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Circulation Research. 1997;80:45-51

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(Circulation Research. 1997;80:45-51.)
© 1997 American Heart Association, Inc.


Articles

p22phox mRNA Expression and NADPH Oxidase Activity Are Increased in Aortas From Hypertensive Rats

Toshiki Fukui, Nobukazu Ishizaka, Sanjay Rajagopalan, Jørn Bech Laursen, Quinn Capers, IV, W. Robert Taylor, David G. Harrison, Hector de Leon, Josiah N. Wilcox, Kathy K. Griendling

the Department of Medicine, Divisions of Cardiology (T.F., N.I., S.R., J.B.L., Q.C. IV, W.R.T., D.G.H., K.K.G.) and Hematology/Oncology (H. de L., J.N.W.), Emory University; The Atlanta Veteran's Affairs Medical Center (W.R.T., D.G.H.), Atlanta, Ga; and Medical Department B (J.B.L.), National University Hospital, Rigshospitalet, Copenhagen, Denmark.

Correspondence to Kathy K. Griendling, PhD, Division of Cardiology, Emory University School of Medicine, 1639 Pierce Dr, 319 Woodruff Memorial Building, Atlanta, Ga 30322. E-mail kgriend@emory.edu

Recent studies suggest that superoxide production by the NADPH/NADH oxidase may be involved in smooth muscle cell growth and the pathogenesis of hypertension. We previously showed that angiotensin II (Ang II) activates a p22phox-based NADPH/NADH oxidase in cultured rat vascular smooth muscle cells and in animals made hypertensive by infusion of Ang II. To investigate the mechanism responsible for this increased oxidase activity, we examined p22phox mRNA expression in rats made hypertensive by implanting an osmotic minipump that delivered Ang II (0.7 mg/kg per day). Blood pressure began to increase 3 days after the start of Ang II infusion and remained elevated for up to 14 days. Expression of p22phox mRNA in aorta was also increased after 3 days and reached a maximum increase of 338±41% by 5 days after pump implantation compared with the value after sham operation. This increase in mRNA expression was accompanied by an increase in the content of the corresponding cytochrome (twofold) and NADPH oxidase activity (179±11% of that in sham-operated rats 5 days after pump implantation). Treatment with the antihypertensive agents losartan (25 mg/kg per day) or hydralazine (15 mg/kg per day) inhibited this upregulation of mRNA levels and activity. Furthermore, infusion of recombinant heparin-binding superoxide dismutase decreased both blood pressure and p22phox mRNA expression. In situ hybridization of aortic tissue showed that p22phox mRNA was expressed in medial smooth muscle as well as in the adventitia. These findings suggest that Ang II–induced hypertension activates the NADPH/NADH oxidase system by upregulating mRNA levels of one or several components of this oxidase system, including the p22phox, and that the NADPH/NADH oxidase system is associated with the pathology of hypertension in vivo.


Key Words: NADPH oxidase • p22phox • hypertension • angiotensin II • muscle, smooth, vascular




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T. Chabrashvili, C. Kitiyakara, J. Blau, A. Karber, S. Aslam, W. J. Welch, and C. S. Wilcox
Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2003; 285(1): R117 - R124.
[Abstract] [Full Text] [PDF]


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Journal of Renin-Angiotensin-Aldosterone SystemHome page
D. G Harrison, Hua Cai, U. Landmesser, and K. K Griendling
The Pickering Lecture British Hypertension Society, 10th September 2002: Interactions of angiotensin II with NAD(P)H oxidase, oxidant stress and cardiovascular disease
Journal of Renin-Angiotensin-Aldosterone System, June 1, 2003; 4(2): 51 - 61.
[Abstract] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
J. Liu, F. Yang, X.-P. Yang, M. Jankowski, and P. J. Pagano
NAD(P)H Oxidase Mediates Angiotensin II-Induced Vascular Macrophage Infiltration and Medial Hypertrophy
Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 776 - 782.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
J. Redon, M. R. Oliva, C. Tormos, V. Giner, J. Chaves, A. Iradi, and G. T. Saez
Antioxidant Activities and Oxidative Stress Byproducts in Human Hypertension
Hypertension, May 1, 2003; 41(5): 1096 - 1101.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
A. Avogaro, E. Pagnin, and L. Calo
Monocyte NADPH Oxidase Subunit p22phox and Inducible Hemeoxygenase-1 Gene Expressions Are Increased in Type II Diabetic Patients: Relationship with Oxidative Stress
J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1753 - 1759.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
J. W. E. Rush, J. R. Turk, and M. H. Laughlin
Exercise training regulates SOD-1 and oxidative stress in porcine aortic endothelium
Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1378 - H1387.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
F. E. Rey and P. J. Pagano
The Reactive Adventitia: Fibroblast Oxidase in Vascular Function
Arterioscler Thromb Vasc Biol, December 1, 2002; 22(12): 1962 - 1971.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
A. Tojo, M. L. Onozato, N. Kobayashi, A. Goto, H. Matsuoka, and T. Fujita
Angiotensin II and Oxidative Stress in Dahl Salt-Sensitive Rat With Heart Failure
Hypertension, December 1, 2002; 40(6): 834 - 839.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
C. A. Hamilton, M. J. Brosnan, S. Al-Benna, G. Berg, and A. F. Dominiczak
NAD(P)H Oxidase Inhibition Improves Endothelial Function in Rat and Human Blood Vessels
Hypertension, November 1, 2002; 40(5): 755 - 762.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
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]


