Renal vasodilation induced by Glucagon‐like peptide‐1 is mediated only by the known receptor

Abstract

Glucagon‐like peptide‐1 (GLP‐1) stimulates insulin release after a meal. The GLP‐1 receptor is found in many tissues including the renal vasculature. GLP‐1 increases renal blood flow (RBF) and glomerular filtration rate by inducing a renal vasodilation. The GLP‐1 receptor knock‐out (KO) mouse has increased glomerular filtration rate (GFR) suggesting a dilation of the afferent arteriole. Moreover, GLP‐1 elicits a vasodilation in mesenteric arteries from the GLP‐1 receptor KO mouse suggesting that GLP‐1 can induce vasodilation through other mechanisms that by the known receptor. Also, the metabolite of GLP‐1 (GLP‐1(9–36)) has been suggested to have vasodilatory effects.Using wire‐myography and isolated segmental arteries from GLP‐1 receptor KO and wild‐type (WT) mice we show that GLP‐1 only elicits renal vasodilation via the known receptor and not by any indirect pathways. In preconstricted segmental arteries GLP‐1 induces a vasodilation that can be inhibited by exendin(9–39) (a GLP‐1 receptor antagonist). Also, GLP‐1(9–36) has no vasodilatory effect on isolated renal vessels from WT and KO showing that in the renal vasculature the metabolite has no effect either directly on the GLP‐1 receptor or through any other pathway.In the isolated juxtamedullary nephron preparation the autoregulatory response in afferent arterioles measured during acute pressure increases in isolated kidneys from WT and GLP‐1 receptor KO mice is normal. This indicates that the pre‐glomerular vasculature in the kidney is not affected functionally by the loss of the GLP‐1 receptor. GLP‐1 only attenuates the autoregulatory response in afferent arterioles from WT mice showing that also in afferent arterioles there is no alternative signaling pathway. GLP‐1 primarily attenuates the myogenic response and not the tubuloglomerular feedback (TGF).Using pressure myography we show that GLP‐1 reduces the myogenic response in WT segmental arteries but has no effect in the GLP‐1 receptor KO vessels. GLP‐1 increases the diameter of WT segmental arteries but a further diameter increase is still found during passive conditions (Ca2+ free media) suggesting that GLP‐1 dose not completely remove all vascular tension.ConclusionThe renal vascular effects of GLP‐1 are elicited only via the known GLP‐1 receptor. The metabolite GLP‐1(9–36) has no effect on the renal GLP‐1 receptor or through alternative pathways. Afferent arterioles and segmental arteries from GLP‐1 receptor KO mice respond normally to acute pressure increases.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.