Renal Extraction and Acute Effects of Glucagon-like peptide-1 on Central and Renal Hemodynamics in Healthy Men

The present experiments were performed in order 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-hour infusion of either GLP-1 (1.5 pmol kg-1 min-1) or saline, cardiac output was estimated non-invasively, and intra-arterial 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. The subjects remained supine during the experiments. During GLP-1 infusion, the systolic blood pressure and arterial pulse pressure both increased by 5 ± 1 mm Hg (p=0.015 and p=0.002, respectively). Heart rate increased by 5 ± 1 bpm (p=0.005) and cardiac output increased by 18 % (p=0.016). Renal plasma flow and glomerular filtration rate as well as clearance of sodium and lithium were not affected by GLP-1. However, plasma renin activity decreased (p=0.037), whereas plasma levels of atrial natriuretic peptide (ANP) were unaffected. Renal extraction of intact GLP-1 was 43% (p<0.001) while 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 an increased cardiac output due to a simultaneous increase in stroke volume and heart rate, while no effect on renal hemodynamics could be demonstrated in spite of significant extraction of both the intact hormone and its primary metabolite.