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Oxidative Stress in Aging pp 229–251Cite as

Oxidative Stress in Hypertension

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Part of the book series: Aging Medicine ((AGME))

Summary

Oxidative stress refers to increases in reactive metabolites of molecular oxygen that occur as a result of increases in formation and/or reductions in scavenging or degradation. Oxidative stress plays an important role in the pathogenesis of hypertension. In this chapter, we examine the relationship between oxidative stress in the development and maintenance of hypertension and changes in vascular structure and function. We focus primarily on enzymatic systems that contribute to oxidative stress, such as NAD(P)H oxidase, and those that limit oxidative stress, including superoxide dismutase, glutathione peroxidase, and catalase.

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References

  1. Commoner B, Townsend J, Pake GE. Free radicals in biological materials. Nature 1954;174:689–691.

    PubMed  CAS  Google Scholar 

  2. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser T. Free radicals and antioxi-dants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44–84.

    PubMed  CAS  Google Scholar 

  3. Darley-Usmar V, Halliwell B. Blood radicals: reactive nitrogen species, reactive oxygen species, transition metal ions, and the vascular system. Pharm Res 1996;13:649–662.

    PubMed  CAS  Google Scholar 

  4. Faraci FM, Didion SP. Vascular protection: superoxide dismutase isoforms in the vessel wall. Arterioscler Thromb Vasc Biol 2004;24:1367–1373.

    PubMed  CAS  Google Scholar 

  5. Wei EP, Kontos HA, Christman CW, DeWitt DS, Povlishock JT. Superoxide generation and reversal of acetylcholine-induced cerebral arteriolar dilation after acute hypertension. Circ Res 1985;57:781–787.

    PubMed  CAS  Google Scholar 

  6. Luscher TF, Vanhoutte PM. Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. Hypertension 1986;8:344–348.

    PubMed  CAS  Google Scholar 

  7. Mayhan WG, Faraci FM, Heistad DD. Impairment of endothelium-dependent responses of cerebral arterioles in chronic hypertension. Am J Physiol 1987;253:H1435–H1440.

    PubMed  CAS  Google Scholar 

  8. Auch-Schwelk W, Katusic ZS, Vanhoutte PM. Contractions to oxygen-derived free radicals are augmented in aorta of the spontaneously hypertensive rat. Hypertension 1989;13:859–864.

    PubMed  CAS  Google Scholar 

  9. Rubanyi GM, Vanhoutte PM. Oxygen-derived free radicals, endothelium, and responsiveness of vascular smooth muscle. Am J Physiol 1986;250:H815–H821.

    PubMed  CAS  Google Scholar 

  10. Mayhan WG. Impairment of endothelium-dependent dilatation of basilar artery during chronic hypertension. Am J Physiol 1990;259:H1455–H1462.

    PubMed  CAS  Google Scholar 

  11. Yang D, Feletou M, Boulanger CM, Wu HF, Levens N, Zhang JN, Vanhoutte PM. Oxygen-derived free radicals mediate endothelium-dependent contractions to acetylcholine in aortas from spontaneously hypertensive rats. Br J Pharmacol 2002;136:104–110.

    PubMed  CAS  Google Scholar 

  12. Ceriello A, Giugliano D, Quatraro A, Lefebvre PJ. Anti-oxidants show an anti-hypertensive effect in diabetic and hypertensive subjects. Clin Sci 1991;81:739–742.

    PubMed  CAS  Google Scholar 

  13. Nakazono K, Watanabe N, Matsuno J, Saski J, Sato T, Inoue M. Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci U S A 1991;88:10045–10048.

    PubMed  CAS  Google Scholar 

  14. Pedro-Botet J, Covas MI, Martin S, Rubies-Prat J. Decreased endogenous antioxidant enzymatic status in essential hypertension. J Hum Hypertens 2000;14:343–345.

    PubMed  CAS  Google Scholar 

  15. Redon J, Oliva MR, Tormos C et al. Antioxidant activities and oxidative stress byproducts in human hypertension. Hypertension 2003;41:1096–1101.

    PubMed  CAS  Google Scholar 

  16. Chaves FJ, Mansego ML, Blesa S et al. Inadequate cytoplasmic antioxidant enzymes response contributes to the oxidative stress in human hypertension. Am J Hypertens 2007;20:62–69.

    PubMed  CAS  Google Scholar 

  17. Saez GT, Tormos C, Giner V, Chaves J, Lozano JV, Iradi A, Redon J. Factors related to the impact of antihypertensive treatment in antioxidant activities and oxidative stress by-products in human hypertension. Am J Hypertens 2004;17:809–816

    PubMed  CAS  Google Scholar 

  18. Ulker S, McMaster D, McKeown PP, Bayraktutan U. Impaired activities of antioxidant enzymes elicit endothelial dysfunction in spontaneous hypertensive rats despite enhanced vascular nitric oxide generation. Cardiovasc Res 2003;59:488–500.

    PubMed  CAS  Google Scholar 

  19. Zhang Y, Jang R, Mori TA, Croft KD, Schyvens CG, McKenzie KU, Whitworth JA. The anti-oxidant Tempol reverses and partially prevents adrenocorticotrophic hormone-induced hypertension in the rat. J Hypertens 2003;21:1513–1518.

    PubMed  CAS  Google Scholar 

  20. Laursen JB, Rajagopalan S, Galis Z, Tarpey M, Freeman BA, Harrison DG. Role of superoxide in angiotensin II-induced but not catecholamine-induced hypertension. Circulation 1997;95:588–593.

