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Biomedical subjects

I A Reid

Publications and source records attributed to I A Reid.

At least 37 records · Page 2Linked to original sources
PubMed1994

Role of nitric oxide in the renin and heart rate responses to beta-adrenergic stimulation.

Studies in vitro and in vivo have implicated nitric oxide in the control of renin secretion. In the present study, the effect of inhibition of nitric oxide synthesis with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) on the renin secretory response to beta-adrenergic stimulation was investigated in conscious, chronically prepared rabbits. Intravenous infusion of isoproterenol at 0.02 microgram.kg-1 x min-1 for 30 minutes increased mean arterial pressure by 5 mm Hg (P < .05), heart rate by 51 beats per minute (P < .001), and plasma renin activity by 56% (P < .001). Intravenous infusion of L-NAME at 0.5 mg.kg-1 x min-1 increased mean arterial pressure by 6 mm Hg (P < .01) and decreased heart rate by 15 beats per minute (P < .01) and plasma renin activity by 31% (P < .05). L-NAME reduced the heart rate response to isoproterenol by 50% and inhibited the renin response. Infusion of isoproterenol at 0.05 microgram.kg-1 x min-1 did not change blood pressure but increased heart rate by 62 beats per minute (P < .001) and plasma renin activity by 283% (P < .001). Treatment with L-NAME again suppressed the heart rate response to isoproterenol and inhibited the renin response. Intravenous infusion of the nitric oxide donor nitroprusside at 2 micrograms.kg-1.min-1 in the presence of L-NAME decreased mean arterial pressure by 7 mm Hg (P < .05), increased heart rate by 14 beats per minute (P < .05), but did not change plasma renin activity. Nitroprusside fully restored the heart rate response to isoproterenol and partially restored the renin response.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Losartan inhibits sympathetic and cardiovascular responses to carotid occlusion.

We have reported that inhibition of angiotensin-converting enzyme with captopril attenuates the cardiovascular responses to bilateral carotid occlusion in conscious rabbits and proposed that the attenuation results from removal of a facilitatory action of angiotensin II on the sympathetic nervous system. The aim of the present study was to assess the effect of carotid occlusion on renal sympathetic nerve activity in conscious rabbits and to investigate the effect of the angiotensin II subtype 1 (AT1) receptor antagonist losartan on the cardiovascular and renal sympathetic nerve activity responses to carotid occlusion. In seven conscious, aortic depressor nerve-sectioned rabbits, carotid occlusion elicited prompt and reproducible increases in mean arterial pressure from 75 +/- 2 to 124 +/- 5 mm Hg (P < .001), heart rate from 285 +/- 8 to 317 +/- 9 beats per minute (P < .01), and renal sympathetic nerve activity to 165 +/- 11% of control (P < .01). In the same rabbits, losartan (5 mg/kg i.v.) decreased mean arterial pressure by 9 +/- 2 mm Hg (P < .01), increased renal sympathetic nerve activity to 143 +/- 13% of control (P < .05), but did not alter heart rate. Losartan significantly attenuated (P < .01) the mean arterial pressure (66 +/- 2 to 81 +/- 2 mm Hg), heart rate (282 +/- 9 to 289 +/- 7 beats per minute), and renal sympathetic nerve activity (143 +/- 13% to 159 +/- 15% of control) responses to carotid occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1994

Angiotensin II exerts differential actions on renal nerve activity and heart rate.

Angiotensin II (Ang II) exerts complex actions on sympathetic nerve activity and heart rate, but these actions are incompletely understood. We performed three series of experiments in conscious rabbits to analyze the actions of exogenous and endogenous Ang II on renal sympathetic nerve activity and heart rate. (1) Graded intravenous doses of phenylephrine and Ang II suppressed renal sympathetic nerve activity to the same degree, whereas Ang II decreased heart rate much less than phenylephrine. (2) Ang II infusion at 10 ng/kg per minute increased mean arterial pressure by 13 +/- 2 mm Hg (P < .01) and decreased renal sympathetic nerve activity by 67 +/- 13% (P < .01) but did not change heart rate. In the same rabbits, nitroprusside and phenylephrine infusions were used to generate baroreceptor reflex curves. Ang II shifted the heart rate-mean arterial pressure curve to the right but did not alter the renal nerve activity-mean arterial pressure curve. (3) The Ang II type 1 receptor antagonist losartan decreased mean arterial pressure by 8 +/- 3 mm Hg (P < .01) and increased renal sympathetic nerve activity by 63 +/- 15% (P < .05) but did not change heart rate. Losartan shifted the heart rate-mean arterial pressure curve to the left but did not alter the renal nerve activity-mean arterial pressure curve. These results demonstrate that whereas exogenous Ang II resets the baroreceptor reflex control of heart rate to a higher pressure, it does not increase resting renal sympathetic nerve activity or alter the baroreceptor reflex control of renal nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1993

Role of V1 receptors in the action of vasopressin on the baroreflex control of heart rate.

Arginine vasopressin (AVP) elicits a larger decrease in heart rate for a given increase in arterial pressure than do other vasoconstrictors, but there is disagreement as to whether this results from an increase in baroreflex gain or a resetting of the baroreflex to a lower blood pressure. It is also unclear which type of vasopressin receptor mediates the action of vasopressin on the baroreflex. In the present study, the effects of vasopressin, selective vasopressin V1 and V2 receptor agonists, oxytocin, and a vasopressin V1 receptor antagonist on the baroreflex control of heart rate were investigated in conscious, chronically prepared rabbits. Baroreflex curves were generated with intravenous infusions of phenylephrine and nitroprusside and analyzed using a four-parameter logistic model. Intravenous infusion of vasopressin at 5 ng.kg-1.min-1 increased mean arterial pressure by 9 mmHg and decreased heart rate by 31 beats/min. The arterial pressure at the midrange of the baroreflex curve (BP50) decreased from 75.9 +/- 4.8 to 57.6 +/- 1.7 mmHg (P < 0.01), indicating a shift of the baroreflex curve to a lower pressure, but the gain did not change significantly. The actions of vasopressin on blood pressure, heart rate, and BP50 were completely blocked by pretreatment with d(CH2)5[Tyr(Me)2]AVP, a selective V1 receptor antagonist. Infusion of [Phe2,Ile3,Orn8]AVP, a selective V1 receptor agonist, produced cardiovascular effects similar to those of vasopressin and decreased the BP50 of the baroreflex from 73.0 +/- 2.2 to 63.8 +/- 2.2 mmHg (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Role of AT1 receptors in the resetting of the baroreflex control of heart rate by angiotensin II in the rabbit.

Angiotensin II (Ang II) resets the baroreflex control of heart rate to a higher blood pressure. This action is apparently mediated via Ang II receptors in the area postrema, but it is not known if these are of the AT1 or AT2 subtype. In the present study the effects of losartan, a selective AT1 receptor antagonist, and PD 123319, a selective AT2 antagonist, on the cardiac baroreflex response to Ang II were investigated in conscious rabbits with chronically implanted arterial and venous catheters. Baroreflex curves were generated with intravenous infusions of phenylephrine and nitroprusside (2.6-25 micrograms/kg per min) and analyzed using a four-parameter logistic model to yield their upper and lower plateaus, arterial pressure at the midpoint of the heart rate range (BP50), and slope coefficient. From these four parameters, the gain and range of the baroreflex were calculated. Background intravenous infusion of Ang II at 10 ng/kg per min increased mean arterial pressure by 17 mmHg but did not change heart rate. Ang II shifted the baroreflex curve to the right as indicated by an increase in BP50 from 70.9 +/- 2.0 to 89.3 +/- 2.7 mmHg (P < 0.05), but did not change baroreflex gain significantly. Ang II did not alter the upper plateau of the baroreflex, but decreased the lower plateau from 119.4 +/- 10.3 to 73.6 +/- 11.5 beats per minute (bpm) (P < 0.05), extending the heart rate range by 52.5 bpm. Pretreatment with losartan completely abolished the pressor and cardiac baroreflex responses to Ang II. In contrast, PD 123319 had no effect on these responses. Administration of losartan alone to block endogenous Ang II shifted the baroreflex curve to the left as indicated by a decrease in BP50 from 71.2 +/- 2.7 to 64.7 +/- 2.5 mmHg (P < 0.05). These results demonstrate that the resetting of the baroreflex control of heart rate by Ang II is mediated by AT1 receptors, and that basal levels of endogenous Ang II exert a tonic action on the cardiac baroreflex to increase the setpoint around which the baroreflex regulates heart rate.

