Rosiglitazone Protects Against Renal Damage in Ovariectomized Female Dahl Rats

Abstract

Estradiol (E) has been shown to be protective against renal injury in aging female Dahl Salt‐sensitive rats (DS). New evidence suggests that the peroxisome proliferator activator receptor gamma agonist, rosiglitazone (RO), confers renal protection in humans and animal models of various diseases. We tested the hypothesis that RO protects against renal damage in female DS during salt‐induced rise in blood pressure (BP). Methods: Intact (Int) and ovariectomized (Ovx) female DS (10 weeks; n=15/group) received low salt diet (LS: 0.3% NaCl) or LS+RO (100mg/kg diet) for 1 week and then challenged for 1 week to high salt (HS: 8% NaCl) or HS+RO. BP was recorded by telemetry. Plasma estradiol, urinary protein and renal mass were assessed on HS. Results: On HS diet BP increased in Int and Ovx rats and RO blunted the rise in BP only in Ovx. RO also decreased proteinuria and prevented kidney enlargement only in Ovx. These data show for the first time that RO prevents renal damage in ovx DS on HS diet and provides support for its use as a therapeutic tool for treatment of renal injury associated with salt‐sensitive hypertension in postmenopausal women (supported by NIH HL 66072, AHA 0725561B)