Differential regulation of renal regional blood flow by endothelin-1

The present study evaluated the effects and mechanisms of action of endothelin-l (ET-1) on medullary and cortical blood flow (MBF and CBF, respectively). CBF and MBF were measured simultaneously by laser-Doppler flowmetry in anesthetized male Wistar rats. Bolus injection of ET-1 (1.0 nmol/kg iv) produced a sustained decrease in CBF (Delta = -30%) and a transient increase in MBF (Delta = +35%). The medullary vasodilation induced by ET-1 was observed with doses lower than that required to produce cortical vasoconstriction; was completely blocked by bosentan, a mixed ET(A/B)-receptor antagonist; and was mimicked by IRL-1620, a specific ET(B)-receptor agonist. In contrast, BQ-123, an ET(A)-receptor antagonist, failed to inhibit the ET-1-dependent medullary vasodilation but effectively blocked the cortical vasoconstriction induced by the peptide. Finally, inhibition of nitric oxide (NO) synthase completely abolished, whereas cylooxygenase inhibition attenuated, the effect of ET-1 on MBF. The data demonstrate that FT-1 exerts opposite effects on renal cortical and medullary circulation, i.e., ET(A)-receptor-mediated cortical vasoconstriction and ET(B)-mediated medullary vasodilation. Furthermore, the medullary vasodilation induced by ET-1 is dependent on the NO system and, to a lesser extent, on prostaglandin generation.