The renal and systemic hemodynamic effects of a nitric oxide-synthase inhibitor are reversed by a selective endothelin(A) receptor antagonist in men

There is evidence for an interaction between nitric oxide (NO) and endothel in (ET) at the level of the renal vasculature. We hypothesized that acute r enal effects of systemic NO synthase inhibition (N-G-monomethyl-L-arginine, L-NMMA) may be blunted by coadministration of a specific ETA receptor anta gonist (BQ-123) in healthy humans. Fifteen healthy young male subjects part icipated in this randomized, double-blind, placebo-controlled 3-way crossov er study. These sodium-repleted volunteers received L-NMMA alone, or BQ-123 alone, or L-NMMA with a subsequent coinfusion of BQ-123. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were determined with the PAH an d inulin clearance method, respectively. Mean arterial pressure (MAP) and p ulse rate were measured noninvasively at baseline and every 15 min after th e start of the study period. L-NMMA, alone reduced RPF (-22%, P < 0.001) an d GFR (-8%, P < 0.009) and increased MAP (+10%, P < 0.001). BQ-123 alone di d not affect these parameters. However, coinfusion of BQ-123 blunted the ef fects of L-NMMA on RPF (P < 0.001), GFR (P < 0.001), and MAP (P = 0.006). P eripheral and renal hemodynamic effects of acute systemic NO synthase inhib ition are at least partially reversed by ETA receptor blockade with BQ-123. This indicates a functional antagonism between specific ETA receptor antag onist and NO synthase inhibitors at the level of the renal vasculature. (C) 2001 Academic Press.