(Circulation. 1997;95:588-593.)
© 1997 American Heart Association, Inc.
Articles |
Role of Superoxide in Angiotensin II–Induced but Not Catecholamine-Induced Hypertension
the Department of Medicine, Cardiology Division, Emory University School of Medicine (J.B.L., S.R., Z.G., D.G.H.), Atlanta, Ga; the Atlanta (Ga) Veterans Administration Medical Center (D.G.H.); the Department of Anesthesiology (M.T., B.A.F.), University of Alabama at Birmingham; and Medical Department B, Division of Cardiology (J.B.L.), Rigshospitalet, Denmark.
Correspondence to David G. Harrison, MD, PO Box LL, Cardiology Division, Emory University School of Medicine, Atlanta, GA 30322.
Background The major source of superoxide (·O2-) in vascular tissues is an NADH/NADPH-dependent, membrane-bound oxidase. We have previously shown that this oxidase is activated in angiotensin II– but not norepinephrine-induced hypertension. We hypothesized that hypertension associated with chronically elevated angiotensin II might be caused in part by vascular ·O2- production.
Methods and Results We produced hypertension in rats by a 5-day infusion of angiotensin II or norepinephrine. Rats were also treated with liposome-encapsulated superoxide dismutase (SOD) or empty liposomes. Arterial pressure was measured in conscious rats under baseline conditions and during bolus injections of either acetylcholine or nitroprusside. Vascular ·O2- production was assessed by lucigenin chemiluminescence. In vitro vascular relaxations were examined in organ chambers. Norepinephrine infusion increased blood pressure to a similar extent as angiotensin II infusion (179±5 and 189±4 mm Hg, respectively). In contrast, angiotensin II–induced hypertension was associated with increased vascular ·O2- production, whereas norepinephrine-induced hypertension was not. Treatment with liposome-encapsulated SOD reduced blood pressure by 50 mm Hg in angiotensin II–infused rats while having no effect on blood pressure in control rats or rats with norepinephrine-induced hypertension. Similarly, liposome-encapsulated SOD enhanced in vivo hypotensive responses to acetylcholine and in vitro responses to endothelium-dependent vasodilators in angiotensin II–treated rats.
Conclusions Hypertension caused by chronically elevated angiotensin II is mediated in part by ·O2-, likely via degradation of endothelium-derived NO·. Increased vascular ·O2- may contribute to vascular disease in high renin/angiotensin II states.
Key Words: hypertension • angiotensin • endothelium-derived factors
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 T. H. Schindler, E. U. Nitzsche, M. Olschewski, I. Brink, M. Mix, J. Prior, A. Facta, M. Inubushi, H. Just, and H. R. Schelbert PET-Measured Responses of MBF to Cold Pressor Testing Correlate with Indices of Coronary Vasomotion on Quantitative Coronary Angiography J. Nucl. Med., March 1, 2004; 45(3): 419 - 428. [Abstract] [Full Text]
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W. Ni, S. Kitamoto, M. Ishibashi, M. Usui, S. Inoue, K.-i. Hiasa, Q. Zhao, K.-i. Nishida, A. Takeshita, and K. Egashira Monocyte Chemoattractant Protein-1 Is an Essential Inflammatory Mediator in Angiotensin II-Induced Progression of Established Atherosclerosis in Hypercholesterolemic Mice Arterioscler. Thromb. Vasc. Biol., March 1, 2004; 24(3): 534 - 539. [Abstract] [Full Text]
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M. Galinanes and A. G Fowler Role of clinical pathologies in myocardial injury following ischaemia and reperfusion Cardiovasc Res, February 15, 2004; 61(3): 512 - 521. [Abstract] [Full Text] [PDF]
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 S. CUZZOCREA, E. MAZZON, L. DUGO, R. DI PAOLA, A. P. CAPUTI, and D. SALVEMINI Superoxide: a key player in hypertension FASEB J, January 1, 2004; 18(1): 94 - 101. [Abstract] [Full Text] [PDF]
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Y. Taniyama and K. K. Griendling Reactive Oxygen Species in the Vasculature: Molecular and Cellular Mechanisms Hypertension, December 1, 2003; 42(6): 1075 - 1081. [Abstract] [Full Text] [PDF]
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 S. Oparil, M. A. Zaman, and D. A. Calhoun Pathogenesis of Hypertension Ann Intern Med, November 4, 2003; 139(9): 761 - 776. [Full Text] [PDF]
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T. Munzel, R. Feil, A. Mulsch, S. M. Lohmann, F. Hofmann, and U. Walter Physiology and Pathophysiology of Vascular Signaling Controlled by Cyclic Guanosine 3',5'-Cyclic Monophosphate-Dependent Protein Kinase Circulation, November 4, 2003; 108(18): 2172 - 2183. [Full Text] [PDF]
