title: Nicorandil elevates tissue cGMP levels in a nitric-oxide-independent manner.
abstract: The K(+) channel opener nicorandil is a hybrid compound that contains nitrate in its structure. It has been reported that nicorandil can relax vascular tissue in vitro via a mechanism that involves activation of K(ATP) channels and stimulation of soluble guanylyl cyclase. However, it is not known whether the increase of cGMP levels occurs through an elevation of nitric oxide (NO). The aim of the present study was to determine whether NO release was a direct effect of nicorandil. We reported here that nicorandil did not generate NO using ozone chemiluminescence detection methods in human or rat liver microsomes (P450-rich fractions) with addition of NADPH. However, nicorandil elevated cGMP levels in rat liver, aorta, and human coronary smooth muscle cells in vitro. The elevation was not inhibited by the NO trapping agent carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (carboxy-PTIO). These results suggest that nicorandil elevates cGMP without NO generation.
authors.affiliation: Department of Anti-Aging Food Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho, Yokohama 700-8558, Japan. yukiko-m@md.okayama-u.ac,jp
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Minamiyama
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Takemura
authors.forename: Seikan
authors.initials: S
authors.lastname: Hai
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Suehiro
authors.forename: Shigeru
authors.initials: S
authors.lastname: Okada
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Funae
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000737:chemistry; D006152:Cyclic GMP / Q000032:analysis*; D008099:Liver / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry; D020108:Nicorandil / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015221:Potassium Channels; D020108:Nicorandil; D009569:Nitric Oxide; D006152:Cyclic GMP