No 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 a-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. À6 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 a-receptors and potassium channel opening.

Sildenafil, a highly selective inhibitor of PDE 5, is effective in the treatment of erectile dysfunction. Penile erection involves relaxation of smooth muscle of corpus cavernosum and its associated arterioles. The objective of this study was to investigate the effect of sildenafil on nitric oxide/cyclic guanosine monophosphate (NO/cGMP)-dependent relaxation of rat aortic rings. The contribution of sildenafil to the vasorelaxation of rat aortic rings was also investigated. Sildenafil produced significant potentiation of acetylcholine (ACh, 2 x 10(-6) m)-induced relaxation at concentration > or =1 x 10(-8) m. Addition of sildenafil (1 x 10(-7) m) to aortic rings failed to alter the effect of N(G)-nitro-L-arginine (l-NNA, 3 x 10(-5) m) or methylene blue (MB, 3 x 10(-5) m) on ACh response. Similarly, sildenafil (1 x 10(-7) m) augmented significantly the vasorelaxation induced by sodium nitroprusside over the range of 1 x 10(-9)-1 x 10(-8) m. When added to phenylephrine (3 x 10(-6) m)-precontracted rat aortic rings, sildenafil (1 x 10(-9)-1 x 10(-4) m) induced concentration-dependent relaxation reaching a maximum of 96.48 +/- 1.44%. These relaxations were not significantly attenuated by previous incubation with L-NNA (3 x 10(-5) m) or MB (3 x 10(-5) m). Denudation did not significantly affect the vasorelaxant effect of sildenafil. Sildenafil may act in the rat aortic rings through the amplification of NO/cGMP pathway. It may augment both basal endothelial NO function and exogenous NO-dependent vasodilatation. However, sildenafil may act by a mechanism independent of NO/cGMP pathway and this mechanism contributes to its smooth muscle relaxant effect.

Penile erection involves relaxation of smooth muscle of corpus cavernosum and associated arterioles. Sildenafil, a highly selective inhibitor of phosphodiesterase type 5, is effective in the treatment of erectile dysfunction. The aim of this study is to investigate the effect of sildenafil on smooth muscle of the rabbit corpus cavernosum (RCC) and to compare its effect with those of phentolamine, yohimbine and L-arginine. The effects of sildenafil, phentolamine, yohimbine and L-arginine were studied on the response of the RCC to electrical field stimulation (EFS) as well as on the phenylephrine (PE, 3 x 10(-6) M)-induced tone. EFS caused transient, frequency-dependent relaxation of the RCC that was inhibited by the nitric oxide synthase inhibitor NG-nitro-L-arginine (3 x 10(-5) M). Sildenafil (1 x 10(-9)-1 x 10(-6) M) and phentolamine (1 x 10(-9)-1 x 10(-6) M) enhanced the EFS-induced relaxation in a concentration-dependent manner with ED50 of 0.056 +/- 0.004 and 0.572 +/-0.035 microM at 8 Hz, respectively, yohimbine (3 x 10(-7)-3 x 10(-5) M) and L-arginine (3 x 10(-6)-3 x 10(-4) M) did not show significant effects (ED50 at 8 Hz = 35.84 +/-2.24 and 2.164 +/- 0.174 microM, respectively). Sildenafil (1 x 10(-9) and 1 x 10(-8) M) potentiated the EFS-induced relaxation caused by L-arginine (3 x 10(-5) m). Sildenafil, phentolamine, yohimbine and L-arginine reduced the PE-induced tone to different extents; the ED50 values were 0.81 +/- 0.097, 0.49 +/- 0.025 and 13.97 +/- 1.10 microM, respectively. Maximum concentration of L-arginine used failed to produce 50% relaxation (ED20 = 221.82 +/- 15.71 microM). The muscle relaxant effects of different combinations of sildenafil and L-arginine on PE-induced tone did not differ significantly from the sum of the individual effects. The results demonstrate that sildenafil, when compared to other drugs used in penile erection dysfunction, shows the highest potency on the nitrergic transmission in the RCC. On the other hand, phentolamine was found to possess the highest potency in inducing relaxation of RCC proving that its action is independent on the stimulated neurogenic system. In addition, the combination of less effective doses of sildenafil and L-arginine has a potential advantage on erectile functions. The importance of this combination remains to be solved clinically.