(Hypertension. 1996;27:136-143.)
© 1996 American Heart Association, Inc.
Articles |
Role of Vasopressin in Neurocardiogenic Responses to Hemorrhage in Conscious Rats
From the Second Department of Medicine, Tohoku University School of Medicine, Sendai, Japan.
Correspondence to Yutaka Imai, MD, Department of Medicine, Tohoku University School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, 980, Japan.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion References |
|---|
Abstract Vasovagal reflexes, such as hypotension and bradycardia, are induced by rapid hemorrhage and mimic neurocardiogenic reflexes in mammals. We examined the role of vasopressin in the neurocardiogenic responses to mild, rapid hemorrhage (1 mL/100 g for 30 seconds) and severe hemorrhage (1 mL/100 g body wt for 30 seconds repeated three times at 11-minute intervals) in homozygous Brattleboro and Long-Evans rats. Mild, rapid hemorrhage induced severe bradycardia and hypotension only in Long-Evans rats. Exogenous vasopressin (1.85 pmol/kg per minute for 1 hour) restored both the bradycardic and hypotensive responses in Brattleboro rats. DDAVP, a vasopressin V2-receptor agonist (0.19 pmol/kg per minute for 24 hours), did not affect the cardiovascular responses to hemorrhage in Brattleboro rats, although it maintained urine production within normal limits. However, OPC-31260 (21.6 µmol/kg IV), a vasopressin V2-receptor antagonist, attenuated both the hypotensive and bradycardic responses to hemorrhage in Long-Evans rats. A vasopressin V1-receptor antagonist attenuated bradycardia and delayed the recovery of arterial pressure after hemorrhage but did not affect the hypotension that occurred immediately after hemorrhage in Long-Evans rats. Methylatropine also attenuated both the bradycardic and hypotensive responses induced by hemorrhage, but propranolol had no effect on the cardiovascular responses to hemorrhage in Long-Evans rats. The recovery of arterial pressure after repeated hemorrhage was less adequate in Brattleboro rats than in Long-Evans rats. Our results suggest that the neurocardiogenic responses to hemorrhage, especially hypotension, may be related to vasodilation induced by a V2-receptor–mediated mechanism and by the vagal reflex, both of which are substantiated by the existence of vasopressin. The coexistence of V1- and V2-receptor mechanisms may be necessary for the hypotensive response to hemorrhage. We found that a V2-receptor antagonist attenuated the hypotension mediated by the so-called neurocardiogenic reflex.
Key Words: vasopressins • hemorrhage • bradycardia • hypotension • rats, Brattleboro
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Decreased venous return due to mild hemorrhage causes decreases in cardiac filling pressure, stroke volume, and arterial pressure, triggering reflex tachycardia and vasoconstriction, decreased parasympathetic tone, and release of renin and AVP.1 In the presence of rapid, severe hemorrhage this compensatory response is interrupted and replaced by a paradoxical decrease in sympathetic activity and increase in parasympathetic activity, causing profound vasodilation and bradycardia.2 3 4 5 6 7 8 9 10 11 12 13 14 15 The sudden failure of vasoconstriction and absence of tachycardia during acute hemorrhage resemble the vasovagal or neurocardiogenic reflexes induced by orthostasis, lower body negative pressure, venesection, and emotional stress in humans. The release of AVP is markedly increased during hypotensive hemorrhage.16 17 18 In situations such as severe hemorrhage, an elevated concentration of AVP is believed to modulate or correct hypotension by exerting a direct pressor effect.19 20 Therefore, elevated concentrations of AVP appear to contribute to the maintenance of blood pressure during paradoxical vasodilation mediated by the neurocardiogenic reflex in response to hemorrhage. If circulating AVP had such an effect in normal rats, the compensatory response to hemorrhage would be expected to be absent in AVP-deficient DI rats: That is, paradoxical vasodilation and the resultant hypotension induced by hemorrhage should be enhanced in DI rats compared with normal LE rats.
AVP has been found to inhibit sympathetic neural tone,21 22 23 24 25 26 27 stimulate parasympathetic tone,28 29 30 31 32 33 and cause vasodilation via a direct effect on resistance vessels.34 35 36 37 38 39 If the cardiodepressive and vasodepressive effects of AVP occurred predominantly during acute hemorrhage, the paradoxical vasodilation and bradycardia and resultant hypotension would be increased in normal LE rats compared with DI rats. The mechanisms of AVP-mediated neurocardiogenic responses during hemorrhage have not been clarified.40 In the present study we examined the role of AVP in the neurocardiogenic responses to rapid hemorrhage (1 mL/100 g body wt for 30 seconds) in conscious LE and DI rats and investigated the mechanisms responsible for AVP-mediated neurocardiogenic responses during hemorrhage.40
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
We studied male homozygous Brattleboro rats with hereditary hypothalamic DI and male LE rats (the parent strain) originating from Monash University Animal Center (Melbourne, Australia) and bred and supplied by the Experimental Animal Center, Tohoku University School of Medicine. Rats were anesthetized with ether, and the left femoral artery and vein were catheterized with polyethylene tubing. The tip of the arterial catheter (Intramedic PE-100, Clay Adams) was tapered by heating and inserted into the femoral artery. Intramedic PE-50 tubing was used as the venous catheter. The catheters, which were passed subcutaneously and brought out at the neck, were filled with heparinized saline (1000 IU/mL) and heat sealed. The rats were allowed to recover for at least 24 hours after surgery and were conscious and unrestrained during subsequent studies.
