title: Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow.
abstract: Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using (125)I-labeled GLP-1, (125)I-labeled exendin-4 (GLP-1 analog), and (125)I-labeled exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na(+) and K(+) excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of (125)I-labeled GLP-1, (125)I-labeled exendin-4, and (125)I-labeled exendin 9-39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9-39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats.
authors: Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, Panum Institute, University of Copenhagen, Copenhagen, Denmark; and.
authors: Elisa P
authors: EP
authors: Jensen
authors: Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, Panum Institute, University of Copenhagen, Copenhagen, Denmark; and.
authors: Steen S
authors: SS
authors: Poulsen
authors: Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, Panum Institute, University of Copenhagen, Copenhagen, Denmark; and.
authors: Hannelouise
authors: H
authors: Kissow
authors: Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;
authors: Niels-Henrik
authors: NH
authors: Holstein-Rathlou
authors: Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, Panum Institute, University of Copenhagen, Copenhagen, Denmark; and.
authors: Carolyn F
authors: CF
authors: Deacon
authors: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors: Boye L
authors: BL
authors: Jensen
authors: Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, Panum Institute, University of Copenhagen, Copenhagen, Denmark; and.
authors: Jens J
authors: JJ
authors: Holst
authors: Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; cmehlin@sund.ku.dk.
authors: Charlotte M
authors: CM
authors: Sorensen
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001345:Autoradiography; D001794:Blood Pressure; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D006339:Heart Rate; D006706:Homeostasis; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply*; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000097:blood / Q000652:urine; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000819:agonists / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects; D065667:Renal Elimination; D012083:Renin / Q000097:blood; D015398:Signal Transduction; D012964:Sodium / Q000097:blood / Q000652:urine; D013997:Time Factors; D014563:Urodynamics; D014688:Venoms / Q000494:pharmacology
chemical_list: C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D012964:Sodium; D000077270:Exenatide; D012083:Renin; D011188:Potassium
keywords: afferent arteriole; glucagon-like peptide-1; glucagon-like peptide-1 receptor; kidney; renal blood flow