Renal hemodynamic effects of glucagon-like peptide-1 agonist are mediated by nitric oxide but not prostaglandin

The incretin hormone, glucagon-like peptide-1 (GLP-1), is known for responding to dietary fat and carbohydrate. It elicits effects on pancreas, gut, and brain to stabilize blood glucose levels. We have previously reported that the GLP-1 agonist, exenatide, vasodilates the kidney and suppresses proximal reabsorption. The present study was undertaken to determine whether the renal effects of exenatide are mediated by nitric oxide (NO) and/or prostaglandins. Inulin clearance (glomerular filtration rate, GFR) and urine flow rate (UV) were measured in anesthetized rats before and during exenatide infusion (1 nmol/h iv). Animals were pretreated with cyclooxygenase (COX) inhibitor (meclofenamate), NO synthase (NOS) inhibitor (NG-monomethyl-l-arginine, l-NMMA), NO clamp (l-NMMA + sodium nitroprusside), or placebo. Effectiveness of COX inhibition was tested by measuring urinary prostaglandin E2 (UPGE2). Effectiveness of NOS blockade and NO clamp was determined by urinary NO degradation products (UNOx). Exenatide i...