Antioxidant effects of vitamins C and E are associated with altered activation of vascular NADPH oxidase and superoxide dismutase in stroke-prone SHR

Ascorbic acid (vitamin Q and alpha -tocopherot (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; n=6), vitamin C-treated (vit C, 1000 mg/day; n=7), and vitamin E-treated (vit E, 1000 IU/day, n=8). 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(-) 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 212 +/-7 to 265 +/-6 mm Hg in controls. Treatment prevented progression of hypertension (vit C, 222 +/-6 to 234 +/- 14 mm Hg; vit E, 220 +/-9 to 227 +/- 10 mm Hg). Acetylcholine-induced vasodilation was improved (P <0.05), and media-to-lumen ratio was reduced (P <0.05) in the treated rats. O-2(-) was lower in vitamin-treated groups compared with controls (vit C, 10 +/-4 nmol (.) min(-1) (.) g(-1) dry tissue weight, vit E, 9.6 +/-3.5 nmol (.) min(-1) (.) g(-1) dry tissue weight; C, 21 +/-9 nmol (.) min(-1) (.) g(-1) dry tissue weight; P <0.05). Both vitarnin-treated groups showed significant improvement (P <0.01) in TAS. These effects were associated with decreased activation of vascular NADPH oxidase (vit C, 46 +/- 10; vit E, 50 +/-9; C, 70 +/- 16 nmol (.) min(-1) (.) g(-1) dry tissue weight, P <0.05) and increased activation of SOD (vit C, 12 +/-2; vit E, 8 +/-1; C, 4.6 +/-1 U/mg; P <0.05). 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.