1: Hypertension. 2004 Nov;44(5):739-45. Epub 2004 Sep 20. 

NO synthase inhibition increases aldosterone in humans.

Muldowney JA 3rd, Davis SN, Vaughan DE, Brown NJ.

Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt
University Medical Center, Nashville, TN 37232-6602, USA.

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 microg/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 P< or =0.02) 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.

Publication Types:
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15381675 [PubMed - indexed for MEDLINE]