Effects of antagonists for endothelin ETA and ETB receptors on coronary endothelial and myocardial function after ischemia-reperfusion in anesthetized goats

To compare the effects of antagonists for endothelin ETA and ETB receptors on the action of ischemia-reperfusion on endothelial and myocardial function, 30 min of partial or total occlusion followed by 60 min of reperfusion of the left circumflex coronary artery was induced in anesthetized goats treated with intracoronary administration of saline (vehicle), BQ-123 (endothelin ETA receptors antagonist) or BQ-788 (endothelin ETB receptors antagonist). During reperfusion after partial occlusion, coronary vascular conductance and left ventricle dP/dt were decreased after saline or BQ-788, and they normalized after BQ-123. In these three groups of animals, the coronary effects of acetylcholine (3–100 ng) and sodium nitroprusside (1–10 μg) during reperfusion were as under control. During reperfusion after total occlusion, coronary vascular conductance and left ventricle dP/dt were decreased after saline, and they normalized after BQ-123 or BQ-788. In these three groups of animals, the coronary effects of acetylcholine but not those of sodium nitroprusside during reperfusion were decreased after saline, and they reversed after BQ-123 or BQ-788. Therefore, selective antagonists of endothelin ETB and ETA receptors may produce similar protection of coronary vasculature and myocardium against reperfusion after severe ischemia. Selective antagonists of endothelin ETB receptors, contrarily to those of endothelin ETA receptors, may be ineffective to protect coronary vasculature and myocardium against reperfusion after mild ischemia.