    PubMed  CAS  Google Scholar 

  21. Rey FE, Cifuentes ME, Kiarash A, Quinn MT, Pagano PJ. Novel competitive inhibitor of NAD(P)H oxidase assembly attenuates vascular O2 • and systolic blood pressure in mice. Circ Res 2001;89:408–414.

    PubMed  CAS  Google Scholar 

  22. Ortiz MC, Manriquez MC, Romero JC, Juncos LA. Antioxidants block angiotensin II-induced increases in blood pressure and endothelin. Hypertension 2001;38:655–659.

    PubMed  CAS  Google Scholar 

  23. Nishiyama A, Fukui T, Fujisawa Y, Rahman M, Tian RX, Kimura S, Abe Y. Systemic and regional hemodynamic responses to Tempol in angiotensin II-infused hypertensive rats. Hypertension 2001;37:77–83.

    PubMed  CAS  Google Scholar 

  24. Wang HD, Xu S, Johns DG, Du Y, Quinn MT, Cayatte AJ, Cohen RA. Role of NADPH oxidase in the vascular hypertrophic and oxidative stress response to angiotensin II in mice. Circ Res 2001;88:947–953.

    PubMed  CAS  Google Scholar 

  25. Dobrian AD, Schriver SD, Prewitt RL. Role of angiotensin II and free radicals in blood pressure regulation in a rat model of renal hypertension. Hypertension 2001;38:361–366.

    PubMed  CAS  Google Scholar 

  26. Meng S, Roberts LJ II, Cason GW, Curry TS, Manning RD Jr. Superoxide dismutase and oxidative stress in Dahl salt-sensitive and -resistant rats. Am J Physiol 2002;283: R732–R738.

    CAS  Google Scholar 

  27. Swei A, Lacy F, DeLano FA, Schmid-Schonbein GW. Oxidative stress in the Dahl hypertensive rat. Hypertension 1997;30:1628–1633.

    PubMed  CAS  Google Scholar 

  28. Schnackenberg CG, Welch WJ, Wilcox CS. Normalization of blood pressure and renal vascular resistance in SHR with a membrane-permeable superoxide dismutase mimetic: role of nitric oxide. Hypertension 1998;32:59–64.

    PubMed  CAS  Google Scholar 

  29. Schnackenberg CG, Wilcox CS. Two-week administration of tempol attenuates both hypertension and renal excretion of 8-iso prostaglandin F2-α. Hypertension 1999; 33:424–428.

    PubMed  CAS  Google Scholar 

  30. Yanes L, Romero D, Iliescu R et al. Systemic arterial pressure response to two weeks of Tempol therapy in SHR: involvement of NO, the RAS, and oxidative stress. Am J Physiol 2005;288:R903–R908.

    CAS  Google Scholar 

  31. Park JB, Touyz RM, Chen X, Schiffrin EL. Chronic treatment with a superoxide dismutase mimetic prevents vascular remodeling and progression of a hypertension in salt loaded stroke-prone spontaneously hypertensive rats. Am J Hypertens 2002;15:78–84.

    PubMed  CAS  Google Scholar 

  32. Uddin M, Yang H, Shi M, Polley-Mandal M, Guo Z. Elevation of oxidative stress in the aorta of genetically hypertensive mice. Mech Ageing Dev 2003;124:811–817.

    PubMed  CAS  Google Scholar 

  33. Bendall JK, Rinze R, Adlam D, Tatham AL, de Bono J, Channon KM. Endothelial Nox2 overexpression potentiates vascular oxidative stress and hemodynamic response to angiotensin II. Studies in endothelial-targeted Nox2 transgenic mice. Circ Res 2007;100:1016–1025.

    PubMed  CAS  Google Scholar 

  34. Laude K, Cai H, Fink B et al. Hemodynamic and biochemical adaptations to vascular smooth muscle overexpression of p22phox in mice. Am J Physiol 2005;288:H7–H12.

    CAS  Google Scholar 

  35. Didion SP, Ryan MJ, Baumbach GL, Sigmund CD, Faraci FM. Superoxide contributes to vascular dysfunction in mice that express human renin and angiotensinogen. Am J Physiol 2002;283:H1569–H1576.

    CAS  Google Scholar 

  36. Baumbach GL, Sigmund CD, Faraci FM. Cerebral arteriolar structure in mice overexpress-ing human renin and angiotensinogen. Hypertension 2003;41:50–55.

    PubMed  CAS  Google Scholar 

  37. Touyz RM, Mercure C, He Y et al. Angiotensin II-dependent chronic hypertension and cardiac hypertrophy are unaffected by gp91phox-containing NADPH oxidase. Hypertension 2005;45:530–537.

    PubMed  CAS  Google Scholar 

  38. Hassanain HH, Gregg D, Marcelo ML et al. Hypertension caused by transgenic overexpression of Rac1. Antioxid Redox Signal 2007;9:91–100.

    PubMed  CAS  Google Scholar 

  39. Jin L, Beswick RA, Yamamoto T et al. Increased reactive oxygen species contributes to kidney injury in mineralocorticoid hypertensive rats. J Physiol Pharmacol 2006;57:343–357.

    PubMed  CAS  Google Scholar 

  40. Beswick RA, Dorrance AM, Leite R, Webb RC. NADH/NADPH oxidase and enhanced super-oxide production in the mineralocorticoid hypertensive rat. Hypertension 2001;38:1107–1111.

    PubMed  CAS  Google Scholar 

  41. Somers MJ, Mavromatis K, Galis ZS, Harrison DG. Vascular superoxide production and vasomotor function in hypertension induced by deoxycorticosterone acetate-salt. Circulation 2000;101:1722–1728.

