Effects of sildenafil on human penile blood vessels

Objectives. To investigate the effects of sildenafil on human penile blood vessels and evaluate the interaction of sildenafil with neurogenic-mediated responses. Sildenafil is currently used in the treatment of erectile dysfu nction. Methods. Penile dorsal arteries and deep dorsal veins were obtained from 14 multiorgan donors. Vascular rings were suspended in organ bath chambers, a nd the isometric tension was recorded. We then studied the effects of silde nafil on precontracted vessels and the neurogenic (noradrenergic and nitrer gic) responses. Results. Sildenafil (10(-9) to 3 x 10(-6) M) caused concentration-dependent relaxation and amplified the relaxation induced by sodium nitroprusside. R elaxation was unaffected by the inhibitor of nitric oxide synthase N-G-mono methyl-L-arginine (10(-4) M). Compared with zaprinast, sildenafil was 8 to 10 times more potent in terms of the median effective concentration (EC50) values. Electrical field stimulation of the vessels under resting tension c aused frequency-dependent contractions that were attenuated in the presence of sildenafil. When penile vessels were contracted after blockade of norep inephrine release with guanethidine (10(-6) M), electrical stimulation indu ced frequency-dependent, nitric oxide-dependent relaxations that were enhan ced by sildenafil. Conclusions. These results indicate that the relaxation of human penile art eries and veins induced by sildenafil involves inhibition of noradrenergic contraction, enhancement of neurogenic nitric oxide-mediated relaxation, an d inhibition of smooth muscle contraction. UROLOGY 56: 539-543, 2000. (C) 2 000, Elsevier Science Inc.