Urocortin, a member of corticotropin releasing factor (CRF) peptide family, has positive chronotrophic and inotropic effects on heart and also shows a vasodilatory effect. However, the mechanism underlying its vasodilatory effect has yet to be elucidated. Endotheliumdependent relaxation of resistance arteries is mainly achieved by activation of K + channels. Therefore, we investigated possible role of K + channels and hyperpolarization for the vasodilatory effect of urocortin using the isolated perfused rat mesenteric arteries. Urocortin (0.2 nM) produced a slow-onset decrease in the perfusion pressure of the mesenteric vascular bed, which was elevated by an α 1-adrenoceptor agonist, phenylephrine (2-4 μ M). Urocortin also hyperpolarized the main mesenteric artery. Removal of endothelium with saponin treatment considerably inhibited the relaxation and hyperpolarization induced by urocortin. In contrast, the hyperpolarization was not significantly changed by cyclooxygenase inhibitor, indomethacin (1 μ M) and/or nitric oxide synthase inhibitor, N ω -nitro-L-arginine (100 μ M). Urocortin-induced relaxation was not affected by the combination of a guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 μ M), indomethacin and N ω -nitro-L-arginine. However, the relaxation and hyperpolarization were abolished by high extracelluler potassium concentration (40 mM) or by a large conductance Ca 2+ -activated K + channel blocker, charybdotoxin (1 nM). Glibenclamide (1 μ M), an ATPdependent K + channel inhibitor, did not affect the relaxation and hyperpolarization. These results suggest that urocortin causes endothelium-dependent relaxation and hyperpolarization of rat mesenteric arteries, probably through the activation of charybdotoxin sensitive Ca 2+ -activated K + channels. These findings also indicate an essential role of the endothelium for the urocortin-elicited vascular relaxation and hyperpolarization.urocortin; Ca 2+ -activated K + channels; charybdotoxin; mesenteric artery; hyperpolarization

No abstract

No abstract