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HypertensionHome page
U. Landmesser, H. Cai, S. Dikalov, L. McCann, J. Hwang, H. Jo, S. M. Holland, and D. G. Harrison
Role of p47phox in Vascular Oxidative Stress and Hypertension Caused by Angiotensin II
Hypertension, October 1, 2002; 40(4): 511 - 515.
[Abstract] [Full Text] [PDF]


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DiabetesHome page
M. Christ, J. Bauersachs, C. Liebetrau, M. Heck, A. Gunther, and M. Wehling
Glucose Increases Endothelial-Dependent Superoxide Formation in Coronary Arteries by NAD(P)H Oxidase Activation: Attenuation by the 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor Atorvastatin
Diabetes, August 1, 2002; 51(8): 2648 - 2652.
[Abstract] [Full Text] [PDF]


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J. Clin. Pathol.Home page
L Van Heerebeek, C Meischl, W Stooker, C J L M Meijer, H W M Niessen, and D Roos
NADPH oxidase(s): new source(s) of reactive oxygen species in the vascular system?
J. Clin. Pathol., August 1, 2002; 55(8): 561 - 568.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
R. M. Touyz, X. Chen, F. Tabet, G. Yao, G. He, M. T. Quinn, P. J. Pagano, and E. L. Schiffrin
Expression of a Functionally Active gp91phox-Containing Neutrophil-Type NAD(P)H Oxidase in Smooth Muscle Cells From Human Resistance Arteries: Regulation by Angiotensin II
Circ. Res., June 14, 2002; 90(11): 1205 - 1213.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
H. Mollnau, M. Wendt, K. Szocs, B. Lassegue, E. Schulz, M. Oelze, H. Li, M. Bodenschatz, M. August, A. L. Kleschyov, et al.
Effects of Angiotensin II Infusion on the Expression and Function of NAD(P)H Oxidase and Components of Nitric Oxide/cGMP Signaling
Circ. Res., March 8, 2002; 90 (4): e58 - e65.
[Abstract] [Full Text] [PDF]


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Nephrol Dial TransplantHome page
M. Rathaus and J. Bernheim
Oxygen species in the microvascular environment: regulation of vascular tone and the development of hypertension
Nephrol. Dial. Transplant., February 1, 2002; 17(2): 216 - 221.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
S. Wassmann, U. Laufs, K. Muller, C. Konkol, K. Ahlbory, A. T. Baumer, W. Linz, M. Bohm, and G. Nickenig
Cellular Antioxidant Effects of Atorvastatin In Vitro and In Vivo
Arterioscler Thromb Vasc Biol, February 1, 2002; 22(2): 300 - 305.
[Abstract] [Full Text] [PDF]


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DiabetesHome page
Y. K. Kim, M.-S. Lee, S. M. Son, I. J. Kim, W. S. Lee, B. Y. Rhim, K. W. Hong, and C. D. Kim
Vascular NADH Oxidase Is Involved in Impaired Endothelium-Dependent Vasodilation in OLETF Rats, a Model of Type 2 Diabetes
Diabetes, February 1, 2002; 51(2): 522 - 527.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
K. Szocs, B. Lassegue, D. Sorescu, L. L. Hilenski, L. Valppu, T. L. Couse, J. N. Wilcox, M. T. Quinn, J.D. Lambeth, and K. K. Griendling
Upregulation of Nox-Based NAD(P)H Oxidases in Restenosis After Carotid Injury
Arterioscler Thromb Vasc Biol, January 1, 2002; 22(1): 21 - 27.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
N. Ishizaka, T. Aizawa, M. Ohno, S.-i. Usui, I. Mori, S.-S. Tang, J. R. Ingelfinger, S. Kimura, and R. Nagai
Regulation and Localization of HSP70 and HSP25 in the Kidney of Rats Undergoing Long-Term Administration of Angiotensin II
Hypertension, January 1, 2002; 39(1): 122 - 128.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
G. Zalba, G. S. Jose, M. U. Moreno, M. A. Fortuno, A. Fortuno, F. J. Beaumont, and J. Diez
Oxidative Stress in Arterial Hypertension: Role of NAD(P)H Oxidase
Hypertension, December 1, 2001; 38(6): 1395 - 1399.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
R. A. Beswick, A. M. Dorrance, R. Leite, and R. C. Webb
NADH/NADPH Oxidase and Enhanced Superoxide Production in the Mineralocorticoid Hypertensive Rat
Hypertension, November 1, 2001; 38(5): 1107 - 1111.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
P. Silacci, A. Desgeorges, L. Mazzolai, C. Chambaz, and D. Hayoz
Flow Pulsatility Is a Critical Determinant of Oxidative Stress in Endothelial Cells
Hypertension, November 1, 2001; 38(5): 1162 - 1166.
[Abstract] [Full Text] [PDF]


