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GLP-1-induced renal vasodilation in rodents depends exclusively on the known GLP-1 receptor and is lost in prehypertensive rats

GLP-1-induced renal vasodilation in rodents depends exclusively on the known GLP-1 receptor and... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Physiology-Renal Physiology The American Physiological Society

GLP-1-induced renal vasodilation in rodents depends exclusively on the known GLP-1 receptor and is lost in prehypertensive rats

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ISSN
1931-857x
eISSN
1522-1466
DOI
10.1152/ajprenal.00579.2019
Publisher site
See Article on Publisher Site

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.

Journal

American Journal of Physiology-Renal Physiology – The American Physiological Society

Published: Jun 1, 2020

References

  • Renoprotective effect of sitagliptin against hypertensive nephropathy induced by chronic administration of l-NAME in rats: role of GLP-1 and GLP-1 receptor
    Abd El Motteleb, DM; Elshazly, SM
  • Renal extraction and acute effects of glucagon-like peptide-1 on central and renal hemodynamics in healthy men
    Asmar, A; Simonsen, L; Asmar, M; Madsbad, S; Holst, JJ; Frandsen, E; Moro, C; Jonassen, T; Bülow, J
  • Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways
    Ban, K; Noyan-Ashraf, MH; Hoefer, J; Bolz, SS; Drucker, DJ; Husain, M
  • Neural contribution to the effect of glucagon-like peptide-1-(7−36) amide on arterial blood pressure in rats
    Barragán, JM; Eng, J; Rodríguez, R; Blázquez, E
  • On the local reactions of the arterial wall to changes of internal pressure
    Bayliss, WM
  • Contribution of endothelin to renal vascular tone and autoregulation in the conscious dog
    Berthold, H; Münter, K; Just, A; Kirchheim, HR; Ehmke, H
  • Use of ultrasound to assess renal reperfusion and P-selectin expression following unilateral renal ischemia
    Boesen, EI; Crislip, GR; Sullivan, JC
  • Myoendothelial coupling through Cx40 contributes to EDH-induced vasodilation in murine renal arteries: evidence from experiments and modelling
    Brasen, JC; de Wit, C; Sorensen, CM
  • Sex differences in the pressor and tubuloglomerular feedback response to angiotensin II
    Brown, RD; Hilliard, LM; Head, GA; Jones, ES; Widdop, RE; Denton, KM
  • In vitro perfusion of juxtamedullary nephrons in rats
    Casellas, D; Navar, LG
  • Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1
    Crajoinas, RO; Oricchio, FT; Pessoa, TD; Pacheco, BP; Lessa, LM; Malnic, G; Girardi, AC
  • GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis
    De Marinis, YZ; Salehi, A; Ward, CE; Zhang, Q; Abdulkader, F; Bengtsson, M; Braha, O; Braun, M; Ramracheya, R; Amisten, S; Habib, AM; Moritoh, Y; Zhang, E; Reimann, F; Rosengren, A; Shibasaki, T; Gribble, F; Renström, E; Seino, S; Eliasson, L; Rorsman, P
  • Abnormalities in glomerular function in rats developing spontaneous hypertension
    Dilley, JR; Stier, CT; Arendshorst, WJ
  • GLP-1 inhibits VEGFA-mediated signaling in isolated human endothelial cells and VEGFA-induced dilation of rat mesenteric arteries
    Egholm, C; Khammy, MM; Dalsgaard, T; Mazur, A; Tritsaris, K; Hansen, AJ; Aalkjaer, C; Dissing, S
  • Afferent arteriole responsiveness to endothelin receptor activation: does sex matter
    Gohar, EY; Cook, AK; Pollock, DM; Inscho, EW
  • Functional importance of L- and P/Q-type voltage-gated calcium channels in human renal vasculature
    Hansen, PB; Poulsen, CB; Walter, S; Marcussen, N; Cribbs, LL; Skøtt, O; Jensen, BL
  • Renal segmental microvascular responses to ANG II in AT1A receptor null mice
    Harrison-Bernard, LM; Cook, AK; Oliverio, MI; Coffman, TM
  • Gender differences in pressure-natriuresis and renal autoregulation: role of the Angiotensin type 2 receptor
    Hilliard, LM; Nematbakhsh, M; Kett, MM; Teichman, E; Sampson, AK; Widdop, RE; Evans, RG; Denton, KM
  • The physiology of glucagon-like peptide 1
