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- Title
Involvement of α-receptors and potassium channels in the mechanism of action of sildenafil citrate.
- Authors
El-Metwally, M. A.; Sharabi, F. M.; Daabees, T. T.; Senbel, A. M.; Mostafa, T.
- Abstract
Modulation of the adrenergic activity and interfering with channels such as potassium channels may affect relaxation and contraction of the corpus cavernosum. Sildenafil is a selective phosphodiesterase-5 inhibitor, proven effective in treating erectile dysfunction.In this study, the effect of sildenafil citrate on α-receptors modulation and potassium channels was tested. The direct relaxant effect of sildenafil citrate was studied by measuring changes in isometric tension in isolated strips of rabbit corpus cavernosum and rat aortic ring precontracted with phenylephrine or KCl compared to that of diazoxide in the presence and absence of tetraethylammonium. The inhibitory effect of sildenafil on electrical field stimulation-induced contraction of rabbit corpus cavernosum and rat anococcygeus muscle was also studied compared to that of phentolamine. Muscle relaxant effect of sildenafil (1 × 10−9–1 × 10−6 M on phenylephrine-precontracted rabbit corpus cavernosum strips was not attenuated by NG-nitro-L-arginine (3 × 10−5 M). Cumulative addition of sildenafil (1 × 10−9–1 × 10−6 M) and phentolamine (1 × 10−9–1 × 10−6 M) to the organ bath dose-dependently inhibited electrical field stimulation-induced contraction of rabbit corpus cavernosum and rat anococcygeus muscle, with almost similar EC50 values. Sildenafil (1 × 10−7 M) also inhibited phenylephrine-induced contraction of rat aortic rings by 39.83±3.01%. In addition, tetraethylammonium (1 × 10−3 M) significantly attenuated the muscle relaxant effect of sildenafil (1 × 10−9–1 × 10−6 M) on phenylephrine-precontracted strips of rabbit corpus cavernosum.Sildenafil citrate is capable of producing cavernosal smooth muscle relaxation by an additional mechanism that may involve α-receptors and potassium channel opening.International Journal of Impotence Research (2007) 19, 551–557; doi:10.1038/sj.ijir.3901590; published online 2 August 2007
- Subjects
SEXUAL dysfunction; IMPOTENCE; SILDENAFIL; PHOSPHODIESTERASES; POTASSIUM channels
- Publication
International Journal of Impotence Research, 2007, Vol 19, Issue 6, p551
- ISSN
0955-9930
- Publication type
Article
- DOI
10.1038/sj.ijir.3901590