Impact of obesity on hypertension-induced cardiac remodeling: role of oxidative stress and its modulation by gemfibrozil treatment in rats.
This study investigated the possible synergistic role of obesity in hypertension-induced cardiac remodeling and its modulation by gemfibrozil treatment in rats. Male Wistar rats were fed a high-fat diet (HFD) for 90 days. Normal rats were subjected to hypertension by partial abdominal aortic constriction (PAAC) for 28 days. In the HFD+PAAC control group, rats on HFD were subjected to PAAC on the 62nd day and were sacrificed on the 90th day. HFD and PAAC individually resulted in significant cardiac hypertrophy and fibrosis along with increased oxidative stress and mean arterial blood pressure (MABP) in rats as evidenced by various morphological, biochemical, and histological parameters. Moreover, the HFD + PAAC control group showed marked cardiac remodeling compared to rats subjected to HFD or PAAC alone. The HFD+gemfibrozil and HFD+PAAC+gemfibrozil groups showed significant reduction in cardiac remodeling along with reduction in oxidative stress and MABP. Hence, it may be concluded that oxidative stress plays a key role in obesity-mediated synergistic effects on induction and progression of PAAC-induced cardiac remodeling, and its deleterious effects could be reversed by gemfibrozil treatment in rats through its antioxidant activity.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
Randhir
R
Singh
Amrit Pal
AP
Singh
Manjeet
M
Singh
Pawan
P
Krishan
D000818:Animals; D001012:Aorta, Abdominal / Q000503:physiopathology*; D001794:Blood Pressure; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004041:Dietary Fats / Q000009:adverse effects*; D015248:Gemfibrozil / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D006973:Hypertension / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008297:Male; D009765:Obesity / Q000503:physiopathology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D004041:Dietary Fats; D000960:Hypolipidemic Agents; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D005978:Glutathione; D015248:Gemfibrozil