Nitric Oxide Regulates Renin Release During Salt Depletion but Does Not Alter Angiotensin Responses in Normal Humans

BACKGROUND: Animal studies suggest that nitric oxide regulates the renin-angiotensin-aldosterone system, but this effect varies among species. The effects of nitric oxide on the renin-angiotensin-aldosterone system in humans were assessed using L-nitrosomonomethyl-arginine (L-NMMA) an antagonist of nitric oxide synthase. METHODS AND RESULTS: In experiment 1, subjects were pretreated with furosemide to induce salt depletion and received placebo-controlled infusions of L-NMMA followed by measurements of plasma renin activity. In experiment 2, subjects were given angiotensin I and II intravenously with and without L-NMMA to assess the effects of nitric oxide on systemic pressor and aldosterone responses. In experiment 3, brachial arterial infusions of angiotensin I and II were given with and without L-NMMA, and the forearm blood flow was measured to assess the effects of nitric oxide on vascular responses to the angiotensin peptides. During salt depletion, L-NMMA infusion resulted in significant higher plasma renin activity. L-NMMA had no effect on systemic or forearm pressor responses or aldosterone responses to angiotensin I and II infusions. CONCLUSIONS: These results indicate that nitric oxide regulates the renin response to salt depletion in health humans but does not affect responses to angiotensin.