Open Collections

UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Cation and water shifts in response to pressor agents in the conscious dog Warren, James Darcy 1960

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

Item Metadata

Download

Media
831-UBC_1961_A6_7 W2 C2.pdf [ 2.63MB ]
Metadata
JSON: 831-1.0106285.json
JSON-LD: 831-1.0106285-ld.json
RDF/XML (Pretty): 831-1.0106285-rdf.xml
RDF/JSON: 831-1.0106285-rdf.json
Turtle: 831-1.0106285-turtle.txt
N-Triples: 831-1.0106285-rdf-ntriples.txt
Original Record: 831-1.0106285-source.json
Full Text
831-1.0106285-fulltext.txt
Citation
831-1.0106285.ris

Full Text

CATION AND WATER SHIFTS IN RESPONSE TO PRESSOR AGENTS IN THE CONSCIOUS DOG  by James D„ Warren  A Thesis Submitted in Partial Fulfilment of the Requirements for the Degree of MASTER OF SCIENCE in the department of ANATOMY  WJe accept this thesis as conforming to the standard required from candidates for the degree of  Master of Science  Members of the Department of Anatomy THE UNIVERSITY OF BRITISH COLUMBIA September 30, 1960  In presenting  t h i s t h e s i s i n p a r t i a l f u l f i l m e n t of  the requirements f o r an advanced degree at the U n i v e r s i t y of B r i t i s h Columbia, I agree t h a t the L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r reference and study. f o r extensive  I f u r t h e r agree that permission  copying of t h i s t h e s i s f o r s c h o l a r l y purposes may  granted by the Head of my Department or by h i s  be  representatives.  I t i s understood that copying or p u b l i c a t i o n of t h i s t h e s i s f o r f i n a n c i a l gain s h a l l not be allowed without my w r i t t e n permission.  Department of The U n i v e r s i t y of B r i t i s h Columbia, Vancouver 3, Canada. Date  - II ABSTRACT The h a l l m a r k of e s s e n t i a l h y p e r t e n s i o n i s a p e r s i s t e n t e l e v a t i o n of b l o o d p r e s s u r e .  C e r t a i n changes a r e a s s o c i a t e d w i t h t h e s t a t e of  h y p e r t e n s i o n i n c l u d i n g a derangement of water and work i n d i c a t e s t h e upset i n sodium and water may the h y p e r t e n s i o n . of d r u g s .  electrolytes.  Recent  be c a u s a l l y r e l a t e d t o  T r a n s i t a r y , a c u t e h y p e r t e n s i o n may  be produced by means  The drug induced b l o o d p r e s s u r e r i s e i s accompanied by a d i s -  t u r b a n c e i n water and e l e c t r o l y t e s .  F u r t h e r work i s r e q u i r e d t o c l a r i f y  the r e l a t i o n s h i p between s h i f t s i n e l e c t r o l y t e s and a g e n t s t h a t may  increase  blood pressure (pressor agents). In o r d e r t o c a r r y out the programme o f r e s e a r c h on p r e s s o r agents i t was  n e c e s s a r y t o r e v i e w the fundamental t o o l , namely the a c c u r a t e  measurement of s h i f t s i n w a t e r .  This review lead t o a refinement  t e c h n i q u e o f measuring water by i n f u s i n g i n u l i n . c o n t i n u o u s l y . nephrectomized  i n the  With  animals the i n u l i n d i l u t i o n technique i s a s a t i s f a c t o r y  method t o measure the e x t r a c e l l u l a r space.  An e q u a l l y a c c u r a t e i n d e x o f  the e x t r a c e l l u l a r space can be p r o v i d e d w i t h an i n u l i n i n f u s i o n which m a i n t a i n s the e x t r a c e l l u l a r i n u l i n c o n c e n t r a t i o n a t a c o n s t a n t  level.  In the p r e s e n t study t h e c a t i o n and water s h i f t s between c e l l s and the e x t r a c e l l u l a r space a s s o c i a t e d w i t h two d i s s i m i l a r p r e s s o r agents were o b s e r v e d ,  u s i n g t r a i n e d , c o n s c i o u s dogs.  The p r e s s o r agents used  were n o r e p i n e p h r i n e , e l a b o r a t e d by t h e a d r e n a l medulla and e l a b o r a t e d by t h e p o s t e r i o r p i t u i t a r y g l a n d . e f f e c t , i n our hands, on sodium, potassium  pitressin,  Norepinephrine  or water movement.  had  no  Pitressin  had d i s t i n c t e f f e c t s , w i t h r a p i d d e p r e s s i o n o f the e x t r a c e l l u l a r volume and the e x t r a c e l l u l a r sodium c o n c e n t r a t i o n , and e l e v a t i o n of t h e e x t r a c e l l u l a r potassium  concentration.  associated with a pressor  The changes caused by p i t r e s s i n were  response.  - Ill «  TABLE OF CONTENTS Page INTRODUCTION THE EFFECT OF NOREPINEPHRINE ON WATER AND CATIONS  1  THE EFFECT OF PITRESSIN ON WATER AND CATIONS  4  THE INULIN INFUSION TECHNIQUE  6  EXPERIMENTAL PURPOSE  7  METHODS AND MATERIAL  8  OBSERVATIONS THE INULIN INFUSION TECHNIQUE  10  THE EFFECTS OF NOREPINEPHRINE INJECTION  21  THE EFFECTS OF PITRESSIN INJECTION  36  DISCUSSION  46  CONCLUSIONS  48  TABLES & GRAPHS  Pages INULIN INFUSION * » o • >  o o o o a o o o o o o o  INULIN INFUSION © a  p a e « * o « - o e a o o o « o o o  INULIN INFUSION INULIN INFUSION  0>  oO <O  O O O O O 0 O 4  o e o o ip o o o o o o e o o O o e o o o  •  0  0  o 0 0 0 0 0 0 0 0 0 0  •  o o e o o • •« > o- o •  0  0  o o o o o a o o o o o o o  O O O O O O O O O O O O «  • • O O 0  o o o  0  0  0  13 & 14 15 & 16  o o « o  17 & 18  O O 0  19 & 20  o oo  24 & 25 26 & 27  « •  INULIN INFUSION WITH 0.4 jug/Kg NOREPINEPHRINE  o «  O 0  INULIN INFUSION WITH 1.6 -ug/Kg NOREPINEPHRINE  o o  0  o a  0  o  0  o  0  0 0-  O'  0  0  o  oo oo  30 & 31  INULIN INFUSION WITH 3.2 ;ug/Kg NOREPINEPHRINE  o e> a o o- o- o  32 & 33  INULIN INFUSION WITH 4.8 jig/Kg NOREPINEPHRINE  O  a • o- o *  34 & 35  o o O  0  39 & 40  INULIN INFUSION WITH 2.4 ^g/Kg NOREPINEPHRINE INULIN INFUSION WITH 2.4 /ug/Kg NOREPINEPHRINE  INULIN INFUSION WITH 200 mU/Kg PITRESSIN .....  0  0 ©  0  28 & 29  INULIN INFUSION WITH 40 mU/Kg PITRESSIN  o  e  41 & 42  INULIN INFUSION WITH 40 mU/Kg PITRESSIN  o o a o o- o 0  43 & 44  PRESSOR EFFECT WITH 40 mU/Kg PITRESSIN ..... •  o  * 0  0  0  o o  0 0  oo  45  ~ 1 -  INTRODUCTION THE EFFECT OF NOREPINEPHRINE ON WATER AND CATIONS The e s s e n t i a l f e a t u r e s o f t h e s a l t and water s h i f t s a s s o c i a t e d with a norepinephrine infusion a r e : 1)  C e l l u l a r uptake o f sodium and water and r e l e a s e o f p o t a s s i u m  are c l o s e l y a s s o c i a t e d w i t h a p r e s s o r response. precede  the pressor response. 2)  lyte  These changes l i k e l y  Dibenamine and DHE-45 b l o c k both t h e p r e s s o r and t h e e l e c t r o -  responses. 3)  A sodium i n f u s i o n b l o c k s t h e p r e s s o r r e s p o n s e .  