From the Department of Medicine, Division of Cardiology, Emory
University, Atlanta, Ga.
Correspondence to Kathy K. Griendling, PhD, Division of Cardiology, Emory University School of Medicine, 1639 Pierce Dr, Room 319, Atlanta, GA 30322. E-mail kgriend{at}emory.edu
AbstractRecent evidence
suggests that oxidative mechanisms may be involved in vascular smooth
muscle cell (VSMC) hypertrophy. We previously showed that
angiotensin II (Ang II) increases superoxide
production by activating an NADH/NADPH oxidase, which
contributes to hypertrophy. In this study, we determined
whether Ang II stimulation of this oxidase results in
H2O2 production by studying the effects
of Ang II on intracellular H2O2 generation,
intracellular superoxide dismutase and catalase activity, and
hypertrophy. Ang II (100 nmol/L) significantly increased
intracellular H2O2 levels at 4 hours. Neither
superoxide dismutase activity nor catalase activity was affected by Ang
II; the SOD present in VSMCs is sufficient to metabolize Ang
IIstimulated superoxide to H2O2, which
accumulates more rapidly than it is degraded by catalase. This increase
in H2O2 was inhibited by extracellular
catalase, diphenylene iodonium, an inhibitor of the
NADH/NADPH oxidase, and the AT1 receptor blocker
losartan. In VSMCs stably transfected with antisense p22phox, a
critical component of the NADH/NADPH oxidase in which oxidase activity
was markedly reduced, Ang IIinduced production of
H2O2 was almost completely inhibited,
confirming that the source of Ang IIinduced
H2O2 was the NADH/NADPH oxidase. Using a novel
cell line that stably overexpresses catalase, we showed that this
increased H2O2 is a critical step in VSMC
hypertrophy, a hallmark of many vascular diseases.
Inhibition of intracellular superoxide dismutase by
diethylthiocarbamate (1 mmol/L) also resulted in attenuation of
Ang IIinduced hypertrophy (62±2% inhibition). These
data indicate that AT1 receptormediated
production of superoxide generated by the NADH/NADPH oxidase is
followed by an increase in intracellular H2O2,
suggesting a specific role for these oxygen species and scavenging
systems in modifying the intracellular redox state in vascular
growth.
© 1998 American Heart Association, Inc.
Scientific Contributions
Role of NADH/NADPH OxidaseDerived H2O2 in Angiotensin IIInduced Vascular Hypertrophy
Key Words: vascular smooth muscle angiotensin II NADH NADPH oxidase hydrogen peroxide superoxide dismutase catalase hypertrophy
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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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G. NICKENIG, S. BAUDLER, C. MULLER, C. WERNER, N. WERNER, H. WELZEL, K. STREHLOW, and M. BOHM Redox-sensitive vascular smooth muscle cell proliferation is mediated by GKLF and Id3 in vitro and in vivo FASEB J, July 1, 2002; 16(9): 1077 - 1086. [Abstract] [Full Text] [PDF] |
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C. Mueller, S. Baudler, H. Welzel, M. Bohm, and G. Nickenig Identification of a Novel Redox-Sensitive Gene, Id3, Which Mediates Angiotensin II-Induced Cell Growth Circulation, May 21, 2002; 105(20): 2423 - 2428. [Abstract] [Full Text] [PDF] |
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C. Kumaran and K. Shivakumar Calcium- and superoxide anion-mediated mitogenic action of substance P on cardiac fibroblasts Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1855 - H1862. [Abstract] [Full Text] [PDF] |
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M. Nishida, K. L. Schey, S. Takagahara, K. Kontani, T. Katada, Y. Urano, T. Nagano, T. Nagao, and H. Kurose Activation Mechanism of Gi and Go by Reactive Oxygen Species J. Biol. Chem., March 8, 2002; 277(11): 9036 - 9042. [Abstract] [Full Text] [PDF] |
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D. JAVESGHANI, S. A. MAGDER, E. BARREIRO, M. T. QUINN, and S. N. A. HUSSAIN Molecular Characterization of a Superoxide-Generating NAD(P)H Oxidase in the Ventilatory Muscles Am. J. Respir. Crit. Care Med., February 1, 2002; 165(3): 412 - 418. [Abstract] [Full Text] [PDF] |
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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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S. Hirotani, K. Otsu, K. Nishida, Y. Higuchi, T. Morita, H. Nakayama, O. Yamaguchi, T. Mano, Y. Matsumura, H. Ueno, et al. Involvement of Nuclear Factor-{kappa}B and Apoptosis Signal-Regulating Kinase 1 in G-Protein-Coupled Receptor Agonist-Induced Cardiomyocyte Hypertrophy Circulation, January 29, 2002; 105(4): 509 - 515. [Abstract] [Full Text] [PDF] |
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K. El Hadri, M. Moldes, N. Mercier, M. Andreani, J. Pairault, and B. Feve Semicarbazide-Sensitive Amine Oxidase in Vascular Smooth Muscle Cells: Differentiation-Dependent Expression and Role in Glucose Uptake Arterioscler Thromb Vasc Biol, January 1, 2002; 22(1): 89 - 94. [Abstract] [Full Text] [PDF] |
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W. Droge Free Radicals in the Physiological Control of Cell Function Physiol Rev, January 1, 2002; 82(1): 47 - 95. [Abstract] [Full Text] [PDF] |
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N. Uhlenius, O. Vuolteenaho, and I. Tikkanen Renin-angiotensin blockade improves renal cGMP production via non-AT2-receptor mediated mechanisms in hypertension-induced by chronic NOS inhibition in rat Journal of Renin-Angiotensin-Aldosterone System, December 1, 2001; 2(4): 233 - 239. [Abstract] [PDF] |
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C. Berry, R. Touyz, A. F. Dominiczak, R. C. Webb, and D. G. Johns Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2337 - H2365. [Abstract] [Full Text] [PDF] |
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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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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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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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E. A. Jaimes, C. Sweeney, and L. Raij Effects of the Reactive Oxygen Species Hydrogen Peroxide and Hypochlorite on Endothelial Nitric Oxide Production Hypertension, October 1, 2001; 38(4): 877 - 883. [Abstract] [Full Text] [PDF] |
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T. Munzel and J. F. Keaney Jr Are ACE Inhibitors a "Magic Bullet" Against Oxidative Stress? Circulation, September 25, 2001; 104(13): 1571 - 1574. [Full Text] [PDF] |
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S. L. Lee, A. R. Simon, W. W. Wang, and B. L. Fanburg H2O2 signals 5-HT-induced ERK MAP kinase activation and mitogenesis of smooth muscle cells Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L646 - L652. [Abstract] [Full Text] [PDF] |
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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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H. L Reeve, S. Tolarova, D. P Nelson, S. Archer, and E K. Weir Redox control of oxygen sensing in the rabbit ductus arteriosus J. Physiol., May 15, 2001; 533(1): 253 - 261. [Abstract] [Full Text] [PDF] |
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K. Irani Angiotensin II-Stimulated Vascular Remodeling : The Search for the Culprit Oxidase Circ. Res., May 11, 2001; 88(9): 858 - 860. [Full Text] [PDF] |
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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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G. A. Stouffer, C. Patterson, N. Madamanchi, and M. S. Runge Role of Reactive Oxygen Species in Angiotensin II Signaling : The Plot Thickens Arterioscler Thromb Vasc Biol, April 1, 2001; 21(4): 471 - 472. [Full Text] [PDF] |
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