Acute GLP-1 infusion in male adults lowers circulating angiotensin II without changing angiotensinogen, ACE, ACE2, or...

Glucagon-like peptide-1 (GLP-1) receptor agonists elicit cardiovascular and renal protection. In humans, GLP-1 reduces plasma angiotensin II (ANGII) and increases renal perfusion, leading to increased natriuresis. The mechanisms underlying suppression of ANGII remain unclear but may involve ACE2 activation and/or a decrease in angiotensinogen. To address this hypothesis, we performed post-hoc analyses on stored arterial plasma samples from a published study. The study used a randomized, placebo-controlled cross-over design in which eight healthy male adults ingested a sodium-standardized diet for 4 days to reach steady state. Participants were examined during a 3-h infusion of GLP-1 (1.5 pmol/kg/min) or vehicle concurrent with an intravenous infusion of 0.9% NaCl (750 mL/h) to expand the extracellular volume. As previously published, GLP-1 infusion significantly increased urinary sodium excretion, and plasma ANGII concentrations decreased significantly only during GLP-1 infusion. The present analyses demonstrated that plasma angiotensinogen and ACE concentrations decreased similarly (parallel to renin concentrations) during GLP-1 and vehicle. Plasma ACE2 and Ang-(1-7) peptide concentrations remained unchanged during infusions of saline with and without GLP-1. In conclusion, the acute ANGII-lowering effect of GLP-1 does not depend on changes in circulating concentrations of angiotensinogen, ACE, ACE2, or Ang-(1-7). Changes in enzyme activities independent of concentrations cannot be excluded.