Protective role of the Angiotensin AT2 Receptor in obesity‐induced renal inflammation

Abstract

The Angiotensin AT2 receptor (AT2R) is up‐regulated in response to tissue injury and is implicated in tissue protection and repair. Recent studies have also suggested an anti‐inflammatory role for the AT2R. The present study was designed to investigate whether chronic activation of the AT2R offers renoprotection by attenuating early stage obesity‐induced inflammation in the kidney. For this purpose, 5 weeks old lean and pre‐hypertensive obese Zucker rats (OZR) were treated for 2 weeks with either vehicle, AT2R agonist C21 (1 μg/kg/day, i.p.), AT2R antagonist PD123319 (50 μg/kg/min, osmotic pump) or both PD and C21. OZR had higher plasma and renal cortical levels of cytokines (TNF‐α, IL‐6 and MCP‐1) which were lowered by C21 treatment. Interestingly, C21 treatment raised the levels of the anti‐inflammatory cytokine IL‐10 in the plasma and renal cortices of OZR, while there was a marked reduction in IL‐10 levels in the OZR PD group. Renal histology revealed mesangial matrix expansion and mild mesangial hypercellularity in the OZR vehicle and PD treated rats, while the glomeruli of the OZR C21 group were normal. Our results suggest an anti‐inflammatory role for the AT2R in obesity‐linked renal inflammation. Pharmacological activation of AT2R in the early stages of obesity‐induced renal injury may serve as a potential therapy to prevent progression of the disease. Supported by NIH R01 DK‐61578.