CHARACTERIZATION OF RECEPTORS FOR ENDOTHELINS IN THE GUINEA-PIG MESENTERIC VASCULATURE

In the present study we characterized the effects of and receptors for endothelins (ETs) in the guinea pig mesenteric arterial and venous va sculatures. Endothelin-1 (ET-1) (10-500 pmol) induced a dose-dependent increase of perfusion pressure of the arterial and venous beds. ET-2 (10-500 pmol) also induced a dose-dependent vasoconstriction on both s ides of the mesenteric circulation but was less potent than ET-1. In c ontrast, ET-3 (10-1,000 pmol) and the selective ET(B) agonist IRL 1620 (1,000 pmol) were inactive. A nitric oxide (NO) synthase inhibitor, L -NAME (200 mu M), markedly potentiated the vasoconstrictor response to ET-1 (100 pmol arterial side; 1,000 pmol venous side) on both sides o f the mesenteric vasculature. In precontracted mesenteric vessels, ET- 1 (0.1-5 pmol) and IRL-1620 (1,000 pmol) induced a small yet significa nt vasodilation only on the arterial side. Furthermore, BQ-123 (1 mu M ), an ET(A) receptor antagonist, significantly reduced the ET-1-induce d venoconstriction and completely blocked the vasoconstriction on the arterial side. Hence, the arterial and venous mesenteric vessels of th e guinea pig respond to ETs by activation of ET(A) receptors. Furtherm ore, the endothelium may act as a physiologic barrier to the constrict or effects of ETs by basally releasing NO.