Endogenous angiotensin II and the reflex response to stimulation of cardiopulmonary serotonin 5HT(3) receptors

1 Angiotensin (Ang) II modulates cardiovascular baroreflexes; whether or no t the peptide influences chemosensitive cardiovascular reflexes is not know n. We tested the hypothesis that Ang II modulates the reflex control of sym pathetic nerve activity exerted by 5-hydroxytryptamine 3 (5HT(3)) cardiopul monary receptors. 2 The 5HT(3) receptor agonist phenylbiguanide (PBG), infused intravenously for 15 min, elicited a sustained reflex decrease of renal sympathetic nerve activity (RSNA) but only transient (<3 min) changes of arterial blood pres sure (BP) and heart rate (HR) in methohexital-anaesthesized rats. 3 Infusion of Ang II at a dose that did not affect baseline BP, HR and RSNA enhanced the PBG-evoked reflex decrease of RSNA (- 54 +/- 5% in Ang II tre ated versus - 33 +/- 6% in control rats after 15 min PEG, P<0.05, n = 6 eac h) in methohexital-anaesthetized rats. 4 The angiotensin converting enzyme (ACE) inhibitor lisinopril blunted the reflex responses to PEG in anaesthetized as well as conscious animals. The effect of the ACE inhibitor was abolished by concomitant infusion of Ang II . 5 The reflex response to stimulation of cardiopulmonary 5HT3 afferents 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 indu ced a gradual decrease of RSNA which was impaired by exogenous Ang II (RSNA -26+/-6% in Ang II treated versus -47+/-6% in control rats after volume lo ad, P<0.05, n=6 each) but unaffected by ACE inhibition. 7 The reflex control of RSNA by cardiopulmonary 5HT(3) receptors is enhance d by Ang II via AT(1) receptors. Thus, Ang II facilitates a chemosensitive cardiovascular reflex, in contrast to its inhibitory influences on mechanos ensitive reflexes.