During each experiment the rats were placed in metabolic cages and allowed free movement and access to water. Arterial pressure was recorded from the femoral arterial catheter with a pressure transducer (Statham P23 Db) and a strain-gauge amplifier (model 1321, NEC-San-ei). Heart rate was recorded with a cardiotachometer (model 1257, NEC-San-ei or model Unicon Kfh 122B, Baker Institute). Both arterial pressure and heart rate were recorded continuously on a recorder (Rectigraph-8K, NEC-San-ei or model 440, Gould-Brush). Arterial pressure and heart rate were allowed to stabilize for 1 hour before experiments.
The drugs used in the present study included methylatropine bromide (Takeda Pharmaceutical), propranolol hydrochloride (Sigma Chemical Co), [Arg8]-AVP (Sigma), DDAVP (Ferring), 1-(ß-mercapto-ß,ß-cyclopentamethylene-propionic acid), 2-O-methyltyrosine,4-valine AVP [d(CH2)5 Tyr(Me)AVP] (Peninsula Laboratories), and (±)-5-dimethylamino-1-[4-(2-methylbenzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzazepin (OPC-31260, Otsuka Pharmaceutical).41 42 Stock solutions of AVP and its analogue were prepared in 0.1 mol/L acetic acid and diluted with 0.9% saline to the desired concentrations. The remaining drugs were dissolved in 0.9% saline. AVP solutions were infused intravenously at a rate of 30 µL/min with a Princeton infusion pump (model 575). Drug solutions were administered intravenously through the implanted venous catheter in a volume of less than 150 µL.
All experimental procedures were in accordance with the institutional guidelines of Tohoku University School of Medicine.
Procedure for Acute Hemorrhage
After a 1-hour stabilization
period blood was withdrawn from the
femoral artery catheter into a sterile plastic syringe at a rate of 2
mL/100 g body wt per minute over a 30-second period (1 mL/100 g body wt
for 30 seconds). In some experiments the withdrawn blood was reinfused
11 minutes after the hemorrhage, and hemorrhage was
induced for a second time after an interval of at least 24 hours and
selected drug pretreatment. In the remaining experiments blood was
withdrawn three times at 11-minute intervals by the same protocol.
Experimental Protocols
Cardiovascular Responses to
Acute
Hemorrhage in LE and DI Rats
Acute hemorrhage was evoked in 11 LE rats
(mean age,
23.5±1.3 weeks; mean weight, 330±7 g) and 11 DI rats
(25.8±1.0
weeks, 310±6 g). The cardiovascular responses to acute
hemorrhage were measured at 1-minute intervals for 11 minutes
after induction of hemorrhage.
The reproducibility of the response to acute hemorrhage was examined in 5 LE rats in a preliminary experiment, allowing an interval of 24 hours between procedures.
Effect of AVP Infusion on
Cardiovascular Responses
to Acute Hemorrhage in DI Rats
Cardiovascular responses to acute
hemorrhage were examined before and during AVP infusion in 5 DI
rats (24.3±2.0 weeks, 302±8 g). AVP was infused for 1 hour at a
rate
of 1.85 pmol/kg per minute.
Effect of AVP-Specific Vascular
Receptor Antagonist on
Cardiovascular Responses to Acute Hemorrhage in
LE Rats
Acute hemorrhage was induced in five LE rats (24.5±2.0
weeks, 330±7 g) with and without treatment with
d(CH2)5 Tyr(Me)AVP, an AVP
V1-receptor antagonist. Ten minutes after
administration of 4.41 nmol/kg of the V1-receptor
antagonist, the cardiovascular responses to
acute hemorrhage were reexamined. The effect of the
V1-receptor antagonist on the pressor response
to intravenous AVP was examined in a preliminary
experiment.
Effect of DDAVP on Cardiovascular Responses to
Acute Hemorrhage in DI Rats
Acute hemorrhage was induced in six DI
rats (28.1±2.1
weeks, 325±6 g) before and during infusion of DDAVP, an AVP
V2-receptor agonist. DDAVP was infused at a rate of 0.19
pmol/kg per minute for 24 hours. Urine volume was measured during the
control period and during DDAVP infusion.
Effect of
OPC-31260 on Cardiovascular Responses to
Acute Hemorrhage in LE Rats
Acute hemorrhage was induced in six LE
rats (34.0±0
weeks, 357±16 g) with and without treatment with OPC-31260, an AVP
V2-receptor antagonist. One hour after
administration of 21.6 µmol/kg of the V2-receptor
antagonist, the cardiovascular responses to
acute hemorrhage were reexamined. The effect of OPC-31260 on
urine volume was examined in six LE rats in a preliminary
experiment.