    PubMed  CAS  Google Scholar 

  42. Heitzer T, Wenzel U, Hink U et al. Increased NAD(P)H oxidase-mediated superoxide production in renovascular hypertension: evidence for an involvement of protein kinase C. Kidney Int 1999;55:252–260.

    PubMed  CAS  Google Scholar 

  43. Jung O, Marklund SL, Xia N, Busse R, Brandes RP. Inactivation of extracellular superoxide dismutase contributes to the development of high-volume hypertension. Arterioscler Thromb Vasc Biol 2007;27:470–477.

    PubMed  CAS  Google Scholar 

  44. Lacy F, O'Connor DT, Schmid-Schonbein GW. Plasma hydrogen peroxide production in hypertensives and normotensive subjects at genetic risk of hypertension. J Hypertens 1998;16:291–303.

    PubMed  CAS  Google Scholar 

  45. Lacy F, Kailasam MT, O'Connor DT, Schmid-Schonbein GW, Parmer RJ. Plasma hydrogen peroxide production in human essential hypertension: role of heredity, gender, and ethnicity. Hypertension 2000;36:878–884.

    PubMed  CAS  Google Scholar 

  46. Kumar KV, Das UN. Are free radicals involved in the pathobiology of human essential hypertension? Free Radic Res Commun 1993;19:59–66.

    PubMed  CAS  Google Scholar 

  47. Fortuno A, Olivan S, Beloqui O, San Jose G, Moreno MU, Diez J, Zalba G. Association of increased phagocytic NADPH oxidase-dependent superoxide production with diminished nitric oxide generation in essential hypertension. J Hypertens 2004;22:2169–2175.

    PubMed  CAS  Google Scholar 

  48. Garcia CE, Kilcoyne CM, Cardillo C, Cannon RO III, Quyyumi AA, Panza JA. Effect of copper-zinc superoxide dismutase on endothelium-dependent vasodilation in patients with essential hypertension. Hypertension 1995;26:863–868.

    PubMed  CAS  Google Scholar 

  49. Schiffrin EL, Deng LY, Larochelle P. Progressive improvement in the structure of resistance arteries of hypertensive patients after treatment with an angiotensin I-converting enzyme inhibitor comparison with effects of a β-blocker. Am J Hypertens 1995;8:229–236.

    PubMed  CAS  Google Scholar 

  50. Schiffrin EL, Deng LY. Structure and function of resistance arteries of hypertensive patients treated with a β-blocker or a calcium channel antagonist. J Hypertens 1996;14:1247–1255.

    PubMed  CAS  Google Scholar 

  51. Rizzoni D, Muiesan ML, Porteri E et al. Effects of long-term antihypertensive treatment with lisinopril on resistance arteries in hypertensive patients with left ventricular hypertrophy. J Hypertens 1997;15:197–204.

    PubMed  CAS  Google Scholar 

  52. Minuz P, Patrignani P, Gaino S et al. Increased oxidative stress and platelet activation in patients with hypertension and renovascular disease. Circulation 2002;106:2800–2805.

    PubMed  CAS  Google Scholar 

  53. Higashi Y, Sasaki S, Nakagawa K, Matsuura H, Oshima T, Chayama K. Endothelial function and oxidative stress in renovascular hypertension. N Engl J Med 2002;346:1954–1962.

    PubMed  CAS  Google Scholar 

  54. Rizzoni D, Porteri E, Castellano M et al. Vascular hypertrophy and remodeling in secondary hypertension. Hypertension 1996;28:785–790.

    PubMed  CAS  Google Scholar 

  55. Rizzoni D, Porteri E, Guefi D et al. Cellular hypertrophy in subcutaneous small arteries of patients with renovascular hypertension. Hypertension 2000;35:931–935.

    PubMed  CAS  Google Scholar 

  56. Fennell JP, Brosnan MJ, Frater AJ et al. Adenovirus-mediated overexpression of extracellular superoxide dismutase improves endothelial dysfunction in a rat model of hypertension. Gene Ther 2002;9:110–117.

    PubMed  CAS  Google Scholar 

  57. Alexander M Y, Brosnan MJ, Hamilton CA et al. Gene transfer of endothelial nitric oxide synthase but not Cu/Zn superoxide dismutase restores nitric oxide availability in the SHRSP. Cardiovasc Res 2000;47:609–617.

    PubMed  CAS  Google Scholar 

  58. Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 1994;74:1141–1148.

    PubMed  CAS  Google Scholar 

  59. Cifuentes ME, Rey FE, Carretero OA, Pagano PJ. Upregulation of p67(phox) and gp91(phox) in aortas from angiotensin II-infused mice. Am J Physiol 2000;279:H2234–H2240.

    CAS  Google Scholar 

  60. Pagano PJ, Clark JK, Cifuentes-Pagano ME, Clark SM, Callis GM, Quinn MT. Localization of a constitutively active, phagocyte-like NADPH oxidase in rabbit aortic adventitia: enhancement by angiotensin II. Proc Nat Acad Sci U S A 1997;94:14483–14488.

    CAS  Google Scholar 

  61. Pagano PJ, Chanock SJ, Siwik DA, Colucci WS, Clark JK. Angiotensin II induces p67phox mRNA expression and NADPH oxidase superoxide generation in rabbit aortic adventitial fibroblasts. Hypertension 1998;32:331–337.

    PubMed  CAS  Google Scholar 

  62. Bleeke T, Zhang H, Madamanchi N, Patterson C, Faber JE. Catecholamine-induced vascular wall growth is dependent on generation of reactive oxygen species. Circ Res 2004;94:37–45.

    PubMed  CAS  Google Scholar 

  63. Ghiadoni L, Magagna A, Versari D et al. Different effect of antihypertensive drugs on conduit artery endothelial function. Hypertension 2003;41:1281–1286.