The c a t i o n i c s h i f t s have been examined from both t h e c e l l u l a r and t h e e x t r a c e l l u l a r s t a n d p o i n t and t h e r e s u l t s s u b s t a n t i a t e one a n o t h e r . Robertson and P e y s e r  (19) i n 1951 examined t h e myocardium o f c a t s a f t e r  the i n j e c t i o n o f l a r g e doses o f e p i n e p h r i n e  I n order t o increase t h e  c e l l u l a r sodium and t o d e c r e a s e t h e c e l l u l a r p o t a s s i u m s i g n i f i c a n t l y . 500 Mg o f e p i n e p h r i n e was needed. Tobian and Fox (21) i n 1956 showed t h a t t h e s e c a t i o n i c changes were n o t l i m i t e d t o h e a r t muscle.  They examined t h e e f f e c t s o f a n o r e p i -  n e p h r i n e i n f u s i o n on t h e a r t e r i a l smooth muscle o f d o g s . c o n s c i o u s dogs were used.  Twelve  trained,  One f e m o r a l a r t e r y was l i g a t e d under l o c a l  a n a e s t h e s i a , and a segment q u i c k l y removed.  A n o r e p i n e p h r i n e i n f u s i o n was  begun and t h e dose was a d j u s t e d t o e l e v a t e and s u s t a i n t h e b l o o d p r e s s u r e 100mm Hg above t h e normal base.  The i n f u s i o n was a l l o w e d t o c o n t i n u e  f o r h a l f an hour and a t t h a t time a segment o f t h e o p p o s i t e f e m o r a l a r t e r y was s i m i l a r l y e x c i s e d .  A n a l y s i s o f t h e a r t e r i a l segments showed  -  2  -  that the potassium content of the artery had dropped from 8 1 mg/lOO Gm B  solids before, to 5.9 mg/100 Gm solids after infusion. The artery segment gained 1.7 mg of sodium/100 Gm solids in the same interval. The sodium gain was more variable than the potassium loss. The dogs showed considerable individual variation in both the pressor and the cationic responses. Muirhead, Goth and Jones (15) examined the effects of a norepinephrine infusion on plasma water and electrolytes in anaesthetized dogs. The doses of norepinephrine used were massive. Eleven dogs were given an average of 70 jug/Kg/min of norepinephrine for short periods varying from fifteen to f i f t y minutes. The plasma sodium concentration became depressed two minutes after the onset of the infusion, returned to normal y minutes after termination of the infusion, and was throughout a mirror image of the pressor effect. In the example shown the plasma sodium concentration changed from 145 mEq/L to 130 mEq/L„ The plasma potassium concentration showed no distinct relationship to the pressor effect. The radio-sulfate space showed no change. Muirhead et al pointed out that small doses of norepinephrine cause no distinct change in the plasma sodium concentration. (8) Friedman, Butt and Friedman also showed that the plasma sodium concentration in dogs does not change in response to small doses of norepinephrine.  They observed, however, that a measurable change in the  total extracellular sodium occurred in anaesthetized dogs with one-tenth the dose of norepinephrine used by Muirhead et a l . In addition, they showed that total extracellular potassium rose coincidentally with the pressure change. Eight anaesthetized nephrecfcomiaed dogs were given  - 3 from 3 - 6 5 JUg/Kg/min of norepinephrine by infusion. Plasma sodium 0  concentration did not change but inulin space decreased so a f a l l in total extracellular sodium was calculated.  The curves for total extra-  cellular sodium formed mirror images of the blood pressure  0  Friedman et a l noted that the cationic changes may precede the pressor effect. Since they had found similar cationic changes with pressor agents other than norepinephrine they advanced the theory that the cationic changes were causally related to pressor effects. Support for this contention was provided by the demonstration of suppression of the pressor response by infusion of sodium, Friedman et al (11) pointed out that the agent responsible for this pressor response suppression is the sodium ion. In a rat a sodium infusion blocked the pressor response to both norepinephrine and pitressin. Moreover, the amount of sodium required to block the pressor response corresponded to the amount lost from the extracellular space with the infusion of the pressor agent. The results of experimental work on the rat by Friedman, Friedman and Nakashima (9) using a norepinephrine infusion were similar to the results described for the dog.  They stressed the rapidity with which  these changes occur in the rat and found i t necessary to establish hypotension prior to the infusion to detect an early shift of water. The rise of the plasma potassium concentration in response to an epinephrine infusion has been recognized for some time. This was first observed by D'Silva (6,7). He felt that the rise of the plasma potassium concentration was due to the glycogenolytic effect of epinephrine  on the l i v e r  Obrien, Murphy and Meek (17) have shown that dibenamine  0  blocks the potassium shift as well as the pressor response to epinephrine. This has also been shown by Friedman, Friedman and Nakashima (10) in regard to both sodium and potassium,, Since dibenamine blocks the pressor response but not the glycogenolytic action of epinephrine (Nickerson and Goodman (16) ) D'Silva's contention is probably in error„ Friedman 0  believes the rise in extracellular potassium i s in part a loss from the cells and i t is in part due to concentration from the extracellular water loss. Certainly an adequate source of potassium has been demonstrated in arterial smooth muscle and in the myocardium. The rise of the plasma potassium concentration in response to a norepinephrine infusion in the work of Muirhead et a l was slow, slight and slow to return to normal. In the work of Friedman et a l , in dogs and rats, the rise of total extracellular potassium coincided closely with the blood pressure rise but the change was not as rapid as the change in the total extracellular sodium. THE EFFECT OF PITRESSIN ON WATER AND CATIONS Studies of the effect of the posterior pituitary gland on blood pressure and cation shifts have resolved around 1) Supraoptico-hypothalmic lesions 2) Stimulation of the supraoptico-hypothalamic tract. 3) Infusion and injection of pitressin The observations of Friedman, Webber, Scherrer, and Friedman (12) have important implications for our work. They produced lesions of the supraoptico-hypothalamic tract in rats and observed changes in salt and water distribution which are the reverse of those found in association  - 5-  with a pitressin infusion.  