NO Synthase Inhibition Increases Aldosterone in Humans

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.