Direct effect of glucagon‐like peptide‐1 on the autoregulatory response of the afferent arteriole (692.2)

Abstract

It has become clear that glucagon‐like peptide‐1 (GLP‐1) has many effects and the GLP‐1 receptor is expressed in many tissues outside the pancreas. GLP‐1 increases renal blood flow (RBF), glomerular filtration rate and sodium and water excretion. The aim of this study was to examine expression of the GLP‐1 receptor in the renal vasculature and assess the effects of GLP‐1 in the afferent arteriole.The GLP‐1 receptor was localized using 125I‐GLP‐1 in kidney slices. In the isolated juxtamedullary nephron preparation, renal perfusion pressure was increased in steps and changes in afferent arteriolar diameter were measured before and after perfusion with GLP‐1. In vivo experiments were performed on rats monitoring blood pressure (BP), RBF and urine flow. GLP‐1 was infused directly into the kidney before and after infusion of the GLP‐1 receptor blocker Exendin9‐39 and indomethacin and L‐NAME.Strong binding of 125I‐GLP‐1 was found in the vascular smooth muscle cells in afferent arterioles. Perfusion with GLP‐1 in isolated kidneys completely abolished the autoregulatory response of the afferent arteriole. Intrarenal infusion of GLP‐1 increased BP, RBF and urine flow significantly in rats. Heart rate and plasma renin were unchanged. The effect on RBF was inhibited by Exendin9‐39 whereas the increase in BP and urine flow was still present. Infusion of indomethacin and L‐NAME did not change the GLP‐1 effect on BP, RBF or urine flow.