TY - JOUR

T1 - GLP-1-induced renal vasodilation in rodents depends exclusively on the known GLP-1 receptor and is lost in pre-hypertensive rats

AU - Jensen, Elisa P

AU - Møller, Sophie

AU - Hviid, Aleksander V R

AU - Veedfald, Simon

AU - Holst, Jens J

AU - Pedersen, Jens

AU - Ørskov, Cathrine

AU - Sorensen, Charlotte M

PY - 2020

Y1 - 2020

N2 - Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate postprandial insulin release. However, GLP-1 also exerts extra-pancreatic 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 expression and vascular function of GLP-1 receptors in kidneys from young pre-hypertensive rats. We also examined GLP-1-induced vasodilation in the renal vasculature in wild-type (WT) and GLP-1 receptor knock-out (KO) 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 pre-hypertensive 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 KO 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 pre-hypertensive 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.

AB - Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate postprandial insulin release. However, GLP-1 also exerts extra-pancreatic 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 expression and vascular function of GLP-1 receptors in kidneys from young pre-hypertensive rats. We also examined GLP-1-induced vasodilation in the renal vasculature in wild-type (WT) and GLP-1 receptor knock-out (KO) 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 pre-hypertensive 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 KO 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 pre-hypertensive 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.

U2 - 10.1152/ajprenal.00579.2019

DO - 10.1152/ajprenal.00579.2019

M3 - Journal article

C2 - 32390511

VL - 318

SP - F1409-F1417

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 6

ER -