GLP-1-induced renal vasodilation in rodents depends exclusively on the known GLP-1 receptor and is lost in prehypertensive rats
- 1 June 2020
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Renal Physiology
- Vol. 318 (6), F1409-F1417
- https://doi.org/10.1152/ajprenal.00579.2019
Abstract
Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate postprandial insulin release. However, GLP-1 also exerts extrapancreatic effects, including renal effects. Some of these renal effects are attenuated in hypertensive rats, where renal expression of GLP-1 receptors is reduced. Here, we assessed the expression and vascular function of GLP-1 receptors in kidneys from young prehypertensive rats. We also examined GLP-1-induced vasodilation in the renal vasculature in wild-type (WT) and GLP-1 receptor knockout mice using wire and pressure myography and the isolated perfused juxtamedullary nephron preparation. We investigated whether GLP-1 and the metabolite GLP-1(9-36)amide had renal vascular effects independent of the known GLP-1 receptor. We hypothesized that hypertension decreased expression of renal GLP-1 receptors. We also hypothesized that GLP-1-induced renal vasodilatation depended on expression of the known GLP-1 receptor. In contrast to normotensive rats, no immunohistochemical staining or vasodilatory function of GLP-1 receptors was found in kidneys from prehypertensive rats. In WT mice, GLP-1 induced renal vasodilation and reduced the renal autoregulatory response. The GLP-1 receptor antagonist exendin 9-39 inhibited relaxation, and GLP-1(9-36)amide had no vasodilatory effect. In GLP-1 receptor knockout mice, no relaxation induced by GLP-1 or GLP-1(9-36)amide was found, the autoregulatory response in afferent arterioles was normal, and no GLP-1-induced reduction of autoregulation was found. We conclude that in prehypertensive kidneys, expression and function of GLP-1 receptors is lost. The renal vasodilatory effect of GLP-1 is mediated exclusively by the known GLP-1 receptor. GLP-1(9-36)amide has no renal vasodilatory effect. GLP-1 attenuates renal autoregulation by reducing the myogenic response.Funding Information
- Læge Sophus Carl Emi Friis og Hustru Olga Doris Friis
- Michaelsen Foundation
- Læge Sophus Carl Emil Friis og Hustru Olga Friis
This publication has 45 references indexed in Scilit:
- Sex Differences in the Pressor and Tubuloglomerular Feedback Response to Angiotensin IIHypertension, 2012
- Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal VasculatureHypertension, 2011
- Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1American Journal of Physiology-Renal Physiology, 2011
- Gender Differences in Pressure-Natriuresis and Renal AutoregulationHypertension, 2011
- Sex differences in acute ANG II-mediated hemodynamic responses in miceAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2010
- GLP-1 Inhibits and Adrenaline Stimulates Glucagon Release by Differential Modulation of N- and L-Type Ca2+ Channel-Dependent ExocytosisCell Metabolism, 2010
- Cardioprotective and Vasodilatory Actions of Glucagon-Like Peptide 1 Receptor Are Mediated Through Both Glucagon-Like Peptide 1 Receptor–Dependent and –Independent PathwaysCirculation, 2008
- The Physiology of Glucagon-like Peptide 1Physiological Reviews, 2007
- Autoregulation of Total and Zonal Glomerular Filtration Rate in Spontaneously Hypertensive Rats During Antihypertensive TherapyJournal of Cardiovascular Pharmacology, 1996
- Exaggerated natriuretic response to atrial natriuretic factor in rats developing spontaneous hypertension.Hypertension, 1990