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C. Kitiyakara, T. Chabrashvili, Y. Chen, J. Blau, A. Karber, S. Aslam, W. J. Welch, and C. S. Wilcox Salt Intake, Oxidative Stress, and Renal Expression of NADPH Oxidase and Superoxide Dismutase J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2775 - 2782. [Abstract] [Full Text] [PDF]
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D. Wang, Y. Chen, T. Chabrashvili, S. Aslam, L. J. Borrego Conde, J. G. Umans, and C. S. Wilcox Role of Oxidative Stress in Endothelial Dysfunction and Enhanced Responses to Angiotensin II of Afferent Arterioles from Rabbits Infused with Angiotensin II J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2783 - 2789. [Abstract] [Full Text] [PDF]
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M.-S. Zhou, A. G. Adam, E. A. Jaimes, and L. Raij In Salt-Sensitive Hypertension, Increased Superoxide Production Is Linked to Functional Upregulation of Angiotensin II Hypertension, November 1, 2003; 42(5): 945 - 951. [Abstract] [Full Text] [PDF]
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S. Fujii, L. Zhang, J. Igarashi, and H. Kosaka L-Arginine Reverses p47phox and gp91phox Expression Induced by High Salt in Dahl Rats Hypertension, November 1, 2003; 42(5): 1014 - 1020. [Abstract] [Full Text] [PDF]
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K. K. Griendling and G. A. FitzGerald Oxidative Stress and Cardiovascular Injury: Part II: Animal and Human Studies Circulation, October 28, 2003; 108(17): 2034 - 2040. [Full Text] [PDF]
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Y. Wang, K. P. Patel, K. G. Cornish, K. M. Channon, and I. H. Zucker nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1660 - H1667. [Abstract] [Full Text] [PDF]
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A. D. Dobrian, S. D. Schriver, T. Lynch, and R. L. Prewitt Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity Am J Physiol Renal Physiol, October 1, 2003; 285(4): F619 - F628. [Abstract] [Full Text] [PDF]
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G. E. Callera, R. M. Touyz, S. A. Teixeira, M. N. Muscara, M. H. C. Carvalho, Z. B. Fortes, D. Nigro, E. L. Schiffrin, and R. C. Tostes ETA Receptor Blockade Decreases Vascular Superoxide Generation in DOCA-Salt Hypertension Hypertension, October 1, 2003; 42(4): 811 - 817. [Abstract] [Full Text] [PDF]
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K. K. Koh, J. Y. Ahn, S. H. Han, D. S. Kim, D. K. Jin, H. S. Kim, M.-S. Shin, T. H. Ahn, I. S. Choi, and E. K. Shin Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients J. Am. Coll. Cardiol., September 3, 2003; 42(5): 905 - 910. [Abstract] [Full Text] [PDF]
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L. Li, S. W. Watts, A. K. Banes, J. J. Galligan, G. D. Fink, and A. F. Chen NADPH Oxidase-Derived Superoxide Augments Endothelin-1-Induced Venoconstriction in Mineralocorticoid Hypertension Hypertension, September 1, 2003; 42(3): 316 - 321. [Abstract] [Full Text] [PDF]
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B. Lassegue and R. E. Clempus Vascular NAD(P)H oxidases: specific features, expression, and regulation Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R277 - R297. [Abstract] [Full Text] [PDF]
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S. P. Didion and F. M. Faraci Angiotensin II Produces Superoxide-Mediated Impairment of Endothelial Function in Cerebral Arterioles Stroke, August 1, 2003; 34(8): 2038 - 2042. [Abstract] [Full Text] [PDF]
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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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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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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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B. Yuan, M. Liang, Z. Yang, E. Rute, N. Taylor, M. Olivier, and A. W. Cowley Jr. Gene expression reveals vulnerability to oxidative stress and interstitial fibrosis of renal outer medulla to nonhypertensive elevations of ANG II Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2003; 284(5): R1219 - R1230. [Abstract] [Full Text] [PDF]
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C. Rugale, S. Delbosc, J.-P. Cristol, A. Mimran, and B. Jover Sodium restriction prevents cardiac hypertrophy and oxidative stress in angiotensin II hypertension Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1744 - H1750. [Abstract] [Full Text] [PDF]
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 Z S Nedeljkovic, N Gokce, and J Loscalzo Mechanisms of oxidative stress and vascular dysfunction Postgrad. Med. J., April 1, 2003; 79(930): 195 - 200. [Abstract] [Full Text] [PDF]
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