Pathophysiological roles of peroxynitrite in circulatory shock

Shock

Volumn 34, Issue SUPPL. 1, 2010, Pages 4-14

  Szabó, Csaba ^a,b   Módis, Katalin ^a  

^a University of Texas Medical Branch School of Medicine   (United States)

^b SEMMELWEIS UNIVERSITY OF MEDICINE   (Hungary)

Author keywords

contraction; endotoxin; inflammation; Nitric oxide; poly(ADP ribose) polymerase; superoxide; vascular dysfunction

Indexed keywords

ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; NITRIC OXIDE; PEROXYNITRITE; SODIUM CHANNEL;

AEROBIC METABOLISM; CELL DAMAGE; CELL DEATH; CELL MEMBRANE PERMEABILITY; CYTOTOXICITY; DNA STRAND BREAKAGE; ENDOTHELIUM INJURY; ENDOTOXEMIA; ENZYME INHIBITION; HEART DISEASE; HEMORRHAGIC SHOCK; HUMAN; KIDNEY DYSFUNCTION; LIPID PEROXIDATION; LIVER DYSFUNCTION; LUNG DISEASE; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PATHOPHYSIOLOGY; PROTEIN MODIFICATION; REVIEW; SEPTIC SHOCK; SHOCK; VASCULAR DISEASE;

ANIMALS; CATECHOLAMINES; CELLS, CULTURED; DNA DAMAGE; ENDOTHELIUM, VASCULAR; HUMANS; KIDNEY; LIPID PEROXIDATION; LIVER; LUNG; MODELS, ANIMAL; MYOCARDIAL CONTRACTION; NITRIC OXIDE; OXIDATION-REDUCTION; PEROXYNITROUS ACID; RATS; SHOCK; SHOCK, SEPTIC; SUPEROXIDES;

EID: 77955984387     PISSN: 10732322     EISSN: None     Source Type: Journal    
DOI: 10.1097/SHK.0b013e3181e7e9ba     Document Type: Review

References (190)

1. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA: Apparent hydroxyl radical production by peroxynitrite: implications for endothe-lial injury from nitric oxide and superoxide. Proc Natl Acad Sci\USA 87: 1620-1624, 1990
2. Pryor WA, Squadrito GL: The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol 268:L699-L722, 1995
3. Rubbo H, Radi R, Trujillo M, Telleri R, Kalyanaraman B, Barnes S, Kirk M, Freeman BA: Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. J Biol Chem 269:26066-26075, 1994
4. Szabo C, Ischiropoulos H, Radi R: Peroxynitrite: biochemistry, pathophysiology and development of therapeutics. Nat Rev Drug Discov 6:662-680, 2007
5. Pacher P, Szabo C: Role of the peroxynitrite-poly(ADP-ribose) polymerase pathway in human disease. Am J Pathol 173:2-13, 2008
6. Virag L, Szabo E, Gergely P, Szabo C: Peroxynitrite-induced cytotoxicity: mechanism and opportunities for intervention. Toxicol Lett 140-141:113-124, 2003
7. Szabo C, Salzman AL, Ischiropoulos H: Peroxynitrite-mediated oxidation of dihydrorhodamine 123 occurs in early stages of endotoxic and hemorrhagic shock and ischemia-reperfusion injury. FEBS Lett 372:229-232, 1995
8. Villa LM, Salas E, Darley-Usmar M, Radomski MW, Moncada S: Peroxyni-trite induces both vasodilatation and impaired vascular relaxation in the isolated perfused rat heart. Proc Natl Acad Sci\USA 91:12383-12387, 1994
9. Bauer ML, Beckman JS, Bridges RJ, Fuller CM, Matalon S: Peroxynitrite inhibits sodium uptake in rat colonic membrane vesicles. Biochim Biophys Acta 1104:87-94, 1992
10. Castro L, Rodriguez M, Radi R: Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide. J Biol Chem 269:29409-29415, 1994
11. Crow JP, Beckman JS, McCord JM: Sensitivity of the essential zinc-thiolate moiety of yeast alcohol dehydrogenase to hypochlorite and peroxynitrite. Biochemistry 34:3544-3552, 1995
12. Guzman NJ, Fang MZ, Tang SS, Ingelfinger JR, Garg LC: Autocrine inhibition of Na+/K(+)-ATPase by nitric oxide in mouse proximal tubule epithelial cells. J Clin Invest 95:2083-2088, 1995
13. Hausladen A, Fridovich I: Superoxide and peroxynitrite inactivate aconitases, but nitric oxide does not. J Biol Chem 269:29405-29408, 1994
14. Hu P, Ischiropoulos H, Beckman JS, Matalon S: Peroxynitrite inhibition of oxygen consumption and sodium transport in alveolar type II cells. Am J Physiol 266:L628-L634, 1994
15. Ischiropoulos H, Duran D, Horwitz J: Peroxynitrite-mediated inhibition of DOPA synthesis in PC12 cells. J Neurochem 65:2366-2372, 1995
16. Ischiropoulos H, Zhu L, Chen J, Tsai M, Martin JC, Smith CD, Beckman JS: Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys 298:431-437, 1992
17. Miles AM, Bohle DS, Glassbrenner PA, Hansert B, Wink DA, Grisham MB: Modulation of superoxide-dependent oxidation and hydroxylation reactions by nitric oxide. J Biol Chem 271:40-47, 1996
18. Mohr S, Stamler JS, Brune B: Mechanism of covalent modification of glyceraldehyde-3-phosphate dehydrogenase at its active site thiol by nitric oxide, peroxynitrite and related nitrosating agents. FEBS Lett 348:223-227, 1994
19. Pou S, Nguyen SY, Gladwell T, Rosen GM: Does peroxynitrite generate hydroxyl radical? Biochim Biophys Acta 1244:62-68, 1995
20. Radi R, Rodriguez M, Castro L, Telleri R: Inhibition of mitochondrial electron transport by peroxynitrite. Arch Biochem Biophys 308:89-95, 1994
21. Rubbo H, Denicola A, Radi R: Peroxynitrite inactivates thiol-containing enzymes of Trypanosoma cruzi energetic metabolism and inhibits cell respiration. Arch Biochem Biophys 308:96-102, 1994
22. Salman-Tabcheh S, Guerin MC, Torreilles J: Nitration of tyrosyl-residues from extra-and intracellular proteins in human whole blood. Free Radic Biol Med 19:695-698, 1995
23. Selden LA, Gersham LC, Estes JE, Ferro TJ, A J: Peroxynitrite-induced tyrosine nitration mediates decreased polymerization of actin. Mol Biol Cell 6:20A, 1995
24. Bolanos JP, Heales SJ, Land JM, Clark JB: Effect of peroxynitrite on the mitochondrial respiratory chain: differential susceptibility of neurones and astrocytes in primary culture. J Neurochem 64:1965-1972, 1995
25. Radi R, Beckman JS, Bush KM, Freeman BA: Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys 288:481-487, 1991
