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

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

doi:10.1152/ajprenal.00527.2014

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

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

63 Citations (Scopus)

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 ¹²⁵I-labeled GLP-1, ¹²⁵I-labeled exendin-4 (GLP-1 analog), and¹²⁵I-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 of¹²⁵I-labeled GLP-1, ¹²⁵I-labeled exendin-4, and¹²⁵I-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.

Original language	English
Journal	A J P: Renal Physiology (Online)
Volume	308
Issue number	8
Pages (from-to)	F867-F877
Number of pages	11
ISSN	1522-1466
DOIs	https://doi.org/10.1152/ajprenal.00527.2014
Publication status	Published - 15 Apr 2015

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10.1152/ajprenal.00527.2014

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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. A J P: Renal Physiology (Online), 308(8), F867-F877. https://doi.org/10.1152/ajprenal.00527.2014

Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow. / Jensen, Elisa Pouline; Poulsen, Steen Seier ; Kissow, Hannelouise et al.
In: A J P: Renal Physiology (Online), Vol. 308, No. 8, 15.04.2015, p. F867-F877.

Research output: Contribution to journal › Journal article › Research › peer-review

Jensen, EP, Poulsen, SS , Kissow, H , Holstein-Rathlou, N-H , Deacon, CF, Jensen, BL, Holst, JJ & Sorensen, CM 2015, 'Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow', A J P: Renal Physiology (Online), vol. 308, no. 8, pp. F867-F877. https://doi.org/10.1152/ajprenal.00527.2014

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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 125I-labeled GLP-1, 125I-labeled exendin-4 (GLP-1 analog), and125I-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 of125I-labeled GLP-1, 125I-labeled exendin-4, and125I-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.",

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

note = "Copyright {\textcopyright} 2014, American Journal of Physiology - Renal Physiology.",

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doi = "10.1152/ajprenal.00527.2014",

language = "English",

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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.

PY - 2015/4/15

Y1 - 2015/4/15

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 125I-labeled GLP-1, 125I-labeled exendin-4 (GLP-1 analog), and125I-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 of125I-labeled GLP-1, 125I-labeled exendin-4, and125I-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.

AB - 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 125I-labeled GLP-1, 125I-labeled exendin-4 (GLP-1 analog), and125I-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 of125I-labeled GLP-1, 125I-labeled exendin-4, and125I-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.

U2 - 10.1152/ajprenal.00527.2014

DO - 10.1152/ajprenal.00527.2014

M3 - Journal article

C2 - 25656368

SN - 1522-1466

VL - 308

SP - F867-F877

JO - A J P: Renal Physiology (Online)

JF - A J P: Renal Physiology (Online)

IS - 8

ER -

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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