Relaxant Effects of Sildenafil on the Human Isolated Bladder Neck

Objective: To evaluate potential in vitro relaxant actions of sildenafil on human isolated bladder neck smooth muscle. Methods: 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 × 0.5-cm pieces and suspended in an organ bath containing 30 mL of a modified Krebs Henseleit solution, bubbled with 95% O2/5% CO2. 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 Nω-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). Result: 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 × 10−4 M). Both l-NAME and ODQ significantly reduced sildenafil-induced relaxation. Conclusions: 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. [Copyright &y& Elsevier]