Relaxant effects of sildenafil on the human isolated bladder neck

To evaluate potential in vitro relaxant actions of sildenafil on human isolated bladder neck smooth muscle.

Bladder neck strips were sampled from patients (aged 55-77 years) submitted to prostatic surgery (6 adenomectomies and 1 radical prostatectomy). These were carefully dissected into 1-2 x 0.5-cm pieces and suspended in an organ bath containing 30 mL of a modified Krebs Henseleit solution, bubbled with 95% O(2)/5% CO(2). After tissue stabilization and viability test with KCl, the tissue was precontracted with phenylephrine, and a concentration-response relaxant curve to sildenafil was constructed. The effect of sildenafil was also assessed in tissues treated with N(omega)-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (inhibitors of nitric oxide synthase and guanylyl cyclase, respectively).

Sildenafil induced significant bladder neck relaxation at all concentrations tested. The maximum relaxation was 86.97% +/- 6.69%, obtained with a high concentration of sildenafil (5.1 x 10(-4) M). Both L-NAME and ODQ significantly reduced sildenafil-induced relaxation.

Sildenafil was effective in inducing bladder neck smooth muscle relaxation in vitro. This effect was almost abolished by L-NAME and ODQ, clearly demonstrating a dependence of the nitric oxide-cyclic guanosine monophosphate pathway. Our in-vitro results suggest that sildenafil might be useful in improving lower urinary tract symptoms due to benign prostatic hyperplasia.