Dietary antioxidant supplementation reduces lipid peroxidation but impairs vascular function in small mesenteric arteries of the streptozotocin-diabetic rat.

Impaired endothelium-dependent relaxation could underlie many of the vascular complications associated with insulin-dependent diabetes mellitus, and may be mediated by increased oxidative stress. The effect of antioxidants on vascular endothelial function and oxidative stress of streptozotocin-diabetic rats was assessed by dietary supplementation with vitamins E and C. Diabetic (i. v. streptozotocin, 45 mg/kg) male Sprague-Dawley rats were fed one of six supplemented diets containing 75.9, 250, or 500 mg vitamin E/kg chow, 250 mg vitamin C/kg H₂0, 250 mg vitamin E/kg chow plus 250 mg vitamin C/kg H₂O, or chow deficient in vitamin E, and then compared to standard-fed control rats. After 4 weeks, small mesenteric arteries were dissected and mounted on a small vessel myograph, concentration response curves were then constructed to noradrenaline, acetylcholine and sodium nitroprusside. Acetylcholine-mediated relaxation was impaired in arteries from diabetic rats (pEC₅₀ 6.701 ± SEM 0.120, n = 8) compared to controls (7.386 ± 0.078, n = 6; p < 0.05). The 500 mg/kg vitamin E diet further impaired maximum relaxation to acetylcholine (58.2 ± 10.5 vitamin E, n = 7 vs 84.4 ± 5.3 % standard, p < 0.05), and the combined vitamin E plus C diet impaired maximum relaxation to sodium nitroprusside (48.5 ± 4.1 in vitamin E + C, n = 8 vs 75.6 ± 3.9 % standard; p < 0.01). However, plasma 8-epi-prostaglandin (PG)F₂α (measured as an estimate of oxidative stress) was dose-dependently decreased in rats on vitamin E supplemented diets. Dietary antioxidant supplementation did not reverse impaired endothelial function in this model of uncontrolled diabetes despite a concomitant decrease in oxidative stress. [Diabetologia (1998) 41: 148–156] [ABSTRACT FROM AUTHOR]