (1923/24) The r e g u l a t i o n of b r e a t h i n g . Pt. II Normal type. J . P h y s i o l . 58, 111-126. Majcherczyk, S., J.C.G. C o l e r i d g e , H.M. C o l e r i d g e , M.P. Kaufman and D.G. Baker (1980) C a r o t i d sinus nerve e f f e r e n t s : p r o p e r t i e s and p h y s i o l o g i c a l s i g n i f i c a n c e . F e d e r a t i o n Proc. 39, 2662-2667. McDonald, Donald M. (1981) P e r i p h e r a l chemoreceptors, s t r u c t u r e f u n c t i o n r e l a t i o n s h i p s of the c a r o t i d body. In: Lung Bi o l o g y i n Health and Disease, V o l . 17, Ch 3, R e g u l a t i o n of B r e a t h i n g ed. Thomas Hornbein, 105-319. 72 McKean, Tom. (1982) C a r d i o v a s c u l a r adjustments to l a b o r a t o r y d i v i n g i n beavers and n u t r i a . Am. J . P h y s i o l . 242, R434-R440. Mc R i t c h i e , R.J. and S.W. White (1974) Role of t r i g e m i n a l , o l f a c t o r y , c a r o t i d s i n u s and a o r t i c nerves i n the r e s p i r a t o r y and c i r c u l a t o r y response to nasal i n h a l a t i o n of c i g a r e t t e smoke and other i r r i t a n t s i n the r a b b i t . AJEBAK 52 (Pt. 1), 127-140. Murdaugh, H.V., C.E. Cross, J.E. M i l l e n , J.B.L. Gee and E.D. Robin (1968) D i s s o c i a t i o n of b r a d y c a r d i a and a r t e r i a l c o n s t r i c t i o n during d i v i n g in the s e a l Phoca v i t u l i n a . Science 162, 364-365. N e i l , E. and R.G. O'Regan (1971) E f f e r e n t and a f f e r e n t impulse a c t i v i t y recorded from f e w - f i b r e p r e p a r a t i o n s of otherwise i n t a c t s i n u s and a o r t i c nerves. J . P h y s i o l . 215, 33-47 Ninomiya I. and H. Irisawa (1975) Non-uniformity of the sympathetic nerve a c t i v i t y i n response to baroreceptor i n p u t s . B r a i n Res. 87, 313-322. Ninomiya, I., A. Irisawa and N. Nisimaru (1973) Non-uniformity of sympathetic nerve a c t i v i t y to the s k i n and kidney. Am. J . P h y s i o l . 224, 256-264. O'Regan, R.G. (1981) Responses of c a r o t i d body chemosensory a c t i v i t y and blood flow to s t i m u l a t i o n of sympathetic nerves i n the c a t . J . P h y s i o l . 315, 81-98 Okada, Hiromasa and Irwin J . Fox (1976) R e s p i r a t o r y grouping of abdominal sympathetic a c t i v i t y i n the dog. Am. J . P h y s i o l . 213, 48-56. P a i n t a l , A.S. (1973) Vagal sensory r e c e p t o r s and t h e i r r e f l e x e f f e c t s . P h y s i o l . Rev. 53, 159-227. Pasche, A r v i d and John Krog (1980) Heart r a t e i n r e s t i n g s e a l s on land and in water. Comp. Biochem. P h y s i o l . 67A, 77-83 73 Peveler, R.C., D.H. B e r g e l , J.L. Robinson, and P. S l e i g h t (1983) The e f f e c t of phenylephrine upon a r t e r i a l p r e s s u r e , c a r o t i d sinus r a d i u s and b a r o r e f l e x s e n s i t i v i t y i n the c o n s c i o u s greyhound.' C l r n i c a ' l Screhce*6'4'!p PP V 4'5'5-46*1" Purves, M.J. (1975) The c o n t r o l of the avian c a r d i o v a s c u l a r system. In Avian Physiology, ed. M. Peaker, 13-32. Sampson, S.R. and T.J. Biscoe (1970) E f f e r e n t c o n t r o l of the c a r o t i d body chemoreceptor. Separatum E x p e r i e n t i a 26, 261-262 T a n j i , D.G., J . Weste and R.W. Dykes (1975) I n t e r a c t i o n s of r e s p i r a t i o n and the b r a d y c a r d i a of submersion in harbor s e a l s . Can. J . P h y s i o l . Pharmacol. 53, 555-559. Tomomatsu and K. N i s h i (1981) Increased a c t i v i t y of c a r o t i d s i n u s b a r o r e c e p t o r s by sympathetic s t i m u l a t i o n and n o r e p i n e p h r i n e . Am. J . P h y s i o l . 240, H650-H658 White, S.W. and R.J. M c R i t c h i e (1973) Nasopharyngeal r e f l e x e s : i n t e g r a t i v e a n a l y s i s of evoked r e s p i r a t o r y and c a r d i o v a s c u l a r e f f e c t s . AJEBAK 51 (Pt. 1), 17-31. White, S.W., R.J. McRitchie and D.L. F r a n k l i n (1974) Autonomic c a r d i o v a s c u l a r e f f e c t s of n a s a l i n h a l a t i o n of c i g a r e t t e smoke i n the r a b b i t . AJEBAK 52 (Pt. 1), 111-126. Zapol, Warren M. , G.C. Liggi.ns, Robert C. Schneider, J . Q v i s t , M i c h a e l T. Snider, Robert K. Creasy and Peter W. Hochachka (1979) Regional blood flow d u r i n g simulated d i v i n g in the c o n s c i o u s Weddell s e a l . J . Appl. P h y s i o l . 47, 968-973. 

Cite

Citation Scheme:

        

Citations by CSL (citeproc-js)

Usage Statistics

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
http://iiif.library.ubc.ca/presentation/dsp.831.1-0096075/manifest

Comment

Related Items