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

被引：0
作者：
GC Hsieh
T Kolasa
JP Sullivan
JD Brioni
机构：
[1] Neurological and Urological Diseases Research,
[2] Abbott Laboratories,undefined
来源：
International Journal of Impotence Research | 2001年 / 13卷
关键词：
nicorandil; erectile dysfunction; K; channel; guanylate cyclase;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
The potential of ATP-sensitive potassium channel openers (KCOs) for the treatment of male erectile dysfunction has recently been suggested based on positive clinical outcomes following intra-cavernosal administration of pinacidil. 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 corpus cavernosum. The in vitro regulation of smooth muscle tone was assessed in isolated cavernosal tissues pre-contracted with phenyl-ephrine. Nicorandil, but not its major metabolite, relaxed phenylephrine-precontracted cavernosum smooth muscle with an EC50 of 15 μM. The effects of nicorandil were only partially reversed by the KATP channel blocker glyburide (10 μM) or by a soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4] oxadiazole [4,3-a] quinoxalin-1-one (ODQ, 3 μM). However, a combination of ODQ and glyburide completely blocked the relaxant effects of nicorandil. The results of the present study indicate that nicorandil can relax rabbit cavernosal tissue in vitro via a mechanism that involves activation of KATP channels and stimulation of soluble guanylate cyclase.
引用
收藏
页码：240 / 246
页数：6
相关论文
共 60 条
  • [1] Moreland RB(2000)Prospectives for pharmacotherapy of male erectile dysfunction. Current Opinions CPNS Drugs 2 283-302
  • [2] Nakane M(1999)Alpha adrenergic receptors in the penis. J Androl 20 671-682
  • [3] Hsieh GC(1997)Nitric oxide in the penis: physiology and pathology. J Urol 157 320-324
  • [4] Brioni JD(1999)Comparative tolerability and efficacy of treatment for impotence. Drug Safety 20 133-146
  • [5] Traish AM(1997)New developments in nitrosovasodilator therapy. Vasc Med 2 190-202
  • [6] Kim NN(2000)Potassium channel openers as potential therapeutic weapons in ion channel disease. Kidney Int 57 838-845
  • [7] Goldstein I(1999)Characterization of ATP-sensitive potassium channels in human corporal smooth muscle cells. Int J Impot Res 11 179-188
  • [8] Moreland A(1995)The effect of intracavernous injection of potassium channel openers in monkeys and dogs. Int J Impot Res 7 41-48
  • [9] RB W(1990)Effects of pinacidil upon penile erectile tissue, Pharmacol Toxicol 67 235-238
  • [10] Burnett RF(1990) and J Urol 144 146-151
123456