Modulation of Cardiovascular Responses to Acute
Hemorrhage by Autonomic Blockade in LE Rats
Cardiovascular responses
to acute
hemorrhage were examined in 5 LE rats 10 minutes after
intravenous administration of 6.76 µmol/kg
propranolol (24.0±0.9 weeks, 331±7 g) or 2.60 µmol/kg
methylatropine (26.5±1.8 weeks, 332±8 g). The results were
compared
with those from 11 untreated LE rats (23.5±1.3 weeks, 330±7 g).
Cardiovascular Responses to Repeated
Hemorrhage in LE and DI Rats
Cardiovascular responses to repeated
hemorrhage (1 mL/100 g body wt repeated three times at
11-minute intervals) were examined in 5 LE rats (24.2±0.9 weeks,
327±6 g) and 5 DI rats (26.5±0.8 weeks, 312±5 g).
Parameters were measured 2 and 11 minutes after each
hemorrhagic episode. Plasma renin activity and plasma AVP
concentration43 were measured in blood samples obtained
after each hemorrhagic episode by radioimmunoassays. Rats were killed
by intravenously administered pentobarbital sodium 10
minutes after the third hemorrhagic episode.
Statistical Methods
Values are mean±SEM. Differences
in the time course of changes
in heart rate and blood pressure after hemorrhage were compared
with two-way ANOVA, and the slopes of recovery were compared with
ANCOVA. Differences between the two strains and between different
treatment groups at particular time points were analyzed by
one-way ANOVA. A value of P<.05 was accepted as
statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Cardiovascular Responses to Acute Hemorrhage in LE and DI Rats
There were no significant differences in mean arterial pressure and heart rate in protocol 1 between LE rats (108±5 mm Hg and 367±8 bpm, n=11) and DI rats (108±5 mm Hg and 375±7 bpm, n=11) in the control period. Rapid hemorrhage (1 mL/100 g) caused marked hypotension and bradycardia lasting approximately 10 minutes in LE rats. The reproducibility of the cardiovascular responses to rapid hemorrhage was quite favorable (Fig 1
).
Hypotensive and bradycardic responses to rapid
hemorrhage were significantly less in DI rats than those in LE
rats (Fig 2). Changes in arterial pressure
and heart rate were similar in both strains 11 minutes after
hemorrhage (the recovery period).
|
indicate control responses; 
,
responses to a second hemorrhagic episode; 
MAP, change in mean
arterial pressure; and
|
Effects of AVP on Cardiovascular Responses to Acute
Hemorrhage in DI Rats
Intravenous administration of AVP (1.85 pmol/kg
per
minute for 1 hour) induced significant bradycardia in DI rats (368±7
versus 324±9 bpm, P<.01) without causing any change in
arterial pressure (101±3 versus 102±4 mm Hg).
Hemorrhage-induced hypotension (F=63.8, P<.001)
and bradycardia (F=31.1, P<.001) were potentiated by AVP
infusion, but these parameters were not significantly
different from control values during the recovery period (Fig
3). Plasma AVP concentration was 37.1±5.4 pmol/L in DI
rats during AVP infusion (n=5).
|
Effects of AVP V1-Receptor Antagonist on
Cardiovascular Responses to Acute Hemorrhage in
LE Rats
Mean arterial pressure and heart rate 11 minutes after
administration of the V1-receptor antagonist
(95±3 mm Hg and 357±6 bpm) were not significantly different from
control values (99±4 mm Hg and 359±6 bpm). There was no
significant
difference in the time course of the changes in arterial
pressure induced by rapid hemorrhage between the control and
V1-receptor antagonist experiments (Fig 4)
(F=0.3, P>.5). However, the recovery of
arterial pressure after administration of the
V1-receptor antagonist was slower than in the
control experiment (Fig 4) (F=8.4, P<.001).
Arterial pressure 11 minutes after hemorrhage in
the antagonist-treated group was significantly lower
than in the control group (P<.05). The bradycardic response
to hemorrhage was significantly attenuated by treatment with
the V1-receptor antagonist (F=14.4,
P<.001). The pressor effect of AVP (92.3 pmol/kg) was
almost completely inhibited (53.0±2.8 versus 3.2±0.8 mm Hg) by
the
V1-receptor antagonist (n=5).
|
Effects of DDAVP (V2-Receptor Agonist) on
Cardiovascular Responses to Acute
Hemorrhage in DI Rats
Mean arterial pressure and heart rate in DI rats
before and 24 hours after DDAVP treatment were similar
(arterial pressure, 116±7 versus 116±9 mm Hg; heart
rate, 373±16 versus 364±21 bpm). However, DDAVP markedly
inhibited
urine production (312±35 versus 15±4 mL/24 h,
P<.001). DDAVP did not influence the
cardiovascular responses to hemorrhage.
Effects of OPC-31260 (V2-Receptor
Antagonist) on Cardiovascular Responses to
Acute Hemorrhage in LE Rats
There were no significant differences in
mean arterial
pressure and heart rate before and 1 hour after administration of the
V2-receptor antagonist (arterial
pressure, 127±4 versus 114±5 mm Hg; heart rate, 345±13
versus
327±12 bpm). Hemorrhage-induced hypotension (F=92.7,
P<.001) and bradycardia (F=30.5, P<.001) were
attenuated by the V2-receptor antagonist (Fig 5).
