EFFECTS OF NICORANDIL ON HUMAN ISOLATED CORPUS CAVERNOSUM AND CAVERNOUS ARTERY

Nitric oxide (NO) released from nonadrenergic-noncholinergic (NANC) ne rves seems to be a principal mediator of the relaxation of penile erec tile tissue necessary for erection, and drugs acting by release of NO have been shown to produce el:ection when injected intracorporeally in to impotent patients. By producing hyperpolarization, K+ channel opene rs are effective in relaxing isolated penile erectile tissue from rabb it and man, and can produce tumescence and erection when injected intr acorporeally into animals. Nicorandil is classified as a K+ channel op ener, but it also acts as a donor of NO. In the present study, the eff ects of nicorandil on isolated preparations from human corpus cavernos um (CC) and deep cavernous artery (Ace) were compared with those of cr omakalim (K+ channel opener) and SIN-1 (NO donor). Nicorandil produced a concentration-dependent relaxation of CC and Ace preparations. The relaxations obtained at the highest nicorandil concentration used (10( -4) M.) were 75 +/- 3% and 66 +/- 4% in CC preparations contracted by noradrenaline and endothelin-l, respectively. The corresponding effect s in Ace preparations were 70 +/- 14% and 73 +/- 5%. Glibenclamide (bl ocking ATP-dependent K+ channels) significantly reduced the nicorandil -induced relaxation in CC, but not in Ace. Methylene blue (believed to block soluble guanylate cyclase) reduced nicorandil's relaxant effect in CC, although statistical significance was not obtained. NG-nitro-L -arginine 10(-4) M. (NO synthase inhibitor) did not significantly infl uence the effect of nicorandil on precontracted preparations in either tissue. In CC preparations contracted by electrical field stimulation , nicorandil and cromakalim concentration dependently inhibited the re sponses. This effect was significantly counteracted by glibenclamide. It is concluded that nicorandil is effective in relaxing human CC chie fly by its K+ channel opening action, and to some extent by its abilit y to release NO. For nicorandil's relaxing effect on Ace, ATP dependen t K+ channels seem to be of limited importance. If effective in impote nt patients, the drug may represent a new, interesting approach to the treatment of erectile dysfunction.