Cardiac tissue endothelin-1 levels under basal, stimulated, and ischemic conditions.
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.
Brunner
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Department of Pharmacology and Toxicology, University of Graz, Austria.
D000818:Animals; D016232:Endothelins / Q000032:analysis* / Q000502:physiology; D006020:Glycopeptides / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry*; D051381:Rats
D016232:Endothelins; D006020:Glycopeptides; C008890:phosphoramidon