Glucagon‐like peptide‐1 mediated renal sympathetic activation in obese rats: role of intrarenal mechanisms

Abstract

Accumulated evidence indicates that obesity is associated with enhanced sympathetic activation. Chronic sympathetic activation increases the risk of cardiovascular complications and subsequent mortality. The mechanisms linking obesity with sympathetic activation are complex and not completely understood. Gut produced hormone glucagon‐like peptide‐1 (GLP‐1) affects cardiovascular function via regulating blood pressure and sympathetic nerve activity. The aim of the study was to determine the role of intrarenal GLP‐1 mediated renal sympathetic activation in obese rats. In anesthetic Sprague Dawley rats, renal intra‐pelvic infusion of GLP‐1 receptor agonist exendin‐4 increased afferent renal sympathetic nerve activity (A‐RSNA), efferent renal sympathetic nerve activity (T‐RSNA), arterial pressure and heart rate. All the sympathetic and hemodynamic responses to the exendin‐4 infusion were significantly enhanced in high fat diet (HFD, 42% of calories from fat for 12 weeks) induced obese rats. The natriuretic and diuretic effects mediated by intrarenal exendin‐4 infusion was significantly blunted in the obese rats. Furthermore, ablation of renal sympathetic nerves significantly improved the diuretic and natriuretic responses to exendin‐4 infusion in obese rats. We also found significant altered GLP‐1 level and GLP‐1 receptor expression in the kidney of obese rats. The results suggest that altered intrarenal GLP‐1 mediated mechanisms may contribute to the development of obesity‐related high sympathetic activation and obesity hypertension.Support or Funding InformationThe study was supported by the author’s faculty start‐up fund from Sanford School of Medicine of the University of South Dakota Department of Basic Biomedical Sciences.