A pitressin infusion produces a f a l l in the  extracellular water and sodium concentration and a rise in extracellular potassium.  They were able to show that these changes were not renal in  origin since they could be produced in the bilaterally nephrectomisedxrat  0  Oliver and Shafer (18) were the f i r s t to describe the pressor effect of posterior pituitary hormone. Kolls and Geiling (14) were the f i r s t to observe the hormone's action in the conscious dog.  These latter  workers, using Armour's liquid pituitary, noted the rise in mean and diastolic blood pressure and the sudden bradycardia that follows the blood pressure rise. Scherrer and Friedman (20) have described a sustained blood pressure rise following electrical stimulation of the posterior hypothalamic area. The studies of Friedman, Butt and Friedman (8) have direct application to our work and will be dealt with in some detail. Their experiments were performed on anaesthetized dogs, using small and large doses of intravenous pitressin.  In the f i r s t experiment 12 mU/Kg/min of  pitressin was infused for twenty minutes,, Plasma sodium concentration f e l l from 146 5 mEq/L to 143.8 mEq/L while plasma potassium concentration Q  rose from 4.89 mEq/L to 5.11 mEq/L. Diastolic pressure rose 40 mm Hg in this periodo  In the second experiment 50 mU/Kg/min of pitressin was  infused for seventeen minutes. In this case bilateral nephrectomy had been previously performed. Extracellular sodium (product of inulin space and plasma Na) f e l l from 28.79 mEq/Kg to 28.13 mEq/Kg. Extracellular potassium rose from 0.8 mEq/Kg to 0.9 mEq/Kg  0  The diastolic pressure  rose 30 mm Hg in this period. In the third experiment 200 mU/Kg/min of pitressin was infused for ten minutes. Plasma sodium concentration  - 6 -  f e l l from 147.2 mEq/L to 141.7 mEq/L while plasma potassium concentration rose from 4.7 mEq/l, to 5 19 mEq/L. 0  In the dog the cation and water changes produced by a pitressin infusion are more defined than the changes produced by an infusion of norepinephrine. With pitressin these changes are like the pressor response, slower to appear. Similar changes have been shown in the rat by Friedman et al with pitressin. They point out that the magnitude of the cation and water change is greater with pitressin than with norepinephrine for a comparable pressor response As observed with a norepinephrine infusion, the administration of sodium ions as sodium phosphate or sodium acetate w i l l abort or suppress the normal pressor response to a pitressin infusion. The amount of sodium required approximates the amount the drug normally displaces. THE INULIN INFUSION TECHNIQUE The measurement of changes in extracellular volume in the conscious animal depends on an infusion of inulin which maintains the extracellular inulin concentration at a constant level. The merits of inulin as an accurate measure of extracellular space are well known and a subject of many investigations (1, 2, 3, 4). One of the main disadvantages of inulin is i t s rapid excretion by glomerular filtration.  This property prevents a uniform distribution of  inulin in the extracellular space after a single injection and has limited i t s usefulness to the nephrectomized animal. In 1949 Gaudino and Levitt (3) described a constant inulin infusion procedure for use in trained, conscious dogs. Using the recovery  - 1 -  technique they were able to measure inulin space that corresponded closely to the inulin space measured in the same dog after nephrectomy*  Gaudino  and Levitt observed that with a steady infusion of an inulin solution equilibration is reached in about two hours,, A state of equilibration was inferred from steady plasma inulin concentrations,, They noted that the state of equilibration was maintained in one dog up to twelve hours, whereas with nephrectomized dogs both the radio-sulphate space and the inulin space begin to rise after six hours. This rise is presumably a pathological water shift  a  Inulin equilibration in the extracellular  space two hours after the onset of an infusion has been confirmed by other workers (1, 2, 4). Thus i t has been shown that inulin achieves complete distribution and equilibration in the extracellular space in two hours and that this state can be maintained for long periods by a constant inulin infusion. Changes in the volume of the extracellular space would be reflected by increases and/or decreases of inulin concentration. This being so, i t should be possible to ascertain the direction of water movement in the extracellular space in response to various drugs such as norepinephrine and pitressin. EXPERIMENTAL PURPOSE - The aim of the present work was twofold. (1) To establish a workable index for changes of extracellular fluid volume in the conscious dog. (2)  To determine the effect of two dissimilar pressor agents  on that index and on plasma sodium and potassium in the conscious dog.  et  8—  METHODS AND MATERIALS Two healthy female labradors were used throughout and they were well at the finish of these experiments. Both dogs were a year and a half old at the beginning of the work and were weighed at that time Dog D weighed 24.8 Kgms. Dog M weighed 23.4 Kgms. They were placed in an outdoor compound daily and were exercised, in addition to this, two to three times weekly. They were familiarized with experimental handling over a three month period. This familiarization was greatly facilitated by similar training during the year prior to this experiment. In every instance the dogs were in an 18-hour post-absorptive state and allowed water ad l i b . During experiments the dogs, loosely restrained, rested supine on a board. They assumed this position voluntarily and showed no inclination to struggle. The hind limbs were used for infusion, injection and sampling. In the f i r s t phase of the work the constancy of serial inulin values in the extracellular space during constant inulin infusion was determined. For this purpose a constant infusion apparatus was set up to deliver inulin solution at the rate of 0.75 ml/min. The rate was irregular within any thirty second interval but varied only ± 0.03 ml/30 seconds,. The rate varied from day to day but was constant for each experiment. The small volume of infusion was used in order to avoid undue expansion of the extracellular fluid volume. This small volume necessitated the use of a fairly concentrated inulin solution. A. 10% inulin solution of 40 ml was diluted with 60 ml of saline to give an inulin solution of  - 9 -  40 mg/ml. This solution permitted the controlled administration of 30 mg inulin per minute. A loading dose of 10 ml of 10% inulin solution was given i n i t i a l l y over a ten second interval. In the earlier experiments to be described this loading dose of inulin was too high and accounted for high plasma levels with a steep f a l l o f f . After the leg had been prepared and local anaesthetic injected the vein selected for infusion was cannulated with a No. 19 short bevel needle. A vein in the opposite hind limb was similarly cannulated and used for serial blood samples. Clotting in the needle was avoided by attaching a 2 ml syringe with heparin solution to the sampling needle and injecting a small amount in the interval between sampling.  