DMA对正常大鼠离体心脏和乳头肌的正性变力作用及其机制  

Positive inotropic action of dimethylamiloride in normal rat isolated hearts and papillary muscle and its primary mechanism

作　　者：师锐赞[1] 高福平[1] 李洁[1] 张明升[1] 武冬梅[1] 

机构地区：[1]山西医科大学药理教研室,山西太原030001

出　　处：《中国药理学通报》2007年第12期1609-1612,共4页Chinese Pharmacological Bulletin

基　　金：山西省自然科学基金资助项目(No20041107)

摘　　要：目的研究二甲基氨氯吡咪（dimethylamiloride,DMA）对正常大鼠离体心脏和乳头肌的正性变力作用,并探讨其机制。方法采用Langendorff心脏灌流和离体乳头肌灌流方法观察DMA的变力性作用,并应用L-型钙通道阻滞药和Na^＋/Ca^2＋交换体（sodium calcium exchanger,NCX）抑制剂探讨其作用机制。结果①1-20μmol·L^-1DMA对正常大鼠离体心脏产生正性变力作用,即增强左室主动收缩压（LVSP-LVDP）、左室压最大上升速率（＋dp/dtmax）、左室压最大下降速率（-dp/dtmax）;增强乳头肌收缩功能,即升高发展张力（TC）,缩短收缩至最大速率的时间（T-dp/dtmax）。与用药前相比,差异有显著性（P〈0.05或P〈0.01）。②DMA的正性变力作用不能被L-型钙通道阻滞药尼卡地平（nicardipine）阻断。③NCX抑制剂氯化镍（NiCl2）可阻断DMA的正性变力作用。结论①（1-20）μmol·L^-1 DMA对正常大鼠离体心脏和乳头肌产生正性变力作用。②DMA正性变力作用与L-型钙通道无关。③DMA通过激动NCX产生正性变力作用。Aim To study the inotropic action of DMA in normal rat isolated hearts and papillary muscle and search for its primary mechanism. Methods With Lansendorff-perfusion and isolated papillary muscle perfusion, cardiac performance and the systolic function of papillary muscle were measured to estimate the inotropic action of DMA; L-calcium channel blocker and sodium calcium exchanger （ NCX ） inhibitor were used to search for its primary mechanism. Results ①（1 - 20）μmol · L^-1 DMA exerted a positive inotropic action in normal rat isolated hearts, that is in Langen-dorff-perfused hearts, DMA enhanced cardiac performance, i. e. LVSP-LVDP, ＋ dp/dtmax, - dp/dtmax significantly（ P 〈 0. 05 or P 〈 0. 01 ） ; in isolated papillary muscle, DMA improved TC （developed tension of contraction） and shortened T-dp/dmax significantly （P 〈 0. 05 or P 〈 0. 01 ）. ② The positive inotropic action of DMA in normal rat isolated hearts could not be blocked by nicardipine （one of L-calcium channel blockers）. ③ The positive inotropic action of DMA in normal rat isolated hearts could be inhibited by NiCl2 （ one of sodium calcium exchanger inhibitors）. Concision （ 1 - 20） μmol· L^-1 DMA exerts positive inotropic action in normal rat isolated hearts. By agitating NCX, instead of L-calcium channel, DMA enhances cardiac performance and the systolic function of papillary muscle.

关 键 词：二甲基氨氯吡咪(DMA) 钠钙交换体(NCX) 正性变力作用 

分 类 号：R-332[医药卫生] R322.11