VIP antagonist [N-Ac-Tyr1,D-Phe2]-GRF-(1-29)-NH2: an inhibitor of vasodilation in the feline colon

Abstract

The effect of the vasoactive intestinal polypeptide (VIP) antagonist [N-Ac-Tyr1,D-Phe2]-GRF-(1-29)-NH2 on pelvic nerve-induced colonic vasodilation and VIP release was investigated in chloralose-anesthetized cats. VIP antagonist (10 and 50 nmol/kg in saline) or saline alone was injected into a branch of the superior mesenteric artery immediately before bilateral pelvic nerve stimulation. The increase in conductance in the inferior mesenteric artery during pelvic nerve stimulation was reduced in an apparently dose-dependent fashion by the VIP antagonist (by 35 +/- 10 and 42 +/- 9%, respectively) compared with the pelvic nerve-induced increase in conductance after injection of saline alone. Injection of the VIP antagonist (50 nmol/kg) did not alter conductance in the absence of pelvic nerve stimulation. VIP was released into portal venous blood during pelvic nerve stimulation in the presence of the antagonist (from 103 +/- 29 to 165 +/- 45 pmol/l). This was not significantly different from release in the presence of saline. The effect of the VIP antagonist (10 nmol.kg-1.min-1) on inferior mesenteric arterial vasodilation induced by exogenous VIP was also quantitated. The increase in conductance after VIP injection (0.2 nmol/kg) was significantly reduced when accompanied by simultaneous infusion of the VIP antagonist (by 54 +/- 6%) compared with the increase in conductance during simultaneous infusion of saline. We conclude that [N-Ac-Tyr1,D-Phe2]-GRF-(1-29)-NH2 is an inhibitor of pelvic nerve-induced vasodilation in the feline colon and does not act by modulating VIP release.(ABSTRACT TRUNCATED AT 250 WORDS)