    PubMed  CAS  Google Scholar 

  64. Ghiadoni L, Huang Y, Magagna A, Burali S, Taddei S, Salvetti A. Effect of acute blood pressure reduction on endothelial function in the brachial artery of patients with essential hypertension. J Hypertens 2001;19:547–551.

    PubMed  CAS  Google Scholar 

  65. Cohuet G, Struijker-Boudier H. Mechanisms of target organ damage caused by hypertension: therapeutic potential. Pharmacol Ther 2006;111:81–98.

    PubMed  CAS  Google Scholar 

  66. Thuillez C, Richard V. Targeting endothelial dysfunction in hypertensive subjects. J Hum Hypertens 2005;19:S21–S25.

    PubMed  CAS  Google Scholar 

  67. Zimmerman MC, Lazartiques E, Lang JA et al. Superoxide mediates the actions of angiotensin II in the central nervous system. Circ Res 2002;91:1038–1045.

    PubMed  CAS  Google Scholar 

  68. Makino A, Skelton MM, Zou AP, Cowley AW Jr. Increased renal medullary H2O2 leads to hypertension. Hypertension 2003;42:25–30.

    PubMed  CAS  Google Scholar 

  69. Makino A, Skelton MM, Zou AP, Roman RJ, Cowley AW Jr. Increased renal medullary oxidative stress produces hypertension. Hypertension 2002;39:667–672.

    PubMed  CAS  Google Scholar 

  70. Wilcox CS. Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension. Am J Physiol 2005; 289:R913–R935.

    CAS  Google Scholar 

  71. Zimmerman MC, Davisson RL. Redox signaling in central neural regulation of cardiovascular function. Prog Biophys Mol Biol 2004;84:125–149.

    PubMed  CAS  Google Scholar 

  72. Geiszt M. NADPH oxidases: new kids on the block. Cardiovasc Res 2006;71:289–299.

    PubMed  CAS  Google Scholar 

  73. Bedard K, Krause KH. The Nox family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007;87:245–313.

    PubMed  CAS  Google Scholar 

  74. Zalba G, San Jose G, Moreno MU et al. Oxidative stress in arterial hypertension: role of NAD(P)H oxidase. Hypertension 2001;38:1395–1399.

    PubMed  CAS  Google Scholar 

  75. Fortuno A, San Jose G, Moreno MU, Diez J, Zalba G. Oxidative stress and vascular remodelling. Exp Physiol 2005;90:457–462.

    PubMed  CAS  Google Scholar 

  76. Lassegue B, Griendling KK. Reactive oxygen species in hypertension: an update. Am J Hypertens 2004;17:852–860.

    PubMed  CAS  Google Scholar 

  77. Guzik TJ, Sadowski J, Kapelak B et al. Systemic regulation of vascular NAD(P)H oxidase activity and Nox isoform expression in human arteries and veins. Arterioscler Thromb Vasc Biol 2004;24:1614–1620.

    PubMed  CAS  Google Scholar 

  78. Hamilton CA, Brosnan MJ, Al-Benna S, Berg G, Dominiczak AF. NAD(P)H oxidase inhibition improves endothelial function in rat and human blood vessels. Hypertension 2002;40:755–762.

    PubMed  CAS  Google Scholar 

  79. Brosnan MJ, Hamilton CA, Graham D, Lygate CA, Jardine E, Dominiczak AF. Irbesartan lowers superoxide levels and increases nitric oxide bioavailability in blood vessels from spontaneously hypertensive stroke-prone rats. J Hypertens 2002;20:281–286.

    PubMed  CAS  Google Scholar 

  80. Rodrigo E, Maeso R, Munoz-Garcia R et al. Endothelial dysfunction in spontaneously hypertensive rats: consequences of chronic treatment with losartan or captopril. J Hypertens 1997;15:613–618.

    PubMed  CAS  Google Scholar 

  81. Ago T, Kitazono T, Ooboshi H et al. Nox4 as the major catalytic component of an endothelial NAD(P)H oxidase. Circulation 2004;109:227–233.

    PubMed  CAS  Google Scholar 

  82. Ago T, Kitazono T, Kuroda J et al. NAD(P)H oxidases in rat basilar artery endothelial cells. Stroke 2005;36:1040–1046.

    PubMed  CAS  Google Scholar 

  83. Miller AA, Drummond GR, Schmidt HH, Sobey CG. NADPH oxidase activity and function are profoundly greater in cerebral versus systemic arteries. Circ Res 2005;97:1055–1062.

    PubMed  CAS  Google Scholar 

  84. Matsuno K, Yamada H, Iwata K et al. Nox1 is involved in angiotensin II-mediated hypertension: a study in Nox1-deficient mice. Circulation 2005;112:2677–2685.

    PubMed  CAS  Google Scholar 

  85. Gavazzi G, Banfi B, Deffert C, Fiette L, Schappi M, Herrmann F, Krause KH. Decreased blood pressure in NOX1-deficient mice. FEBS Lett 2006;580:497–504.

    PubMed  CAS  Google Scholar 

  86. Dikalova A, Clempus R, Lassegue B et al. Nox1 overexpression potentiates angiotensin II-induced hypertension and vascular smooth muscle hypertrophy in transgenic mice. Circulation 2005;112:2668–2676.

    PubMed  CAS  Google Scholar 

  87. Wang HD, Xu S, Johns DG, Du Y, Quinn MT, Cayatte AJ, Cohen RA. Role of NADPH oxi-dase in the vascular hypertrophic response and oxidative stress response to angiotensin II in mice. Circ Res 2001;88:947–953.

