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

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 whethe...

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Main Authors: Yukiko Minamiyama (Author), Shigekazu Takemura (Author), Seikan Hai (Author), Shigefumi Suehiro (Author), Shigeru Okada (Author), Yoshihiko Funae (Author)
Format: Book
Published: Elsevier, 2007-01-01T00:00:00Z.
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100 1 0 |a Yukiko Minamiyama  |e author 
700 1 0 |a Shigekazu Takemura  |e author 
700 1 0 |a Seikan Hai  |e author 
700 1 0 |a Shigefumi Suehiro  |e author 
700 1 0 |a Shigeru Okada  |e author 
700 1 0 |a Yoshihiko Funae  |e author 
245 0 0 |a Nicorandil Elevates Tissue cGMP Levels in a Nitric-Oxide-Independent Manner 
260 |b Elsevier,   |c 2007-01-01T00:00:00Z. 
500 |a 1347-8613 
500 |a 10.1254/jphs.FP0061003 
520 |a 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. Keywords:: nicorandil, nitric oxide (NO), cGMP, P450 
546 |a EN 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Journal of Pharmacological Sciences, Vol 103, Iss 1, Pp 33-39 (2007) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S1347861319343361 
787 0 |n https://doaj.org/toc/1347-8613 
856 4 1 |u https://doaj.org/article/ed742e22dc784e6ca872ed7c21b86c76  |z Connect to this object online.