抑制一氧化氮合成后内皮素在冠状动脉反应性充血扩张中的作用的实验研究

Experimental study on role of endogenous endothelin in echocardiographic evaluation of flow-dependent epicardial coronary vasodilation induced by reactive hyperemia after blockade of nitric oxide formation

目的评价内皮素(ET)在超声心动图检测犬一氧化氮(NO)合成抑制后的冠状动脉反应性充血扩张中的作用。方法健康成年杂种犬6条。应用超声心动图仪分别检测冠状动脉内注射NO合成抑制剂N硝基L精氨酸单甲基酯(LNAME)前、后及LNAME加用内皮素A型(ETA)受体拮抗剂BQ123后反应性充血试验诱发的冠状动脉左前降支(LAD)内径的变化。冠状动脉反应性充血试验采用将LAD环扎30s后迅速放松的方法。结果冠状动脉内注射LNAME前,反应性充血试验诱发LAD内径明显增宽[由(2.24±0.21)mm增至(2.51±0.23)mm,P<0.001],LAD内径百分变化率为(12.22±2.49)%;冠状动脉内注射LNAME后,反应性充血试验诱发的LAD内径百分变化率为(1.23±3.83)%,较前显著减小(P<0.001);LNAME加用BQ123时反应性充血试验诱发的LAD内径百分变化率为(4.76±2.36)%,较单用LNAME时增大(P=0.038)。结论在抑制NO形成后超声心动图观察到的血流介导性冠状动脉内径的变化与内皮来源的缩血管物质ET有关,超声心动图可用于检测冠状动脉内皮依赖性扩张功能。

Objective To determine whether endogenous endothelin(ET) plays a role in the echocardiographic evaluation of the flow-dependent epicardial coronary vasodilation induced by reactive hyperemia(RH) after blockade of nitric oxide(NO) formation. Methods In six anesthetized open-chest dogs, changes in internal diameter of the left anterior descending coronary artery(LAD) induced by RH were investigated via echocardiography before intracoronary infusion of GN-nitro-L-arginine methyl ester(L-NAME), after blockade of NO formation by L-NAME, and after L-NAME plus intracoronary infusion of BQ-123, an ETA receptor blocker.Results Before intracoronary infusion of L-NAME, the diameter of LAD increased significantly from((2.24)±(0.21))mm to ((2.51)±(0.23))mm (P<(0.001)) after RH, and the percent change in diameter of LAD was ((12.22)±(2.49))%. After intracoronary infusion of L-NAME, the percent change in diameter of LAD ((1.23)±(3.83))% induced by RH was dramatically lower than that before intracoronary infusion of L-NAME (P<(0.001)). After intracoronary infusion of L-NAME plus BQ-123, the percent change in diameter of LAD induced by RH increased to ((4.76)±(2.36))%,showing significance over L-NAME alone(P(0.038)). Conclusions The flow-dependent change in diameter of LAD after blockade of NO formation detected by echocardiography is associated with endothelium-derived ET. Echocardiography can be used for assessment of coronary endothelial function.