on July 19, 2004
Hypertension. 2004
Published online before print July 19, 2004, doi: 10.1161/01.HYP.0000138070.47616.9d
Published online before print July 19, 2004, doi: 10.1161/01.HYP.0000138070.47616.9d
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on May 10, 2004
From the CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada. * To whom correspondence should be addressed. E-mail: touyzr{at}ircm.qc.ca.
Abstract--Metabolism of oxygen by cells generates potentially deleterious reactive oxygen species (ROS). Under normal conditions the rate and magnitude of oxidant formation is balanced by the rate of oxidant elimination. However, an imbalance between prooxidants and antioxidants results in oxidative stress, which is the pathogenic outcome of oxidant overproduction that overwhelms the cellular antioxidant capacity. The kidney and vasculature are rich sources of NADPH oxidase-derived ROS, which under pathological conditions play an important role in renal dysfunction and vascular damage. Strong experimental evidence indicates that increased oxidative stress and associated oxidative damage are mediators of renovascular injury in cardiovascular pathologies. Increased production of superoxide anion and hydrogen peroxide, reduced nitric oxide synthesis, and decreased bioavailability of antioxidants have been demonstrated in experimental and human hypertension. These findings have evoked considerable interest because of the possibilities that therapies targeted against free radicals by decreasing ROS generation or by increasing nitric oxide availability and antioxidants may be useful in minimizing vascular injury and renal dysfunction and thereby prevent or regress hypertensive end-organ damage. This article highlights current developments in the field of ROS and hypertension, focusing specifically on the role of oxidative stress in hypertension-associated vascular damage. In addition, recent clinical trials investigating cardiovascular benefits of antioxidants are discussed, and some explanations for the rather disappointing results from these studies are addressed. Finally, important avenues for future research in the field of ROS, oxidative stress, and redox signaling in hypertension are considered.
Revised on May 25, 2004
Reactive Oxygen Species, Vascular Oxidative Stress, and Redox Signaling in Hypertension. What is the Clinical Significance?
Rhian M. Touyz*
Key words: free radicals • antioxidants • resistance • arteries • hypertension, essential
This article has been cited by other articles:
 |
|
 |
|
  C. D. Baker, S. L. Ryan, D. A. Ingram, G. J. Seedorf, S. H. Abman, and V. Balasubramaniam Endothelial Colony-forming Cells from Preterm Infants Are Increased and More Susceptible to Hyperoxia Am. J. Respir. Crit. Care Med., September 1, 2009; 180(5): 454 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Tobin, B. K. Joseph, H. N. Al-Kindi, S. Albarwani, J. A. Madden, L. T. Nemetz, N. J. Rusch, and S. W. Rhee Loss of cerebrovascular Shaker-type K+ channels: a shared vasodilator defect of genetic and renal hypertensive rats Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H293 - H303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Virdis, R. Colucci, D. Versari, N. Ghisu, M. Fornai, L. Antonioli, E. Duranti, E. Daghini, C. Giannarelli, C. Blandizzi, et al. Atorvastatin Prevents Endothelial Dysfunction in Mesenteric Arteries From Spontaneously Hypertensive Rats: Role of Cyclooxygenase 2-Derived Contracting Prostanoids Hypertension, June 1, 2009; 53(6): 1008 - 1016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Thompson and A. M. Hakim Living Beyond Our Physiological Means: Small Vessel Disease of the Brain Is an Expression of a Systemic Failure in Arteriolar Function: A Unifying Hypothesis Stroke, May 1, 2009; 40(5): e322 - e330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. de Cavanagh, M. Ferder, F. Inserra, and L. Ferder Angiotensin II, mitochondria, cytoskeletal, and extracellular matrix connections: an integrating viewpoint Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H550 - H558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Drobiova, M. Thomson, K. Al-Qattan, R. Peltonen-Shalaby, Z. Al-Amin, and M. Ali Garlic Increases Antioxidant Levels in Diabetic and Hypertensive Rats Determined by a Modified Peroxidase Method Evid. Based Complement. Altern. Med., February 20, 2009; (2009) nep011v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sun, O. A. Carretero, J. Xu, N.-E. Rhaleb, J. J. Yang, P. J. Pagano, and X.