Angiotensin II↗
PubMed1992

Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure.

The renin-angiotensin system plays an important role in the regulation of arterial blood pressure and in the development of some forms of clinical and experimental hypertension. It is an important blood pressure control system in its own right but also interacts extensively with other blood pressure control systems, including the sympathetic nervous system and the baroreceptor reflexes. Angiotensin (ANG) II exerts several actions on the sympathetic nervous system. These include a central action to increase sympathetic outflow, stimulatory effects on sympathetic ganglia and the adrenal medulla, and actions at sympathetic nerve endings that serve to facilitate sympathetic neurotransmission. ANG II also interacts with baroreceptor reflexes. For example, it acts centrally to modulate the baroreflex control of heart rate, and this accounts for its ability to increase blood pressure without causing a reflex bradycardia. The physiological significance of these actions of ANG II is not fully understood. Most evidence indicates that the actions of ANG to enhance sympathetic activity do not contribute significantly to the pressor response to exogenous ANG II. On the other hand, there is considerable evidence that the actions of endogenous ANG II on the sympathetic nervous system enhance the cardiovascular responses elicited by activation of the sympathetic nervous system.

Adrenal Medulla↗
PubMed1992

Effect of intrarenal bradykinin infusion on vasopressin release in rabbits.

Electrical stimulation of afferent renal nerves and activation of renal mechanoreceptors increase plasma vasopressin concentrations. In the present study, the effect of renal chemoreceptor activation on plasma vasopressin concentration was investigated in anesthetized rabbits. Renal chemoreceptors were activated with intrarenal infusions of bradykinin. With intrarenal infusion of bradykinin at 136 ng/min, plasma vasopressin concentration increased from 4.5 +/- 1.5 to 26.8 +/- 14.2 pg/ml at 5 minutes (p less than 0.01), whereas with infusion at 1,360 ng/min, plasma vasopressin increased from 5.9 +/- 2.0 to 54.4 +/- 16.4 pg/ml at 5 minutes (p less than 0.01). There was no significant change in plasma vasopressin during intravenous infusion of bradykinin at 136 ng/min. Infusion at 1,360 ng/min increased plasma vasopressin from 2.7 +/- 0.5 to 14.8 +/- 6.4 pg/ml (p less than 0.01), but this increase was significantly less than that produced by intrarenal infusion of the same dose of bradykinin. Similar effects on plasma vasopressin were observed during paired intrarenal and intravenous infusions of bradykinin at 136 ng/min. Renal denervation markedly reduced the vasopressin responses to intrarenal infusion of bradykinin at 136 ng/min (2.8 +/- 0.5 to 4.0 +/- 0.7 pg/ml, p less than 0.01) and 1,360 ng/min (3.2 +/- 0.7 to 7.8 +/- 1.8 pg/ml, p less than 0.05). These results indicate that bradykinin stimulates vasopressin release by an intrarenal action and suggest that this action is mediated by afferent renal nerves.

Animals↗
PubMed1991

Effect of baroreceptor denervation on stimulation of drinking by angiotensin II in conscious dogs.

