-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 Ϫ1 ·min Ϫ1 ) 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 Ϯ 1 mmHg (P ϭ 0.015 and P ϭ 0.002, respectively). Heart rate increased by 5 Ϯ 1 beats/min (P ϭ 0.005), and cardiac output increased by 18% (P ϭ 0.016). Renal plasma flow and glomerular filtration rate as well as the clearance of Na ϩ and Li ϩ were not affected by GLP-1. However, plasma renin activity decreased (P ϭ 0.037), whereas plasma levels of atrial natriuretic peptide were unaffected. Renal extraction of intact GLP-1 was 43% (P Ͻ 0.001), whereas 60% of the primary metabolite GLP-1 9-36amide was extracted (P ϭ 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.glucagon-like peptide-1; blood pressure; heart rate; cardiac output; renal plasma flow GLUCAGON-LIKE PEPTIDE (GLP)-1 is a 30-amino acid peptide hormone primarily synthesized by enteroendocrine L cells distributed in the small and large intestines and secreted in a nutrient-dependent manner. GLP-1 stimulates insulin secretion and inhibits glucagon secretion and gastric emptying, resulting in reduced postprandial glycemia (14). The GLP-1 receptor is a G protein-coupled receptor and a member of the glucagon receptor family (18). The GLP-1 receptor was originally identified in islet -cells in the pancreas, but it is also widely expressed in extrapancreatic tissues in humans (17,25,33).GLP-1 receptor agonists have been approved for the treatment of hyperglycemia in subjects with diabetes, and, in addition, they may have significant cardiovascular effects (6, 28). However, results regarding the effects on arterial blood pressure are conflicting (2, 9, 11, 20 -22, 29, 31). The reasons for the apparent discrepancies are not clear, although differences between species, doses applied, and durations of treatment may contribute.Human studies have reported a natriuretic effect of native GLP-1, possibly due to reduced Na ϩ reabsorption in the proximal tubule (12,29). However, in a recent study (25) validating a new, monoclonal GLP-1 receptor antibody, GLP-1 receptors could not be identified in the proximal tubule, whereas they were expressed in renin-secreting ...