Antioxidant Effects of Vitamins C and E Are Associated With Altered Activation of Vascular NADPH Oxidase and Superoxide Dismutase in Stroke-Prone SHR

Abstract

Abstract — — Ascorbic acid (vitamin C) and α-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; 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 vitamin-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.