Angiotensin II causes marked stimulation of drinking when it is injected centrally but is a relatively weak dipsogen when administered intravenously. However, it has been proposed that the dipsogenic action of systemically administered angiotensin II may be counteracted by the pressor action of the peptide. To test this hypothesis, the dipsogenic action of angiotensin II was investigated in dogs, in which low and high baroreceptor influences had been eliminated by denervation of the carotid sinus, aortic arch, and heart. In five sham-operated dogs, infusion of angiotensin II at 10 and 20 ng.kg-1.min-1 increased plasma angiotensin II concentration to 109.2 +/- 6.9 and 219.2 +/- 38.5 pg/ml and mean arterial pressure by 20 and 29 mmHg, respectively, but did not induce drinking. In four baroreceptor-denervated dogs, the angiotensin II infusions produced similar increases in plasma angiotensin II concentration and mean arterial pressure but, in contrast to the results in the sham-operated dogs, produced a dose-related stimulation of drinking. Water intake with the low and high doses of angiotensin II was 111 +/- 44 and 255 +/- 36 ml, respectively. The drinking responses to an increase in plasma osmolality produced by infusion of hypertonic sodium chloride were not different in the sham-operated and baroreceptor-denervated dogs. These results demonstrate that baroreceptor denervation increases the dipsogenic potency of intravenous angiotensin II and provides further support for the hypothesis that the dipsogenic action of intravenous angiotensin II is counteracted by the rise in blood pressure.

Angiotensin II↗
PubMed1991

Activation of renal mechanoreceptors increases vasopressin release in rabbits.

Electrical stimulation of afferent renal nerves increases plasma vasopressin (AVP) concentration, but the role of these nerves in the control of AVP release is not known. The aim of the present study was to investigate the effect of activation of renal mechanoreceptors and chemoreceptors on plasma AVP concentration in anesthetized rabbits. Intrapelvic pressure was increased to activate renal mechanoreceptors, and the renal pelvis was perfused with 1.0 M NaCl, 0.1 M KCl, and 1.0 M mannitol solutions to activate R2 chemoreceptors. With increased pelvic pressure, plasma AVP concentration increased from 12.4 +/- 3.8 to 36.2 +/- 16.1 pg/ml at 5 min and to 37.4 +/- 16.1 pg/ml at 10 min (P less than 0.01). Plasma renin activity increased from 15.7 +/- 4.0 to 22.1 +/- 3.3 ng.ml-1.2 h-1 (P less than 0.05), but blood pressure and heart rate did not change significantly. Similar increases in plasma AVP concentration occurred during perfusion of the renal pelvis with 1.0 M NaCl (17.6 +/- 8.1 to 53.7 +/- 24.0 pg/ml), 0.1 M KCl (9.2 +/- 2.1 to 39.7 +/- 17.3 pg/ml), and 1.0 M mannitol (27.5 +/- 10.9 to 77.5 +/- 30.8 pg/ml) solutions. However, because pelvic pressure increased by 40-50 mmHg during the perfusions, the experiments were repeated with use of a different perfusion method in which pelvic pressure increased by less than 5 mmHg. Under these conditions, plasma AVP concentration did not change significantly during perfusion with any of the solutions. To determine whether the mechanoreceptor-induced increase in AVP release is mediated by the renal nerves, pelvic pressure was increased in another group of rabbits after renal denervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Role of endogenous angiotensin II in the control of vasopressin secretion during hypovolemia and hypotension in conscious rabbits.

