Endothelin ETA and ETB Receptors Mediate Vascular Smooth-Muscle Contraction

Endothelin (ET) ETA receptors on vascular smooth muscle are believed to mediate the vasoconstrictor effects of ET isopeptides, and ETB receptors on the endothelium are thought to mediate the vasodilator effects. This study has investigated the receptors mediating endothelin-induced contraction of isolated ring preparations of rat thoracic aorta (RTA) and rabbit carotid artery (RCA), pulmonary artery (RPA), and jugular vein (RJV). In RTA and RCA, ET-1 (EC50 4.5 and 5.2 nM, respectively) was 82- and 108-fold, respectively, more potent than ET-3, whereas the ETB receptor-selective agonists sarafotoxin S6c (S6c) and Ala-ET-1 (4-Ala-ET-1) were without effect up to ≥1 μM. In contrast, in RPA and RJV, ET-1 (EC50 3.1 and 0.7 nM, respectively) and ET-3 (EC50 4.4 and 0.9 nM, respectively) were equipotent and 4-Ala-ET-1 (EC50 10.7 and 2.1, respectively) and S6?? (EC50 0.4 and 0.1 nM, respectively) were potent contrac tile agonists. The ETA receptor antagonist BQ123 (D-Val-Leu-D-Trp-D-Asp-Pro) competitively antagonized the ef?? fects of ET-1 in RTA and RCA (pA2 values 6.9 ± 0.1 and?? 6.8 ± 0.2, respectively) but did not antagonize (at 10 μM?? contractions to ET-1, ET-3, or 4-Ala-ET-1 in RPA and?? RJV. In conclusion, contraction of vascular smooth mus?? cle by endothelins can be mediated by both ETA and ETB?? receptors.