The  first ml of sampled blood was always discarded. The blood was centrifuged immediately and the plasma drawn off, appropriately diluted and stored. Plasma inulin concentration was measured by the method of Hagishi ahd  /  Peters (5). Timed urine specimens were collected. The bladder raas cleared of urine by two washouts of ten ml of tap water each, followed by thirty ml of air.  The delay time was set at six minutes and though this i s open  to criticism i t is not important since the same delay time was used in a l l experiments. Drugs were always administered by single injection in the sampling needle. The intra-arterial pressure was recorded from the right femoral artery. The inulin used was:  Solution Purified Inulin. (U.S. Standard  Products Co.) . The Norepinephrine used was: The Pitressin used was:  Levophed (Winthrop Stearns)  Pitressin (Parke Davis & Co.)  - 10 -  OBSERVATIONS INULIN INFUSION TECHNIQUE The f i r s t seven experiments deal with the development of a method to maintain plasma inulin values at a constant level. The f i r s t three experiments in this group were spoiled due to faulty apparatus and are therefore not presented. In experiment IV the priming dose of inulin, 1.3 grams was given at 10:35 A.M. The sustaining dose of inulin was begun simultaneously and continued for three and one-half hours.  Blood samples were  taken at approximately fifteen minute intervals after thirty minutes of infusion. The results are presented in Table I and Figure I. The large priming dose resulted in early, high levels of plasma inulin. The observed variation in the plasma inulin concentration was calculated on the figures obtained after two hours of infusion.  In experiment IV  the variation from the mean was & 0.875 mgm% plasma inulin. In experiment V the priming dose of inulin, 1.3 grams was given at 11:30 A.M. The sustaining dose of inulin was given simultaneously and continued for five hours. Blood samples were taken at approximately fifteen minute intervals after one hour of infusion. The results are presented in Table II and Figure I I . The large priming dose again resulted in early, high plasma inulin levels. The period from the onset of the infusion to two hours after the onset is considered to be the equilibration time. The plasma inulin levels in this period were not included in the calculation of variation. In experiment V the variation from the mean was t. 1.0 mgms% plasma inulin.  - 11 In experiment VI the priming dose of inulin, 1.0 grams was given at 10:30 A.M. The sustaining dose of inulin was given simulteneously and continued for four and one-half hours. Blood samples were taken every fifteen minutes after f i f t y minutes of infusion. The results are presented in Table III and Figure III. The equilibration time is shortened, probably due to the modified priming dose. The observed variation from the mean was t 1.25 mgms% plasma inulin.  All  the figures for plasma inulin concentration were taken into account. The priming dose of 1.0 grams of inulin was used for a l l succeeding experiments. In experiment VII the priming dose of inulin, 1.0 grams was given 0  at 11:30 A.M. The sustaining dose of inulin was given simultaneously and continued for three and one-half hours.  Blood samples were taken  every fifteen minutes after forty minutes of infusion. At 12:40 P.M. and 1:40 P.M. the period within two fifteen minute intervals was examined with blood samples taken every three minutes.  The urine  excreted during these two intervals was collected and the inulin excretion is presented in Table IV. The results of the plasma inulin concentration are presented in Table IV and Figure IV. The observed variation from the mean was t 1.5 mgm% plasma inulin. The plasma inulin concentration in the three minute intervals showed the same constancy as the plasma inulin concentration in the fifteen minute intervals. In experiments IV and V, 1.3 grams of inulin was used as a loading dose. In Experiments VI and VII this was reduced to 1.0 gram. In Experiments IV and V, the observations on variation from the mean were begun after 2 hours of inulin infusion.  The period between the  onset of the infusion and two hours after the onset was considered to  - 12 -  be the equilibration time. The observed variations in the plasma inulin concentration are shown for each experiment,, In Experiments VI and VII the equilibration point was shortened, probably due to the modified loading dose„ In Experiments IV, V, and VI the samples are fifteen minutes apart. In Experiment VI the fifteen minute intervals were examined on two occasions by sampling every three minutes. This was considered a prerequisite to later experiments involving acute water shifts. The greatest variation from the mean plasma inulin concentration over several hours was 1.5 mgm % plasma inulin. The plasma inulin concentration in the three minute intervals showed the same constancy as the plasma inulin concentration in the fifteen minute intervals.  - 13 -  TABLE I  EXPERIMENT IV Sample  INULIN INFUSION  DOG M  Time  In. mg%  Start 10.35 1  11:00  37.0  2  11:18  36.25  3  11:34  35 75  4  11:54  35.75  5  12:12  37.0  6  0  -spoiled-  7  12:46  30.75  8  12:59  32.5  9  1:14  32,25  10  1:30  31.25  11  1:44  31.25  12  1:52  30.75  13  2:00  31.75  Exp.Iffi: 31-62-i-mg % MEAN  40  PLASMA  + «87-L nig % VARIATION FROM MEAN  INULIN mgm %  —  2  30  20 2  r i  21 TIME-HOURS  Figure 1  31 2  - 15 -  TABLE II EXPERIMENT Y Sample  INULIN INFUSION Time  DOG D In. mg$  Start 11:30 1  12:25  44.0  2  12:42  35.75  3  1:02  33.0  4  1:20  30.5  5  1:35  30.5  6  1:51  28.0  7  2:09  26.0  8  2:26  24.5  9  2:42  24.5  10  3:00  25.75  11  3:15  26.5  12  3:30  26.0  13  3:45  25.5  14  4:02  25.75  15  4:17  25.0  16  4:30  25.0  Exprs:  Figure 2  -17TABLB ni EXPERIMENT VI Sample  INULIN INFUSION Time  BOG D In. mg$.':  Start 10:30 1  11:20  27.0  2  11:45  25.5  3  12:00  27.25  4  12:15  28.0  5  12:37  28.0  6  12:53  28.0  7  1:08  28.5  8  1:25  28.25  9  1:40  28.75  10  1:53  27.75  11  2:03  27.75  12  2:15  28.5  13  2:31  28.0  14  2:45  27.25  15  2:58  26.25  4 0 - Exp.lZE PLASMA INULIN  27-5 m g % MEAN ± I-25 m g % VARIATION FROM MEAN  mgm % 30-  _  J  I  I  Ii 2  •  2  '  21 2 TIME  Figure 3  I  3 HOURS  I  3J_ 2  I  4  1  4J2  -1%  TABLE IV EXPERIMENT VII  INULIN INFUSION  Sample  Time Start  DOG D In. m  11130  1  12.10  24.5  2  12:27  22.5  3  12.40  22.5  4  12:43  23.0  5  12:46  22.25  6  12:49  23.0  7  12:52  22.25  8  12:55  23.0  9  1:10  23.0  10  1:25  23.75  11  1:40  23.75  12  1:43  21.25  13  1:46  21.25  14  1:49  20.75  15  1:52  21.25  16  1:55  21.5  17  2:12  21.5  18  2:25  21.5  URINE - Sample I collected 12:47-1:03 - 336ragIn. or 21 mg In./min. Sample I I collected 1:48-2:04 - 280 mg In. or 17*5 mg In./min.  PLASMA INULIN  Exp.izn  22-25 mg% MEAN  mgm %  ± 1-5 mg% VARIATION FROM MEAN  30f  20 21 2  n 2  TIME  Figure 4  3L HOURS  2  - 21 -  THE EFFECTS OF NOREPINEPHRINE INJECTION The effect of norepinephrine injection on water and cation shifts was tested in six experiments.  Water movement was estimated by  the method previously established. In experiment VIII the priming dose of inulin, 1.0 grams was given at 11:20 A.M. The sustaining infusion was begun simultaneously and continued for thvee and one-half hours. Norepinephrine (0.4 ug/Kg) was given at 2:03 P.M.  Blood samples were taken every three minutes  for fifteen minutes following the norepinephrine injection and at fifteen minute intervals after this.  Blood samples were taken as a control every  three minutes for fifteen minutes and at fifteen minute intervals prior to norepinephrine injection. Results are presented in Table V and Figure V, Urinary inulin excretion in the fifteen minute interval before and after norepinephrine injection is presented in Table V.  No  consistent movement of plasma inulin concentration is seen following the injection of 0.4 .jug/Kg  norepinephrine.  In experiment LX the priming dose of inulin, 1.0 grams was given at 11:00 A.M. The sustaining infusion was begun simultaneously and continued for three and one-half hours. Norepinephrine (1.6 jng/Kg) was given at 1:58 P.M.  Blood samples were taken as before. Urinary inulin  excretion was measured as before. Results are shown in Table VI and Figure VI. No consistent movement of plasma inulin concentration is seen following the injection of 1.6 4ig/kg norepinephrine. In experiment X the priming dose of inulin, 1.0 grams was given at 10:00 A.M. The sustaining infusion was begun simultaneously and continued for four hours. Norepinephrine (2.4 jig/Kg) w.as given at 1:14 P.M.  Blood samples were taken as before. Urinary inulin  - 22 -  excretion was measured as before. Plasma sodium and potassium were measured in each sample, fiesults are presented in Table VII and Figure VII.  No consistent movement of plasma sodium or plasma potassium  is seen. The possibility of a slight f a l l of plasma inulin concentration thirty minutes after norepinephrine injection is suggested. In experiment XI the priming dose of inulin, 1.0 grams was given at 11:15 A.M. The sustaining dose was begun simultaneously and continued for three and one-half hours. Norepinephrine (2.4 ;ug/Kg) was given at 2:12 P.M. Blood samples were taken as before. Urinary inulin excretion was measured as before. Plasma sodium and potassium were measured in each sample.  Results are presented in Table VIII and Figure VIII. No  consistent movement of plasma sodium or potassium is seen. The possibility of a slight f a l l of plasma inulin concentration thirty minutes after norepinephrine injection is suggested again. In experiment XII the priming dose of inulin, 1.0 grams was given at 10:00 A.M. The sustaining dose of inulin was begun simultaneously and continued for four and one-quarter hours. Norepinephrine (3.2 /ug/Kg) was given at 12:46 P.M. Blood samples were taken at fifteen minute intervals only. Plasma sodium and potassium were measured in each sample.  Urinary inulin excretion was measured over intervals of an  hour before and an hour after norepinephrine injection. Results are presented in Table IX and Figure IX. No consistent movement of plasma sodium or potassium is seen. The suggestion that plasma inulin concentration decreases thirty minutes after norepinephrine injection is not supported.  - 23 -  In experiment XIII the priming dose of inulin, 1.0 grams was given at 11:00 A.M.  The sustaining dose of inulin was begun  simultaneously and continued for four hours. Norepinephrine (4.8 ;ug/Kg) was given at 1:46 P.M.. Blood samples were taken at fifteen minute intervals only. Plasma sodium and potassium were measured with each sample. Urinary excretion of inulin was measured over intervals of forty minutes before and f i f t y minutes after norepinephrine injection. Results are presented in Table X and Figure X.  No consistent movement  of plasma sodium or potassium is seen. A decrease of plasma inulin at thirty minutes is not observed. Increasing doses of norepinephrine were used in these experiments. In each case the test interval was preceded by a similar control interval. Experiments 8, 9, 10, 11 show no consistent pattern of inulin movement in the fifteen minute interval following norepinephrine injection. Experiments 10 and 11 suggested the possibility of a slight f a l l in plasma inulin concentration at thirty minutes but Experiments 12 and 13 offer this no support. Experiments 10, 11 and 12 and 13 examine the effect of norepinephrine in large doses on the cations both in the fifteen minute interval and over ninety minutes. No significant cation movement is observed. The blood pressure was not recorded in these experiments. With doses of 1.6 ;ug/Kg norepinephrine and over, the animal reacted violently and abruptly. She began to pant, groan and whine, an abrupt tachycardia ensued, followed closely by a more prolonged bradycardia which lasted five to ten minutes.  TABLE V EXPERIMENT VIII Sample  INULIN INFUSION fflTH NORE PINSPHRINS INJECTION Time  DOG D  In. mg??  Start 11:20 1  12:30  30.0  2  12.50  29.5  3  1:10  30.75  4  1:13  33.0  5  1:16  34.0  6  1:19  34.25  7  1:22  31.5  8  1:25  33.5  9  1:28  32.5  10  1.31  32.25  11  1:50  33.5  2:03  - 0.4 yg/kg • norepinephrine I.V.  12  2.05  35.5  13  2:08  34.25  14  2:11  33.5  15  2:14  34.25  16  2:17  33.5  17  2:20  32.75  18  2:23  33.5  19  2:26  33.5  20  2:40  34.25  21  2:50  35.25  URINE - Sample I collected 1:17-1:33 - 352 mg In. or 23.5 mg/ln./min Sample II collected 2:11-2:28 - 350 mg In. or 20.6 mg/ln./min  Exp.izm 40PLASMA INULIN m g m %  us  30-  20 3  T I M E — HOURS  Figure 5  r  - 2& -  TABLE VI EXHSRIMENT IX  INULIN INFUSION WITH NOREPINEPHRINE INJECTION  Sample  Time  DOG M  In. mg%  Start lliOO 1  12:45  26.75  2  1:00  26.25  3  1:15  27.0  4  Iil8  26.75  5  1:21  26.25  6  1:24  26.25 = spoiled -  7 8  1:30  27.0  9  1:45  25.5  1:58 - 1.6 $tg/&g:. nor e pine pi 10  2»00  24.0  11  2:03  24.25  12  2:06  25 .5  13  2:09  24.25  14  2:12  23.5  15  2:15  24.25  16  2:18  25.0  17  2:30  25.0  collected 1:20-1:36  - 502 mg  In. or 31.2 mg  In./min.  Sample II c o l l e c t e d 2:05-2:21  - 355 mg  In. or 22.2 mg  In./min.  URINE - Sample I  40| PLASMA INULIN hngm%  Exp.-TX 40yLxgm NOREPINEPHRINE  30l-  20'  4  3 TIME  Figure 6  HOURS  3  i  TABLE VII EXPERIMENT X.  INULIN INFUSION WITH NOREPINEPHRINE INJECTION  Sample  Time  DOG M -  In.rng^  K.mSq/L  Na.mEq/L  Start 10:00 1  12:00  20.75  3.49  156.88  2  12:15  22.0  3.34  153.29  3  12:30 .  23.0  3.34  152.57  4  12.45  24.0  3.80  150.06  5  12.48  23.5  3.70  156.16  6  12:51  25.0  3.60  152.57  7  12.54  23.5  3.62  152.57  8  12:57  24.0  3.71  153.29  9  1:00  25.0  -Spoiled-  153.65  . 1:14 - 2.4|Jg/Kgj;inorepinephrine I.V. 10  1:15  25.25  3.68  152.57  11  1:18  25.25  3.46  153.29  12  1:21  25.25  3.35  152.57  13  1:24  24.25  3.33  153.29  14  1:27  24.75  3.22  150.06  15  1:30  25.5  3.38  150.06  16  1:45  25.5  3.48  152.57  17  2:00  24.25  3.72  152.57  URINE  Sample I collected 12:51 - 1:07 - 527mg In. or 33 mg In/min. Sample II collected 1:21 - 1:37 - 637 mg In. or 39. mg In/min.  Figure 7  -30TABLE VIII EXPERIMENT XI  INULIN INFUSION WITH NOREPINEPHRINE INJECTION  Sample  Time  In.rng^  K.mEq/L  DOG D Na.mEq/L  Start 1 1 : 1 5 1  l ! l 5  36.5  3 . 1  151o49  2  1 . 3 0  37c 0  3.3  151o49  3  1 : 3 3  3 8 oO  3.35  1 4 7 . 1 9  4  1.36  39.5  3 . 3  1 5 0 . 7 5  5  1:39  39.5  3.35  1 4 7 . 9 0  6  1.42  3 9 . 5  3.3  1 4 8 . 9 8  7  1 . 4 5  36.75  3.0  1 4 5 . 3 9  8  2 . 0 0  3 8 . 0  3 » 2  1 4 7 o l 9  2.12 - 2.4£4g/KgJ norepinephrine I.V.  9  2sl5  39.0  3.1  152.57  10  2.18  39.75  3.2  148.98  11  2.21  40.75  3.3  147.90  12  2.24  40.5  3.1  148.98  13  2827  39.5  3o4  145.39  14  2s30  39=35  3.3  147.90  15  2.40  38.25  3.1  145.39  16  2.50  38.75  3.2  145o39  U1INE - Sample I collected 1:36 - 3:52 - 900 mg In. or 56.2 mg In/Min. Sample I I collected 2:19 - 2:37 - 892 mg In. or 49.5 mg In/min.  PLASMA N o INULIN mgm% mEq/L  40  Exp.3L 60/i.gm NOREPINEPHRINE (2-4/i.gm/kgm)  160  30-  150-  20-  140-  TIME  Figure 8  HOURS  -32TABLE IX EXPERIMENT XII  INULIN INFUSION WITH NOREPINEPHRINE INJECTION  Sample  Time  DOG M  In.mg#  K.ra!Bq/L  Na.mEq/L  Start 16:00 1  12:00  26.25  3.40  155.08  2  12:10  -26.75  3.30  156.16  3  12i30 - Spoiled -  4  12:45  3.12  152.57  26.5  12:46 - 3.2 Xg/Kga norepinephrine I.V. 5  1:00  27.0  3.10  148.26  6  1:15  27.25  3.12  155.80  7  1:30  28.75  3.15  151.85  8  .1:45  28.5  3.35  152.57  9  2:00  27.0  3.12  154.72  10  2:15  27.25  3.02  145.03  URINE - Sample I collected 12:00 - 1:05 - 1401.75 mg In. or 21.6 mg In/min. Sample I I collected 1:05 - 2:05 - 1336»,mg In. or 22.6 mg In/min. 6  Figure 9  TABLE X EXPERIMENT XIII Sample  INULIN INFUSION WITH NOREPINEPHRINE INJECTION Time  DOG M  In.mg$  K.mBq/L  Na.mEq/L  Start 11:00 1  1:00  26.75  3.05  151.85  2  lsl5  27.0  3.08  151.13  3  1:30  27.5  3.02  152.93  4  1:45  25.0  2.90  150.78  1:46 - 4.8 tig/Kgi. norepinephrine I.V. 5  2:00  24.75  3.00  153.65  6  2:15  26.0  3.02  151.85  7  2:30  25.0  3.03  151.45  8  2:45  25.25  3.01  159.75  9  3:00  25.25  3.91  151.85  Urine not measured for Volume but: Sample I collected 1:10 - 1:50 - 36.5 mg In/cc* Sample I I collected 1:50 - 2:40 - 36.75 mg In/cc* # including washout.  PLASMA No Exp.TTTT INULIN mEq/L mgm % 40 160-  30  I20^gm NOREPINEPHRINE (4-8/igm/kgm)  K mEq/L 4  150  3-5 ZD -  140  K  -o-  TIME  HOURS  Figure 10  - 36 -  THE EFFECTS OF PITRESSIN INJECTION The effects of pitressin injection on water and cation shifts were tested in three experiments.  Water movement was estimated by the  method previously established. In experiment XIV the priming dose of inulin, 1.0 grams was given at 9:45 A.M. The sustaining infusion was begun simultaneously and continued for three hours and twenty minutes.  Pitressin (200 mU/Kg)  was given at 12:29 P.M. Blood samples were taken every three minutes for fifteen minutes following the pitressin injection and at ten minute intervals after this. Blood samples were taken as a control every three minutes for fifteen minutes and at fifteen minute intervals prior to the pitressin injection. Plasma sodium and plasma potassium were measured in each sample. Urinary inulin excretion was measured as before. Results are presented in Table XI and Figure XI. With the administration of 200 mU/Kg of pitressin the plasma inulin concentration rose from 32.75 mgm % to 39 mgm % in six minutes.  The plasma sodium concentration f e l l from  153.4 mEq/L to 144.67 mEq/L in three minutes.  The plasma potassium  concentration rose from 3.26 mEq/L to 3.42 mEq/L over a fifteen minute interval. In experiment XV the priming dose of inulin, 1.0 grams was given at 10:15 A.M.  The sustaining infusion was begun simultaneously and contin-  ued for four hours. Pitressin (40 mO/Kg) was given at 1:44 P.M. Blood samples were taken as before. Urinary inulin excretion was measured as before. Results are presented in Table XII and Figure XII. With the administration of 40 mU/Kg of pitressin the plasma inulin concentration rose from 34,5 mgm % to 36.25 mgm % in three minutes.  The plasma sodium  - 37 -  concentration f e l l from 159.3 mEq/L to 154.01 mEq/L in six minutes. The plasma potassium concentration rose from 3.80 mEq/L to 4.09 mEq/L in an interval of 12 minutes. In experiment XVI the priming dose of inulin, 1.0 grams was given at 10:20 A.M. The sustaining infusion was begun simultaneously and continued for four and one-half hours. Pitressin (40 mU/Kg) was given at 1:32 and again at 2:11.  Blood samples were taken as before. Urinary  inulin excretion was measured as before. The results are shown in Table XIII and Figure XIII. With the f i r s t injection of 40 mU/Kg of pitressin, plasma inulin concentration rose from 25.0 mgm % to 26.75 mgm % in thirteen minutes. Plasma sodium concentration f e l l from 150.06 mEq/L to 147.19 mEq/L in seven minutes. Plasma potassium concentration rose from 3.4 mEq/L to 4.08 mEq/L in thirteen minutes. With the second pitressin injection of 40 mU/Kg the plasma inulin concentration rose from 23.75 mgm % to 25.0 mgm % in eleven minutes. The plasma sodium concentration f e l l from 152.6 mEq/L to 148.6 mEq/L in five minutes. The plasma potassium concentration rose from 3.77 mEq/L to 3.96 mEq/L in eleven minutes. A blood pressure tracing was taken with the administration of the second dose of pitressin.  The result is shown in Figure XIV.  In experiment 14 the administration of a large dose of pitressin (200 mU/Kg ) was followed by a sudden and distinct rise of 6.25 mg % plasma inulin. The rise in plasma inulin concentration reached i t s peak in six minutes and remained elevated for fifteen minutes. Plasma sodium concentration behaved as a mirror image of plasma inulin. Plasma sodium concentration f e l l 9 mEq/L in three minutes and then rose coincidentally with the f a l l of the plasma inulin concentration. Plasma potassium  - 38 -  concentration rose 0.16 mEq/L reaching i t s peak at fifteen minutes. Similar changes were noted with 40 mU/Kg doses of pitressin in three occasions in experiments 15 and 16. These changes were of less magnitude than in experiment 14. Though the direction of shift i s similar in a l l experiments there is variation in the magnitude of movement of cations relative to water and of sodium relative to potassium. The blood pressure responsenwas observed in experiment 16. This is shown in Figure 14. Our findings correspond with those of Kolls and Gelling (14)„ A. rise of diastolic pressure of 30-40 mm/Hg i s recorded. The systolic pressure rose less, so the pulse pressure diminished. The bradycardia observed developed over a thirty second period. The clinical description of the reaction corresponded closely with the description given by Kolls and Geiling.  - 3 9 -  TABLE XI EXPERIMENT XIV Sample  INULIN INFUSI0B1 WITH PITRESSIN INJECTION Time  Start  DOG D  In.mg^  K.mEq/L  Na.mEq/L  9:45  1  11:45  32.5  3.58  154.37  2  12:00  31.5  3.18  153.65  3  12:03  3?.5  3.30  153.65  4  12:06  33.0  3.50  150.78  5  12:09  32.0  3.36  153.29  6  12:12  31.25  3.06  147.19  7  12:15  32.5  3.18  148.98  12:29 - 200 mU./Kgfi pitressin I.V. 8  12:30  32.75  3.26  153.39  9  12:33  ' 34.75  3.24  144.67  10  12:36  39  3.41  150.78  11  12:39  34.75  3.38  147.19  *2  12:42  34.0  3.36  147.90  13  12:45  33.5  3.42  148.62  14  liOO  29.75  3.40  153.29  15  1:10  29.25  3.40  153.29  28.75  3.27  150.06  16  1:20  17  1:25  29.25  3.52  148.98  18  }:35  29.25  3.50  148.62  URINE - Volume not recorded Sample I collected 12:02 - 12:18 - 40 mg In/cc Sample I I collected 12:30 - 12:47 " 37 mg In/cc Sample III collected 1:09 - 1:26 - 34 mg In/cc  3  TIME  HOURS  Figure 11  T  4  -'CI-  TABLE XII EXPERIMENT XV  INULIN INFUSION WITH PITRESSIN.: INJECTION  Sample  Time  In„mg#  K.mEq/L  DOG D Na.mEq/L  Start 1 0 : 1 5 1  12815  34o5  3.91  160.83  2  1 2 : 3 0  35.25  4.12  156.52  3  1 2 : 4 5  37.0  4.0  152.93  4  1:00  37.25  4.02  1 5 5 . 8 0  5  1 : 0 3  36oO  3.89  156.52  1 : 0 6  34.25  3.65  1 5 1 . 4 9  7  1:09  32.5  3.74  1 5 5 . 8 0  a  1:12  9  1:15  33.0  3.75  1 6 0 . 4 7  1:30  34.75  3.90  1 6 3 . 2 6  10  1 : 4 4  - Spoiled  -  -  4 0 mU/Kgi pitressin I.V.  11  1:45  34.5  3.80  159.03  12  1 : 4 8  3 6 . 2 5  4o01  1 5 7 . 9 6  13  1 : 5 1  34.0  3.75  1 5 4 . 0 1  14  1 : 5 4  34.0  3.99  1 5 7 . 2 4  15  1:57  34.5  4.09  1 5 7 . 2 4  16  2 : 0 0  33.25  3.89  1 5 7 . 2 4  17  2 : 1 0  32.5  4.18  1 5 0 . 0 6  18  2:20  31.75  4.01  1 4 7 . 5 4  URINE - Sample I collected 1 : 0 5 - 1 : 1 6 - 3 9 0 mg In. or 3 5 . 5 mg In/min. Sample I I collected 1 : 4 8 - 2 : 0 4 - 8 9 0 mg In. or 5 5 mg In/min.  Figure 12  •43-  TABLE XTII EXPERIMENT XVI Sample  INULIN INFUSION WITH PITRESSIN INJECTION Time  Irumg^  KmEq/L  DOG M Na.mEq/L  Start 10:20 1  12.25  26.0  3.5  1 5 0 . 0 6  2  12:45  26.0  3.25  147*90  3  12:55  25o75  3.55  144.32  4  1:00  26.0  3.5  150.78  5  1:10  26.0  3.47  148.63  6.  1:30  25  oO  3.4  150.06  1:32>  40  miU/Kgu pitressin I.V.  7  1:33  - spoiled -  3.35  148.63  8  1:36  25.5  3.7  147.90  9  1:39  25«5  3.7  147.19  10  1.42  2 5 . 7 5  3.92  148.63  11  1:45  26.75  4.08  1 5 2 . 9 3  12  1:48  23.0  3.4  1 5 2 . 5 7  13  2:00  23.75  3.92  153.29  14  2sl0  23.75  3.77  1 5 2 . 5 7  2:11 - 40 mtf/kg).. pitressin I.V. 15  2:13  24 75  3.6  153.29  16  2:16  24o75  3.65  148.63  17  2:19  24.25  3o72  148.63  18  2:22  25.0  3.96  152.57  19  2:36  24.25  3.85  150.06  0  24.25 3.85 145.04 URINE - Sample I collected 12:39 - 1 2 : 5 8 - 399.5 mg In. or 2 6 . 7 5 mg In/min. Sample II collected 2:13 - 2 : 2 5 - 410 mg In. or 31.5 mg In/min. Blood pressure was recorded from 2:11 to 2:16 and shown i n Figure 14. 20  2:45  Figure 13  - 46 -  DISCUSSION The r e l i a b i l i t y of the inulin infusion technique was tested, A fairly constant level of extracellular inulin can be maintained for up to three hours by this technique. The greatest variation from the mean was 1,5 mg% of plasma inulin. The plasma inulin concentration measured over three minute intervals showed no more variation than i t did in fifteen minute intervals. Enough control of the plasma inulin concentration was thus achieved to justify the use of the technique to indicate the direction of extracellular water shift. In addition to providing constant extracellular inulin levels the inulin infusion technique has the advantage of simplicity. No c r i t i c a l intake and output methods are necessary. The technique simply involves the administration of an approximate concentration of inulin solution at a constant rate. Norepinephrine and pitressin show different effects on cation and water movement in the conscious dog  D  Six experiments with norepine-  phrine injection were performed and our results do not conflict with those results recorded in the literature for the anaesthetized animal. We observed no change in the plasma sodium concentration with the doses of norepinephrine we administered. Friedman et al (8) observed no change in the plasma sodium concentration in anaesthetized dogs with comparable doses of norepinephrine. Muirhead et all  (15) noted a  significant decrease in the extracellular sodium concentration with a norepinephrine infusion but the doses in his experiments were twenty times the doses used in our work. Similar comment can be made in respect to the work of Robertson and Peyser (19).  - 47 -  Muirhead et al (15) observed no change in the radiosulfate space with a norepinephrine infusion.  