多沙唑嗪以及阿夫唑嗪对映体对小鼠离体心房心率和收缩力的影响  

Effects of enantiomers of alfuzosin and doxazosin on heart rate and contractile force in the isolated mouse atrium

作　　者：孙家安[1] 王亚伟[1] 任雷鸣[1] 

机构地区：[1]河北医科大学药学院药理学教研室,河北石家庄050017

出　　处：《中国药理学通报》2010年第11期1476-1480,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30940088);河北省自然科学基金资助项目(NoC2009001070)

摘　　要：目的分析多沙唑嗪以及阿夫唑嗪的光学异构体及其外消旋体与药物调节小鼠离体心房心率和心肌收缩力效应的关系。方法制备小鼠离体左心房和离体右心房标本,观察消旋多沙唑嗪[(±)DOX]、左旋多沙唑嗪[(-)DOX]、右旋多沙唑嗪[(+)DOX]、消旋阿夫唑嗪[(±)ALF]、左旋阿夫唑嗪[(-)ALF]以及右旋阿夫唑嗪[(+)ALF]对小鼠离体右心房心率及左心房心肌收缩力的影响。结果 (+)DOX组的16例标本中,加入30μmol·L-1药物后,5例(31.3%)发生停搏;(±)DOX组、(-)DOX组各有1例发生停搏;其他各组标本未出现停搏反应。(+)DOX和(±)DOX各浓度均减慢小鼠右心房心率(P<0.01),并具有浓度依赖关系;(+)DOX减慢心率的作用强于同浓度(±)DOX(P<0.01)。10和30μmol·L-1浓度的(-)DOX减慢心率(P<0.01),其作用弱于同浓度(+)DOX(P<0.01)。(-)ALF、(+)ALF及(±)ALF在10和30μmol·L-1浓度时均轻度减慢小鼠右心房心率(P<0.05)。在小鼠离体左心房标本,(+)DOX(10和30μmol·L-1)抑制心肌收缩力(P<0.05);而(-)DOX(3～30μmol·L-1)增强心肌收缩力(P<0.05),其增强作用强于同浓度(±)DOX(P<0.05)。(±)ALF及其对映体(3～30μmol·L-1)对小鼠离体左心房心肌收缩力无影响。结论 DOX对小鼠离体心房的心率和心肌收缩力具有明显的影响,高浓度尚可诱发心脏停博反应;DOX的手性结构对其上述活性具有明显的影响。相反,ALF仅影响小鼠心率,ALF的手性结构对其心脏效应无明显影响。Aim To study the relationship between chiral structure of doxazosin and alfuzosin and their effects on heart rate and contractile force of the isolated mouse atrium.Methods Isolated right and left atria of the mouse were prepared,and the effects of doxazosin,alfuzosin and their enantiomers on the heart rate and contractile force were recorded.Results （＋） DOX at 30 μmol·L-1 induced cardiac arrest by 31.3% （5 out of 16） in the isolated right atrium,and（-） DOX and （±） DOX at the same concentration induced cardiac arrest by 8.3% （1 out of 12）,respectively.No cardiac arrest was induced in other groups.（＋） DOX and （＋） DOX at used concentrations decreased the heart rate in a concentration-dependent manner（P0.01）,and the inhibition on the heart rate （HR） by （＋） DOX was stronger than that by （±） DOX in the isolated right atrium（P0.01）.（-） DOX at 10 and 30 μmol·L-1 decreased HR（P0.01）,but its effect was weaker than （＋） DOX.The HR was mildly decreased by（±） ALF and its enantiomers at 10 and 30 μmol·L-1（P0.05）.The contractile force of the isolated left atrium was decreased by （＋） DOX at 10 and 30 μmol·L-1 （P0.05）,but was increased by （-） DOX at 3 ～30 μmol·L-1（P0.05）.The increased force by （-） DOX was stronger than that by （±） DOX（P0.05）.（±） ALF and its enantiomers did not affect the contractile force in the isolated left atrium.Conclusion Doxazosin significantly affects the HR and contraction of the isolated mouse atrium,and induces cardiac arrest at high concentration.Chiral structure of doxazosin has an obvious effect on its bioactivity.Alfuzosin,however,decreases the HR mildly without chiral recognition in the isolated mouse atrium.

关 键 词：多沙唑嗪 阿夫唑嗪 对映体 心率 心肌收缩力 离体心脏 小鼠 

分 类 号：R-332[医药卫生] R313