The V2-receptor antagonist
increased urine volume from 0.9±0.1 to 7.4±0.7 mL/h.
|
Effect of Autonomic Blockade on Cardiovascular
Responses to Acute Hemorrhage in LE Rats
Methylatropine significantly
increased heart rate (382±12 versus
496±12 bpm, P<.001) but had no effect on
arterial pressure (101±4 versus 102±3 mm Hg).
Methylatropine almost completely inhibited the bradycardia (F=40.2,
P<.001) and significantly attenuated the hypotension
(F=15.9, P<.001) induced by rapid hemorrhage in LE
rats (Fig 6). However, the hypotensive response to
hemorrhage was still greater in the
methylatropine-treated LE rats than in DI rats (F=5.2,
P<.05).
|
Propranolol significantly reduced the heart rate in LE rats (380±7 versus 288±13 bpm, P<.001) and caused a transient rise in arterial pressure, although arterial pressure returned to the control level within 10 minutes (103±3 versus 104±4 mm Hg). Propranolol did not influence the hemorrhage-induced hypotension or bradycardia.
Cardiovascular Responses to Repeated
Hemorrhage in LE and DI Rats
Control mean arterial pressure and heart
rate were
similar in LE rats (108±6 mm Hg and 366±9 bpm) and DI rats
(104±5
mm Hg and 375±9 bpm). The initial hemorrhage-induced
hypotensive response was greater in LE rats than in DI rats (Fig
7),
but there was no difference in the hypotensive responses during the
second and third hemorrhagic episodes. In LE rats blood pressure
recovered nearly to the control level within 10 minutes of each
hemorrhage, whereas in DI rats the recovery was incomplete.
Overall, the recovery of blood pressure after hemorrhage was
significantly less in DI rats than in LE rats (F=27.8,
P<.001).
|
The heart rate response to repeated hemorrhage varied with the strain and the hemorrhagic episode. Although the first hemorrhagic episode caused less bradycardia in DI rats than in LE rats, the response to the second episode was similar in both strains. The third episode caused bradycardia in DI rats, whereas it evoked tachycardia in LE rats.
There was a stepwise linear increase in the
plasma AVP concentration in
LE rats, but the plasma AVP concentration was not detectable in the DI
strain (Fig 7
). Plasma renin activity was significantly
higher in DI rats than in LE rats (F=17.1, P<.001).
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
AVP as a Blood Pressure Maintenance Mechanism After Hemorrhage
The plasma concentration of AVP is elevated in hemorrhage-induced hypotension.16 17 18 AVP modulates or corrects hypotension via a direct pressor effect.19 20 In the present study arterial blood pressure 1 minute after the first hemorrhagic episode (1 mL/100 g) was similar in DI rats and LE controls, indicating that in conscious DI rats blood pressure recovers after hemorrhage in the absence of AVP, probably via activation of the renin-angiotensin system, sympathetic system, or both. However, this does not necessarily indicate that AVP did not contribute to blood pressure maintenance after hemorrhage in LE rats. Administration of an AVP vascular receptor antagonist attenuated recovery of arterial blood pressure in LE rats after hemorrhage. Complete recovery of blood pressure after repeated hemorrhage was observed only in LE rats, suggesting that blood pressure maintenance during repeated hemorrhage depends on the presence of AVP. These results are consistent with previous findings.19 20 In addition to confirming that AVP plays a major role in the maintenance and recovery of arterial pressure after hemorrhage, the present study also showed that AVP plays a role in the neurocardiogenic (vasovagal) reflex induced by hemorrhage.
Mechanisms Responsible for the Bradycardic Response to
Hemorrhage
Arterial baroreceptors normally mediate reflex
tachycardia in response to hypotension. However, in several
species hypotension induced by hemorrhage or other rapid blood
loss is accompanied by bradycardia under certain
circumstances.2 3 4 5 6 7 8 9 10 11 12 13 14 15
In unanesthetized rats
hemorrhage-induced bradycardia is inhibited by
atropine44 and is eliminated by the combination of
atropine and propranolol.4 However, in the
present study hemorrhage-induced bradycardia in
conscious rats was not affected by propranolol and was
eliminated by methylatropine, suggesting that the heart rate
response in conscious rats was mediated mainly by a vagal reflex.
