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 Pouline
AU - Poulsen, Steen Seier
AU - Kissow, Hannelouise
AU - Holstein-Rathlou, Niels-Henrik
AU - Deacon, Carolyn F.
AU - Jensen, Boye L.
AU - Holst, Jens J.
AU - Sorensen, Charlotte M.
N1 - Copyright © 2014, American Journal of Physiology - Renal Physiology.
PY - 2015/4/15
Y1 - 2015/4/15
N2 - 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.
AB - 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.
U2 - 10.1152/ajprenal.00527.2014
DO - 10.1152/ajprenal.00527.2014
M3 - Journal article
C2 - 25656368
VL - 308
SP - F867-F877
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
SN - 0363-6127
IS - 8
ER -