In order to investigate the physiological role of angiotensin II (ANG II) in the control of vasopressin (VP) secretion, the VP responses to hypotension induced by hemorrhage (20 ml/kg, n = 10) or nitroprusside infusion (1-10 micrograms/kg.min, n = 9) were studied with or without blockade of ANG II formation by the converting enzyme inhibitor captopril in conscious rabbits. Administration of captopril (5 mg/kg, iv) caused a small decrease in mean arterial pressure but did not enhance the hypotensive response to subsequent hemorrhage or nitroprusside infusion. The renin response to both stimuli was enhanced by captopril, whereas the increase in plasma ANG II concentration was attenuated. Plasma VP (PAVP) concentration increased during hemorrhage (2.0 +/- 0.2-113.6 +/- 47.7 pg/ml, P less than 0.01) and nitroprusside infusion (2.1 +/- 0.3-5.1 +/- 1.0 pg/ml, P less than 0.01). Captopril did not change basal plasma PAVP, nor did it attenuate the VP responses to hemorrhage or nitroprusside. Indeed, captopril tended to enhance the VP responses to hemorrhage (2.3 +/- 0.3-147.1 +/- 65.9 pg/ml) and nitroprusside infusion (1.9 +/- 0.2-15.4 +/- 6.0 pg/ml). The relationship between log PAVP and mean arterial pressure during hemorrhage and nitroprusside infusion in the presence of captopril was not different than in the absence of captopril. These results indicate that in conscious rabbits, the renin-angiotensin system does not contribute to the increase in VP secretion during hypotension induced by hemorrhage or nitroprusside infusion.

Angiotensin II↗
PubMed1991

Role of afferent renal nerves in the control of vasopressin secretion.

Several lines of evidence indicate that the kidneys can influence the secretion of vasopressin. We have reported that electrical stimulation of the renal nerves increases plasma vasopressin concentration in dogs and rabbits, and other investigators have reported that selective stimulation of afferent renal nerves in cats and rats increases plasma vasopressin concentration or the activity of neurosecretory neurons in the supraoptic nucleus. Intrarenal infusion of bradykinin, which is known to excite afferent renal nerves, has also been reported to increase the activity of putative vasopressin neurons in the supraoptic nucleus of rats. Recently, we observed that intrarenal infusion of bradykinin in rabbits increases plasma vasopressin concentration, and that this response is markedly reduced by renal denervation. We have also reported that activation of renal mechanoreceptors by elevating intrarenal pressure increases plasma vasopressin concentration in rabbits, and that this response is blocked by renal denervation. In order to determine if the kidneys participate in the physiological regulation of vasopressin release, we investigated the effect of renal denervation on the osmotic and non-osmotic control of vasopressin secretion in conscious, chronically-prepared rabbits. We found that renal denervation did not significantly reduce the vasopressin responses to hypertonic saline infusion, 24-hour water deprivation, hemorrhage or nitroprusside infusion. In summary, these observations indicate that the kidneys can influence the secretion of vasopressin via the afferent renal nerves. However, the physiological significance of the observations remains to be determined.

Animals↗
PubMed1990

Effects of baroreceptor denervation on endocrine and drinking responses to caval constriction in dogs.

Plasma arginine vasopressin (AVP), plasma renin activity (PRA), and water intake (H2OIN) are increased by thoracic inferior vena caval constriction (TIVCC). To assess the role of the cardiac and sinoaortic baroreceptors in these responses, 9 sham-, 10 cardiac-(CD), 6 sinoaortic-(SAD), and 4 combined cardiac and sinoaortic-(CD + SAD) denervated conscious dogs were studied. All animals were studied while normally hydrated 1) with no access to water (H2O-) and 2) while drinking was permitted (H2O+). TIVCC caused similar reductions (P less than 0.001) of mean arterial (-32 +/- 4 mmHg), left atrial pressure (-6.5 +/- 1.1 cmH2O), and right atrial pressure (-4.2 +/- 0.8 cmH2O) in all groups. After TIVCC in sham dogs with H2O-, AVP increased from 3.6 +/- 0.7 to 72.8 +/- 12.6 pg/ml (P less than 0.001). AVP was similar with SAD (57.1 +/- 6.9) but was reduced with CD (30.9 +/- 3.0) and CD + SAD (17.7 +/- 4.0). In all groups, PRA increased from 4.5 +/- 0.7 to 23.8 +/- 3.0 ng.ml-1 x 3 h-1 and plasma angiotensin II (ANG II) increased from 14.0 +/- 2.8 to 59.5 +/- 13.0 pg/ml (P less than 0.001). Plasma adrenocorticotropic hormone (ACTH) increased similarly in all groups (55 +/- 5 to 128 +/- 25 pg/ml). Plasma norepinephrine (NE) levels increased similarly in all groups (298 +/- 61 to 654 +/- 88 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1990

