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(Hypertension. 1997;30:557.)
© 1997 American Heart Association, Inc.

Articles

Angiotensin II Blockade Does Not Prevent Renal Effects of L-NAME in Sodium-Repleted Humans

Alberto Montanari; Enrico Tateo; Elena Fasoli; Daniela Giberti; Patrizia Perinotto; Almerico Novarini; Pierpaolo Dall’Aglio

From the Istituto di Patologia Medica (A.M., E.T., D.G., P.P., P.D’A.), and Istituto di Semeiotica Medica (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}ipruniv.cce.unipr.it

Abstract In seven healthy, young subjects on a 240 mmol sodium diet, mean arterial pressure (MAP), renal hemodynamics, and renal handling of Na and exogenous Li were measured at baseline and during short-term nitric oxide (NO) blockade with a 90-minute infusion of 3.0 µg · kg^-1 · min^-1 of N^G-L-arginine methyl ester (L-NAME). The infusion was performed twice: after a 3-day pretreatment with either placebo or 50 mg losartan to block Ang II receptors. With placebo, L-NAME produced no change in MAP from 0 to 45 minutes (period 1) and only a 5% increase at 45 to 90 minutes (period 2) of infusion. Effective renal plasma flow (ERPF, PAH clearance) and glomerular filtration rate (GFR, inulin clearance) declined by 11.7% and 8.0%, respectively in period 1 and by 14.6% and 11.6%, respectively, in period 2. Calculated renal vascular resistance (RVR) increased by 13.0% to 20.6%. Fractional excretion of Na (FE_Na) and Li (FE_Li) fell by 30.0% and 21.0%, respectively, in period 1 and by 44.2% and 31.1% in period 2. All these variations were significant versus baseline. With losartan, the rise in MAP at 45 to 90 minutes was completely abolished, whereas all changes in ERPF, GFR, RVR, FE_Na, and FE_Li in response to L-NAME were the same as those observed with placebo. The present data show that NO blockade with low-dose systemic infusion of L-NAME produces renal vasoconstriction, reduced GFR, and increased tubular Na reabsorption independent of changes in MAP. Reduced FE_Li indicates an effect of NO on the proximal tubule. Since these changes are not prevented by losartan, we conclude that in Na-repleted humans, renal vasoconstriction and Na-retaining effects of inhibition of basal NO production are not due to the unopposed action of endogenous Ang II.

Key Words: L-NAME • human • kidney • nitric oxide • angiotensin II • hemodynamics

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