    PubMed  CAS  Google Scholar 

  88. Byrne JA, Grieve DJ, Bendall JK et al. Contrasting roles of NADPH oxidase isoforms in pressure-overload versus angiotensin II-induced cardiac hypertrophy. Circ Res 2003;93: 802–804.

    PubMed  CAS  Google Scholar 

  89. Bendall JK, Cave AC, Heymes C, Gall N, Shah AM. Pivitol role of a gp91(phox) -containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice. Circulation 2002;105;293–296.

    PubMed  CAS  Google Scholar 

  90. Jung O, Schreiber JG, Geiger H, Pedrazzini T, Busse R, Brandes RP. gp91phox -containing NADPH oxidase mediates endothelial dysfunction in renovascular hypertension. Circulation 2004;109:1795–1801.

    PubMed  CAS  Google Scholar 

  91. Weber DS, Rocic P, Mellis AM et al. Angiotensin II-induced hypertrophy is potentiated in mice overexpressing p22phox in vascular smooth muscle. Am J Physiol 2005;288:H37–H42.

    CAS  Google Scholar 

  92. Fukui T, Ishizaka N, Rajagopalan S et al. p22phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats. Circ Res 1997;80:45–51.

    PubMed  CAS  Google Scholar 

  93. Zalba G, San Jose G, Moreno MU, Fortuno A, Diez J. NADPH oxidase-mediated oxidative stress: genetic studies of the p22(phox) gene in hypertension. Antioxid Redox Signal 2005;7:1327–1336.

    PubMed  CAS  Google Scholar 

  94. Zalba G, San Jose G, Beaumont FJ, Fortuno MA, Fortuno A, Diez J. Polymorphisms and promoter overactivity of the p22(phox) gene in vascular smooth muscle cells from spontaneously hypertensive rats. Circ Res 2001;88:217–222.

    PubMed  CAS  Google Scholar 

  95. San Jose G, Moreno MU, Olivan S, Beloqui O, Fortuno A, Diez J, Zalba G. Functional effect of the p22phox -930A/G polymorphism on p22phox expression and NADPH oxidase activity in hypertension. Hypertension 2004;44:163–169.

    PubMed  CAS  Google Scholar 

  96. Moreno MU, San Jose G, Orbe J, Paramo JA, Beloqui O, Diez J, Zalba G. Preliminary characterization of the promoter of the human p22(phox) gene: identification of a new polymorphism associated with hypertension. FEBS Lett 2003;542:27–31.

    PubMed  CAS  Google Scholar 

  97. Castejon AM, Bracero J, Hoffmann IS, Alfieri AB, Cubeddu LX. NAD(P)H oxidase p22phox gene C242T polymorphism, nitric oxide production, salt sensitivity and cardiovascular risk factors in Hispanics. J Hum Hypertens 2006;20:772–779.

    PubMed  CAS  Google Scholar 

  98. Kokubo Y, Iwai N, Tago N et al. Association analysis between hypertension and CYBA, CLCNKB, and KCNMB1 functional polymorphisms in the Japanese population-the Suita study. Circ J 2005;69:138–142.

    PubMed  CAS  Google Scholar 

  99. Lavigne MC, Malech HL, Holland SM, Leto TL. Genetic demonstration of p47phox-depend-ent superoxide anion production in murine vascular smooth muscle cells. Circulation 2001;104:79–84.

    PubMed  CAS  Google Scholar 

  100. Touyz RM, Yao G, Schiffrin EL. c-Src induces phosphorylation and translocation of p47phox: role in superoxide generation by angiotensin II in human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2003;23:981–987.

    PubMed  CAS  Google Scholar 

  101. Li JM, Shah AM. Mechanism of endothelial cell NADPH oxidase activation by angiotensin II. Role of the p47phox subunit. J Biol Chem 2003;278:12094–12100.

    PubMed  CAS  Google Scholar 

  102. Li JM, Mullen AM, Yun S, Wientjes F, Brouns GY, Thrasher AJ, Shah AM. Essential role of the NADPH oxidase subunit p47(phox) in endothelial cell superoxide production in response to phorbol ester and tumor necrosis factor-alpha. Circ Res 2002;90:143–150.

    PubMed  CAS  Google Scholar 

  103. Li JM, Wheatcroft S, Fan LM, Kearney MT, Shah AM. Opposing roles of p47phox in basal versus angiotensin II-stimulated alterations in vascular O2 • production, vascular tone, and mitogen-activated protein kinase activation. Circulation 2004;109:1307–1313.

    PubMed  CAS  Google Scholar 

  104. Landmesser U, Cai H, Dikalov S et al. Role of p47(phox) in vascular oxidative stress and hypertension caused by angiotensin II. Hypertension 2002;40:511–515.

    PubMed  CAS  Google Scholar 

  105. Cai H, Li Z, Dikalov S et al. NAD(P)H oxidase-derived hydrogen peroxide mediates endothelial nitric oxide production in response to angiotensin II. J Biol Chem 2002;277:48311–48317.

    PubMed  CAS  Google Scholar 

  106. Grote K, Ortmann M, Salguero G et al. Critical role for p47phox in renin-angiotensin system activation and blood pressure regulation. Cardiovasc Res 2006;71:596–605.

    PubMed  CAS  Google Scholar 

  107. Hsich E, Segal BH, Pagano PJ et al. Vascular effects following homozygous disruption of p47(phox): an essential component of NADPH oxidase. Circulation 2000;101:1234–1236.

    PubMed  CAS  Google Scholar 

  108. Brandes RP, Miller FJ, Beer S et al. The vascular NADPH oxidase subunit p47phox is involved in redox-mediated gene expression. Free Radic Biol Med 2002;32:1116–1122.

