CHARACTERIZATION OF RECEPTORS FOR ENDOTHELINS IN THE PERFUSED ARTERIAL AND VENOUS MESENTERIC VASCULATURES OF THE RAT

1 Endothelin-1 and -3 induced marked arterial and venous constrictions in the perfused mesenteric vasculature of the rat with endothelin-3 being at least 20 times less active than endothelin-1, on both arterial and venous sides of the vasculature. 2 Two ET(B) selective agonists, BQ-3020 and IRL 1620 (500 pmol), induced weak constrictions of the venous mesenteric vasculature and were inactive in the arterial side at doses up to 1000 pmol. 3 In mesenteric vasculatures precontracted with either methoxamine (arterial side) or the thromboxane A2-mimetic, U46619 (venous side), acetylcholine or bradykinin produced vasodilatations of both arterial and venous vessels, whereas endothelin-3 induced vasodilatations only on the arterial side. 4 A selective ET(A) receptor antagonist, BQ-123, blocked, in a concentration-dependent and reversible fashion, the vasoconstrictions induced by endothelin-1 on both sides of the mesenteric circulation (IC50; arterial side: 0.013 muM; venous side: 0.032 muM). 5 In contrast, the vasodilator responses induced by endothelin-3 on the arterial side of the precontracted mesenteric vasculature were not affected by BQ-123. 6 The present study illustrates the presence of ET(A) receptors which are responsible for vasoconstriction by endothelins in the arterial and venous mesenteric vasculatures. Furthermore, we suggest that the vasodilatations induced by endothelin-3 in the arterial vasculature uniquely, are ET(B) receptor-mediated.