Renal extraction and acute effects of glucagon-like peptide-1 on central and renal hemodynamics in healthy men

The present experiments were performed to elucidate the acute effects of intravenous infusion of glucagon-like peptide (GLP)-1 on central and renal hemodynamics in healthy men. Seven healthy middle-aged men were examined on two different occasions in random order. During a 3-h infusion of either GLP-1 (1.5 pmol.kg(-1).min(-1)) or saline, cardiac output was estimated noninvasively, and intraarterial blood pressure and heart rate were measured continuously. Renal plasma flow, glomerular filtration rate, and uptake/release of hormones and ions were measured by Fick's Principle after catheterization of a renal vein. Subjects remained supine during the experiments. During GLP-1 infusion, both systolic blood pressure and arterial pulse pressure increased by 5 +/- 1 mmHg (P = 0.015 and P = 0.002, respectively). Heart rate increased by 5 +/- 1 beats/min (P = .005), and cardiac output increased by 18% (P = 0.016). Renal plasma flow and glomerular filtration rate as well as the clearance of Na+ and Li+ were not affected by GLP-1. However, plasma renin activity decreased (P = 0.037), whereas plasma levels of atrial natriuretic peptide were unaffected. Renal extraction of intact GLP-1 was 43% (P < 0.001), whereas 60% of the primary metabolite GLP-1 9-36amide was extracted (P = 0.017). In humans, an acute intravenous administration of GLP-1 leads to increased cardiac output due to a simultaneous increase in stroke volume and heart rate, whereas no effect on renal hemodynamics could be demonstrated despite significant extraction of both the intact hormone and its primary metabolite.