多沙唑嗪对映体对麻醉猫心血管功能的选择性作用

Effects of doxazosin enantiomers on blood pressure in anesthetized cat

目的研究多沙唑嗪对映体对麻醉猫心血管功能的影响。方法采用八道生理仪记录麻醉猫股动脉血压、心率以及左心室收缩压、左心室舒张末期压和左心室内压最大变化率(±dp/dtmax)。结果十二指肠给予右旋多沙唑嗪[(+)doxazosin,(+)DOX]0.03～1.0 mg.kg-1剂量依赖性降低麻醉猫收缩压、舒张压、平均动脉压和左心室收缩压(P<0.05)。十二指肠给予同等剂量的左旋多沙唑嗪[(-)doxazosin,(-)DOX]和消旋多沙唑嗪[(±)doxazosin,(±)DOX]对麻醉猫收缩压、舒张压、平均动脉压和左心室收缩压无影响(P>0.05)。3种药物对左心室舒张末期压、左心室-dp/dt、左心室+dp/dt和心率无影响(P>0.05)。结论麻醉猫十二指肠给药时,(+)DOX降低动脉血压并抑制心室收缩功能,相同剂量的(-)DOX无作用;提示DOX的手性结构对药物的心血管效应具有明显的影响。

Aim To study effects of intraduodenal administration of（-）doxazosin,（＋）doxazosin and（±）doxazosin on the femoral artery blood pressure,heart rate and left ventricle systolic pressure,end-diastolic pressure,the change of left ventricle pressure（±dp/dtmax） in anesthetized cats.Methods The various parameters of femoral artery blood pressure,heart rate,and left ventricle pressure of the anesthetized cats were recorded with an AD instruments PowerLab/8s data recording and analysis system.Results（＋）Doxazosin（0.03~1.0 mg·kg-1） administered intraduodenally decreased the systolic pressure,diastolic pressure,mean arterial blood pressure and left ventricle systolic pressure significantly in anesthetized cats in a dose-dependent manner while（-）doxazosin and（±）doxazosin had no significant effects.（-）Doxazosin,（＋）doxazosin and（±）doxazosin had no effects on left ventricle end-diastolic pressure,±dp/dtmax and heart rate in anesthetized cats.Conclusion（＋）Doxazosin decreases the femoral artery blood pressure and left ventricle systolic pressure significantly in anesthetized cats,（-）doxazosin has no significant effects,indicating that chiral carbon atom in the molecular structure of doxazosin significantly affects its cardiovascular effects.