title: The nicorandil-induced vasodilation in humans is inhibited by miconazole.
abstract: Nicorandil, N-(2-hydroxyethyl)-nicotinamide nitrate, exerts its vasodilatory effects by opening ATP-sensitive potassium (K-ATP) channels and by acting as the exogenous nitric oxide (NO). It is not clear, however, whether the actions of other endothelium-dependent vasodilators, such as NO, endothelium-derived hyperpolarizing factor (EDHF), and prostaglandins, contribute to nicorandil-induced vasodilation in the vasculature in humans. We evaluated forearm blood flow (FBF) response to intraarterial infusion of nicorandil alone and in the presence of glibenclamide, a K-ATP channel inhibitor, N(G)-monomethyl-L-arginine, an NO synthase inhibitor, indomethacin, a cyclooxygenase inhibitor, or miconazol, a cytochrome P-450 inhibitor, in 24 healthy male subjects. FBF was measured using strain-gauge plethysmography. Infusion of nicorandil significantly increased the FBF response in a dose-dependent manner. Intraarterial infusion of glibenclamide attenuated nicorandil-induced vasodilation (160.9 +/- 21.2% versus 90.2 +/- 19.4%, P < 0.01), and miconazole also attenuated the FBF response to nicorandil (160.9 +/- 21.2% versus 66.1 +/- 9.2%, P < 0.001). N-monomethyl-L-arginine or indomethacin did not alter the FBF response to nicorandil. These findings suggest that nicorandil causes vasodilation in forearm circulation in humans, at least in part through a pathway that is dependent on K-ATP channels and cytochrome P-450, but not on endogenous NO and prostaglandins. EDHF may contribute to nicorandil-induced vasodilation in humans.
authors.affiliation: Department of Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ueda
authors.forename: Chikara
authors.initials: C
authors.lastname: Goto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Jitsuiki
authors.forename: Takashi
authors.initials: T
authors.lastname: Umemura
authors.forename: Kenji
authors.initials: K
authors.lastname: Nishioka
authors.forename: Masashi
authors.initials: M
authors.lastname: Kimura
authors.forename: Kensuke
authors.initials: K
authors.lastname: Noma
authors.forename: Keigo
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oshima
authors.forename: Masao
authors.initials: M
authors.lastname: Yoshizumi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008825:Miconazole / Q000494:pharmacology*; D020108:Nicorandil / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D020108:Nicorandil; D008825:Miconazole