Endogenous angiotensin II and the reflex response to stimulation of cardiopulmonary serotonin 5HT₃ receptors

Abstract

1 Angiotensin (Ang) II modulates cardiovascular barore¯exes; whether or not the peptide in¯uences chemosensitive cardiovascular re¯exes is not known. We tested the hypothesis that Ang II modulates the re¯ex control of sympathetic nerve activity exerted by 5-hydroxytryptamine 3 (5HT 3 ) cardiopulmonary receptors. 2 The 5HT 3 receptor agonist phenylbiguanide (PBG), infused intravenously for 15 min, elicited a sustained re¯ex decrease of renal sympathetic nerve activity (RSNA) but only transient (53 min) changes of arterial blood pressure (BP) and heart rate (HR) in methohexital-anaesthesized rats. 3 Infusion of Ang II at a dose that did not aect baseline BP, HR and RSNA enhanced the PBGevoked re¯ex decrease of RSNA (754+5% in Ang II treated versus 733+6% in control rats after 15 min PBG, P50.05, n=6 each) in methohexital-anaesthetized rats. 4 The angiotensin converting enzyme (ACE) inhibitor lisinopril blunted the re¯ex responses to PBG in anaesthetized as well as conscious animals. The eect of the ACE inhibitor was abolished by concomitant infusion of Ang II. 5 The re¯ex response to stimulation of cardiopulmonary 5HT 3 aerents was also impaired by the Ang II type 1 receptor (AT 1 ) blocker ZD7155 but not by the type 2 (AT 2 ) blocker PD 123319. 6 Infusion of a volume load to stimulate cardiopulmonary baroreceptors induced a gradual decrease of RSNA which was impaired by exogenous Ang II (RSNA 726+6% in Ang II treated versus 747+6% in control rats after volume load, P50.05, n=6 each) but unaected by ACE inhibition. 7 The re¯ex control of RSNA by cardiopulmonary 5HT 3 receptors is enhanced by Ang II via AT 1 receptors. Thus, Ang II facilitates a chemosensitive cardiovascular re¯ex, in contrast to its inhibitory in¯uences on mechanosensitive re¯exes.

Chronic angiotensin II infusion attenuates the renal sympathoinhibitory response to acute volume expansion

“…Veelken et al (42) reported that acutely administered ANG II blunted, but did not abolish, the renal sympathoinhibitory response to VE (42). Our data, however, do not confirm this finding.…”

“…This is surprising given that normal VE-induced inhibition of renal SNA is attenuated in animals with established congestive heart failure (CHF) (5,11,12), which is subsequently improved after AT 1 receptor blockade (12). These results indicate that ANG II may alter the cardiopulmonary-renal reflex (12,42), potentially contributing to the sympathoexcitation in disease states such as CHF in which extracellular fluid (ECF) volume becomes progressively increased in the presence of elevated circulating ANG II.…”

“…Two groups of animals were used: one received ANG II at the same rate as used chronically (12 ng·kg −1 ·min −1 , n = 6), and the other received ANG II at the rate (12 ng/min, n = 3) used by Veelken et al (42). The latter dose was shown to attenuate VE-induced renal sympathoinhibition (42). Experiments were carried out in animals chronically infused with vehicle only.…”

“…This is surprising given that normal VE-induced inhibition of renal SNA is attenuated in animals with established congestive heart failure (CHF) (5,11,12), which is subsequently improved after AT 1 receptor blockade (12). These results indicate that ANG II may alter the cardiopulmonary-renal reflex (12,42), potentially contributing to the sympathoexcitation in disease states such as CHF in which extracellular fluid (ECF) volume becomes progressively increased in the presence of elevated circulating ANG II.In this study, to characterize the extent to which ANG II can influence the cardiopulmonaryrenal reflex, experiments were performed to test the hypothesis that inhibition of renal SNA by acute VE is attenuated when circulating ANG II is chronically infused. The role of AT 1 receptors in mediating this effect was tested by giving losartan acutely, just before VE.…”

Complex regional haemodynamic effects of anandamide in conscious rats

“…Indeed, the pro®le of cardiovascular eects of anandamide resembled, in several respects, those of 5-HT, which triggers the von Bezold-Jarisch re¯ex through stimulating 5-HT 3 -receptors on vagal aerent ®bres, with subsequent vagal eerent activation (Veelken et al, 1998). The only vascular bed to show vasodilatation in response to anandamide was the hindquarters, which is consistent with the eects of the synthetic cannabinoid, WIN 55212-2, in our model (Gardiner et al, 2001;2002a, b).…”