    Holst, JJ
  • Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow
    Jensen, EP; Poulsen, SS; Kissow, H; Holstein-Rathlou, NH; Deacon, CF; Jensen, BL; Holst, JJ; Sorensen, CM
  • GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure
    Kim, M; Platt, MJ; Shibasaki, T; Quaggin, SE; Backx, PH; Seino, S; Simpson, JA; Drucker, DJ
  • Protein kinase Cβ mediates downregulated expression of glucagon-like peptide-1 receptor in hypertensive rat renal arteries
    Liu, L; Liu, J; Gao, Y; Ng, CF; Yu, X; Dou, D; Huang, Y
  • Dipeptidyl peptidase 4 inhibitor sitagliptin protects endothelial function in hypertension through a glucagon-like peptide 1-dependent mechanism
    Liu, L; Liu, J; Wong, WT; Tian, XY; Lau, CW; Wang, YX; Xu, G; Pu, Y; Zhu, Z; Xu, A; Lam, KS; Chen, ZY; Ng, CF; Yao, X; Huang, Y
  • Influence of connexin45 on renal autoregulation
    Møller, S; Jacobsen, JCB; Braunstein, TH; Holstein-Rathlou, NH; Sorensen, CM
  • Renal effects of glucagon-like peptide in rats
    Moreno, C; Mistry, M; Roman, RJ
  • Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats
    Mulvany, MJ; Halpern, W
  • Acute renal haemodynamic effects of glucagon-like peptide-1 receptor agonist exenatide in healthy overweight men
    Muskiet, MH; Tonneijck, L; Smits, MM; Kramer, MH; Diamant, M; Joles, JA; van Raalte, DH
  • Endothelial dysfunction induced by triglycerides is not restored by exenatide in rat conduit arteries ex vivo
    Nathanson, D; Erdogdu, O; Pernow, J; Zhang, Q; Nyström, T
  • Renal autoregulation: perspectives from whole kidney and single nephron studies
    Navar, LG
  • Insulin sensitivity and hemodynamic responses to insulin in Wistar-Kyoto and spontaneously hypertensive rats
    Pître, M; Nadeau, A; Bachelard, H
  • Exaggerated natriuretic response to atrial natriuretic factor in rats developing spontaneous hypertension
    Pollock, DM; Arendshorst, WJ
  • GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody
    Pyke, C; Heller, RS; Kirk, RK; Ørskov, C; Reedtz-Runge, S; Kaastrup, P; Hvelplund, A; Bardram, L; Calatayud, D; Knudsen, LB
  • Natriuretic effect by exendin-4, but not the DPP-4 inhibitor alogliptin, is mediated via the GLP-1 receptor and preserved in obese type 2 diabetic mice
    Rieg, T; Gerasimova, M; Murray, F; Masuda, T; Tang, T; Rose, M; Drucker, DJ; Vallon, V
  • Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors
    Ronn, J; Jensen, EP; Wewer Albrechtsen, NJ; Holst, JJ; Sorensen, CM
  • Pressure-dependent contraction of rat juxtamedullary afferent arterioles
    Sanchez-Ferrer, CF; Roman, RJ; Harder, DR
  • Attenuated diuresis and natriuresis in response to glucagon-like peptide-1 in hypertensive rats are associated with lower expression of the glucagon-like peptide-1 receptor in the renal vasculature
    Savignano, FA; Crajoinas, RO; Pacheco, BPM; Campos, LCG; Shimizu, MHM; Seguro, AC; Girardi, ACC
  • Sex differences in acute ANG II-mediated hemodynamic responses in mice
    Schneider, MP; Wach, PF; Durley, MK; Pollock, JS; Pollock, DM
  • Changes in renal blood flow, extraction of inulin, glomerular filtration rate, tissue pressure and urine flow with acute alterations of renal artery blood pressure
    Shipley, RE; Study, RS
  • Short-term effects of liraglutide on kidney function and vasoactive hormones in type 2 diabetes: a randomized clinical trial
    Skov, J; Pedersen, M; Holst, JJ; Madsen, B; Goetze, JP; Rittig, S; Jonassen, T; Frøkiaer, J; Dejgaard, A; Christiansen, JS
  • Glucagon-like peptide-1 receptor stimulation increases GFR and suppresses proximal reabsorption in the rat
    Thomson, SC; Kashkouli, A; Singh, P
  • Autoregulation of total and zonal glomerular filtration rate in spontaneously hypertensive rats during antihypertensive therapy
    Wang, X; Aukland, K; Iversen, BM
  • Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons
    Yamamoto, H; Lee, CE; Marcus, JN; Williams, TD; Overton, JM; Lopez, ME; Hollenberg, AN; Baggio, L; Saper, CB; Drucker, DJ; Elmquist, JK