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The effects of alpha adrenergic receptor stimulation, using epinephrine, on lung fluid production in in vitro preparations of lung from fetal guinea pigs (Cavia porcellus) Doe, Sam
Abstract
This study examined the effects of epinephrine on fluid production and reabsorption by fetal guinea pig lungs. Catecholamine levels in the fetus have been found to increase significantly near term and epinephrine has been proposed to play a role in the reabsorption of lung fluid. Improper fluid reabsorption at birth leads to a condition called respiratory distress syndrome which is the leading cause of death among newborns. Our procedure involved supporting the lungs in vitro for a duration of three hours in Krebs' saline and the rates of fluid production were measured using a dye-dilution technique. The control rates ranged from 0.98 to 1.34 ml/kg*hr with gestational ages between 59 to 65 days (gestation is 67 days) which is comparable to rates reported from fetal sheep. The lungs were exposed to different concentrations of epinephrine, ranging from 10⁻⁸ M to 10⁻⁵ M, during the second hour of experimentation, following an ABA design. Epinephrine produced reductions in fluid secretion in a dose dependent manner except at pharmacological levels where the response disappeared. Optimal responses to epinephrine were obtained at 10⁻⁷ M. The unexpected results at high concentrations of epinephrine warranted further investigation using specific alpha-adrenergic receptor blockers. However, tests with general alpha and beta-adrenergic receptor antagonists were carried out beforehand to confirm previous work which showed that epinephrine works through alpha and not beta receptors. Propranolol, a general beta blocker, did not block the effect of 10⁻⁷ M epinephrine whereas phentolamine, a general alpha blocker, eliminated the effect of epinephrine. Thus, epinephrine in the fetal guinea pig lung appears to work through alpha-adrenergic receptors rather than beta-adrenoreceptors. Experiments with specific alpha-adrenoreceptor antagonists have suggested that epinephrine stimulates two opposing mechanisms at high pharmacological concentrations while at physiological levels, epinephrine stimulates a single process. Studies with yohimbine (10⁻⁴ M), a specific alpha₂~adrenoreceptor antagonist, and epinephrine at 10⁻⁵ M as well as 10⁻⁷ M suggest that alpha₁-receptor stimulation causes a significant increase in lung fluid secretion. This is the first reported case where an increase in lung liquid production was obtained on a consistent basis. Tests with prazosin (10⁻⁵ M), a specific alphas-receptor blocker, and epinephrine (10-* M) appears to show that alpha₂-receptor stimulation cause a significant reduction in lung liquid secretion. However, the lack of an effect of prazosin (10⁻⁵ M) at physiological levels of epinephrine (10~7 M) implies that alpha₁-receptors function only at pharmacological levels. Therefore, at physiological levels of epinephrine, only alpha₂_adrenoreceptors are activated to reabsorb lung liquid and at pharmacological levels, two opposing mechanisms (alpha₁ and alpha₂-adrenoreceptors) are stimulated to eliminate the effects of epinephrine.
Item Metadata
Title |
The effects of alpha adrenergic receptor stimulation, using epinephrine, on lung fluid production in in vitro preparations of lung from fetal guinea pigs (Cavia porcellus)
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
1994
|
Description |
This study examined the effects of epinephrine on fluid
production and reabsorption by fetal guinea pig lungs.
Catecholamine levels in the fetus have been found to
increase significantly near term and epinephrine has been
proposed to play a role in the reabsorption of lung fluid.
Improper fluid reabsorption at birth leads to a condition
called respiratory distress syndrome which is the leading
cause of death among newborns.
Our procedure involved supporting the lungs in vitro
for a duration of three hours in Krebs' saline and the rates
of fluid production were measured using a dye-dilution
technique. The control rates ranged from 0.98 to 1.34
ml/kg*hr with gestational ages between 59 to 65 days
(gestation is 67 days) which is comparable to rates reported
from fetal sheep.
The lungs were exposed to different concentrations of
epinephrine, ranging from 10⁻⁸ M to 10⁻⁵ M, during the
second hour of experimentation, following an ABA design.
Epinephrine produced reductions in fluid secretion in a dose
dependent manner except at pharmacological levels where the
response disappeared. Optimal responses to epinephrine were
obtained at 10⁻⁷ M. The unexpected results at high
concentrations of epinephrine warranted further
investigation using specific alpha-adrenergic receptor
blockers. However, tests with general alpha and beta-adrenergic
receptor antagonists were carried out beforehand to confirm
previous work which showed that epinephrine works through
alpha and not beta receptors. Propranolol, a general beta
blocker, did not block the effect of 10⁻⁷ M epinephrine
whereas phentolamine, a general alpha blocker, eliminated
the effect of epinephrine. Thus, epinephrine in the fetal
guinea pig lung appears to work through alpha-adrenergic
receptors rather than beta-adrenoreceptors.
Experiments with specific alpha-adrenoreceptor
antagonists have suggested that epinephrine stimulates two
opposing mechanisms at high pharmacological concentrations
while at physiological levels, epinephrine stimulates a
single process. Studies with yohimbine (10⁻⁴ M), a specific
alpha₂~adrenoreceptor antagonist, and epinephrine at 10⁻⁵ M
as well as 10⁻⁷ M suggest that alpha₁-receptor stimulation
causes a significant increase in lung fluid secretion. This
is the first reported case where an increase in lung liquid
production was obtained on a consistent basis. Tests with
prazosin (10⁻⁵ M), a specific alphas-receptor blocker, and
epinephrine (10-* M) appears to show that alpha₂-receptor
stimulation cause a significant reduction in lung liquid
secretion. However, the lack of an effect of prazosin (10⁻⁵
M) at physiological levels of epinephrine (10~7 M) implies
that alpha₁-receptors function only at pharmacological
levels. Therefore, at physiological levels of epinephrine,
only alpha₂_adrenoreceptors are activated to reabsorb lung liquid and at pharmacological levels, two opposing
mechanisms (alpha₁ and alpha₂-adrenoreceptors) are
stimulated to eliminate the effects of epinephrine.
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Extent |
3186768 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-02-25
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0087436
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
1994-05
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.