The present results demonstrated that rapid hemorrhage (1 mL/100 g) induced less bradycardia in DI rats than in the parent LE strain. Administration of exogenous AVP induced significant bradycardia in DI rats, suggesting that endogenous AVP may contribute to the vagally mediated bradycardia induced by hemorrhage. These findings are consistent with those of Peuler et al.12 Circulating AVP has been found to affect the structures involved in cardiovascular control, possibly by affecting the baroreceptor reflex.21 22 23 24 25 26 27 28 29 30 31 32 33 45 46 47
Mechanisms Responsible for the Hypotensive Response to
Hemorrhage
Immediately after the first hemorrhagic episode LE rats
exhibited
marked hypotension, whereas DI rats showed almost no hypotension. In
cases of rapid, severe hemorrhage, the compensatory response to
hemorrhage is interrupted and replaced by a paradoxical
decrease in sympathetic activity and increase in parasympathetic
activity, leading to profound vasodilation and bradycardia, which
result in severe
hypotension.2 3 4 5 6 7 8 9 10 11 12 13 14 15
These paradoxical
cardiohemodynamic responses to hemorrhage
are believed to be mediated by neurocardiogenic
reflexes.48 49 50 51 In turn,
neurocardiogenic reflexes are
believed to be mediated by afferent impulses from
ventricular mechanoreceptors; these impulses increase
during severe hemorrhage,3 4 causing AVP
release,17 18 eliciting reflex parasympathetic
stimuli,3 4 7 12 and
inhibiting sympathetic neural
tone.5 6 8 9 10 11 13 14 15
Parasympathetic Component
When the bradycardic response
in LE rats was blocked by
methylatropine, hypotension was also attenuated. The first hemorrhagic
episode did not induce bradycardia and hypotension in DI rats;
exogenous AVP induced both hypotension and bradycardia. These findings
suggest that the hypotension induced by the first hemorrhagic episode
in LE rats was mediated at least in part by reflex-induced
cardiodepression and was substantiated by the presence of AVP.
Although methylatropine completely inhibited the bradycardic response
to hemorrhage in LE rats, the hypotensive response to
hemorrhage in methylatropine-treated LE rats was still
greater than that observed in DI rats. These findings suggest that
vasodepression was mediated at least in part by mechanisms other than a
parasympathetic mechanism.
Sympathetic Component
The paradoxical vasodilation induced by hemorrhage
is thought to be mediated by the inhibition of sympathetic
vasoconstrictor activity,51 52 53
suggesting that circulating
AVP is crucial to the inhibition of sympathetic neural tone during
hemorrhage. AVP enhances reflex
sympathoinhibition.21 22 23 24 25 26 27
Vasopressin
V1-27 46 and V2-like receptor
activation30 54 55 and hybrid AVP
receptor
activation30 54 at a blood-accessible site appear to
enhance the baroreceptor reflex. However, in the present study
DDAVP, a specific V2-receptor agonist, did not influence
hemorrhage-induced bradycardia or hypotension in DI rats,
whereas AVP potentiated both responses. Furthermore, although the
V1-receptor antagonist attenuated the
bradycardic response to hemorrhage, it did not affect the
hypotensive response immediately after hemorrhage in LE rats.
Thus, the hypotensive response immediately after hemorrhage
does not appear to be mediated by sympathoinhibition via a
V1- or V2-receptor mechanism.
Direct
Vasodilating Effect of AVP
In high concentrations AVP exerts a
vasodilator action mediated by
a V2-receptor
mechanism.36 37 56 It is
noteworthy that the specific V2-receptor
antagonist attenuated both bradycardia and hypotension
induced by hemorrhage in normal LE rats in the present
study. Liard57 has reported that the
cardiovascular effects of AVP are mediated by
V1- and V2-receptor mechanisms. When
V1-receptors are blocked, AVP can still bind to
V2-receptors to produce cardiovascular
effects, ie, the baroreceptor reflex, and vascular effects
(vasodilation) that mimic the expected action of
V1-blockade. It is possible that when
V2-receptors are blocked, the major effect of the
V1-receptor mechanism emerges (vasoconstriction), resulting
in the attenuation of the hypotensive response to hemorrhage.
In the present study AVP, which is both a V1- and
V2-receptor agonist, but not the V2-receptor
agonist induced hypotension immediately after hemorrhage in DI
rats. These findings suggest that there is a "cross talk" of
V1- and V2-receptor mechanisms within the
vascular bed. It is possible that vasodilation through a
V2-receptor mechanism is substantiated by the coexistence
of the V1-receptor mechanism and that pure
V2-receptor agonist in AVP-deficient DI rats does not
induce vasodilation. The physiological meaning of
AVP-mediated vasodilation is unknown. However, it has been hypothesized
that V2-mediated vasodilation counteracts
V1-mediated vasoconstriction. Both vasodilation and
vasoconstriction are caused by the release of a high concentration of
AVP in response to massive hemorrhage or other occurrences. The
V2-mediated vasodilation may maintain organ blood
flow.
Other Postulated Mechanisms Responsible for the
Differential
Response to Hemorrhage in LE and DI Rats
The cardiohemodynamic
responses to
hemorrhage in DI rats may also be explained by a stimulated
renin-angiotensin system58 59 and/or basal
cardiohemodynamic parameters, such as a
low circulating blood volume, a low mean circulatory filling pressure,
or both. It is possible that stimulation of the
renin-angiotensin system attenuates the
neurocardiogenic reflex induced by hemorrhage via stimulation
of the sympathetic nervous system60 61 or inhibition
of
the parasympathetic nervous system.62 63 Long-term
infusion of DDAVP maintained normal urine volume in DI rats but did not
influence the hemorrhage-induced
cardiovascular responses in this strain, suggesting
that blood volume and mean circulatory filling pressure did not affect
the response to hemorrhage.
