A NOVEL SUBTYPE OF ENDOTHELIN-B RECEPTOR MEDIATING CONTRACTION IN SWINE PULMONARY VEIN

Effects of agonists and antagonists of endothelin (ET) receptors were examined in swine pulmonary artery and vein and in rabbit saphenous vein. ET-1, but not ET(B) receptor agonists, sarafotoxin S6c (STXc) and IRL 1620, induced contraction in pulmonary artery. This effect was inhibited by the ET(A) receptor antagonists, BQ-123 and FR139317, but not by the ET(B) receptor antagonist, IRL 1038. Pulmonary artery precontracted by norepinephrine was relaxed by ET-3 in an endothelium-dependent manner. This relaxation was inhibited by IRL 1038 but not by BQ-123. In pulmonary vein, ET-1, ET-3, STXc and IRL 1620 induced contractions at a similar concentration range. ET-1 induced contraction also in saphenous vein. These contractions were not inhibited by BQ-123, FR139317 or IRL 1038. These results suggest that the isopeptide-selective ET(A) receptor mediates contraction in swine pulmonary artery whereas the isopeptide-nonselective ET(B) receptor mediates release of endothelium-derived relaxing factor. In contrast, contractions in the veins may be mediated by a novel subtype of isopeptide-nonselective ET(B) receptor which is not inhibited by IRL 1038.