Bittencourt José Augusto F, Tano Tania, Gajar Sessin A, Resende Angela C, de Lemos Neto Miguel, Damião Ronaldo, Criddle David N, de Bem Graziele Freitas, de Moura Roberto Soares
Urology Service, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Urology. 2009 Feb;73(2):427-30. doi: 10.1016/j.urology.2008.06.060. Epub 2008 Sep 6.
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.
评估西地那非对人离体膀胱颈平滑肌的潜在体外舒张作用。
从接受前列腺手术（6例腺瘤切除术和1例根治性前列腺切除术）的患者（年龄55 - 77岁）中获取膀胱颈组织条。将这些组织条小心地切成1 - 2×0.5厘米的小块，并悬挂在含有30毫升改良克雷布斯 - 亨塞尔特溶液的器官浴中，用95% O₂/5% CO₂通气。在用氯化钾进行组织稳定和活力测试后，用去氧肾上腺素使组织预收缩，构建西地那非的浓度 - 反应舒张曲线。还评估了西地那非在分别用Nⁿ - 硝基 - L - 精氨酸甲酯（L - NAME）或1H - [1,2,4]恶二唑并[4,3 - a]喹喔啉 - 1 - 酮（ODQ）（分别为一氧化氮合酶和鸟苷酸环化酶抑制剂）处理的组织中的作用。
在所有测试浓度下，西地那非均能显著诱导膀胱颈舒张。高浓度西地那非（5.1×10⁻⁴ M）时获得的最大舒张率为86.97%±6.69%。L - NAME和ODQ均显著降低了西地那非诱导的舒张作用。
西地那非在体外能有效诱导膀胱颈平滑肌舒张。L - NAME和ODQ几乎完全消除了这种作用，清楚地表明其对一氧化氮 - 环磷酸鸟苷途径的依赖性。我们的体外研究结果表明，西地那非可能有助于改善良性前列腺增生引起的下尿路症状。
