西地那非对大鼠输精管的舒张作用及其机制

Relaxant Effects and Mechanism of Sildenafil on the Vas Deferens of Rats

目的观察西地那非（sil）对体外大鼠输精管平滑肌的舒张效应及其机制。方法①取Wistar成年雄性大鼠16只，随机分为电刺激收缩组和高浓度氯化钾收缩组各8只，将大鼠颈椎脱臼处死，剖取输精管分成两段，其中一组分别以0．1—100．0μmol·L^-1 Sil直接作用于输精管；另一组给予L—NAME后再以0．1—100．0μmol·L^-1 Sil直接作用于输精管，采用台式平衡记录仪检测Sil对输精管平滑肌张力的影响；②将成熟雄性大鼠颈椎脱臼处死，剖取输精管分成两段，取附睾端输精管称重，用作cGMP测定；其他部分分为空白对照组、基础释放组、cGMP激发组（给予0．1mmol·L。SNP激发）和L—NAME（0．1mmol·L^-1）预孵育组，各组均给予3，10，100μmol·L^-1 Sil孵育。提取各组cGMP采用蟛I放射免疫法测定。结果①sil使电刺激和高浓度氯化钾（80mmol·L^-1）刺激体外大鼠输精管平滑肌收缩标本呈浓度依赖性舒张（均P〈0．05），EC50分别为9．82和46．9μmol·L^-1；②当L—NAME存在时，sil对电刺激引起的收缩和高浓度氯化钾刺激引起的收缩的舒张量一效曲线右移，最大效应分别由（87．27±1．91）％降到（68．02±2．29）％（P〈0．05），和（87．46±3．87）％降到（72．99±4．23）％（P〈0．05），EC50分别增加到45．7和63．2μmol·L^-1（均P〈0．05）；③sil可浓度依赖性升高cGMP含量（P〈0．05），而且该作用能被L—NAME完全抑制；在硝普钠存在时，sil能更进一步提高大鼠附睾端输精管平滑肌组织中的cGMP浓度（P〈0．05）。结论sil呈浓度依赖性舒张输精管，该作用可能与NOcGMP途径和NO—cGMP非依赖性途径有关。

Objective To investigate the relaxant effects of sildenafil on the vas deferens of rats. Methods （1）16 Wistar adult male rats were randomly divided into electronic stimulated group and high concentrated KC1 group, one segment of vas deferens from rats was dessected and exposed to 0.1 - 100.0 μmol·L^-1 Sildenafil （sil）. The other segment of vas deferens was first treated with L-NAME then exposed to 0. 1 - 100.0μmol·L^-1 Sil. Effects of Sil on tension of smooth muscles were recorded by desk-top recorder;（2） The vas deferens was isolated from the mature male rats and cut into two parts, the epididymis site of which was weighed and determined for cGMP;the other parts were divided as blank control, basal releasing, cGMP stimulted releasing（0. 1 mmol·L^-1 SNP stimulating） and L-NAME（0. 1 mmol·L^-1） pretreated group, all groups were cultured with 3, 10, 100 μmol·L^-1 Sil. The accumulation of cGMP in the tissue samples was determined by means of 125I radioimmunoassay. Results （1）Sil could concentration-dependently relax the smooth muscle of contracted vas deferens by electronic stimulation（EFS） or KC1 （80 mmol ·L^-1） （ both P 〈 0.05 ）. Their EC50 was 9.82μmol·L^-1 and 46.9 μmol·L^-1 , respectively. （2） The dose-effect curve of sil on relaxation caused by EFS or KC1 stimulation with the presence of L-NAME （0.1 mmol·L^-1 ） could shift right： the maximum effect was decreased from （ 87.27 ± 1.91 ） % to （ 68.02 ± 2.29） % （ P 〈 0.05 ）, and （ 87.46 ± 3.87 ） % to （72.99 ± 4.23 ） % （ P 〈 0.05 ） respectively; EC50 was increased to （45.7 μmol·L^-1） （ P 〈 0.05 ） and （ 63.2 μmol·L^-1 ） （ P 〈 0.05 ） respectively（ both P 〈 0.05 ）. （3）Sil increased basal cGMP concentration directly（ P 〈 0.05 ） and this action could be completely inhibited by L-NAME （P 〈 0. 05 ）. In the presence of sodium nitrosside （SNP）, a stimulatory agent of cGMP, sil could significantly increase cGMP from the epididymis site of vas deferens （P 〈 0.05）. Conclusion Sil could relax vas deferens in a concentration dependent manner, and this effect might be related to the NO-cGMP pathway and the NO-cGMP independent way.