NO synthase inhibition increases aldosterone in humans

James A S Muldowney, Stephen N. Davis, Douglas E. Vaughan, Nancy J. Brown*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


To test the hypothesis that NO influences aldosterone production in humans, we examined the effect of NG-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≤.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; 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.

Original languageEnglish (US)
Pages (from-to)739-745
Number of pages7
Issue number5
StatePublished - Nov 2004


  • Aldosterone
  • Angiotensin-converting enzyme
  • Arginine
  • Nitric oxide

ASJC Scopus subject areas

  • Internal Medicine


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