In conclusion, we hypothesize that endogenous AVP in normal rats contributes to hypotension after hemorrhage. Our results suggest that a V2-receptor antagonist can attenuate the hypotension mediated by the so-called neurocardiogenic reflexes.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
This work was supported by research grants from the Miyagi Prefectural Kidney Association and the Takeda Medical Research Foundation, by a Research Grant for Cardiovascular Disease (No. 4C-3, 5C-2) from the Ministry of Health and Welfare, and by a Research Grant for Scientific Research (07670746) from the Ministry of Education, Science, and Culture of Japan.
Received May 25, 1995; first decision July 24, 1995; accepted September 6, 1995.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Mark AL, Mancia G. Cardiovascular baroreflex in human. In: Shepherd AJ, Abboud FM, eds. Handbook of Physiology. Volume 3, Circulation. Bethesda, Md: American Physiological Society; 1983;795-813.
2. Ebert PA, Austen WG, Greenfield LJ. Effect of neurogenic reflexes on heart rate during systemic hypotension. Am J Physiol. 1962;203:457-460.
3. Öberg B, White S. The role of vagal cardiac nerves and arterial baroreceptors in the circulatory adjustments to hemorrhage in the cat. Acta Physiol Scand. 1970;80:395-403. [Medline] [Order article via Infotrieve]
4. Castenfors J, Sjöstrand T. Circulatory control via vagal afferents, I: adjustment of heart rate by variations of blood volume in the rat. Acta Physiol Scand. 1972;84:347-354. [Medline] [Order article via Infotrieve]
5. Schadt JC, McKown MD, McKown DP, Franklin D. Hemodynamic effects of hemorrhage and subsequent naloxone treatment in conscious rabbits. Am J Physiol. 1984;247:R497-R508.
6. Skoog P, Mansson J, Thoren P. Changes in renal sympathetic outflow during hypotensive haemorrhage in rats. Acta Physiol Scand. 1985;125:655-660. [Medline] [Order article via Infotrieve]
7. Sander-Jensen K, Secher NH, Bie P, Warberg J, Schwartz TW. Bradycardia during haemorrhagic shock in man: is this a regular phenomenon? In: Hainsworth R, McWilliam PN, Mary DASG, eds. Cardiogenic Reflexes. New York, NY: Oxford University Press; 1987:414-415.
8.
Burke SL, Dorward PK. Influence of
endogenous opiates and cardiac afferents on renal nerve
activity during haemorrhage in conscious rabbits.
J Physiol (Lond). 1988;402:9-27.
9.
Morita H, Nishida Y, Motochigawa H, Uemura N, Hosomi
H, Vatner SF. Opiate receptor-mediated decrease in renal
nerve activity during hypotensive hemorrhage in conscious
rabbits. Circ Res. 1988;63:165-172.
10.
Fejes-Toth G, Brinck-Johnsen T, Naray-Fejes-Toth A.
Cardiovascular and hormonal response to
hemorrhage in conscious rats. Am J Physiol. 1988;254:H947-H953.
11.
Victor RG, Thoren P, Morgan DA, Mark AL.
Differential control of adrenal and renal sympathetic nerve
activity during haemorrhagic hypotension in rats.
Circ Res. 1989;64:686-694.
12.
Peuler JD, Schmid PG, Morgan DA, Mark AL.
Inhibition of renal sympathetic activity and heart rate by
vasopressin in hemorrhaged diabetes insipidus rats.
Am J Physiol. 1990;258:H706-H712.
13.
Schadt JC, Hasser EM. Interaction of vasopressin
and opioids during rapid hemorrhage in conscious
rabbits. Am J Physiol. 1991;260:R373-R381.
14.
Brizzee BL, Russ RD, Walker BR. Role of
vasopressin in acutely altered baroreflex sensitivity during
hemorrhage in rats. Am J Physiol. 1991;261:R677-R685.
15. Evans RG, Ludbrook J, Woods RL, Casley D. Influence of higher brain centres and vasopressin on the hemodynamic response to acute central hypovolemia in rabbits. J Auton Nerv Syst. 1991;35:1-14. [Medline] [Order article via Infotrieve]
16.
Share L. Role of peripheral
receptors in the increased release of vasopressin in response to
hemorrhage. Endocrinology. 1967;81:1140-1146.
17.
Wang BC, Flora-Ginter R, Leadley RJ Jr, Goetz KL.
Ventricular receptors stimulate vasopressin release
during hemorrhage. Am J Physiol. 1988;254:R204-R211.
18.
Quail AW, Woods RL, Korner PI. Cardiac and
arterial baroreceptor influences in release of vasopressin
and renin during hemorrhage. Am J Physiol. 1987;252:H1120-H1126.
19.
Cowley AW Jr, Monos E, Guyton AC. Interaction of
vasopressin and the baroreceptor reflex system in the regulation of
arterial blood pressure in the dog.
