Endothelin-A Blockade Attenuates Systemic and Renal Hemodynamic Effects of L-NAME in Humans

Abstract

Abstract —Eight Na-repleted volunteers underwent 3 separate 90-minute infusions of either N G -nitro- l -arginine methyl ester (L-NAME) 3.0 mg · kg −1 · min −1 or endothelin-A receptor (ET-A) blocker BQ-123 (BQ) 0.125 nmol · kg −1 · min −1 or both. Mean arterial pressure (MAP), glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistances (RVR), and sodium excretion rate (UNaV) were measured at baseline (b) and from 0 to 45 minutes (period 1) and 45 to 90 minutes (period 2) of infusion. BQ alone had no effect. GFR declined by 4.9% ( P <0.001 versus b) in period 1, to 9.9% ( P <0.001) in period 2 with L-NAME, and by 3.3% ( P <0.01) to 6.6% ( P <0.001) with L-NAME plus BQ ( P =NS between L-NAME and L-NAME plus BQ). UNaV fell equally with L-NAME or L-NAME plus BQ. MAP rose significantly in period 2 with L-NAME (6.9%; P <0.001) but not with coinfused BQ (2.1%; P =NA versus b, P =0.005 versus L-NAME alone). RBF declined by 12.2% ( P <0.001) to 18.3% ( P <0.001) with L-NAME and by 4.6% ( P <0.005) to 8.2% ( P <0.001) with L-NAME plus BQ. These changes were smaller with L-NAME plus BQ ( P <0.05 in period 1 and P <0.02 in period 2). Blunted changes were also seen for RVR ( P <0.005 in period 1 and P <0.001 in period 2 between L-NAME alone and L-NAME plus BQ). These findings show that systemic and renal vasoconstriction due to L-NAME are attenuated by BQ, which suggests that an interaction between endogenous nitric oxide production and ET-A activity participates in the maintenance of baseline systemic and renal vascular tone in humans.