Copyright © 2006, European Society of Cardiology
Redox signaling in hypertension
Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, 451 Smyth Road, Ottawa, K1H 8M5, Ontario, Canada
* Corresponding author. Tel.: +1 613 562 5800x8241; fax: +1 613 562 5487. Email address: rtouyz{at}uottawa.ca
Diseases such as hypertension, atherosclerosis and diabetes are associated with vascular functional and structural changes including endothelial dysfunction, altered contractility and vascular remodeling. Cellular events underlying these processes involve changes in vascular smooth muscle cell (VSMC) growth, apoptosis/anoikis, cell migration, inflammation, and fibrosis. Many stimuli influence cellular changes, including mechanical forces, such as shear stress, and vasoactive agents, of which angiotensin II (Ang II) appears to be amongst the most important. Ang II mediates many of its pleiotropic vascular effects through NAD(P)H oxidase-derived reactive oxygen species (ROS). Mechanical forces, comprising both unidirectional laminar and oscillatory shear, are increasingly being recognized as important inducers of vascular NO and ROS generation. In general, laminar flow is associated with upregulation of eNOS and NO production and increased expression of antioxidants glutathione peroxidase and superoxide dismutase, thereby promoting a healthy vascular wall and protecting against oxidative vascular injury. On the other hand, oscillatory shear is linked to increased ROS production with consequent oxidative damage, as occurs in hypertension. ROS function as important intracellular and intercellular second messengers to modulate many downstream signaling molecules, such as protein tyrosine phosphatases, protein tyrosine kinases, transcription factors, mitogen-activated protein kinases, and ion channels. Induction of these signaling cascades leads to VSMC growth and migration, expression of pro-inflammatory mediators, and modification of extracellular matrix. In addition, ROS increase intracellular free Ca2+ concentration, a major determinant of vascular reactivity. ROS influence signaling molecules by altering the intracellular redox state and by oxidative modification of proteins. In physiological conditions, low concentrations of intracellular ROS play an important role in normal redox signaling involved in maintaining vascular function and integrity. Under pathological conditions ROS contribute to vascular dysfunction and remodeling through oxidative damage. The present review describes some of the redox-sensitive signaling pathways that are involved in the functional and structural vascular changes associated with hypertension.
KEYWORDS Superoxide; Signal transduction; Angiotensin II; Kinases; Vascular smooth muscle cells; Blood pressure; Vascular remodeling; Inflammation
Time for primary review 21 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Schluter, U. Zimmermann, C. Protzel, B. Miehe, K.-J. Klebingat, R. Rettig, and O. Grisk Intrarenal artery superoxide is mainly NADPH oxidase-derived and modulates endothelium-dependent dilation in elderly patients Cardiovasc Res, November 12, 2009; (2009) cvp346v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H.H. Chan, C.-A. Wu, K. L.H. Wu, Y.-H. Ho, A. Y.W. Chang, and J. Y.H. Chan Transcriptional Upregulation of Mitochondrial Uncoupling Protein 2 Protects Against Oxidative Stress-Associated Neurogenic Hypertension Circ. Res., October 23, 2009; 105(9): 886 - 896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Forman, H. Choi, and G. C. Curhan Fructose and Vitamin C Intake Do Not Influence Risk for Developing Hypertension J. Am. Soc. Nephrol., April 1, 2009; 20(4): 863 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H.H. Chan, K. L.H. Wu, A. Y.W. Chang, M.-H. Tai, and J. Y.H. Chan Oxidative Impairment of Mitochondrial Electron Transport Chain Complexes in Rostral Ventrolateral Medulla Contributes to Neurogenic Hypertension Hypertension, February 1, 2009; 53(2): 217 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Forman, H. Choi, and G. C. Curhan Uric Acid and Insulin Sensitivity and Risk of Incident Hypertension Arch Intern Med, January 26, 2009; 169(2): 155 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Garcia-Redondo, A. M. Briones, A. E. Beltran, M. J. Alonso, U. Simonsen, and M. Salaices Hypertension Increases Contractile Responses to Hydrogen Peroxide in Resistance Arteries through Increased Thromboxane A2, Ca2+, and Superoxide Anion Levels J. Pharmacol. Exp. Ther., January 1, 2009; 328(1): 19 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Garcia-Cazarin, J. L. Smith, D. K. St. Clair, and M. T. Piascik The {alpha}1D-Adrenergic Receptor Induces Vascular Smooth Muscle Apoptosis via a p53-Dependent Mechanism Mol. Pharmacol., October 1, 2008; 74(4): 1000 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Alba, R. El Bekay, P. Chacon, M. E. Reyes, E. Ramos, J. Olivan, J. Jimenez, J. M. Lopez, J. Martin-Nieto, E. Pintado, et al. Heme oxygenase-1 expression is down-regulated by angiotensin II and under hypertension in human neutrophils J. Leukoc. Biol., August 1, 2008; 84(2): 397 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. G. Maier Nicotinamide Adenine Dinucleotide Phosphate Oxidase and Diabetes: Vascular Implications Vascular and Endovascular Surgery, August 1, 2008; 42(4): 305 - 313. [Abstract] [PDF]
|
|
|
|
|
|
D. Liu, L. Gao, S. K. Roy, K. G. Cornish, and I. H. Zucker Role of Oxidant Stress on AT1 Receptor Expression in Neurons of Rabbits With Heart Failure and in Cultured Neurons Circ. Res., July 18, 2008; 103(2): 186 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Dworakowski, S. Walker, A. Momin, J. Desai, A. El-Gamel, O. Wendler, M. T. Kearney, and A. M. Shah Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Derived Superoxide and Vascular Endothelial Dysfunction in Human Heart Failure J. Am. Coll. Cardiol., April 8, 2008; 51(14): 1349 - 1356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. I. Schrader, D. A. Kinzenbaw, A. W. Johnson, F. M. Faraci, and S. P. Didion IL-6 Deficiency Protects Against Angiotensin II Induced Endothelial Dysfunction and Hypertrophy Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2576 - 2581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Arribas, C. J. Daly, M. C. Gonzalez, and J. C. McGrath Imaging the vascular wall using confocal microscopy J. Physiol., October 1, 2007; 584(1): 5 - 9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-X. Zhang, Y. Nagai, T. Nakagawa, H. Miyanaka, Y. Fujisawa, A. Nishiyama, K. Izuishi, K. Ohmori, and S. Kimura Involvement of endogenous nitric oxide in angiotensin II-induced activation of vascular mitogen-activated protein kinases Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2403 - H2408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ruiz-Ortega, J. Rodriguez-Vita, E. Sanchez-Lopez, G. Carvajal, and J. Egido TGF-{beta} signaling in vascular fibrosis Cardiovasc Res, May 1, 2007; 74(2): 196 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Martinson, M. P. Hans, G.-D. David, and A. M. Elizabeth Readers' choice: Hot papers downloaded in 2006 Cardiovasc Res, March 1, 2007; 73(4): 619 - 622. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, J. S. Beckman, and L. Liaudet Nitric Oxide and Peroxynitrite in Health and Disease Physiol Rev, January 1, 2007; 87(1): 315 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Gutierrez, S. W. Ballinger, V. M. Darley-Usmar, and A. Landar Free Radicals, Mitochondria, and Oxidized Lipids: The Emerging Role in Signal Transduction in Vascular Cells Circ. Res., October 27, 2006; 99(9): 924 - 932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Shah and H. Sauer Transmitting biological information using oxygen: Reactive oxygen species as signalling molecules in cardiovascular pathophysiology Cardiovasc Res, July 15, 2006; 71(2): 191 - 194. [Full Text] [PDF]
|
|