Circ Res. 1974;34:505-514.
20.
Zerbe RL, Feuerstein G, Meyer DK, Kopin IJ.
Cardiovascular, sympathetic, and
renin-angiotensin system responses to
hemorrhage in vasopressin-deficient rats.
Endocrinology. 1982;111:608-613.
21.
Undesser KP, Hasser EM, Haywood JR, Johnson AK, Bishop
VS. Interactions of vasopressin with the area postrema in
arterial baroreflex function in conscious rabbits.
Circ Res. 1985;56:410-417.
22. Sharabi FM, Guo GB, Abboud FM, Thames MD, Schmid PG. Contrasting effects of vasopressin on baroreflex inhibition of lumbar sympathetic nerve activity. Am J Physiol. 1985;249:H922-H928.
23. Schmid PG, Guo GB, Abboud FM. Different effects of vasopressin and angiotensin II on baroreflexes. Fed Proc. 1985;44:2388-2392. [Medline] [Order article via Infotrieve]
24.
Imai Y, Abe K, Sasaki S, Minami N, Nobunaga T, Sekino
H, Yoshinaga K. Hypotensive and bradycardic effects of centrally
administered vasopressin in stroke-prone spontaneously hypertensive
rats. Hypertension. 1987;10:346-349.
25.
Veelken R, Danckwart L, Rohmeiss P, Unger T.
Effects of intravenous AVP on cardiac output,
mesenteric hemodynamics, and splanchnic nerve
activity. Am J Physiol. 1989;257:H658-H664.
26.
Suzuki S, Takeshita A, Imaizumi T, Hirooka Y, Yoshida
M, Ando S, Nakamura M. Central nervous system mechanisms
involved in inhibition of renal sympathetic nerve activity induced by
arginine vasopressin. Circ Res. 1989;65:1390-1399.
27.
Hasser EM, Bishop VS. Reflex effect of
vasopressin after blockade of V1 receptors in the area
postrema. Circ Res. 1990;67:265-271.
28.
Montani JP, Liard JF, Schoun J, Möhring J.
Hemodynamic effects of exogenous and
endogenous vasopressin at low plasma concentrations in
conscious dogs. Circ Res. 1980;47:346-355.
29. Liard JF, Deriaz O, Tschopp M, Schoun J. Cardiovascular effects of vasopressin infused into the vertebral circulation in conscious dogs. Clin Sci. 1981;61:345-347. [Medline] [Order article via Infotrieve]
30.
Imai Y, Nolan PL, Johnston CI. Restoration of
suppressed baroreflex sensitivity in rats with hereditary diabetes
insipidus (Brattleboro rats) by arginine vasopressin and DDAVP.
Circ Res. 1983;53:140-149.
31.
Courtice GP, Kwong TE, Lumbers ER, Potter EK.
Excitation of the cardiac vagus by vasopressin in
mammals. J Physiol (Lond). 1984;354:547-556.
32. Imai Y, Nolan PL, Johnston CI. Role of vasopressin in blood pressure regulation through its modulatory effect on baroreceptor reflex. In: Sambhi MP, ed. Fundamental Fault in Hypertension. Dordrecht, Netherlands: Martinus-Nijhoff BV; 1984:251-260.
33.
Caine AC, Lumbers ER, Reid IA. The effects and
interactions of angiotensin and vasopressin on the heart of
unanaesthetized sheep. J Physiol (Lond). 1985;367:1-11.
34. Walker BR. Evidence for a vasodilatory effect of vasopressin in conscious rats. Am J Physiol. 1986;251:H34-H39.
35.
Katusic ZS, Shepherd JT, Vanhoutte PM.
Vasopressin causes endothelium-dependent
relaxations of the canine basilar artery. Circ
Res. 1984;55:575-579.
36. Suzuki S, Takeshita A, Imaizumi T, Hirooka Y, Yoshida M, Ando S, Nakamura M. Biphasic forearm vascular responses to intraarterial arginine vasopressin. J Clin Invest. 1989;84:427-433.
37. Hirsch AT, Dzau VJ, Majzoub JA, Creager MA. Vasopressin-mediated forearm vasodilation in normal humans: evidence for a vascular vasopressin V2 receptor. J Clin Invest. 1989;84:418-426.
38.
Katusic ZS. Endothelial
L-arginine pathway and regional cerebral arterial
reactivity to vasopressin. Am J Physiol. 1992;262:H1557-H1562.
39. Tagawa T, Imaizumi T, Endo T, Shiramoto M, Hirooka Y, Ando S, Takeshita A. Vasodilatory effect of arginine vasopressin is mediated by nitric oxide in human forearm vessels. J Clin Invest. 1993;92:1483-1490.
