Dual mechanism of action of nicorandil on rabbit corpus cavernosal smooth muscle tone

The potential of ATP-sensitive potassium channel openers (KCOs) for the tre atment of male erectile dysfunction has recently been suggested based on po sitive clinical outcomes following intra-cavernosal administration of pinac idil. Agents that increase the levels of cGMP via elevation of nitric oxide (NO) nitroglycerin, for example, are also effective in improving erectile function preclinically and clinically. The aim of the present study was to determine the effects and mechanism of the action of nicorandil on rabbit c orpus cavernosum. The in vitro regulation of smooth muscle tone was assesse d in isolated cavernosal tissues pre-contracted with phenylephrine. Nicoran dil, but not its major metabolite, relaxed phenylephrine-precontracted cave rnosum smooth muscle with an EC50 of 15 muM. The effects of nicorandil were only partially reversed by the K-ATP channel blocker glyburide (10 muM) or by a soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4] oxadiazole [4,3- a] quinoxalin-1-one (ODQ, 3 muM). However, a combination of ODQ and glyburi de completely blocked the relaxant effects of nicorandil. The results of th e present study indicate that nicorandil can relax rabbit cavernosal tissue in vitro via a mechanism that involves activation of K-ATP channels and st imulation of soluble guanylate cyclase.