    PubMed  CAS  Google Scholar 

  109. Wu F, Schuster DP, Tyml K, Wilson JX. Ascorbate inhibits NADPH oxidase subunit p47phox expression in microvascular endothelial cells. Free Radic Biol Med 2007;42:124–131.

    PubMed  CAS  Google Scholar 

  110. Kenney RT, Malech HL, Epstein ND, Roberts RL, Leto TL. Characterization of the p67phox gene: genomic organization and restriction fragment length polymorphism analysis for prenatal diagnosis in chronic granulomatous disease. Blood 1993;82:3739–3744.

    PubMed  CAS  Google Scholar 

  111. Hordijk PL. Regulation of NADPH oxidases: the role of Rac proteins. Circ Res 2006; 98:453–462.

    PubMed  CAS  Google Scholar 

  112. Heyworth PG, Bohl BP, Bokoch GM, Curnutte JT Rac translocates independently of the neutrophil NADPH oxidase components p47phox and p67phox. Evidence for its interaction with flavocytochrome b558. J Biol Chem 1994;269:30749–30752.

    PubMed  CAS  Google Scholar 

  113. Sundaresan M, Yu ZX, Ferrans VJ et al. Regulation of reactive-oxygen-species generation in fibroblasts by Rac1. Biochem J 1996;318:379–382.

    PubMed  CAS  Google Scholar 

  114. Roberts AW, Kim C, Zhen L et al. Deficiency of the hematopoietic cell-specfic Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. Immunity 1999;10:183–196.

    PubMed  CAS  Google Scholar 

  115. Sugihara K, Nakatsuji N, Nakamura K et al. Rac1 is required for the formation of three germ layers during gastrulation. Oncogene 1998;17:3427–3433.

    PubMed  CAS  Google Scholar 

  116. Zimmerman MC, Dunlay RP, Lazartigues E et al. Requirement for Rac1-dependent NADPH oxidase in the cardiovascular and dipsogenic actions of angiotensin II in the brain. Circ Res 2004;95:532–539.

    PubMed  CAS  Google Scholar 

  117. Morikawa K, Shimokawa H, Matoba T et al. Pivotal role of Cu,Zn-superoxide dismutase in endothelium-dependent hyperpolarization. J Clin Invest 2003;112:1871–1879.

    PubMed  CAS  Google Scholar 

  118. Ho YS, Gargano M, Cao J, Bronson RT, Heimler I, Hutz RJ. Reduced fertility in female mice lacking copper-zinc superoxide dismutase. J Biol Chem 1998;273:7765–7769.

    PubMed  CAS  Google Scholar 

  119. Carlsson LM, Jonsson J, Edlund T, Marklund SL. Mice lacking extracellular superoxide dismutase are more sensitive to hyperoxia. Proc Natl Acad Sci U S A 1995;92:6264–6268.

    PubMed  CAS  Google Scholar 

  120. Didion SP, Ryan MJ, Didion LA, Fegan PE, Sigmund CD, Faraci FM. Increase superoxide and vascular dysfunction in CuZnSOD-deficient mice. Circ Res 2002;91:938–944.

    PubMed  CAS  Google Scholar 

  121. Cooke CL, Davidge ST. Endothelial-dependent vasodilation is reduced in mesenteric arteries from superoxide dismutase knockout mice. Cardiovasc Res 2003;60:635–642.

    PubMed  CAS  Google Scholar 

  122. Baumbach GL, Didion SP, Faraci FM. Hypertrophy of cerebral arterioles in mice deficient in expression of the gene for CuZn superoxide dismutase. Stroke 2006;37:1850–1855.

    PubMed  CAS  Google Scholar 

  123. Didion SP, Kinzenbaw DA, Faraci FM. Critical role for CuZn-superoxide dismutase in preventing angiotensin II-induced endothelial dysfunction. Hypertension 2005;46:1147–1153.

    PubMed  CAS  Google Scholar 

  124. Didion SP, Kinzenbaw DA, Schrader LI, Faraci FM. Heterozygous CuZn superoxide dismutase deficiency produces a vascular phenotype with aging. Hypertension 2006;48:1072–1079.

    PubMed  CAS  Google Scholar 

  125. Didion SP, Faraci FM. Ceramide-induced impairment of endothelial function is prevented by CuZn superoxide dismutase overexpression. Arterioscler Thromb Vasc Biol 2005;25: 90–95.

    PubMed  CAS  Google Scholar 

  126. Zhang Y, Griendling KK, Dikalova A, Owens GK, Taylor WR. Vascular hypertrophy in angiotensin II-induced hypertension is mediated by vascular smooth muscle cell-derived H2O2. Hypertension 2005;46:732–737.

    PubMed  CAS  Google Scholar 

  127. Epstein CJ, Avraham KB, Lovett M et al. Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome. Proc Natl Acad Sci U S A 1987;84:8044–8048.

    PubMed  CAS  Google Scholar 

  128. Ceballos I, Nicole A, Briand P et al. Expression of human Cu-Zn superoxide dismutase gene in transgenic mice: model for gene dosage effect in Down Syndrome. Free Radic Res Commun 1991;12–13 Pt 2:581–589.

    Google Scholar 

  129. Ceballos-Picot I, Nicole A, Briand P et al. Neuronal-specific expression of human copper-zinc superoxide dismutase gene in transgenic mice: animal model of gene dosage effects in Down's syndrome. Brain Res 1991;552:198–214.

    PubMed  CAS  Google Scholar 

  130. Wang P, Chen H, Qin H et al. Overexpression of human copper, zinc-superoxide dismutase (SOD1) prevents postischemic injury. Proc Natl Acad Sci U S A 1998;95:4556–4560.