Role of renal nerves in regulation of vasopressin secretion and blood pressure in conscious rabbits.

The observation that electrical stimulation of the renal nerves increases vasopressin secretion raises the possibility that the renal nerves may participate in the control of vasopressin secretion. In the present investigation, the effects of renal denervation on the vasopressin response to two reflex stimuli (nitroprusside infusion and hemorrhage) and two osmotic stimuli (hypertonic saline infusion and water deprivation) were studied in conscious, chronically prepared rabbits. Nitroprusside infusion in 13 intact and 14 denervated rabbits caused similar decreases in mean arterial pressure (MAP) and the increase in plasma arginine vasopressin concentration (PAVP) in intact (2.6 +/- 0.3 to 5.8 +/- 0.9 pg/ml, P less than 0.01) and denervated (2.8 +/- 0.3 to 5.7 +/- 1.3 pg/ml, P less than 0.01) rabbits was not significantly different. Hemorrhage (20 ml/kg) in 15 intact and 14 denervated rabbits caused similar decreases in MAP. Again, the increase in PAVP from 2.7 +/- 0.3 to 159.0 +/- 37.1 pg/ml (P less than 0.01) in intact and from 5.0 +/- 1.7 to 115.4 +/- 45.6 pg/ml (P less than 0.01) in denervated rabbits was not significantly different, nor was the relationship between PAVP and MAP in the two groups. In seven intact rabbits, hypertonic saline infusion increased PAVP from 4.0 +/- 0.9 to 10.9 +/- 2.8 pg/ml (P less than 0.05). The change in six denervated rabbits was not significantly different, nor was the relationship between PAVP and plasma osmolality. During water deprivation (24 h) in six intact rabbits, PAVP increased from 4.0 +/- 0.7 to 6.9 +/- 0.6 pg/ml (P less than 0.05). Again, the increase in PAVP in six denervated rabbits was not significantly different from that in the intact rabbits. The change in MAP during water deprivation in the two groups was also not significantly different. Renal cortical norepinephrine concentration in denervated kidneys was less than 10 ng/g wet wt. These results indicate that, in conscious rabbits, renal denervation does not impair the osmotic or reflex regulation of vasopressin secretion, nor does it interfere with blood pressure regulation during hypovolemia or hypotension.

Animals↗
PubMed1990

Importance of endogenous angiotensin II in the cardiovascular responses to sympathetic stimulation in conscious rabbits.

