Ascorbic acid (vitamin C) and ␣-tocopherol (vitamin E) have antioxidant properties that could improve redox-sensitive vascular changes associated with hypertension. We determined whether vitamins C and E influence vascular function and structure in hypertension by modulating activity of NADPH oxidase and superoxide dismutase (SOD). Adult stroke-prone spontaneously hypertensive rats (SHRSP) were divided into 3 groups: control (C; nϭ6), vitamin C-treated (vit C, 1000 mg/day; nϭ7), and vitamin

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... eated (vit E, 1000 IU/day; nϭ8). All rats were fed 4% NaCl. Blood pressure was measured weekly. After 6 weeks of treatment, the rats were killed, and mesenteric arteries were mounted as pressurized preparations. Vascular O 2 Ϫ generation and NADPH oxidase activity were measured by chemiluminescence. Vascular SOD activity and plasma total antioxidant status (TAS) were determined spectrophotometrically. Blood pressure increased from 212Ϯ7 to 265Ϯ6 mm Hg in controls. Treatment prevented progression of hypertension (vit C, 222Ϯ6 to 234Ϯ14 mm Hg; vit E, 220Ϯ9 to 227Ϯ10 mm Hg). Acetylcholine-induced vasodilation was improved (PϽ0.05), and media-to-lumen ratio was reduced (PϽ0.05) in the treated rats. O 2 Ϫ was lower in vitamin-treated groups compared with controls (vit C, 10Ϯ4 nmol · min Ϫ1 · g Ϫ1 dry tissue weight; vit E, 9.6Ϯ3.5 nmol · min Ϫ1 · g Ϫ1 dry tissue weight; C, 21Ϯ9 nmol · min Ϫ1 · g Ϫ1 dry tissue weight; PϽ0.05). Both vitamin-treated groups showed significant improvement (PϽ0.01) in TAS. These effects were associated with decreased activation of vascular NADPH oxidase (vit C, 46Ϯ10; vit E, 50Ϯ9; C, 70Ϯ16 nmol · min Ϫ1 · g Ϫ1 dry tissue weight, PϽ0.05) and increased activation of SOD (vit C, 12Ϯ2; vit E, 8Ϯ1; C, 4.6Ϯ1 U/mg; PϽ0.05). Our results demonstrate that vitamins C and E reduce oxidative stress, improve vascular function and structure, and prevent progression of hypertension in SHRSP. These effects may be mediated via modulation of enzyme systems that generate free radicals. (Hypertension. 2001; 38[part 2]:606-611.)