REGIONAL HEMODYNAMIC-RESPONSES TO PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE AND VASOACTIVE INTESTINAL POLYPEPTIDE IN CONSCIOUS RATS

1 Regional haemodynamic responses to the homologous peptides, pituitar y adenylate cyclase-activating peptide (1-27) (PACAP27) and vasoactive intestinal polypeptide (VIP) were assessed by giving 20 min infusions (1.5-15 nmol kg(-1) h(-1)) in conscious, chronically-instrumented, Lo ng Evans rats. 2 PACAP27 caused dose-dependent depressor and tachycard ic effects associated with renal, mesenteric and hindquarters vasodila tations, although only in the latter vascular bed was there a sustaine d increase in flow. 3 VIP caused dose-dependent depressor and tachycar dic effects that were not significantly different from those caused by equimolar doses of PACAP27. However, the hindquarters vasodilator eff ects of VIP (at 7.5 and 15 nmol kg(-1) h(-1)) were greater than those of PACAP27 (at the same doses), and accompanied by reductions in renal and mesenteric flows and conductances. 4 In the presence of the nitri c oxide (NO) synthase inhibitor, N-G-nitro-L-arginine methyl ester (L- NAME; 11 mu mol kg(-1) h(-1)), there was significant inhibition of the hindquarters vasodilator effects of PACAP27 and VIP (at 7.5 and 15 nm ol kg(-1) h(-1)). Under these circumstances the renal and mesenteric v asoconstrictor effects of VIP were abolished. 5 The beta(2)-adrenocept or antagonist, ICI 118551 (670 nmol kg(-1) bolus, 335 nmol kg(-1) h(-1 ) infusion), reduced the matched hindquarters vasodilator responses to PACAP27 (15 nmol kg(-1) h(-1)) and VIP (7.5 nmol kg(-1) h(-1)), and a lso abolished the renal vasoconstrictor effects of VIP. 6 The AT(1)-re ceptor antagonist, losartan potassium (20 mu mol kg(-1)), had no signi ficant effect on the haemodynamic response to PACAP27 (15 nmol kg(-1) h(-1)), but augmented the hypotensive action of VIP (7.5 nmol kg(-1) h (-1)). This influence of losartan was associated with conversion of th e renal and mesenteric vasoconstrictor effect of VIP to vasodilatation . 7 Our findings show that similar changes in mean systemic arterial b lood pressure in response to PACAP27 and VIP conceal substantial diffe rences in their regional haemodynamic actions. Although the hindquarte rs vasodilator effects of both peptides involve NO- and beta(2)-adreno ceptor-mediated mechanisms, it appears that activation of the renin-an giotensin system contributes significantly to the haemodynamic effects of VIP, but not to those of PACAP27.