Brunner F
Department of Pharmacology and Toxicology, University of Graz, Austria.
J Cardiovasc Pharmacol. 1995;26 Suppl 3:S44-6.
The role of cardiac endothelin-1 (ET-1) was studied by determining endogenous tissue and coronary ET-1 levels in isolated rat hearts. Hearts were perfused in an upside-down position with a colloid-free buffer and immunoreactive ET-1 was determined in timed collections of coronary effluent (E) and interstitial fluid (transudate, T) produced by the ventricles and appearing on their surface. Basal ET-1 concentrations were 0.2 +/- 0.01 pg/ml (T) and 0.03 +/- 0.002 pg/ml (E), i.e., the T:E concentration ratio was 7. Angiotensin II (0.1 mumol/L) or thrombin (5 U/ml) increased coronary perfusion pressure and ET-1 secretion but had no effect on the T:E ET-1 concentration ratio (5 and 9). In two different protocols of ischemia/reperfusion, T and E concentrations increased up to two- and fivefold, respectively. The T:E ratios were approximately 2, and the highest concentrations in either fluid were < 1 pg/ml. No change in coronary perfusion pressure was observed. In the presence of the ET-1-converting enzyme inhibitor phosphoramidon (1.7 mumol/L), ischemia-induced increases of ET-1 concentrations were attenuated in parallel with a time-dependent rise in coronary perfusion pressure. Therefore, under normoxic conditions and in ischemia/reperfusion, ET-1 is an endogenous vasodilator in the rat heart.
通过测定离体大鼠心脏中的内源性组织和冠状动脉内皮素 -1（ET-1）水平，研究了心脏ET-1的作用。心脏以倒置位置用无胶体缓冲液灌注，在定时收集的由心室产生并出现在其表面的冠状动脉流出液（E）和间质液（渗出液，T）中测定免疫反应性ET-1。基础ET-1浓度为0.2±0.01 pg/ml（T）和0.03±0.002 pg/ml（E），即T:E浓度比为7。血管紧张素II（0.1 μmol/L）或凝血酶（5 U/ml）增加冠状动脉灌注压和ET-1分泌，但对T:E ET-1浓度比无影响（分别为5和9）。在两种不同的缺血/再灌注方案中，T和E浓度分别增加至两倍和五倍。T:E比值约为2，两种液体中的最高浓度均<1 pg/ml。未观察到冠状动脉灌注压的变化。在存在ET-1转换酶抑制剂磷酰胺素（1.7 μmol/L）的情况下，缺血诱导的ET-1浓度增加与冠状动脉灌注压的时间依赖性升高同时减弱。因此，在常氧条件下和缺血/再灌注时，ET-1是大鼠心脏中的内源性血管舒张剂。
