ENDOTHELIN-1 INDUCES VASOCONSTRICTION AND PROSTACYCLIN RELEASE VIA THE ACTIVATION OF ENDOTHELIN ET(A) RECEPTORS IN THE PERFUSED RABBIT KIDNEY

Endothelin-1 (0.005 and 0.01 nmol) induced a dose-dependent increase in perfusion pressure in the perfused rabbit kidney. These pressor effects were markedly reduced by an endothelin ET(A) receptor antagonist, BQ-123 (0.1 muM). Similarly, the release of prostacyclin triggered by intra-arterial infusion of endothelin-1 (10 nM) was significantly reduced in a concentration-dependent manner when the kidney was pretreated with BQ-123 (0.5-1 muM). In contrast, two selective ET(B) receptor agonists, BQ-3020 and IRL 1620, were found to be inactive, both as pressor agents and releasers of prostacyclin at doses (for the pressor effects) and concentrations (for the prostacyclin generation) 50-100 times higher than those of endothelin-1. BQ-123 (1 muM) did not modify the pressor or prostanoid-releasing properties of angiotensin II. These results confirm our previous observations suggesting that pressor responses and prostanoid release induced by endothelin-1 are mediated via the selective activation of ET(A) receptors in the perfused rabbit kidney.