Abstract

Dietary overweight is a major risk factor for the development of cardiovascular diseases. However the effects of high-fat diet (HFD) on vascular oxidative status and endothelial function remain unknown. In this study, we used a mouse model of HFD-induced obesity in C57BL/6 J mice and investigated the relationship between HFD, metabolic disorders and vascular dysfunction. Mice (7 m, n=10/group) were fed with a HFD (45% kcal fat) for 16 weeks. The control mice were fed with a normal chow diet (NCD, 12% kcal fat). Body weight, blood pressure and fasting blood glucose were taken before and after diet intervention. Compared to age-matched control mice, HFD increased significantly the body weight (NCD 42±2.3 vs HFD 56±3.2 g), the fasting blood glucose (NCD 7.4±3.3 vs HFD 8.8±2.2 mM) and the blood pressure (NCD 127±8 vs HFD 142±12 mm Hg). Vascular function was examined using aorta rings by an organ bath. Compared with control mice, HFD increased significantly the levels of vasoconstriction to phenylephrine (Emax NCD 0.15±0.03 vs HFD 0.32±0.07 g), and decreased endothelium-dependent vessel relaxation to acetylcholine (Emax NCD 80.45±7.39% vs HFD 74.41±1.74%), and these were corrected to the control levels by adding a superoxide scavenger, tiron. Accompanied with the vascular dysfunction, there were significant increases (42±5%) in the levels of ROS production in the aortas of HFD-fed mice as compared to the control aortas. In conclusion, HFD and obesity-related metabolic disorders induce vasculature oxidative stress, which contributes to endothelial dysfunction and high blood pressure.