Title: Two Subtypes of the Endothelin Receptor (ETA and ETB) Mediate Vasoconstriction in the Perfused Rat Heart
Abstract: The effects of endothelin-1 (ET-1) are mediated by two subclasses of the endothelin receptor, ETA and ETB. The Langendorff perfused rat heart was used to determine the endothelin receptor subtype mediating rat coronary vasoconstriction. ET-1 (EC50 = 1.5 x 10(-10) M) and endothelin-3 (ET-3) (10(-11)-3 x 10(-8) M) caused dose-dependent increases in coronary perfusion pressure. BQ-123, a selective antagonist of the ETA-receptor subtype, did not cause a parallel shift in the dose-response curves of ET-1 or ET-3. In the presence of 1-3 x 10(-6) M BQ-123, ET-1 and ET-3 exhibited biphasic dose-response curves, suggesting that vasoconstriction was caused by two receptors. The ETB-selective agonist Suc-[Glu9,Ala11,15]-ET-1(8-21) (IRL 1620) maximally increased perfusion pressure by approximately 50% of the maximal response to ET-1 and was not inhibited by BQ-123. These data suggest that the rat coronary vasoconstrictor effects of ET-1 and ET-3 are mediated by both ETA and ETB receptors.