Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow

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Elisa Pouline Jensen, Steen Seier Poulsen, Hannelouise Kissow, Niels-Henrik Holstein-Rathlou, Carolyn F. Deacon, Boye L. Jensen, Jens J. Holst, Charlotte M. Sorensen

Glucagon-like peptide-1 (GLP-1) has a range of extra-pancreatic effects, including renal. 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 this 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 activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using 125I-GLP-1, 125I-exendin-4 (GLP-1 analog) and 125I-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 (BP), renal blood flow (RBF), heart rate (HR), 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 125I-GLP-1, 125I-exendin-4 and 125I-exendin 9-39 was observed in the renal vasculature including afferent arterioles. Infusion of GLP-1 increased BP, RBF and urinary flow rate significantly in rats. HR 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 the afferent arteriole 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 renal blood flow in normotensive rats.

OriginalsprogEngelsk
TidsskriftA J P: Renal Physiology (Online)
Vol/bind308
Udgave nummer8
Sider (fra-til)F867-F877
Antal sider11
ISSN1522-1466
DOI
StatusUdgivet - 15 apr. 2015

ID: 131197639