R. Veelken et al., Endogenous angiotensin II and the reflex response to stimulation of cardiopulmonary serotonin 5HT(3) receptors, BR J PHARM, 125(8), 1998, pp. 1761-1767
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.