Involvement of alpha receptors and potassium channels in the mechanisn of action of sildenafil

ABSTRACT

Modulation of the adrenergic activity and interferring with channels such as potassium channels may affect relaxation and contraction of the corpus cavernosum. Sildenafil is a selective inhibitor of phosphodiesterase 5, proven effective in the treatment of erectile dysfunction. The objective of this study was to test the effect of sildenafil on alpha-receptors modulation and potassium channels. In the present study, it was found that the muscle relaxant effect of sildenafil [1 x 10 [-9] to 1 x 10 [-6] M] on phenylephrineprecontracted rabbit corpus cavernosum strips was not attenuated by NG-nitro-L-arginine [3 x 10 [-5] M]. Cumulative addition of sildenafil [1 x 10 [-9] - 1 x 10 [-6] M] and phentolamine [1 x 10 [-9] to 1 x 10 [-6] M] to the organ bath dose-dependently inhibited electrical field stimulation-induced contraction of rabbit corpus cavernosum and rat anococcygeus muscle with close ED50 values. Sildenafil [1 x 10 [-7] M] also inhibited phenylephrine-induced contraction of rat aortic rings by 39.83 +/- 3.01%. In addition. tetraethylammonium [1 x 10 [-3] M] significantly attenuated the muscle relaxant effect of sildenafil [1 x 10 [-9] - 1 x 10 [-6] M] on phenylephrine-precontracted strips of rabbit corpus cavernosum. sildenafil is capable of producing cavernosal smooth muscle relaxation by an additional mechanism involving alpha-receptors and potassium channel opening