Protective effect of ghrelin on left ventricular remodeling in spontaneously hypertensive rats is associated with the peroxisome proliferator-activated receptor gamma-dependent pathway

Abstract

Studies suggested that exogenous ghrelin administration could prevent early left ventricular remodeling in rats with myocardial infarction. We investigated herein whether ghrelin attenuated left ventricular remodeling induced by hypertension and whether ghrelin's effect was mediated through the peroxisome proliferator-activated receptor gamma (PPAR-gamma)-dependent pathway. Spontaneously hypertensive rats (8-week-old males) were randomly divided into three groups with 12 rats in each: ghrelin group (received ghrelin 100 microg/kg subcutaneously (s.c.) twice daily); ghrelin + GW9662 group (received the PPAR-gamma antagonist GW9662 at 2 mg/kg s.c., and then ghrelin as above); saline controls. Normal male Wistar Kyoto rats (n = 12) served as normal controls. Four weeks later, the effects of ghrelin on cardiac remodeling were evaluated by echocardiographic, hemodynamic, and histopathological examination, and gene expression analysis (PPAR-gamma protein and mRNA expression). The serum levels of C-reactive protein (CRP) and tumor necrosis factor (TNF)-alpha were detected by enzyme linked immunosorbent assay. Ghrelin prevented ventricular remodeling, increased PPAR-gamma expression in the myocardium, suppressed collagen I and collagen III mRNA expression, and also decreased the serum levels of TNF-alpha, but not CRP. All abovementioned effects of ghrelin were inhibited by GW9662. Ghrelin inhibited ventricular remodeling induced by hypertension, and the preventive effects of ghrelin may be mediated by the anti-inflammatory actions of the PPAR-gamma-dependent pathway.