格列本脲对抗高血压新药盐酸埃他卡林心血管作用的影响  

Glybenclamide Attenuates the Cardiovascular Effects of Iptakalim in Rats

作　　者：刘蔚[1] 肖文彬[1] 汪海[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《高血压杂志》2003年第4期359-362,共4页Chinese Journal of Hypertension

基　　金：国家新药研究与发展重点项目No 96 90 10 10 1

摘　　要：目的　在不同的动物模型上观察ATP敏感性K+ 通道拮抗剂格列本脲对盐酸埃他卡林心血管作用的影响。方法　以无损伤性套尾法测定清醒自发性高血压大鼠血压及心率 ,用四导生理记录仪记录麻醉正常血压大鼠股动脉压 ,用SMUP PC软件记录心功能参数。结果　在清醒自发性高血压大鼠上 ,盐酸埃他卡林 1 5mg·kg- 1 po的降压作用确切、平稳 ,持续时间长 ,对心率的影响轻 ,特异性ATP敏感性K+ 通道拮抗剂格列本脲 50mg·kg- 1 po既能对抗也能预防盐酸埃他卡林 1 5mg·kg- 1 po的降压作用 ,并且格列本脲 1 2 5mg·kg- 1 ·po- 50mg·kg- 1 po的预防性对抗效应具有剂量依赖性。在麻醉正常血压大鼠上 ,盐酸埃他卡林 0 1 2 5～ 2 0mg·kg- 1 iv可剂量依赖性地降低外周血压、减慢心率、抑制心脏收缩及舒张功能。同样条件下 ,吡那地尔 1 0mg·kg- 1 iv与硝苯地平 1 0mg·kg- 1 iv也具有上述作用。特异性ATP敏感性K+ 通道拮抗剂格列本脲 2 0mg·kg- 1 iv能完全拮抗盐酸埃他卡林 0 5mg·kg- 1 iv及吡那地尔 1 0mg·kg- 1 iv的心血管作用 ,不影响硝苯地平 1 0mg·kg- 1 iv的心血管作用。结论　盐酸埃他卡林的心血管作用与硝苯地平不同 ,与吡那地尔相似 ,具备ATP敏感性K+Objective To study the cardiovascular effects of Iptakalim and the influence of the glibenclamide(ATP sensitive potassium channel antagonist) on the cardiovascular action of iptakalim Methods Tail cuff was used to record the systolic blood pressure and heart rate in SHR Blood pressure was recorded by physiologic recorder, and the cardiac function parameters were recorded by SMUP PC software Results In pentobarbital anaesthetized normotensive rats, Iptakalim 0 125～2 0 mg·kg -1 ·iv dose dependently decreased blood pressure, heart rate, LVSP, +dp/dt max ,+dp/dt max /IP,Vmax, dp/dt max and increased dp/dt max time dose dependently Suggesting that Iptakalim inhibits myocardial contractility and diastolic function Pinacidil or Nifedipine at the dose of 1 0 mg·kg -1 iv show analogous effect as well Glibenclamide completely antagonized the antihypertensive and cardiac negative inotropic effects by Iptakalim (0 5 mg·kg -1 ) and pinacidil (1 0 mg·kg -1 ) Iptakalim at high dos of 2 0 mg·kg -1 iv with no effect on nifdipine induced depressive effect on myocardium Conclusion The cardiovascular effects of Iptakalim were different from those of nifedipine, but similar to those of pinacidil The pharmacological properties of Iptakalim appears to be a ATP sensitive potassium channel activators

关 键 词：盐酸埃他卡林 ATP敏感性K^+通道 心血管药理作用 

分 类 号：R96[医药卫生—药理学]