(Hypertension. 2000;35:518.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Endothelin-A Blockade Attenuates Systemic and Renal Hemodynamic Effects of L-NAME in Humans
From the Istituto di Patologia Medica (A.M., M.C, F.C., P.P.) and Istituto di Semeiotica Medica (A.B., N.C., E.F., A.N.), University of Parma, Parma, Italy.
Correspondence to Alberto Montanari, MD, Istituto di Patologia Medica, Via Gramsci 14, I-43100 Parma, Italy. E-mail montalbr{at}unipr.it
Abstract—Eight Na-repleted volunteers underwent 3 separate 90-minute infusions of either NG-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.
Key Words: nitric oxide • endothelin • kidney • hemodynamics • L-NAME • man • BQ-123
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