Pharmacological evidence indicates that angiotensin (Ang II) converting enzyme inhibitors attenuate cardiovascular responses to sympathetic stimulation. To investigate the physiological significance of this attenuation, the pressor and heart rate responses to bilateral carotid occlusion (BCO) were studied before and after administration of captopril and again during Ang II replacement in conscious, aortic nerve-sectioned rabbits with chronically implanted carotid occluders. In the control period, BCO produced increases (p less than 0.05) in mean arterial pressure (MAP) and heart rate (HR) of 37.3 +/- 3.0 mm Hg and 21.7 +/- 5.4 beats/min from baseline values of 79.1 +/- 2.5 mm Hg and 255.4 +/- 16.7 beats/min. Captopril (5 mg/kg i.v.) markedly reduced (p less than 0.05) both the pressor (10.2 +/- 2.6 mm Hg) and HR (5.0 +/- 4.0 beats/min) responses to BCO, in parallel with a decrease in plasma Ang II of 75%. Infusion of a subpressor dose of Ang II (5-25 ng/kg/min i.v.) increased plasma Ang II to precaptopril levels and fully restored (p less than 0.05) the pressor (33.0 +/- 5.7 mm Hg) and HR (19.8 +/- 7.7 beats/min) responses to BCO. In two additional series of experiments, the mechanism of the effects of captopril and Ang II were investigated. In the first series, cardiac baroreflex curves (pulse interval versus MAP) were generated by increasing or decreasing blood pressure with phenylephrine or nitroprusside (5-20 micrograms/kg/min i.v.). The slope of the linear region of the curve (2.9 msec/mm Hg) was not changed significantly by captopril treatment (3.1 msec/mm Hg) or Ang II replacement (3.2 msec/mm Hg), indicating that cardiac baroreflex sensitivity was not altered by blockade of the renin-angiotensin system. In the second series, the effect of captopril on the pressor response to exogenous norepinephrine (0.1-2.5 micrograms/kg/min i.v.) was tested. The response was reduced by less than 40%, indicating only a modest postsynaptic component to the action of captopril. These results provide physiological evidence for an important action of endogenous Ang II in facilitating the cardiovascular responses to sympathetic stimulation in conscious rabbits. This facilitation is not due to an action upon the baroreflex per se but results, at least in part, from a presynaptic action of Ang II.

Angiotensin II↗
PubMed1990

Role of the area postrema in the modulation of the baroreflex control of heart rate by angiotensin II.

During angiotensin II (Ang II)-induced elevation of arterial pressure, there is an attenuation of the baroreflex control of heart rate (HR), but the site of this action of Ang II on the baroreflex is not known. To investigate the role of the area postrema, the effects of Ang II on arterial pressure and HR and on the baroreflex control of HR were compared in intact and area postrema-lesioned conscious rabbits. In intact rabbits, infusion of Ang II (2.5-100 ng/kg/min) produced dose-related increases in mean arterial pressure (MAP); the largest dose increased MAP by 32 +/- 3 mm Hg. HR decreased only at the highest dose of Ang II (21 +/- 6 beats/min). In lesioned rabbits, the increase in MAP was reduced (23 +/- 2 mm Hg, p less than 0.05) while the decrease in HR was enhanced (50 +/- 8 beats/min, p less than 0.01). The pressor and HR responses to infusion of phenylephrine (PE) (2-20 micrograms/kg/min) were not different between the two groups. In intact rabbits, the slope of the relation between HR and MAP during Ang II infusion was less than that during PE infusion; in lesioned rabbits, the slopes were not significantly different. Responses to bolus injections of Ang II and PE in intact and lesioned rabbits were similar to those obtained in the infusion study. In another series of experiments, cardiac baroreflex responses with or without background infusion of Ang II were obtained by increasing blood pressure with graded infusions of PE (2-20 micrograms/kg/min). In intact rabbits, infusion of Ang II at 10 ng/kg/min shifted the baroreflex to a higher pressure level (resetting) without changing its slope (sensitivity). Background infusion of PE caused comparable increases in blood pressure, but the subsequent baroreflex response was identical to the response without background PE. In lesioned rabbits, background infusion of Ang II did not change the slope, nor did it reset the baroreflex. The effects of Ang II on baroreflex responses during nitroprusside infusions (2-20 micrograms/kg/min) in intact and lesioned rabbits were the same as those observed during the PE infusions. These findings indicate that the attenuation of the baroreflex control of HR by Ang II results from resetting of the cardiac baroreflex and suggest that this effect is mediated via the area postrema.

Angiotensin II↗
PubMed1990

Analysis of the action of angiotensin II on the baroreflex control of heart rate in conscious rabbits.