    PubMed  CAS  Google Scholar 

  131. Przedborski S, Jackson-Lewis V, Kostic V, Carlson E, Epstein CJ, Cadet JL. Superoxide dis-mutase, catalase, and glutathione peroxidase activities in copper/zinc-superoxide dismutase transgenic mice. J Neurochem 1992;58:1760–1767.

    PubMed  CAS  Google Scholar 

  132. Didion SP, Kinzenbaw DA, Fegan PE, Didion LA, Faraci FM. Overexpression of CuZn-SOD prevents lipopolysaccharide-induced endothelial expression. Stroke 2004;35:1963–1967.

    PubMed  CAS  Google Scholar 

  133. Wang HD, Johns DG, Xu S, Cohen RA. Role of superoxide anion in regulating pressor and vascular hypertrophic response to angiotensin II. Am J Physiol 2002;282:H1697–H1702.

    CAS  Google Scholar 

  134. Forsberg L, de Faire U, Morgenstern R. Oxidative stress, human genetic variation, and disease. Arch Biochem Biophys 2001;389;84–93.

    PubMed  CAS  Google Scholar 

  135. Morrison RA, McGrath A, Davidson G, Brown JJ, Murray GD, Lever AF. Low blood pressure in Down's syndrome; a link with Alzheimer's disease? Hypertension 1996;28:569–575.

    PubMed  CAS  Google Scholar 

  136. Macmillan-Crow LA, Cruthirds DL. Invited review: manganese superoxide dismutase in disease. Free Radic Res 2001;34:325–336.

    PubMed  CAS  Google Scholar 

  137. Lebovitz RM, Zhang H, Vogel H et al. Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc Natl Acad Sci U S A 1996;93:9782–9787.

    PubMed  CAS  Google Scholar 

  138. Li Y, Huang TT, Carlson EJ et al. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 1995;11:376–381.

    PubMed  CAS  Google Scholar 

  139. Rodriguez-Iturbe B, Sepassi L, Quiroz Y, Ni Z, Wallace DC, Vaziri ND. Association of mitochondrial SOD deficiency with salt-sensitive hypertension and accelerated renal senescence. J Appl Physiol 2007;102:255–260.

    PubMed  CAS  Google Scholar 

  140. Chrissobolis S, Didion SP, Faraci FM. Protective role of manganese superoxide dismutase against angiotensin II-induced, Nox2-dependent cerebral endothelial dysfunction. (Abstract). FASEB J 2007;21:A1262–A1263.

    Google Scholar 

  141. Shao J, Chen L, Marrs B et al. SOD2 polymorphisms: unmasking the effect of polymorphisms on splicing. BMC Med Genet 2007;8:7.

    PubMed  Google Scholar 

  142. Hsueh YM, Lin P, Chen HW et al. Genetic polymorphisms of oxidative and antioxidant enzymes and arsenic-related hypertension. J Toxicol Environ Health A 2005;68:1471–1484.

    PubMed  CAS  Google Scholar 

  143. Stralin P, Karlsson K, Johansson BO, Marklund SL. The interstitium of the human arterial wall contains very large amounts of extracellular superoxide dismutase. Arterioscler Thromb Vasc Biol 1995;15:2032–2036.

    PubMed  CAS  Google Scholar 

  144. Jonsson LM, Rees DD, Edlund T, Marklund SL. Nitric oxide and blood pressure in mice lacking extracellular-superoxide dismutase. Free Radic Res 2002;36:755–758.

    PubMed  CAS  Google Scholar 

  145. Jung O, Marklund SL, Geiger H, Pedrazzini T, Busse R, Brandes RP. Extracellular superox-ide dismutase is a major determinant of nitric oxide bioavailability: in vivo and ex vivo evidence from ecSOD-deficient mice. Circ Res 2003;93:622–629.

    PubMed  CAS  Google Scholar 

  146. Welch WJ, Chabrashvili T, Solis G et al. Role of extracellular superoxide dismutase in the mouse angiotensin slow pressor response. Hypertension 2006;48:934–941.

    PubMed  CAS  Google Scholar 

  147. Gongora MC, Qin Z, Laude K et al. Role of extracellular superoxide dismutase in hypertension. Hypertension 2006;48:473–481.

    PubMed  CAS  Google Scholar 

  148. Oury TD, Ho YS, Piantadosi CA, Crapo JD. Extracellular superoxide dismutase, nitric oxide, and central nervous system O2 toxicity. Proc Natl Acad Sci U S A 1992;89:9715–9719.

    PubMed  CAS  Google Scholar 

  149. Sheng H, Kudo M, Mackensen GB, Pearlstein RD, Crapo JD, Warner DS. Mice overexpress-ing extracellular superoxide dismutase have increased resistance to global cerebral ischemia. Exp Neurol 2000;163:392–398.

    PubMed  CAS  Google Scholar 

  150. Demchenko IT, Oury TD, Crapo JD, Piantadosi CA. Regulation of the brain's vascular responses to oxygen. Circ Res 2002;91:1031–1037.

    PubMed  CAS  Google Scholar 

  151. McGirt MJ, Parra A, Sheng H et al. Attenuation of cerebral vasospasm after subarachnoid hemorrhage in mice overexpressing extracellular superoxide dismutase. Stroke 2002; 33:2317–2323.

    PubMed  CAS  Google Scholar 

  152. Chu Y, Iida S, Lund DD et al. Gene transfer of extracellular superoxide dismutase reduces arterial pressure in spontaneously hypertensive rats: role of heparin-binding domain. Circ Res 2003;92:461–468.

