NO Synthase Inhibition Increases Aldosterone in Humans

Abstract

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 P ≤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; r 2 =0.476; P =0.027) and l -NAME infusion ([aldosterone]=7.2·PRA+3.1; r 2 =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; r 2 =0.609; P =0.008) but not during vehicle ( P =0.313). These data suggest that endogenous NO modulates aldosterone synthesis in humans.