-P. Yang Deletion of Inducible Nitric Oxide Synthase Provides Cardioprotection in Mice With 2-Kidney, 1-Clip Hypertension Hypertension, January 1, 2009; 53(1): 49 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Wilcox and A. Pearlman Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides Pharmacol. Rev., December 1, 2008; 60(4): 418 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hahn and M. A. Schwartz The Role of Cellular Adaptation to Mechanical Forces in Atherosclerosis Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2101 - 2107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Schluter, A. C. Steinbach, A. Steffen, R. Rettig, and O. Grisk Apocynin-induced vasodilation involves Rho kinase inhibition but not NADPH oxidase inhibition Cardiovasc Res, November 1, 2008; 80(2): 271 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Sanchez-Lozada, V. Soto, E. Tapia, C. Avila-Casado, Y. Y. Sautin, T. Nakagawa, M. Franco, B. Rodriguez-Iturbe, and R. J. Johnson Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1134 - F1141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Wiggers, F. M. Pecanha, A. M. Briones, J. V. Perez-Giron, M. Miguel, D. V. Vassallo, V. Cachofeiro, M. J. Alonso, and M. Salaices Low mercury concentrations cause oxidative stress and endothelial dysfunction in conductance and resistance arteries Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1033 - H1043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin The Flame That Lights the Fire: Oxidative Stress, Inflammation, and Renal Damage in Angiotensin II-Induced Hypertension Hypertension, August 1, 2008; 52(2): 205 - 206. [Full Text] [PDF]
|
|
|
|
|
|
G. K. Soukhova-O'Hare, R. V. Ortines, Y. Gu, A. D. Nozdrachev, S. D. Prabhu, and D. Gozal Postnatal Intermittent Hypoxia and Developmental Programming of Hypertension in Spontaneously Hypertensive Rats: The Role of Reactive Oxygen Species and L-Ca2+ Channels Hypertension, July 1, 2008; 52(1): 156 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. V. Serebrovskaya, E. B. Manukhina, M. L. Smith, H. F. Downey, and R. T. Mallet Intermittent Hypoxia: Cause of or Therapy for Systemic Hypertension? Experimental Biology and Medicine, June 1, 2008; 233(6): 627 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. You, C. Cochain, C. Loinard, J. Vilar, B. Mees, M. Duriez, B. I. Levy, and J.-S. Silvestre Hypertension Impairs Postnatal Vasculogenesis: Role of Antihypertensive Agents Hypertension, June 1, 2008; 51(6): 1537 - 1544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ceriello Possible Role of Oxidative Stress in the Pathogenesis of Hypertension Diabetes Care, February 1, 2008; 31(Supplement_2): S181 - S184. [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]
|
|
|
|
 |
|
 S. Gharibzadeh, S. S. Hoseini, and S. Mahdavi Acute Hypertensive Crisis May Be a Risk Factor for Alzheimer's Disease Induction and Progression J Neuropsychiatry Clin Neurosci, November 1, 2007; 19(4): 483 - 484. [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Edwards, T. Lyon, S. E. Litwin, A. Rabovsky, J. D. Symons, and T. Jalili Quercetin Reduces Blood Pressure in Hypertensive Subjects J. Nutr., November 1, 2007; 137(11): 2405 - 2411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sharma, A. C. Grobe, D. A. Wiseman, S. Kumar, M. Englaish, I. Najwer, E. Benavidez, P. Oishi, A. Azakie, J. R. Fineman, et al. Lung antioxidant enzymes are regulated by development and increased pulmonary blood flow Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L960 - L971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Chapleau The Continuing Saga of Neuronal Oxidative Stress in Hypertension: Nox, Nox Who's There, and Where? Hypertension, October 1, 2007; 50(4): 600 - 602. [Full Text] [PDF]
|
|
|
|
|
|
A. Jacobson, C. Yan, Q. Gao, T. Rincon-Skinner, A. Rivera, J. Edwards, A. Huang, G. Kaley, and D. Sun Aging enhances pressure-induced arterial superoxide formation Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1344 - H1350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wei, A. T. Whaley-Connell, K. Chen, J. Habibi, G. M.-E. Uptergrove, S. E. Clark, C. S. Stump, C. M. Ferrario, and J. R. Sowers NADPH Oxidase Contributes to Vascular Inflammation, Insulin Resistance, and Remodeling in the Transgenic (mRen2) Rat Hypertension, August 1, 2007; 50(2): 384 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Piotrkowski, C. G. Fraga, and E. M. V. de Cavanagh Mitochondrial function and nitric oxide metabolism are modified by enalapril treatment in rat kidney Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1494 - R1501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. McCormick, D. Gavrila, and N. L. Weintraub Role of Oxidative Stress in the Pathogenesis of Abdominal Aortic Aneurysms Arterioscler Thromb Vasc Biol, March 1, 2007; 27(3): 461 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Szasz, K. Thakali, G. D. Fink, and S. W. Watts A Comparison of Arteries and Veins in Oxidative Stress: Producers, Destroyers, Function, and Disease Experimental Biology and Medicine, January 1, 2007; 232(1): 27 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Shah, R. Baliga, M. Rajapurkar, and V. A. Fonseca Oxidants in Chronic Kidney Disease J. Am. Soc. Nephrol., January 1, 2007; 18(1): 16 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Wiseman, S. M. Wells, M. Hubbard, J. E. Welker, and