Hypertension. 2001;38:606-611
doi: 10.1161/hy09t1.094005
doi: 10.1161/hy09t1.094005
(Hypertension. 2001;38:606.)
© 2001 American Heart Association, Inc.
Cardiovascular Biology |
Antioxidant Effects of Vitamins C and E Are Associated With Altered Activation of Vascular NADPH Oxidase and Superoxide Dismutase in Stroke-Prone SHR
From the Clinical Research Institute of Montreal, University of Montreal (X.C., R.M.T., J.B.P., E.L.S.), Montreal, Quebec, Canada; and Samsung Cheil Hospital, Sungkyunkwan University School of Medicine (J.B.P.), Seoul, Korea.
Correspondence to Rhian M Touyz, MD, PhD, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal, Quebec, Canada H2W 1R7. E-mail touyzr{at}ircm.qc.ca
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; 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.
Key Words: antioxidants • resistance • remodeling • hypertension, malignant
This article has been cited by other articles:
 |
|
 |
|
  N. P. Visavadiya and A. V. R. L. Narasimhacharya Asparagus Root Regulates Cholesterol Metabolism and Improves Antioxidant Status in Hypercholesteremic Rats Evid. Based Complement. Altern. Med., June 1, 2009; 6(2): 219 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nambiar, S. Viswanathan, B. Zachariah, N. Hanumanthappa, and Sridhar Gopalakrishna Magadi Oxidative Stress in Prehypertension: Rationale for Antioxidant Clinical Trials Angiology, April 1, 2009; 60(2): 221 - 234. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Tian, R. S. Moore, W. E. Phillips, L. Lin, S. Braddy, J. S. Pryor, R. L. Stockstill, M. D. Hughson, and R. D. Manning Jr. NADPH oxidase contributes to renal damage and dysfunction in Dahl salt-sensitive hypertension Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1858 - R1865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Matsui, K. Ando, H. Kawarazaki, A. Nagae, M. Fujita, T. Shimosawa, M. Nagase, and T. Fujita Salt Excess Causes Left Ventricular Diastolic Dysfunction in Rats With Metabolic Disorder Hypertension, August 1, 2008; 52(2): 287 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yogi, C. Mercure, J. Touyz, G. E. Callera, A. C.I. Montezano, A. B. Aranha, R. C. Tostes, T. Reudelhuber, and R. M. Touyz Renal Redox-Sensitive Signaling, but Not Blood Pressure, Is Attenuated by Nox1 Knockout in Angiotensin II-Dependent Chronic Hypertension Hypertension, February 1, 2008; 51(2): 500 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Paravicini and R. M. Touyz NADPH Oxidases, Reactive Oxygen Species, and Hypertension: Clinical implications and therapeutic possibilities Diabetes Care, February 1, 2008; 31(Supplement_2): S170 - S180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Grossman Does Increased Oxidative Stress Cause Hypertension? Diabetes Care, February 1, 2008; 31(Supplement_2): S185 - S189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Macarthur, T. C. Westfall, and G. H. Wilken Oxidative stress attenuates NO-induced modulation of sympathetic neurotransmission in the mesenteric arterial bed of spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H183 - H189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Tian, R. S. Moore, S. Braddy, R. A. Rose, J.-W. Gu, M. D. Hughson, and R. D. Manning Jr. Interactions between oxidative stress and inflammation in salt-sensitive hypertension Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3388 - H3395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li and H. E. Schellhorn New Developments and Novel Therapeutic Perspectives for Vitamin C J. Nutr., October 1, 2007; 137(10): 2171 - 2184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L Rainwater, M. C Mahaney, J. L VandeBerg, and X. L. Wang Vitamin E dietary supplementation significantly affects multiple risk factors for cardiovascular disease in baboons Am. J. Clinical Nutrition, September 1, 2007; 86(3): 597 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M Hartge, T. Unger, and U. Kintscher The endothelium and vascular inflammation in diabetes Diabetes and Vascular Disease Research, June 1, 2007; 4(2): 84 - 88. [Abstract] [PDF]
|
|
|
|
|
|
E. A. Ko, F. Amiri, N. R. Pandey, D. Javeshghani, E. Leibovitz, R. M. Touyz, and E. L. Schiffrin Resistance artery remodeling in deoxycorticosterone acetate-salt hypertension is dependent on vascular inflammation: evidence from m-CSF-deficient mice Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1789 - H1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Umeji, S. Umemoto, S. Itoh, M. Tanaka, S. Kawahara, T. Fukai, and M. Matsuzaki Comparative effects of pitavastatin and probucol on oxidative stress, Cu/Zn superoxide dismutase, PPAR-{gamma}, and aortic stiffness in hypercholesterolemia Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2522 - H2532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sarr, M. Chataigneau, S. Martins, C. Schott, J. El Bedoui, M.-H. Oak, B. Muller, T. Chataigneau, and V. B. Schini-Kerth Red wine polyphenols prevent angiotensin II-induced hypertension and endothelial dysfunction in rats: Role of NADPH oxidase Cardiovasc Res, September 1, 2006; 71(4): 794 - 802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Miriyala, M. C. Gongora Nieto, C. Mingone, D. Smith, S. Dikalov, D. G. Harrison, and H. Jo Bone Morphogenic Protein-4 Induces Hypertension in Mice: Role of Noggin, Vascular NADPH Oxidases, and Impaired Vasorelaxation Circulation, June 20, 2006; 113(24): 2818 - 2825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. E. Lau, J. J. Galligan, D. L. Kreulen, and G. D. Fink Activation of ETB receptors increases superoxide levels in sympathetic ganglia in vivo Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R90 - R95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Wilcox Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension? Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R913 - R935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Tian, K. D. Thrasher, P. D. Gundy, M. D. Hughson, and R. D. Manning Jr Antioxidant Treatment Prevents Renal Damage and Dysfunction and Reduces Arterial Pressure in Salt-Sensitive Hypertension Hypertension, May 1, 2005; 45(5): 934 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Welch, J. Blau, H. Xie, T. Chabrashvili, and C. S. Wilcox Angiotensin-induced defects in renal oxygenation: role of oxidative stress Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H22 - H28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Li and A. M Shah Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1014 - R1030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-Y. Zhu, A. R. Chade, M. Rodriguez-Porcel, M. D. Bentley, E. L. Ritman, A. Lerman, and L. O. Lerman Cortical Microvascular Remodeling in the Stenotic Kidney: Role of Increased Oxidative Stress Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1854 - 1859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Endemann and E. L. Schiffrin Endothelial Dysfunction J. Am. Soc. Nephrol., August 1, 2004; 15(8): 1983 - 1992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Endemann, R. M. Touyz, M. Iglarz, C. Savoia, and E. L. Schiffrin Eplerenone Prevents Salt-Induced Vascular Remodeling and Cardiac Fibrosis in Stroke-Prone Spontaneously Hypertensive Rats Hypertension, June 1, 2004; 43(6): 1252 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Vergely, F. Goirand, A. Ecarnot-Laubriet, C. Renard, D. Moreau, J.-C. Guilland, M. Dumas, and L. Rochette Vitamin C Deficiency Exerts Paradoxical Cardiovascular Effects in Osteogenic Disorder Shionogi (ODS) Rats J. Nutr., April 1, 2004; 134(4): 729 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhu, T. Mori, T. Huang, and J. H. Lombard Effect of high-salt diet on NO release and superoxide production in rat aorta Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H575 - H583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ritz and V. Haxsen Angiotensin II and Oxidative Stress: An Unholy Alliance J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2985 - 2987. [Full Text] [PDF]
|
|
|
|
|
|
F. Moritz, C. Monteil, M. Isabelle, F. Bauer, S. Renet, P. Mulder, V. Richard, and C. Thuillez Role of reactive oxygen species in cocaine-induced cardiac dysfunction Cardiovasc Res, October 1, 2003; 59(4): 834 - 843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Javeshghani, R. M. Touyz, M. R. Sairam, A. Virdis, M. F. Neves, and E. L. Schiffrin Attenuated Responses to Angiotensin II in Follitropin Receptor Knockout Mice, a Model of Menopause-Associated Hypertension Hypertension, October 1, 2003; 42(4): 761 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Callera, R. M. Touyz, S. A. Teixeira, M. N. Muscara, M. H. C. Carvalho, Z. B. Fortes, D. Nigro, E. L. Schiffrin, and R. C. Tostes ETA Receptor Blockade Decreases Vascular Superoxide Generation in DOCA-Salt Hypertension Hypertension, October 1, 2003; 42(4): 811 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Virdis, M. Iglarz, M. F. Neves, F. Amiri, R. M. Touyz, R. Rozen, and E. L. Schiffrin Effect of Hyperhomocystinemia and Hypertension on Endothelial Function in Methylenetetrahydrofolate Reductase-Deficient Mice Arterioscler. Thromb. Vasc. Biol., August 1, 2003; 23(8): 1352 - 1357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Pu, M. F. Neves, A. Virdis, R. M. Touyz, and E. L. Schiffrin Endothelin Antagonism on Aldosterone-Induced Oxidative Stress and Vascular Remodeling Hypertension, July 1, 2003; 42(1): 49 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Reckelhoff and J. C. Romero Role of oxidative stress in angiotensin-induced hypertension Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R893 - R912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. F. Lopes, K. L. Martin, K. Nashar, J. D. Morrow, T. L. Goodfriend, and B. M. Egan DASH Diet Lowers Blood Pressure and Lipid-Induced Oxidative Stress in Obesity Hypertension, March 1, 2003; 41(3): 422 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ulker, P. P. McKeown, and U. Bayraktutan Vitamins Reverse Endothelial Dysfunction Through Regulation of eNOS and NAD(P)H Oxidase Activities Hypertension, March 1, 2003; 41(3): 534 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shokoji, A. Nishiyama, Y. Fujisawa, H. Hitomi, H. Kiyomoto, N. Takahashi, S. Kimura, M. Kohno, and Y. Abe Renal Sympathetic Nerve Responses to Tempol in Spontaneously Hypertensive Rats Hypertension, February 1, 2003; 41(2): 266 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rodriguez-Iturbe, C.-D. Zhan, Y. Quiroz, R. K. Sindhu, and N. D. Vaziri Antioxidant-Rich Diet Relieves Hypertension and Reduces Renal Immune Infiltration in Spontaneously Hypertensive Rats Hypertension, February 1, 2003; 41(2): 341 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. V. d'Uscio, S. Milstien, D. Richardson, L. Smith, and Z. S. Katusic Long-Term Vitamin C Treatment Increases Vascular Tetrahydrobiopterin Levels and Nitric Oxide Synthase Activity Circ. Res., January 10, 2003; 92(1): 88 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Iglarz, R. M. Touyz, F. Amiri, M.-F. Lavoie, Q. N. Diep, and E. L. Schiffrin Effect of Peroxisome Proliferator-Activated Receptor-{alpha} and -{gamma} Activators on Vascular Remodeling in Endothelin-Dependent Hypertension Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 45 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Virdis, M. F. Neves, F. Amiri, E. Viel, R. M. Touyz, and E. L. Schiffrin Spironolactone Improves Angiotensin-Induced Vascular Changes and Oxidative Stress Hypertension, October 1, 2002; 40(4): 504 - 510. [Abstract] [Full Text] [PDF]
|
|