Circulation Research. 2002;91:406-413
Published online before print August 15, 2002, doi: 10.1161/01.RES.0000033523.08033.16
Published online before print August 15, 2002, doi: 10.1161/01.RES.0000033523.08033.16
© 2002 American Heart Association, Inc.
Molecular Medicine |
Angiotensin II Stimulation of NAD(P)H Oxidase Activity
Upstream Mediators
From the Division of Cardiology, Emory University, Atlanta, Ga.
Correspondence to Kathy K. Griendling, Emory University, Division of Cardiology, 319 WMB, 1639 Pierce Dr, Atlanta, GA 30322. E-mail kgriend{at}emory.edu
Angiotensin II (Ang II)–stimulated hypertrophy of vascular smooth muscle cells is mediated by reactive oxygen species (ROS) derived from NAD(P)H oxidases. The upstream signaling mechanisms by which Ang II activates these oxidases are unclear but may include protein kinase C, tyrosine kinases, phosphatidylinositol-3-kinase, and Rac, a small molecular weight G protein. We found that Ang II–stimulated ROS production is biphasic. The first phase occurs rapidly (peak at 30 seconds) and is dependent on protein kinase C activation. The larger second phase of ROS generation (peak at 30 minutes) requires Rac activation, because inhibition of Rac by either Clostridium difficile toxin A or dominant-negative Rac significantly inhibits Ang II–induced ROS production. Phosphatidylinositol-3-kinase inhibitors (wortmannin or LY294002) and the epidermal growth factor (EGF) receptor kinase blocker AG1478 attenuate both Rac activation and ROS generation. The upstream activator of EGF receptor transactivation, c-Src, is also required for ROS generation, because PP1, an Src kinase inhibitor, abrogates the Ang II stimulation of both responses. These results suggest that c-Src, EGF receptor transactivation, phosphatidylinositol-3-kinase, and Rac play important roles in the sustained Ang II–mediated activation of vascular smooth muscle cell NAD(P)H oxidases and provide insight into the integrated signaling mechanisms whereby Ang II stimulation leads to activation of the growth-related NAD(P)H oxidases.
Key Words: angiotensin II • reactive oxygen species • vascular smooth muscle • NAD(P)H oxidase • Rac
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D. Feliers, Y. Gorin, G. Ghosh-Choudhury, H. E. Abboud, and B. S. Kasinath Angiotensin II stimulation of VEGF mRNA translation requires production of reactive oxygen species Am J Physiol Renal Physiol, April 1, 2006; 290(4): F927 - F936. [Abstract] [Full Text] [PDF]
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H. Cai A new mechanism for flow-mediated vasoprotection? Focus on "Lung endothelial cell proliferation with decreased shear stress is mediated by reactive oxygen species" Am J Physiol Cell Physiol, January 1, 2006; 290(1): C35 - C36. [Full Text] [PDF]
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M. Janiszewski, L. R. Lopes, A. O. Carmo, M. A. Pedro, R. P. Brandes, C. X. C. Santos, and F. R. M. Laurindo Regulation of NAD(P)H Oxidase by Associated Protein Disulfide Isomerase in Vascular Smooth Muscle Cells J. Biol. Chem., December 9, 2005; 280(49): 40813 - 40819. [Abstract] [Full Text] [PDF]
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E. A. Woolfolk, S. Eguchi, H. Ohtsu, H. Nakashima, H. Ueno, W. T. Gerthoffer, and E. D. Motley Angiotensin II-induced activation of p21-activated kinase 1 requires Ca2+ and protein kinase C{delta} in vascular smooth muscle cells Am J Physiol Cell Physiol, November 1, 2005; 289(5): C1286 - C1294. [Abstract] [Full Text] [PDF]
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S. K. Fellner and W. J. Arendshorst Angiotensin II, reactive oxygen species, and Ca2+ signaling in afferent arterioles Am J Physiol Renal Physiol, November 1, 2005; 289(5): F1012 - F1019. [Abstract] [Full Text] [PDF]
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G. E. Callera, A. C. I. Montezano, A. Yogi, R. C. Tostes, Y. He, E. L. Schiffrin, and R. M. Touyz c-Src-Dependent Nongenomic Signaling Responses to Aldosterone Are Increased in Vascular Myocytes From Spontaneously Hypertensive Rats Hypertension, October 1, 2005; 46(4): 1032 - 1038. [Abstract] [Full Text] [PDF]
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Y. Taniyama, H. Hitomi, A. Shah, R. W. Alexander, and K. K. Griendling Mechanisms of Reactive Oxygen Species-Dependent Downregulation of Insulin Receptor Substrate-1 by Angiotensin II Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1142 - 1147. [Abstract] [Full Text] [PDF]
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S. Wesseling, D. A. Ishola Jr., J. A. Joles, H. A. Bluyssen, H. A. Koomans, and B. Braam Resistance to oxidative stress by chronic infusion of angiotensin II in mouse kidney is not mediated by the AT2 receptor Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1191 - F1200. [Abstract] [Full Text] [PDF]
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P. Meneton, X. Jeunemaitre, H. E. de Wardener, and G. A. Macgregor Links Between Dietary Salt Intake, Renal Salt Handling, Blood Pressure, and Cardiovascular Diseases Physiol Rev, April 1, 2005; 85(2): 679 - 715. [Abstract] [Full Text] [PDF]
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