二甲基氨氯吡咪对心肌肥厚大鼠离体心功能的影响及机制探讨

目的研究二甲基氨氯吡咪(d im ethylam iloride,DMA)对心肌肥厚大鼠离体心功能的影响,并探讨其可能的作用机制。方法应用Langendorff心脏灌流方法观察DMA对心肌肥厚大鼠离体心脏功能的影响,并使用L-型钙通道阻滞剂和Na+/Ca+交换(sod ium calc ium exchanger,NCX)抑制剂探讨其可能机制。结果在Langendorff灌流的大鼠心脏,DMA(0.5~2)μmol.L-1能增强心肌肥厚大鼠离体心脏功能,即增强左室主动收缩压(LVSP-LVDP)、左室压最大上升速率(+dp/dtm ax)、和左室压最大下降速率(-dp/dtm ax),与用药前比较,差异均具有显著性(P<0.05或P<0.01)。DMA对心肌肥厚大鼠离体心功能的增强作用不能被L-型钙通道阻滞剂尼卡地平(n icard ip ine)阻断,但能被NCX抑制剂氯化镍(N iC l2)阻断。结论DMA(0.5~2μmol.L-1)能增强心肌肥厚大鼠心脏的收缩和舒张功能。DMA增强心肌肥厚大鼠心脏功能的作用可能是通过激动NCX实现的,与L-型钙通道无关。

The effects and mechanisms of dimethylamiloride on cardiac function in cardiomegaly rat isolated hearts

Aim To investigate the effects and mechanisms of DMA on cardiac function in cardiomegaly rat isolated hearts.Methods With Langendorff perfusion,the changes in the indicators reflecting cardiac function were observed in cardiomegaly rat isolated hearts.Its probable mechanism was explored with calcium channel blocker and sodium calcium exchange(NCX) blockers.Results DMA(0.5～2 μmol·L~(-1))enchanced cardiac function and exerted positive effects on LVSP-LVDP,+dp/dt_(max)and-dp/dt_(max) in Langendorff-perfused cardiomegaly rat isolated hearts.The effects of DMA on cardiac function in cardiomegaly rat isolated hearts weren′t blocked by nicardipine-one of calcium channel blockers and were blocked by NiCl_2——one of sodium calcium exchange(NCX) blockers.Conclusion DMA can enhance systolic and diastolic function in cardiomegaly rat isolated hearts.By agitating NCX,DMA enhances cardiac function in cardiomegaly rat isolated hearts,independent of L-calcium channel.