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CirculationHome page
M. C. Lavigne, H. L. Malech, S. M. Holland, and T. L. Leto
Genetic Demonstration of p47phox-Dependent Superoxide Anion Production in Murine Vascular Smooth Muscle Cells
Circulation, July 3, 2001; 104(1): 79 - 84.
[Abstract] [Full Text] [PDF]


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Physiol. Rev.Home page
B. C. Berk
Vascular Smooth Muscle Growth: Autocrine Growth Mechanisms
Physiol Rev, July 1, 2001; 81(3): 999 - 1030.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
S. Wassmann, U. Laufs, A. T. Baumer, K. Muller, K. Ahlbory, W. Linz, G. Itter, R. Rosen, M. Bohm, and G. Nickenig
HMG-CoA Reductase Inhibitors Improve Endothelial Dysfunction in Normocholesterolemic Hypertension via Reduced Production of Reactive Oxygen Species
Hypertension, June 1, 2001; 37(6): 1450 - 1457.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
Y. Shi, R. Niculescu, D. Wang, S. Patel, K. L. Davenpeck, and A. Zalewski
Increased NAD(P)H Oxidase and Reactive Oxygen Species in Coronary Arteries After Balloon Injury
Arterioscler Thromb Vasc Biol, May 1, 2001; 21(5): 739 - 745.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
G. Zalba, G. S. Jose, F. J. Beaumont, M. A. Fortuno, A. Fortuno, and J. Diez
Polymorphisms and Promoter Overactivity of the p22phox Gene in Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats
Circ. Res., February 2, 2001; 88(2): 217 - 222.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
N. E. J. West, T. J. Guzik, E. Black, and K. M. Channon
Enhanced Superoxide Production in Experimental Venous Bypass Graft Intimal Hyperplasia : Role of NAD(P)H Oxidase
Arterioscler Thromb Vasc Biol, February 1, 2001; 21(2): 189 - 194.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
H. P. Souza, F. R. M. Laurindo, R. C. Ziegelstein, C. O. Berlowitz, and J. L. Zweier
Vascular NAD(P)H oxidase is distinct from the phagocytic enzyme and modulates vascular reactivity control
Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H658 - H667.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
A. Nishiyama, T. Fukui, Y. Fujisawa, M. Rahman, R.-X. Tian, S. Kimura, and Y. Abe
Systemic and Regional Hemodynamic Responses to Tempol in Angiotensin II-Infused Hypertensive Rats
Hypertension, January 1, 2001; 37(1): 77 - 83.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
V. J. Thannickal and B. L. Fanburg
Reactive oxygen species in cell signaling
Am J Physiol Lung Cell Mol Physiol, December 1, 2000; 279(6): L1005 - L1028.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
H. Cai and D. G. Harrison
Endothelial Dysfunction in Cardiovascular Diseases: The Role of Oxidant Stress
Circ. Res., November 10, 2000; 87(10): 840 - 844.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
M. E. Cifuentes, F. E. Rey, O. A. Carretero, and P. J. Pagano
Upregulation of p67phox and gp91phox in aortas from angiotensin II-infused mice
Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2234 - H2240.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
K. K. Griendling, D. Sorescu, B. Lassegue, and M. Ushio-Fukai
Modulation of Protein Kinase Activity and Gene Expression by Reactive Oxygen Species and Their Role in Vascular Physiology and Pathophysiology
Arterioscler Thromb Vasc Biol, October 1, 2000; 20(10): 2175 - 2183.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
E. Bush, N. Maeda, W. A. Kuziel, T. C. Dawson, J. N. Wilcox, H. DeLeon, and W. R. Taylor
CC Chemokine Receptor 2 Is Required for Macrophage Infiltration and Vascular Hypertrophy in Angiotensin II-Induced Hypertension
Hypertension, September 1, 2000; 36(3): 360 - 363.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
K. M. Channon, H. Qian, and S. E. George
Nitric Oxide Synthase in Atherosclerosis and Vascular Injury : Insights From Experimental Gene Therapy
Arterioscler Thromb Vasc Biol, August 1, 2000; 20(8): 1873 - 1881.
[Abstract] [Full Text] [PDF]