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 ␣-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 E-treated (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.

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

“…In order to further support a role for oxidative stress in experimental hypertension, treatment of hypertensive rats or mice with antioxidant vitamins, SOD mimetics (tempol [4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl]), free radical scavengers, or tetrahydrobiopterin (BH4) attenuate or prevent development of hypertension and its associated target organ damage (37,72).…”

Carotid atherosclerosis in elderly hypertensive patients: potential role of endothelin and plasma antioxidant capacity

“…12,16 It was also shown that vitamin C inhibited activation of mitogen-activated protein kinase and VSMC proliferation in cultured rat aortic smooth muscle cells, 26 and in an in vivo experiment it was demonstrated that vitamin C supplementation decreased activation of NADPH oxidase and superoxide anion generation, prevented vascular hypertrophy and increased plasma total antioxidant status and superoxide dismutase in arterial wall in stroke-prone spontaneously hypertensive rats. 30 Vitamin C also abolished ET-1-induced increased interleukin-6 release in humans. 28 Taken together, these data and our findings suggest that arterial wall hypertrophy is a redoxsensitive process and that plasma antioxidants may prevent the deleterious effect of the ET-1-induced pathway leading to IMT and progression of atherosclerosis.…”

Effects of adding tocotrienol-tocopherol mixed fraction and vitamin C supplementation on coronary risk biomarkers in patients with hypercholesterolaemia with moderate coronary risk

“…The vascular effect of antioxidants has been observed in vitro and in animal models of atherosclerosis (Chen et al, 2001;Wu et al, 2006). However, data on long-term vascular impact of antioxidant supplementation in humans are limited and controversial.…”