Objective: A high fat diet contributes to obesity and acutely impairs endothelium dependent vasorelaxation. While a high cholesterol diet chronically impairs endothelium dependent vasorelaxation in rabbits, this model is associated with severe hypercholesterolemia. The effect of chronic high fat feeding on endothelial function in the setting of more normal lipid levels has not been studied. Our aim was to study vascular function in rats overfed for 6 months and to determine the role of oxidative stress in the alteration of vascular function associated with this diet. Methods: Forty-five male Sprague-Dawley rats were placed on the following diets for 6 months, control diet, high fat diet or high fat diet supplemented with vitamins A, E and selenium. Six months later blood samples were collected and vascular function was assessed in the aorta. Results: The rats fed a high fat diet were heavier than controls (608.4 +/- 41.8 vs. 700.3 +/- 50.1 vs. 699.5 +/- 52.6 g, P < 0.05 for control vs. high fat and high fat plus antioxidant groups) but lipid levels were similar in each group (cholesterol, 145.9 +/- 53.4 vs. 140.5 +/- 44.0 vs. 152.7 +/- 36.1 mg/dl and triglycerides, 173.2 +/- 106.7 vs. 197.4 +/- 131.3 vs. 166.1 +/- 65.3 mg/dl, P, NS). Relaxations to acetylcholine and calcium were significantly impaired in the high fat diet group compared with controls (EC50, 6.90 +/- 0.22, 7.12 +/- 0.32; AUC, 96.9 +/- 51.6, 155.5 +/- 73.7) but were not different between the antioxidant supplemented group and controls (EC50, 7.06 +/- 0.37; AUC, 151.9 +/- 67.4). Relaxations to DEA NONOate were similar in each group. Conclusions: Dietary antioxidants preserved endothelium dependent vasorelaxation in rats fed a high fat diet for 6 months. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.