Endothelin ET(B) receptor-mediated action on systemic and renal hemodynamics and urine formation in deoxycorticosterone acetate-salt-induced hypertensive rats.

Abstract

The pathophysiological role of endothelin ET(B) receptor-mediated action on systemic and renal hemodynamics and urine formation in deoxYcorticosterone acetate (DOCA)-salt hypertensive rats was investigated. An intravenous bolus injection of a selective ET(B) receptor antagonist, BQ788 (1 mg/kg), produced a significant increase in mean arterial pressure (MAP) of DOCA-salt treated rats, whereas the agent-induced increase in MAP was less marked in normotensive sham rats. Administration of BQ788 caused a significant and sustained reduction in renal blood flow both in DOCA-salt and sham rats. No marked effects were observed on urine formation in both groups. Alternatively, a selective ET(A) receptor antagonist, FR139317 (10 mg/kg), produced a potent hypotensive effect, accompanied by significant renal vasodilation in DOCA-salt hypertensive rats, but these effects were partially reversed by the subsequent administration of BQ788. When renal perfusion pressure was protected from FR139317-induced hypotension by an aortic clamp, significant diuresis and natriuresis were observed, events partially reversed by the subsequent administration of BQ788. Our results indicate that the ET(B) receptor-mediated action tonically functions as a hypotensive and a renal vasodilatory factor and that these effects seem to be up-regulated in DOCA-salt hypertension. We also suggest that the ET(A) receptor blockade in DOCA-salt hypertensive rats unmasks the ET(B) receptor-mediated action which partially contributes to the antihypertensive effect induced by FR139317.