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(Hypertension. 2004;44:739.)
© 2004 American Heart Association, Inc.

Scientific Contributions

NO Synthase Inhibition Increases Aldosterone in Humans

From the Divisions of Cardiovascular Medicine (J.A.S.M., D.E.V.), Endocrinology (S.N.D.), and Clinical Pharmacology (N.J.B.), Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn; and the Nashville VA Medical Center (D.E.V.), Tennessee.

Reprint requests to Nancy J. Brown, MD, 560 RRB, Vanderbilt University Medical Center, Nashville, TN 37232-6602. E-mail nancy.j.brown{at}vanderbilt.edu

To test the hypothesis that NO influences aldosterone production in humans, we examined the effect of N^G-nitro-L-arginine methyl ester (L-NAME) on aldosterone concentrations in the presence and absence of the NO precursor L-arginine (3 g TID) and the angiotensin-converting enzyme inhibitor ramipril (10 mg QD). Ten normal subjects were given L-NAME (66 µg/kg per min for 30 minutes) or vehicle in random order on separate days during placebo and after randomized, double-blind treatment with L-arginine, ramipril, or L-arginine plus ramipril. Infusion of L-NAME significantly increased systolic blood pressure (all P<0.05) and decreased heart rate (all P0.02) during all 4 treatment arms. After placebo pretreatment, serum aldosterone was significantly higher during L-NAME infusion than during vehicle (6.6±1.7 versus 3.3±0.5 ng/dL; P=0.045). Combined treatment with L-arginine plus ramipril abolished this effect. There was no effect of L-NAME on plasma renin activity (PRA; P=0.297) or angiotensin II concentrations (P=0.537). However, there was a significant interactive effect of L-NAME and time on serum potassium (P=0.039). There was a significant linear relationship between PRA and aldosterone concentration after vehicle infusion ([aldosterone]=3.9·PRA+1.9; r²=0.476; P=0.027) and L-NAME infusion ([aldosterone]=7.2·PRA+3.1; r²=0.457; P=0.032), and the intercepts of these lines were different (P=0.029). There was a significant linear relationship between serum potassium and aldosterone during L-NAME ([aldosterone]=8.2 · [potassium]–28.9; r²=0.609; P=0.008) but not during vehicle (P=0.313). These data suggest that endogenous NO modulates aldosterone synthesis in humans.

Key Words: aldosterone • nitric oxide • angiotensin-converting enzyme • arginine

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