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 C) and alpha-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.
Chen
X
X
Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec, Canada.
Touyz
R M
RM
Park
J B
JB
Schiffrin
E L
EL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D019255:NADPH Oxidases / Q000187:drug effects* / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013482:Superoxide Dismutase / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D014665:Vasodilator Agents; D013481:Superoxides; D014810:Vitamin E; D009599:Nitroprusside; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D000109:Acetylcholine; D001205:Ascorbic Acid; D009638:Norepinephrine