In our experiments the inulin space did  not change in response to a norepinephrine injection. Both of these observations are at variance with the results of Friedman et al (8) who observed a distinct depression of the inulin space in response to a norepinephrine infusion in the dog. In order to observe this depression in the rat Friedman found i t necessary to induce a hypotensive state, such is the rapidity of the change in the extracellular space. Ondoubtably the infusion of norepinephrine provides a measurable interval not provided by a single injection. It is also conceivable that the conscious dog may have an adaptive capacity not present in the anaesthetized dog. In view of the fact, however, that the space does change with a pitressin injection the latter possibility is unlikely. We observed no change in the plasma potassium concentration in response to the norepinephrine injection. Plasma potassium concentration did not change in response to norepinephrine infusion in the work of Friedman et al (8)  0  Muirhead  et al (15) observed a slight rise in the plasma potassium concentration but with very large doses of norepinephrine. Three experiments were performed with pitressin injections. These three experiments suggest a definite pattern of water and cation movement associated with the pressor response. No inference can, however, be drawn as to which comes f i r s t .  Following a pitressin injection water moves out  of the extracellular space as is shown by the sudden increase in the plasma inulin concentration. The renal excretion of inulin did not diminish during the testing intervals.  In association with the water  movement plasma sodium concentration dropped markedly while plasma  - 48 -  potassium concentration rose slowly,, These responses to a pitressin injection are similar to those responses obtained by Friedman et al (8) on anaesthetized dogs with comparable pitressin doses. It can be seen in Friedman's work and ours that the magnitude of the change varies with the magnitude of the dose„ Tobian and Fox (21) noted the individual variation of cationic changes in dogs and this may explain the relative differences observed by us since experiments 14 and 15 were performed with dog D and experiment 16 with dog M. As stressed by Friedman et a l the shift of water and cations v  is less rapid with pitressin than with norepinephrine, as is the pressor effect. Consequently pitressin changes are more easily measured.  CONCLUSIONS 1  0  An index of extracellular fluid shift has been developed.  2. Norepinephrine has not been shown to affect water or cationic movement in the extracellular compartment,, 3. Pitressin has been shown to affect water and cationic movement in the extracellular compartment. This has been interpreted to indicate a movement of water and sodium into cells and potassium out of cells in association with the pressor response.  - 49 BIBLIOGRAPHY 1.  B e c k e t , E L . and B . J . Joseph: 4  Measurement o f e x t r a c e l l u l a r f l u i d  volume i n normal dogs„ 2.  Berne, R.M.  and N.M. space.  3.  Gaudino, M„ and M.F.  R a i s z , L.G.,  M.K.  J. of P h y s i o l .  1955.  A modified procedure f o r determing i n u l i n  P r o c . o f Soc. o f Exp. B i o l . & Med* 2 1 , 583,  fluid. 4.  Levey:  Am„  L e v i t t : I n u l i n space as a measure of e x t r a c e l l u l a r Am.  J . o f P h y s i o l . 151, 387,  1949.  Young and I . T . S t i n s o n : Comparison o f d i s t r i b u t i o n  of i n u l i n , s u c r o s e and t h i o s u l f a t e i n normal and i z e d dogs.  Am.  5.  H i g a s h i , A„ and L. P e t e r s :  6.  D ' S i l v a , J . L . , The a c t i o n potassium.  7.  D ' S i l v a , J.L„,  J . of P h y s i o l . 174, 72,  of adrenaline-like  J . o f P h y s i o l . 1QS,  The a c t i o n  Friedman, S,M„,  R.M.  9.  Friedman, S.M.,  507,  Friedman, S.M.,  1949.  1934.  B u t t , and C.L. Friedman:  C a t i o n s h i f t s and  i n the dog.  Am.  J . of P h y s i o l ,  1957.  C.L. Friedman, and M. Nakashima:  blood pressure r e g u l a t i o n . 10.  serum  of a d r e n a l i n e on serum p o t a s s i u m .  blood pressure r e g u l a t i o n 12Q,  1950.  s u b s t a n c e s on 218,  neprectom-  1953.  J . Lab. & C l i n . Med. 3 5 , 475,  J . o f P h y s i o l . £2., 393, 8.  1951.  M. Nakashima  C a t i o n s h i f t s and  C i r c u l a t i o n Res. 5_, 261,  and C,L. Friedman:  1957.  S e p a r a b i l i t y o f the  e f f e c t of p i t r e s s i n and a d r e n a l i n e on b l o o d p r e s s u r e and electrolytes. 11.  Friedman, S.M.,  Arch. Internat,  Pharmacodyne, H Q ,  W. Webber, J . Jamieson, C.L. Friedman:  siveness f o l l o w i n g acute elevation  1957.  Friedman, S.M„, W. Webber, H.F. S c h e r r e r , C.L. Friedman:  Changes i n  s a l t and water d i s t r i b u t i o n , b l o o d p r e s s u r e and a d r e n a l a c t i v i t y f o l l o w i n g neurohypophyseal d e n e r v a t i o n i n the rat.  1957.  Pressor respon-  o f sodium i n t h e r a t .  Can. J . of Biochem. & P h y s i o l . 3 5 , 327, 12.  170,  Can. J . of Biochem. & P h y s i o l . 34, 425,  1958.  - 50 13. Friedman, S.M., H. F„ Scherrer, M Nakashima and C.L. Friedman: 0  Extrarenal factors in diabetes insipidus* Am. J, of Physiol. 152, 401, 1958. 14.  Kolls A C. and E'.M.K. Geiling: Contributions to the Pharmacology e  of Extracts of the Posterior Lobe of the Pituitary. J. of Pharm. 24, 67, 1924. 15. Muirhead, E.E., A. Goth and F. Jones: Sodium and Potassium Exchanges Associated with Norepinephrine Infusions. Am. J. of Physiol. 12£, 1, 1954. 16. Nickerson, M. and L.S. Goodman: Pharmacological properties of a new adrenergic blocking agent, N N, Dibenzyl-B-chloro-ethyl9  amine., (Dibenamine).  J. of Pharm. £9_„ 167, 1947.  17. Obrien G.S., Q.R. Murphy and W.J. Meek: Effect of Sympathomimetic amines on arterial plasma potassium and cardiac rythym in anaesthetized dogs. J. of Pharm. 1Q9_, 453, 1953. 18.  Oliver, G. and E.A. Shafer: On the Physiological action of extracts of pituitary body and certain other glandular organs  0  J. of Physiol. Ifi, 277, 1895. 19. Robertson W.Van B. and P. Peyser:  Changes in water and electrolytes  of cardiac muscle following epinephrine. Am„ J. of Physiol. 1M  S  277, 1951.  20. Scherrer H.F. and S.M. Friedman: A sustained pressor response to hypothalmic stimulation in the rat. Acta Endocrinologica. 21, 89, 1958. 21. Tobian, L. and A. Fox:  The effect of norepinephrine on the elect-  rolyte composition of arterial smooth muscle. J. Clin. Invest. 25., 297, 1956.  

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.831.1-0106285/manifest

Comment

Related Items