Renal vasoconstriction to endothelin-1 is enhanced with blockade of endothelin-B receptors or nitric oxide production

Endothelin (ET-1) is a potent renal vasoconstrictor causing an initial transient vasodilation due to activation of ET_B receptors and a long-lasting vasoconstriction thought to be due to ET_A and ET_B receptors. In anesthetized rats ET-1 was infused intravenously {i.V., 1 nmole/kg) after BQ-123 (an ET_A receptor antagonist), BQ-788 (an ET_B receptor antagonist), or vehicle. Left renal artery flow and mean arterial pressure (MAP) were measured. Resistance was calculated as MAP/flow. ET-1 increased renal resistance by 248% (26±2 to 90±13 mmHg/ml/min.). After pretreatment with BQ-123 (1 mg/kg, i.V.), the increase in renal resistance with ET-1 was reduced by 77% (29±5 to 43±7 mmHg/ml/min.), due to a reduction in the increase in MAP by 81% and decrease in flow by 61%. Pretreatment with BQ-788 (1 mg/kg, i.v.) increased renal resistance after ET-1 markedly (26±3 to 234±89 mmHg/ml/min.). BQ-788 did not alter the presser response to ET-1 but totally blocked the transient vasodilation. Pre-treatment with L-NAME (10 mg/kg i.v.) increased MAP 35 mmHg and reduced renal flow 38%; and after ET-1 renal flow was reduced over 90% for 60 minutes. Thus, the renal pressor effects of ET-1 are primarily mediated through ETA receptors and the vasodilation through ET_B receptors in rats. L-NAME does not block the vasodilation with ET-1, so other vasodilators may be involved. There is a considerable amount of constitutive NO released in the rat kidney and ET-1 is much more potent and long-lasting when NO production is blocked.