40. Secher NH, Bie P. Bradycardia during reversible haemorrhagic shock: a forgotten observation? Clin Physiol. 1985;5:315-323. [Medline] [Order article via Infotrieve]
41. Yamamura Y, Ogawa H, Yamashita H, Chihara T, Miyamoto H, Nakamura S, Onogawa T, Yamashita T, Hosokawa T, Mori T, Tominaga M, Yabuuchi Y. Characterization of a novel aquaretic agent, OPC-31260, as an orally effective, nonpeptide vasopressin V2 receptor antagonist. Br J Pharmacol. 1992;105:787-791. [Medline] [Order article via Infotrieve]
42. Ohnishi A, Orita Y, Okahara R, Fujihara H, Inoue T, Yamamura Y, Yabuuchi Y, Tanaka T. Potent aquaretic agent: a novel nonpeptide selective vasopressin 2 antagonist (OPC-31260) in men. J Clin Invest. 1993;92:2653-2659.
43. Woods RL, Johnston CI. Role of vasopressin in hypertension: studies using the Brattleboro rat. Am J Physiol. 1982;242:F727-F732.
44. Pendleton RG, McCafferty JP, Roesler JM. The effects of PNMT inhibitors upon cardiovascular changes induced by hemorrhage in the rat. Eur J Pharmacol. 1980;66:1-10. [Medline] [Order article via Infotrieve]
45.
Abboud FM, Aylward PE, Floras JS, Gupta BN.
Sensitization of aortic and cardiac baroreceptors by arginine
vasopressin in mammals. J Physiol (Lond). 1986;377:251-265.
46.
Barazanji MW, Cornish KG. Vasopressin
potentiates ventricular and arterial reflexes
in the conscious nonhuman primate. Am J Physiol. 1989;256:H1546-H1552.
47.
Gupta BN, Abboud AL, Floras JS, Aylward PE, Abboud FM.
Vasopressin facilitates inhibition of renal nerve activity
mediated through vagal afferent. Am J Physiol. 1987;253:H1-H7.
48. Schadt JC, Ludbrook J. Hemodynamic and neurohumoral responses to acute hypovolemia in conscious mammals. Am J Physiol. 1991;260:305-318.
49. Glick G, Yu PN. Hemodynamic changes during spontaneous vasovagal reactions. Am J Med. 1963;34:42-51. [Medline] [Order article via Infotrieve]
50.
Sra JS, Jazayeri MR, Avitall B, Dhala A, Deshpande S,
Blanck Z, Akhtar M. Comparison of cardiac pacing with drug
therapy in the treatment of neurocardiogenic (vasovagal) syncope with
bradycardia or asystole. N Engl J Med. 1993;328:1085-1090.
51.
Abboud FM. Neurocardiogenic syncope.
N Engl J Med. 1993;328:1117-1120.
52. Wallin BG, Sundlöf G. Sympathetic outflow to muscles during vasovagal syncope. J Auton Nerv Syst. 1982;6:287-291. [Medline] [Order article via Infotrieve]
53.
Aylward PE, Frolas JS, Leimbach WN, Abboud FM.
Effects of vasopressin on the circulation and its baroreflex
control in healthy men. Circulation. 1986;73:1145-1154.
54.
Brizzee BL, Walker BR. Vasopressinergic
augmentation of cardiac baroreceptor reflex in conscious rats.
Am J Physiol. 1990;258:R860-R868.
55. Unger T, Rohmeiss P, Dummert G, Ganten D, Lang RE, Luft FC. Differential modulation of the baroreceptor reflex by brain and plasma vasopressin. Hypertension. 1986;8(suppl II):II-157-II-162.
56.
Imaizumi T, Harada S, Hirooka Y, Masaki H, Momohara M,
Takeshita A. Effects of OPC-21268, an orally effective
vasopressin V1 receptor antagonist, in
humans. Hypertension. 1992;20:54-58.
57.
Liard JF. Cardiovascular effects
associated with antidiuretic activity of vasopressin after
blockade of its vasoconstrictor action in dehydrated dogs.
Circ Res. 1986;58:631-640.
58. Gutman Y, Benzakein F. Effect of an increase and of lack of antidiuretic hormone on plasma renin activity in the rat. Life Sci. 1971;10:1081-1085.
59. Hoffman WE, Ganten U, Schelling P, Phillips MI, Schmid PG, Ganten D. The renin and isorenin-angiotensin system in rats with hereditary diabetes insipidus. Neuropharmacology. 1978;17:919-923. [Medline] [Order article via Infotrieve]
60. Ferrario CM, Dickinson CJ, McCubbin JW. Central vasomotor stimulation by angiotensin. Clin Sci. 1970;39:239-245. [Medline] [Order article via Infotrieve]
61. Khairallah PA. Action of angiotensin on adrenergic nerve endings: inhibition of norepinephrine uptake. Fed Proc. 1972;31:1351-1357. [Medline] [Order article via Infotrieve]
62.
Lee WB, Ismay MJ, Lumbers ER.
Mechanisms by which angiotensin II affects the heart
rate of conscious sheep. Circ Res. 1980;47:286-292.
63. Scroop GC, Lowe RD. Efferent pathways of the cardiovascular response to vertebral artery infusions of angiotensin in the dog. Clin Sci. 1969;37:605-619.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  P. Paczwa and D. Ganten Role of central AT1 and V1 receptors in cardiovascular adaptation to hemorrhage in SD and renin TGR rats Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H1918 - H1926. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||