There is considerable evidence that angiotensin II (Ang II) attenuates the baroreflex control of heart rate (HR), but the mechanism and site of this action have not been precisely defined. In the present study the effects of systemically and centrally administered Ang II on the baroreflex control of HR were investigated in conscious, chronically prepared rabbits. Baroreflex curves (HR vs. mean arterial pressure) were generated with iv infusions of phenylephrine or nitroprusside. Background infusion of Ang II at 10 ng/kg.min increased mean arterial pressure from 77.3 +/- 3.0 to 94.3 +/- 4.1 mm Hg (P less than 0.001) without changing HR [212.1 +/- 7.2 to 218.0 +/- 9.8 beats/min (bpm)] and shifted (reset) the baroreflex curve with phenylephrine to a higher pressure level (P less than 0.001) without changing its slope (-1.40 +/- 0.40 to -1.65 +/- 0.46 bpm/mm Hg; P = 0.4). Background infusion of an equipressor dose of phenylephrine did not shift the baroreflex curve or change its slope. Ang II also shifted the baroreflex curve with nitroprusside to a higher pressure level (P less than 0.01), but again the slope was not significantly changed (-2.30 +/- 1.25 to -1.51 +/- 0.52 bpm/mm Hg; P = 0.2). Background intraventricular infusion of Ang II at 1 ng/kg.min had the same effects as iv infusion of Ang II at 10 ng/kg.min; the curve was shifted to a higher pressure level (P less than 0.001), but the slope was not changed (-0.76 +/- 0.47 to -1.143 +/- 0.48 bpm/mm Hg). Intravenous infusion of Ang II at 1 ng/kg.min had no effect on the baroreflex. The resetting of the baroreflex with phenylephrine by iv Ang II (10 ng/kg.min) was not blocked by propranolol: atropine markedly reduced the baroreflex response to phenylephrine in both the absence and presence of Ang II. These results indicate that in conscious rabbits, Ang II resets the baroreflex control of HR, but does not change its sensitivity. This effect apparently results from an action of Ang II on the brain that is mediated by withdrawal of vagal tone to the heart. The resetting of the baroreflex by Ang II can explain the ability of the peptide to increase arterial pressure without decreasing HR.

Angiotensin II↗
PubMed1990

Effects of carotid occlusion and angiotensin II on vasopressin secretion in intact and vagotomized conscious rabbits.

Experiments were performed in conscious rabbits with sectioned aortic depressor nerves to determine whether there is an interaction between angiotensin II (Ang II) and the baroreceptor reflexes in the control of arginine vasopressin (AVP) secretion. Baroreceptor reflexes were activated by a 5- or 10-min period of bilateral carotid occlusion with or without background infusion of Ang II at 10 or 20 ng/kg.min. Carotid occlusion increased mean arterial pressure, right atrial pressure, and heart rate, but did not change plasma AVP (PAVP) concentration. Infusion of Ang II at 10 ng/kg.min increased PAVP from 4.0 +/- 0.9 to 6.3 +/- 1.8 pg/ml (P less than 0.05). Carotid occlusion during Ang II infusion produced the same cardiovascular changes as before Ang II, but still failed to increase PAVP. Because increased atrial pressure can inhibit AVP secretion, the experiments were repeated in acutely vagotomized rabbits. Vagotomy increased heart rate but did not change mean arterial pressure or PAVP. Carotid occlusion after vagotomy increased PAVP from 2.2 +/- 0.2 to 3.3 +/- 0.5 pg/ml (P less than 0.05). Ang II infusion again increased PAVP but did not enhance the AVP response to carotid occlusion (2.9 +/- 0.4 to 3.9 +/- 0.7 pg/ml). These results provide further evidence for a role of the carotid sinus baroreceptors and vagal afferents in the control of AVP secretion and demonstrate that Ang II stimulates AVP secretion in rabbits. However, they do not reveal any interaction between Ang II and the baroreceptor reflexes in the control of AVP secretion.

Angiotensin II↗