西地那非对离体大鼠膀胱颈平滑肌的舒张作用及途径

Relaxation effects of sildenafil on rat isolated bladder neck smooth muscle and its mechanism

目的探讨西地那非对离体大鼠膀胱颈平滑肌的舒张作用及其可能途径。方法取健康成年SPF级雄性SD大鼠24只，随机分为4组（每组6只）：西地那非组、左旋硝基精氨酸甲脂（L-NAME）＋西地那非组、1H-[1，2，4]恶二唑[4，3-a]喹喔啉-1-酮（ODQ）＋西地那非组、锌原卟啉（ZnPP）＋西地那非组。取其膀胱颈平滑肌组织，用去甲肾上腺素预收缩后，分别加入不同浓度西地那非溶液、L—NAME＋不同浓度西地那非溶液、ODQ＋不同浓度西地那非溶液、ZnPP＋不同浓度西地那非溶液，观察膀胱颈平滑肌的舒张变化。结果西地那非呈浓度依赖性舒张效应，最大舒张效应（Emax）达（91．753±2．457）％，舒张效应达50％时所需药物浓度（IC50）为（6．150±0．784）×10^-7～mol／L。与西地那非组比较，其他3组大鼠Emax均显著下降，IC50均显著升高，差异均有统计学意义（均P〈0．05）；L—NAME＋西地那非组及ZnPP＋西地那非组Emax均明显高于ODO＋西地那非组，IC50均明显低于ODQ＋西地那非组，差异均有统计学意义（均P〈0.05）。结论西地那非呈浓度依赖性舒张作用，能被L—NAME、ODQ、ZnPP阻断，该舒张作用可能与NO—cGMP途径和CO—cGMP途径有关。

Objective To investigate the relaxation effects of sildenafil on rat isolated bladder neck smooth muscle and its mechanism. Methods Twenty four adult male Sprague Dawley rats （SD） weighted 230 - 280g were randomly divided into 4 groups. Bladder neck smooth muscles were isolated in all groups and firstly precontracted with norepinephrine. Then the isolated smooth muscles were treated with different concentration of sildenafil （sildenafil group）; sildenafil with Nw-nitro-L-argi- nine-methyl-ester （L-NAME＋sildenafil group）; sildenafil with 1H- [1,2,4]oxadiazolo [4,3-a]quiNOxalin-l-one （ODQ＋sildenafil group）; or sildenafil with zinc protoporphyrin （ZnPP＋sildenafil group）. Results Sildenafil induced concentration-dependent relaxation on rat isolated bladder neck smooth muscle which was precontracted with norepinephrine, the maximum rate of relaxation （Emax） was （91.753 ± 2.457）% with a IC50 of （6.150 ±0.784） × 10^-7mol/L. Compared with the sildenafil group, the Emax of the other three groups decreased markedly, and the IC50 increased significantly （P〈0.05）.The Emax of L-NAME＋ sildenafil group and ZnPP＋ sildenafil group was higher than that of ODQ＋ sildenafil group significantly, and the IC50 was lower （P〈0.05）. Conclusion Sildenafil can induce concentration-dependent relaxation of rat bladder neck smooth muscle. This effect can be blocked by phosphodiesterase type 5 （PDE5） inhibitors L-NAME, ODQ and ZnPP, indicating the involvement of NO-cGMP pathway or CO-cG M P pathway.