Hemodynamic actions of systemically injected pituitary adenylate cyclase activating polypeptide-27 in the rat

The aims of this study were (1) to characterize the hemodynamic mechanisms underlying the hypotensive effects of pituitary adenylate cyclase activatin g polypeptide-27 (PACAP-27 0.1-2.0 nmol/kg, i.v.) in pentobarbital-anesthet ized rats, and (2) to determine the roles of the autonomic nervous system, adrenal catecholamines and endothelium-derived nitric oxide (NO) in the exp ression of PACAP-27-mediated effects on hemodynamic function. PACAP-27 prod uced dose-dependent decreases in mean arterial blood pressure and hindquart er and mesenteric vascular resistances in saline-treated rats. PACAP-27 als o produced pronounced falls in mean arterial blood pressure in rats treated with the ganglion blocker, chlorisondamine (5 mg/kg, i.v.). The hypotensiv e and vasodilator actions of PACAP-27 were not attenuated by the beta-adren oceptor antagonist, propranolol (1 mg/kg, i.v.), or the NO synthase inhibit or, N-G-nitro-L-arginine methyl ester (L-NAME 50 mu mol/kg, i.v.). PACAP-27 produced dose-dependent increases in heart rate whereas the hypotensive re sponse produced by the nitrovasodilator, sodium nitroprusside (10 mu g/kg, i.v.), was associated with a minimal tachycardia. The PACAP-27-induced tach ycardia was unaffected by chlorisondamine, but was virtually abolished by p ropranolol. These results suggest that the vasodilator effects of PACAP-27 are due to actions in the microcirculation rather than to the release of ad renal catecholamines and that this vasodilation may not involve the release of endothelium-derived NO. These results also suggest that PACAP-27 produc es tachycardia by directly releasing norepinephrine from cardiac sympatheti c nerve terminals rather than by direct or baroreceptor reflex-mediated inc reases in sympathetic nerve activity. (C) 1999 Elsevier Science B.V. All ri ghts reserved.