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Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow.
Am J Physiol Renal Physiol. 2015 Apr 15; 308(8):F867-77.AJ

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+Show Affiliations

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.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.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.Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;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.Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.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.Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; cmehlin@sund.ku.dk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25656368

Citation

Jensen, Elisa P., et al. "Activation of GLP-1 Receptors On Vascular Smooth Muscle Cells Reduces the Autoregulatory Response in Afferent Arterioles and Increases Renal Blood Flow." American Journal of Physiology. Renal Physiology, vol. 308, no. 8, 2015, pp. F867-77.
Jensen EP, Poulsen SS, Kissow H, et al. Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow. Am J Physiol Renal Physiol. 2015;308(8):F867-77.
Jensen, E. P., Poulsen, S. S., Kissow, H., Holstein-Rathlou, N. H., Deacon, C. F., Jensen, B. L., Holst, J. J., & Sorensen, C. M. (2015). Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow. American Journal of Physiology. Renal Physiology, 308(8), F867-77. https://doi.org/10.1152/ajprenal.00527.2014
Jensen EP, et al. Activation of GLP-1 Receptors On Vascular Smooth Muscle Cells Reduces the Autoregulatory Response in Afferent Arterioles and Increases Renal Blood Flow. Am J Physiol Renal Physiol. 2015 Apr 15;308(8):F867-77. PubMed PMID: 25656368.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow. AU - Jensen,Elisa P, AU - Poulsen,Steen S, AU - Kissow,Hannelouise, AU - Holstein-Rathlou,Niels-Henrik, AU - Deacon,Carolyn F, AU - Jensen,Boye L, AU - Holst,Jens J, AU - Sorensen,Charlotte M, Y1 - 2015/02/04/ PY - 2014/09/22/received PY - 2015/02/03/accepted PY - 2015/2/7/entrez PY - 2015/2/7/pubmed PY - 2015/6/18/medline KW - afferent arteriole KW - glucagon-like peptide-1 KW - glucagon-like peptide-1 receptor KW - kidney KW - renal blood flow SP - F867 EP - 77 JF - American journal of physiology. Renal physiology JO - Am. J. Physiol. Renal Physiol. VL - 308 IS - 8 N2 - 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. SN - 1522-1466 UR - https://www.unboundmedicine.com/medline/citation/25656368/Activation_of_GLP_1_receptors_on_vascular_smooth_muscle_cells_reduces_the_autoregulatory_response_in_afferent_arterioles_and_increases_renal_blood_flow_ L2 - http://journals.physiology.org/doi/full/10.1152/ajprenal.00527.2014?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -