Nicorandil Elevates Tissue cGMP Levels in a Nitric-Oxide-Independent Manner

Journal of Pharmacological Sciences

Shigeru Okada¹  Yukiko Minamiyama¹  Seikan Hai²  Shigefumi Suehiro⁴  Shigekazu Takemura²  Yoshihiko Funae³ 

[1] Department of Anti-Aging Food Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan;Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Osaka City University, Japan;Department of Chemical Biology, Graduate School of Medicine, Osaka City University, Japan;Department of Cardiovascular Surgery, Graduate School of Medicine, Osaka City University, Japan

关键词: nicorandil;    nitric oxide (NO);    cGMP;    P450;   

DOI  :  10.1254/jphs.FP0061003

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(19)Cited-By(13)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 KATP 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.

【 授权许可】

Unknown