S. M. Black Alterations in zinc homeostasis underlie endothelial cell death induced by oxidative stress from acute exposure to hydrogen peroxide Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L165 - L177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kitayama, C. Yi, F. M. Faraci, and D. D. Heistad Modulation of Dilator Responses of Cerebral Arterioles by Extracellular Superoxide Dismutase Stroke, November 1, 2006; 37(11): 2802 - 2806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-L. Tain and C. Baylis Dissecting the Causes of Oxidative Stress in an In Vivo Model of Hypertension Hypertension, November 1, 2006; 48(5): 828 - 829. [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Wiseman, S. M. Wells, J. Wilham, M. Hubbard, J. E. Welker, and S. M. Black Endothelial response to stress from exogenous Zn2+ resembles that of NO-mediated nitrosative stress, and is protected by MT-1 overexpression Am J Physiol Cell Physiol, September 1, 2006; 291(3): C555 - C568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Feletou and P. M. Vanhoutte Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture) Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H985 - H1002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsui, T. Shimosawa, Y. Uetake, H. Wang, S. Ogura, T. Kaneko, J. Liu, K. Ando, and T. Fujita Protective Effect of Potassium Against the Hypertensive Cardiac Dysfunction: Association With Reactive Oxygen Species Reduction Hypertension, August 1, 2006; 48(2): 225 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Grobe, S. M. Wells, E. Benavidez, P. Oishi, A. Azakie, J. R. Fineman, and S. M. Black Increased oxidative stress in lambs with increased pulmonary blood flow and pulmonary hypertension: role of NADPH oxidase and endothelial NO synthase Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1069 - L1077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Rodriguez-Iturbe and R. J. Johnson Role of inflammatory cells in the kidney in the induction and maintenance of hypertension Nephrol. Dial. Transplant., February 1, 2006; 21(2): 260 - 263. [Full Text] [PDF]
|
|
|
|
|
|
R. M. Touyz Lipid Rafts Take Center Stage in Endothelial Cell Redox Signaling by Death Receptors Hypertension, January 1, 2006; 47(1): 16 - 18. [Full Text] [PDF]
|
|
|
|
 |
|
 J M Gonzalez-Clemente, G Gimenez-Perez, C Richart, M Broch, A Caixas, A Megia, O Gimenez-Palop, I Simon, D Mauricio, and J Vendrell The tumour necrosis factor (TNF)-{alpha} system is activated in accordance with pulse pressure in normotensive subjects with type 1 diabetes mellitus Eur. J. Endocrinol., November 1, 2005; 153(5): 687 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Didion, D. A. Kinzenbaw, and F. M. Faraci Critical Role for CuZn-Superoxide Dismutase in Preventing Angiotensin II-Induced Endothelial Dysfunction Hypertension, November 1, 2005; 46(5): 1147 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Dikalova, R. Clempus, B. Lassegue, G. Cheng, J. McCoy, S. Dikalov, A. S. Martin, A. Lyle, D. S. Weber, D. Weiss, et al. Nox1 Overexpression Potentiates Angiotensin II-Induced Hypertension and Vascular Smooth Muscle Hypertrophy in Transgenic Mice Circulation, October 25, 2005; 112(17): 2668 - 2676. [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]
|
|
|
|
|
|
M. Mayr, Y.-L. Chung, U. Mayr, X. Yin, L. Ly, H. Troy, S. Fredericks, Y. Hu, J. R. Griffiths, and Q. Xu Proteomic and Metabolomic Analyses of Atherosclerotic Vessels From Apolipoprotein E-Deficient Mice Reveal Alterations in Inflammation, Oxidative Stress, and Energy Metabolism Arterioscler Thromb Vasc Biol, October 1, 2005; 25(10): 2135 - 2142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kopkan and D. S. A. Majid Superoxide Contributes to Development of Salt Sensitivity and Hypertension Induced by Nitric Oxide Deficiency Hypertension, October 1, 2005; 46(4): 1026 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lee, M. Lee, J.-U. Kim, K. I. Song, Y. S. Choi, and S.-S. Cheong Carvedilol Reduces Plasma 8-Hydroxy-2'-Deoxyguanosine in Mild to Moderate Hypertension: A Pilot Study Hypertension, May 1, 2005; 45(5): 986 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Pollock Endothelin, Angiotensin, and Oxidative Stress in Hypertension Hypertension, April 1, 2005; 45(4): 477 - 480. [Full Text] [PDF]
|
|
|
|
|
|
K. K. Griendling ATVB In Focus: Redox Mechanisms in Blood Vessels Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 272 - 273. [Full Text] [PDF]
|
|
|
|
|
|
D. S. A. Majid, A. Nishiyama, K. E. Jackson, and A. Castillo Superoxide scavenging attenuates renal responses to ANG II during nitric oxide synthase inhibition in anesthetized dogs Am J Physiol Renal Physiol, February 1, 2005; 288(2): F412 - F419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Wilcox and D. Gutterman Focus on oxidative stress in the cardiovascular and renal systems Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H3 - H6. [Full Text] [PDF]
|
|