Functionally Distinct Endothelin B Receptors in Vascular Endothelium and Smooth Muscle

Abstract

IRL 1620 {Suc-[Glu 9,Ala 11,15]-ET-1 (8-21)} (0.1 nM - 1μM), a novel ET B-selective endothelin (ET) agonist, produced endothelium-dependent relaxations in precontracted rabbit mesenteric artery (2 nM, EC 50) and endothelium-independent contractions in porcine coronary artery (18 nM, EC 50). ET-3 (0.1 nM-10 nM) produced qualitatively similar responses in the two tissues. The maximal contractions induced by IRL 1620 or ET-3 were substantially smaller (<20%) than that produced by ET-1. BQ-123 (1 μM), an ET A receptor antagonist, inhibited responses to ET-1 without affecting IRL 1620- or ET-3-induced responses in either tissue. Thus functionally distinct ET B receptors mediating vasodilator and vasoconstrictor effects are located on the vascular endothelium and smooth muscle, respectively. The overall effect of ET B receptor activation on vascular tone is tissue-specific and presumably reflects differing receptor distribution at the two sites.