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 &agr;-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 O2− 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. O2− 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.

[1]  E. Schiffrin,et al.  Increased generation of superoxide by angiotensin II in smooth muscle cells from resistance arteries of hypertensive patients: role of phospholipase D-dependent NAD(P)H oxidase-sensitive pathways , 2001, Journal of hypertension.

[2]  S. Salomone,et al.  Lacidipine Prevents Endothelial Dysfunction in Salt-Loaded Stroke-Prone Hypertensive Rats , 2001, Hypertension.

[3]  Robert Luben,et al.  Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study , 2001, The Lancet.

[4]  N. Vaziri,et al.  Effect of Antioxidant Therapy on Blood Pressure and NO Synthase Expression in Hypertensive Rats , 2000, Hypertension.

[5]  A. Carr,et al.  Potential Antiatherogenic Mechanisms of Ascorbate (Vitamin C) and α-Tocopherol (Vitamin E) , 2000 .

[6]  J. Keaney,et al.  Ascorbic acid and glutathione modulate the biological activity of S-nitrosoglutathione. , 2000, Hypertension.

[7]  GiuseppeLembo,et al.  Noradrenergic Vascular Hyper-Responsiveness in Human Hypertension Is Dependent on Oxygen Free Radical Impairment of Nitric Oxide Activity , 2000 .

[8]  L. Fratta,et al.  Noradrenergic vascular hyper-responsiveness in human hypertension is dependent on oxygen free radical impairment of nitric oxide activity. , 2000, Circulation.

[9]  N. Vaziri,et al.  Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. , 2000, Hypertension.

[10]  A. Carr,et al.  The role of natural antioxidants in preserving the biological activity of endothelium-derived nitric oxide. , 2000, Free radical biology & medicine.

[11]  N. Dhalla,et al.  Role of oxidative stress in cardiovascular diseases , 2000, Journal of hypertension.

[12]  M. Roncaglioni,et al.  Effects of low-dose aspirin on clinic and ambulatory blood pressure in treated hypertensive patients , 2000 .

[13]  D. Harrison,et al.  Vascular superoxide production and vasomotor function in hypertension induced by deoxycorticosterone acetate-salt. , 2000, Circulation.

[14]  B. Hoogwerf,et al.  The HOPE study. Ramipril lowered cardiovascular risk, but vitamin E did not. , 2000, Cleveland Clinic journal of medicine.

[15]  J. Keaney,et al.  Pharmacological concentrations of ascorbic acid are required for the beneficial effect on endothelial vasomotor function in hypertension. , 2000, Hypertension.

[16]  G. Ferns,et al.  Effect of vitamin C on ambulatory blood pressure and plasma lipids in older persons , 2000, Journal of hypertension.

[17]  D. Sorescu,et al.  NAD(P)H oxidase: role in cardiovascular biology and disease. , 2000, Circulation research.

[18]  A. Morris,et al.  Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension. , 2000, Hypertension.

[19]  J. Keaney,et al.  Treatment of hypertension with ascorbic acid , 1999, The Lancet.

[20]  M. Olschewski,et al.  Vitamin C improves endothelial function of epicardial coronary arteries in patients with hypercholesterolaemia or essential hypertension--assessed by cold pressor testing. , 1999, European heart journal.

[21]  J. Chaudière,et al.  Intracellular antioxidants: from chemical to biochemical mechanisms. , 1999, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[22]  A. Dominiczak,et al.  Superoxide anion production is increased in a model of genetic hypertension: role of the endothelium. , 1999, Hypertension.

[23]  R. Kvetňanský,et al.  Malondialdehyde, lipofuscin and activity of antioxidant enzymes during physical exercise in patients with essential hypertension. , 1999, Journal of hypertension.

[24]  M. Niaz,et al.  Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease , 1999, Journal of Human Hypertension.

[25]  M. Newaz,et al.  Effect of α-tocopherol on lipid peroxidation and total antioxidant status in spontaneously hypertensive rats , 1998 .

[26]  A. Malik,et al.  E-selectin expression in human endothelial cells by TNF-α-induced oxidant generation and NF-κB activation. , 1998, American journal of physiology. Lung cellular and molecular physiology.

[27]  L. Ghiadoni,et al.  Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. , 1998, Circulation.

[28]  J. Abe,et al.  Reactive oxygen species as mediators of signal transduction in cardiovascular disease. , 1998, Trends in cardiovascular medicine.

[29]  J. Zweier,et al.  Hydrogen peroxide induces intracellular calcium oscillations in human aortic endothelial cells. , 1998, Circulation.

[30]  M. Omata,et al.  Vitamin E ameliorates the renal injury of Dahl salt-sensitive rats. , 1997, American journal of hypertension.

[31]  A. Gapor,et al.  α-tocopherol increased nitric oxide synthase activity in blood vessels of spontaneously hypertensive rats , 1997 .

[32]  S. Rajagopalan,et al.  Role of superoxide in angiotensin II-induced but not catecholamine-induced hypertension. , 1997, Circulation.

[33]  E. Schiffrin,et al.  Structure and function of resistance arteries of hypertensive patients treated with a p-blocker or a calcium channel antagonist , 1996, Journal of hypertension.

[34]  D. Harrison,et al.  Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. , 1996, The Journal of clinical investigation.

[35]  M. Tarpey,et al.  Nitric oxide and reactive oxygen species in vascular injury. , 1995, Biochemical Society symposium.

[36]  B. Berk,et al.  Differential activation of mitogen-activated protein kinases by H2O2 and O2- in vascular smooth muscle cells. , 1995, Circulation research.

[37]  R W Alexander,et al.  Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. , 1994, Circulation research.

[38]  G. Rao,et al.  Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression. , 1992, Circulation research.

[39]  M. Roncaglioni,et al.  Effects of vitamin E on clinic and ambulatory blood pressure in treated hypertensive patients. Collaborative Group of the Primary Prevention Project (PPP)--Hypertension study. , 2000, American journal of hypertension.

[40]  A. Carr,et al.  Potential antiatherogenic mechanisms of ascorbate (vitamin C) and alpha-tocopherol (vitamin E). , 2000, Circulation research.