    PubMed  CAS  Google Scholar 

  153. Zhou LC, Xiang W, Potts J et al. Reduction in extracellular superoxide dismutase activity in African-American patients with hypertension. Free Radic Biol Med 2006;41:1384–1391.

    PubMed  CAS  Google Scholar 

  154. Sandstrom J, Nilsson P, Karlsson K, Marklund SL. 10-fold increase in human plasma extracellular superoxide dismutase content caused by a mutation in heparin-binding domain. J Biol Chem 1994;269:19163–19166.

    PubMed  CAS  Google Scholar 

  155. Marklund SL, Nilsson P, Israelsson K, Schampi I, Peltonen M, Asplund K. Two variants of extracellular-superoxide dismutase: relationship to cardiovascular risk factors in an unse-lected middle-aged population. J Intern Med 1997;242:5–14.

    PubMed  CAS  Google Scholar 

  156. Leopold JA, Loscalzo J. Oxidative enzymopathies and vascular disease. Arterioscler Thromb Vasc Biol 2005;25:1332–1340.

    PubMed  CAS  Google Scholar 

  157. ‘t Hoen PA, Van der Lans CA, Van Eck M, Bijsterbosch MK, Van Berkel TJ, Twisk J. Aorta of ApoE-deficient mice response to atherogenic stimuli by a prelesional increase and subsequent decrease in the expression of antioxidant enzymes. Circ Res 2003;93:262–269.

    PubMed  Google Scholar 

  158. Ho YS, Magnenat JL, Bronson RT et al. Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia. J Biol Chem 1997;272:16644–16651.

    PubMed  CAS  Google Scholar 

  159. Forgione MA, Weiss N, Heydrick S et al. Cellular glutathione peroxidase deficiency and endothelial dysfunction. Am J Physiol 2002;282:H1255–H1261.

    CAS  Google Scholar 

  160. Forgione MA, Cap A, Liao R et al. Heterozygous cellular glutathione peroxidase deficiency in the mouse: abnormalities in vascular and cardiac function and structure. Circulation 2002;106:1154–1158.

    PubMed  CAS  Google Scholar 

  161. Dayal S, Brown KL, Weydert CJ et al. Deficiency of glutathione peroxidase-1 sensitizes hyperhomocysteinemic mice to endothelial dysfunction. Arterioscler Thromb Vasc Biol 2002;22:1996–2002.

    PubMed  CAS  Google Scholar 

  162. Yoshida T, Watanabe M, Engelman DT et al. Transgenic mice overexpressing glutathione peroxidase are resistant to myocardial ischemia reperfusion injury. J Mol Cell Cardiol 1996;28:1759–1767.

    PubMed  CAS  Google Scholar 

  163. Vaziri ND, Wang XQ, Oveisi F, Rad B. Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. Hypertension 2000;36;142–146.

    PubMed  CAS  Google Scholar 

  164. Ford RJ, Graham DA, Denniss SG, Quadrilatero J, Rush JW. Glutathione depletion in vivo enhances contraction and attenuates endothelium-dependent relaxation of isolated rat aorta. Free Radic Biol Med 2006;40:670–678.

    PubMed  CAS  Google Scholar 

  165. Chen X, Liang H, Van Remmen H, Vijg J, Richardson A. Catalase transgenic mice: characterization and sensitivity to oxidative stress. Arch Biochem Biophys 2004;422:197–210.

    PubMed  CAS  Google Scholar 

  166. Yang H, Shi MJ, Van Remmen H, Chen XL, Vijg J, Richardson A, Guo ZM. Reduction of pressor response to vasoconstrictor agents by overexpression of catalase in mice. Am J Hypertens 2003;16:1–5.

    PubMed  Google Scholar 

  167. Kobayashi M, Sugiyama H, Wang DH et al. Catalase deficiency renders remnant kidneys more susceptible to oxidant tissue injury and renal fibrosis in mice. Kidney Int 2005;68:1018–1031.

    PubMed  CAS  Google Scholar 

  168. Jiang Z, Akey JM, Shi J et al. A polymorphism in the promoter region of catalase is associated with blood pressure levels. Hum Genet 2001;109:95–98.

    PubMed  CAS  Google Scholar 

  169. Zhou XF, Cui J, DeStefano AL et al. Polymorphisms in the promoter region of catalase gene and essential hypertension. Dis Markers 2005;21:3–7.

    PubMed  CAS  Google Scholar 

  170. Ho YS, Xiong Y, Ma W, Spector A, Ho DS. Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury. J Biol Chem 2004;279:32804–32812.

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by National Institutes of Health Grants NS-24621, HL-38901, and HL-62984 as well as support from the American Heart Association Beginning Grant-in-Aid (0565486Z).

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Authors and Affiliations

  1. Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa, IA

    Sean P. Didion & Sophocles Chrissobolis

  2. Departments of Internal Medicine and Pharmacology, Carver College of Medicine, University of Iowa, Iowa, IA

    Frank M. Faraci

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  1. Sean P. Didion
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  2. Sophocles Chrissobolis
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  3. Frank M. Faraci
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Editors and Affiliations

  1. Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK

    Satomi Miwa PhD

  2. Functional Genomics Core, Children's Hospital Oakland Research Institute, Oakland, CA, USA

    Kenneth B. Beckman PhD

  3. Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Florian L. Muller PhD

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Didion, S.P., Chrissobolis, S., Faraci, F.M. (2008). Oxidative Stress in Hypertension. In: Miwa, S., Beckman, K.B., Muller, F.L. (eds) Oxidative Stress in Aging. Aging Medicine. Humana Press. https://doi.org/10.1007/978-1-59745-420-9_13

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