Endothelin-1 induces vasoconstriction and prostacyclin release via the activation of endothelin ET A receptors in the perfused rabbit kidney

Abstract

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 μM). 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 μM). 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 μM) 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.