IMPLICATION OF DIFFERENT ENDOTHELIN RECEPTORS IN THE VASCULAR ACTION OF A HYPERTENSIVE DOSE OF ET-1 IN RAT

The role of different endothelin (ET) receptors in the hemodynamic action of ET-1 was investigated with an ET(A)-receptor antagonist, BQ-123, in anesthetized Wistar rat. BQ-123 (10 mg/kg/0.1 ml) was injected 5 min before ET-1 injection (1 nmol/kg). I.v. injection of ET-1 induced a short period of hypotension associated with aortic vasodilation, followed by long-lasting hypertension and aortic vasoconstriction. These effects were concomitant with immediate renal and mesenteric vasoconstriction. In the presence of BQ-123, the hypotension and aortic vasodilation induced by ET-1 were prolonged and the subsequent hypertension and aortic constriction were prevented. In the renal vascular bed, BQ-123 did not significantly affect the initial ET-1-induced constriction but markedly shortened its duration. In contrast, in the mesenteric vascular bed, BQ-123 seemed initially to amplify the ET-1-induced constriction, but afterwards slightly reduced it. The hemodynamic response to ET-1 may be mediated at first by ET(B) receptors, which induce a reduction of systemic blood pressure and regional vasoconstriction. In a second phase, ET(A) receptors operate to induce a systemic pressor effect and participate with ET(B) receptors in regional vasoconstriction. Therefore, ET(A) and ET(B) receptors may exist in various proportions in different vessels, the renal vascular bed appearing to be richer in ET(A) receptors than the mesenteric bed. The results, which demonstrate that ET(B) receptors mediate aortic dilation and regional constriction, are unexpected and suggest the existence of another non-ET(A)-type receptor and/or a different localization of non-ET(A) receptors in the vascular wall.