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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.
Am J Physiol Renal Physiol. 2020 06 01; 318(6):F1409-F1417.AJ

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.

Authors+Show Affiliations

NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32390511

Citation

Jensen, Elisa P., et al. "GLP-1-induced Renal Vasodilation in Rodents Depends Exclusively On the Known GLP-1 Receptor and Is Lost in Prehypertensive Rats." American Journal of Physiology. Renal Physiology, vol. 318, no. 6, 2020, pp. F1409-F1417.
Jensen EP, Møller S, Hviid AV, et al. GLP-1-induced renal vasodilation in rodents depends exclusively on the known GLP-1 receptor and is lost in prehypertensive rats. Am J Physiol Renal Physiol. 2020;318(6):F1409-F1417.
Jensen, E. P., Møller, S., Hviid, A. V., Veedfald, S., Holst, J. J., Pedersen, J., Ørskov, C., & Sorensen, C. M. (2020). GLP-1-induced renal vasodilation in rodents depends exclusively on the known GLP-1 receptor and is lost in prehypertensive rats. American Journal of Physiology. Renal Physiology, 318(6), F1409-F1417. https://doi.org/10.1152/ajprenal.00579.2019
Jensen EP, et al. GLP-1-induced Renal Vasodilation in Rodents Depends Exclusively On the Known GLP-1 Receptor and Is Lost in Prehypertensive Rats. Am J Physiol Renal Physiol. 2020 06 1;318(6):F1409-F1417. PubMed PMID: 32390511.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GLP-1-induced renal vasodilation in rodents depends exclusively on the known GLP-1 receptor and is lost in prehypertensive rats. AU - Jensen,Elisa P, AU - Møller,Sophie, AU - Hviid,Aleksander Vauvert, AU - Veedfald,Simon, AU - Holst,Jens J, AU - Pedersen,Jens, AU - Ørskov,Cathrine, AU - Sorensen,Charlotte M, Y1 - 2020/05/11/ PY - 2020/5/12/pubmed PY - 2020/10/8/medline PY - 2020/5/12/entrez KW - afferent arterioles KW - glucagon-like peptide-1 KW - glucagon-like peptide-1 receptor KW - hypertension KW - interlobar arteries SP - F1409 EP - F1417 JF - American journal of physiology. Renal physiology JO - Am J Physiol Renal Physiol VL - 318 IS - 6 N2 - 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. SN - 1522-1466 UR - https://www.unboundmedicine.com/medline/citation/32390511/GLP_1_induced_renal_vasodilation_in_rodents_depends_exclusively_on_the_known_GLP_1_receptor_and_is_lost_in_prehypertensive_rats_ L2 - https://journals.physiology.org/doi/10.1152/ajprenal.00579.2019?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -