多沙唑嗪对映体对大鼠血压和排尿功能的影响

目的观察十二指肠给予多沙唑嗪(rac-DOX)及其对映体(S-DOX、R-DOX)对麻醉大鼠血压和膀胱排尿功能的影响。方法采用八道生理仪记录麻醉大鼠颈总动脉血压、心率以及膀胱排尿压、排尿间隔,并测量排尿量。结果十二指肠给予S-DOX、R-DOX和rac-DOX均可剂量依赖性降低颈总动脉收缩压、舒张压和平均动脉压,1.0mg.kg-1时3者对平均动脉压的降低幅度分别达到23.5%±4.6%、38.5%±8.9%和42.6%±7.5%,3者降低平均动脉压的ED30值依次为(2.0±0.8)、(0.6±0.7)、(0.6±0.5)mg.kg-1。S-DOX降低收缩压、舒张压和平均动脉压的作用均弱于rac-DOX和R-DOX(P<0.05),rac-DOX与R-DOX的降压作用差异无显著性(P>0.05)。rac-DOX在0.1～3.0mg.kg-1剂量范围内剂量依赖性抑制麻醉大鼠心率,而S-DOX和R-DOX仅在3.0mg.kg-1剂量时对心率有抑制作用。十二指肠给予S-DOX、R-DOX和rac-DOX均剂量依赖性降低麻醉大鼠膀胱排尿压,3种药物对排尿压的最大降低幅度分别为13.4%±5.7%、14.5%±11.0%和10.9%±7.6%,3者降低排尿压的作用差异无显著性(P>0.05)。与S-DOX相比,R-DOX可缩短排尿间隔并减少排尿量(P<0.05),而S-DOX和rac-DOX对排尿间隔和排尿量无影响。结论与R-DOX和rac-DOX相比,S-DOX保留了对麻醉大鼠膀胱排尿压的有利作用,减轻了对血压、心率和膀胱排尿间隔的不良影响。

Effects of doxazosin enantiomers on blood pressure and urinary bladder function in anesthetized rats

Aim To study effects of intraduodenal administration of S-doxazosin, R-doxazosin and rac-doxazosin on the carotid blood pressure and urinary bladder function in anesthetized rats. Methods The various parameters of carotid blood pressure, heart rate, vesical micturition pressure, intercontraction interval in anesthetized rats were recorded with an ADInstruments PowerLab/8s data recording and analysis system, and the vesical micturition volume was measured simultaneously. Results S-Doxazosin, R-doxazosin and rac-doxazosin administered intraduodenally decreased the systolic blood pressure, diastolic blood pressure and mean arterial blood pressure significantly in anesthetized rats in a dose-dependent manner. The inhibition of mean arterial pressure by S-doxazosin, R-doxazosin and rac-doxazosin at 1.0 mg·kg-1 was 23.5%±4.6%, 38.5%±8.9% and 42.6%±7.5%, respectively. The ED30 values of decreasing mean arterial blood pressure by S-doxazosin, R-doxazosin and rac-doxazosin were (2.0±0.8),(0.6±0.7) and (0.6±0.5) mg·kg-1,respectively. S-Doxazosin had a weaker inhibitory effect on the carotid blood pressure compared with R-doxazosin and rac-doxazosin, but no significantly different effect was observed between R-doxazosin and rac-doxazosin on the carotid blood pressure. rac-Doxazosin produced a significant inhibition on the heart rate at the dosage from 0.1 mg·kg-1 to 3.0 mg·kg-1 in a dose-dependent manner, but S-doxazosin and R-doxazosin reduced the heart rate only at 3.0 mg·kg-1. S-Doxazosin, R-doxazosin and rac-doxazosin administered intraduodenally decreased the vesical micturition pressure dose-dependently in anesthetized rats. The maximal inhibition of vesical micturition pressure by S-doxazosin, R-doxazosin and rac-doxazosin was 13.4%±5.7%, 14.5%±11.0% and 10.9%±7.6%, and their inhibitory potency on the vesical micturition pressure was not significantly different each other. R-Doxazosin, however, decreased the intercontraction interval and vesical micturition volume significantly compared with S-doxazosin, but S-doxazosin and rac-doxazosin did not significantly affect the intercontraction interval and vesical micturition volume. Conclusion In comparison with R-doxazosin and rac-doxazosin, S-doxazosin administered intraduodenally remains the beneficial action on vesical micturition pressure and relieves the adverse effects on blood pressure, heart rate and intercontraction interval in anesthetized rats.