多沙唑嗪对映体不同给药途径对豚鼠膀胱排尿功能的影响

Effects of doxazosin enantiomers by different routes of administration on urinary bladder function in guinea pigs

目的比较多沙唑嗪（rac-DOX）及其对映体SDOX和R—DOX对膀胱排尿功能的影响。方法采用八道生理记录仪连续记录给药前及给药后麻醉豚鼠膀胱排尿压（VMP）、排尿阈值压（MTP）、排尿间隔（ICI）的变化，并测量排尿量（VMV）。结果S-DOX，R．DOX和rac—DOX（0．08～2．40mg·k^-1，经十二指肠插管给药），均可剂量依赖性降低VMP；S-DOX对MTP，ICI及VMV无显著影响；R-DOX则可显著降低MTP；R．DOX和rac—DOX均显著缩短ICI，并减少VMV。S—DOX，R-DOX和rac-DOX（0．008～0．800mg·kg^-1，iv），亦可剂量依赖性降低麻醉豚鼠VMP；三者对VMP的作用强度无显著性差异；S-DOX，R-DOX和rac-DOX对MTP无显著影响；S-DOX和R-DOX能显著延长ICI，并增加VMV。结论与R-DOX和rac—DOX相比，S—DOX在保留了原有降低VMP作用的同时，对MTP，ICI及VMV无不良影响。

AIM To compare the effects of Sdoxazosin, R-doxazosin and rac-doxazosin on urinary bladder function. METHODS The vesical micturition pressure （VMP）, micturition threshold pressure （MTP） , and intercontraction interval （ICI） in anesthetized guinea pigs were recorded using a PowerLab/8sp ADInstruments data recording and analysis system, and the vesical micturition volume （VMV） was measured simultaneously. RESULTS S- Doxazosin, R-doxazosin and rac-doxazosin （0.08 - 2.40 mg·kg^- 1, intraduodenally） decreased the VMP in a dose-dependent manner in anesthetized guinea pigs. S-Doxazosin （intraduodenally） did not affect the MTP, ICI and VMV significantly, while R-doxazosin （intraduodenally ） significantly depressed the MTP. R-Doxazosin and rac-doxazosin （intradu- odenally） significantly decreased the ICI, and the VMV. S-Doxazosin, R-doxazosin and racdoxazosin （0.008 - 0. 800 mg· kg^-1, iv） decreased the VMP in a dose-dependent manner in anesthetized guinea pigs, and their inhibitory potencies on the VMP were not significantly different. None of the three agents （iv） affected the MTP significantly. S-Doxazosin and R- doxazosin （iv） significantly increased the ICI and the VMV. CONCLUSION Compared with rac-doxazosin and R-doxazosin, S-doxazosin remains the beneficial action on VMP without adverse effects on MTP, ICI and VMV.