title: Urocortin induces endothelium-dependent vasodilatation and hyperpolarization of rat mesenteric arteries by activating Ca2+-activated K+ channels.
abstract: Urocortin, a member of corticotropin releasing factor (CRF) peptide family, has positive chronotropic and inotropic effects on heart and also shows a vasodilatory effect. However, the mechanism underlying its vasodilatory effect has yet to be elucidated. Endothelium-dependent 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 alpha1-adrenoceptor agonist, phenylephrine (2-4 microM). 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 microM) and/or nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine (100 microM). 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 microM), indomethacin and N(omega)-nitro-L-arginine. However, the relaxation and hyperpolarization were abolished by high extracellular potassium concentration (40 mM) or by a large conductance Ca(2+)-activated K+ channel blocker, charybdotoxin (1 nM). Glibenclamide (1 microM), an ATP-dependent 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 Ca2+-activated K+ channels. These findings also indicate an essential role of the endothelium for the urocortin-elicited vascular relaxation and hyperpolarization.
authors.affiliation: Department of Pharmacology, Cukurova University Medical School, Adana 01130, Turkey. asecilmis@cu.edu.tr
authors.forename: M Ata
authors.initials: MA
authors.lastname: Seçilmiş
authors.forename: Ozlem Yorulmaz
authors.initials: OY
authors.lastname: Ozü
authors.forename: Mustafa
authors.initials: M
authors.lastname: Emre
authors.forename: Kansu
authors.initials: K
authors.lastname: Büyükafşar
authors.forename: Olcay Ergürhan
authors.initials: OE
authors.lastname: Kiroglu
authors.forename: Peyman
authors.initials: P
authors.lastname: Ertuğ
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Karataş
authors.forename: Serpil
authors.initials: S
authors.lastname: Onder
authors.forename: Ergin
authors.initials: E
authors.lastname: Singirik
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D054832:Urocortins; D014664:Vasodilation / Q000187:drug effects*