26. Moore KP, Darley-Usmar V, Morrow J, Roberts LJ 2nd: Formation of F2-isoprostanes during oxidation of human low-density lipoprotein and plasma by peroxynitrite. Circ Res 77:335-341, 1995
27. Cifuentes J, Ruiz-Oronoz J, Myles C, Nieves B, Carlo WA, Matalon S: Interaction of surfactant mixtures with reactive oxygen and nitrogen species. J Appl Physiol 78:1800-1805, 1995
28. Haddad IY, Crow JP, Hu P, Ye Y, Beckman J, Matalon S: Concurrent generation of nitric oxide and superoxide damages surfactant protein A. Am J Physiol 267:L242YL249, 1994
29. Haddad IY, Ischiropoulos H, Holm BA, Beckman JS, Baker JR, Matalon S: Mechanisms of peroxynitrite-induced injury to pulmonary surfactants. Am J Physiol 265:L555YL564, 1993
30. Inoue S, Kawanishi S: Oxidative DNA damage induced by simultaneous generation of nitric oxide and superoxide. FEBS Lett 371:86-88, 1995
31. Yermilov V, Rubio J, Becchi M, Friesen MD, Pignatelli B, Ohshima H: Formation of 8-nitroguanine by the reaction of guanine with peroxynitrite in vitro. Carcinogenesis 16:2045-2050, 1995
32. King PA, Anderson VE, Edwards JO, Gustav G, Plumb RC, Suggs JW: A stable solid that generates hydroxyl radical dissolutions in aqueous solutions: reaction with proteins and nucleic acid. J Am Chem Soc 114:5430-5432, 1992
33. Salgo MG, Bermudez E, Squadrito GL, Pryor WA: Peroxynitrite causes DNA damage and oxidation of thiols in rat thymocytes. Arch Biochem Biophys 322:500-505, 1995
34. Salgo MG, Stone K, Squadrito GL, Battista JR, Pryor WA: Peroxynitrite causes DNA nicks in plasmid pBR322. Biochem Biophys Res Commun 210: 1025-1030, 1995
35. Moro MA, Darley-Usmar VM, Goodwin DA, Read NG, Zamora-Pino R, Feelisch M, Radomski MW, Moncada S: Paradoxical fate and biological action of peroxynitrite on human platelet. Proc Natl Acad Sci\USA 91: 6702-6706, 1994
36. Moro MA, Darley-Usmar VM, Lizasoain I, Su Y, Knowles RG, Radomski MW, Moncada S: The formation of nitric oxide donors from peroxynitrite. Br J Pharmacol 116:1999-2004, 1995
37. Lymar SV, Hurst JK: Rapid reaction between peroxynitrite ion and carbon dioxide: implications for biological activity. J Am Chem Soc 117:8867-8868, 1995
38. Van der Vliet A, Smith D, O'Neill CA, Kaur H, Darley-Usmar V, Cross CE, Halliwell B: Interactions of peroxynitrite with human plasma and its constituents: oxidative damage and antioxidant depletion. Biochem J 303:295-301, 1994
39. Darley-Usmar V, Wiseman H, Halliwell B: Nitric oxide and oxygen radicals: a question of balance. FEBS Lett 369:131-135, 1995
40. Mayer B, Schrammel A, Klatt P, Koesling D, Schmidt K: Peroxynitrite-induced accumulation of cyclic GMP in endothelial cells and stimulation of purified soluble guanylyl cyclase. Dependence on glutathione and possible role of S-nitrosation. J Biol Chem 270:17355-17360, 1995
41. Tarpey MM, Beckman JS, Ischiropoulos H, Gore JZ, Brock TA: Peroxynitrite stimulates vascular smooth muscle cell cyclic GMP synthesis. FEBS Lett 364:314-318, 1995
42. Brunelli L, Crow JP, Beckman JS: The comparative toxicity of nitric oxide and peroxynitrite to Escherichia coli. Arch Biochem Biophys 316:327-334, 1995
43. Szabó C, Salzman AL: Endogenous peroxynitrite is involved in the inhibition of cellular respiration in immuno-stimulated J774.2 macrophages. Biochem Biophys Res Commun 209:739-743, 1995
44. Szabo C: Mechanisms of cell necrosis. Crit Care Med 33:S530YS534, 2005
45. Szabó C, Day BJ, Salzman AL: Evaluation of the relative contribution of nitric oxide and peroxynitrite to the suppression of mitochondrial respiration in immunostimulated macrophages, using a novel mesoporphyrin superoxide dismutase analog and peroxynitrite scavenger. FEBS Lett 381:82-86, 1996
46. Szabó C, Zingarelli B, O'Connor M, Salzman AL: DNA strand breakage, activation of poly-ADP ribosyl synthetase, and cellular energy depletion are involved in the cytotoxicity in macrophages and smooth muscle cells exposed to peroxynitrite. Proc Natl Acad Sci\USA 93:1753-1758, 1996
47. Wu M, Pritchard KA Jr, Kaminski PM, Fayngersh RP, Hintze TH, Wolin MS: Involvement of nitric oxide and nitrosothiols in relaxation of pulmonary arteries to peroxynitrite. Am J Physiol 266:H2108YH2113, 1994
48. deRojas-Walker T, Tamir S, Ji H, Wishnok JS, Tannenbaum SR: Nitric oxide induces oxidative damage in addition to deamination in macrophage DNA. Chem Res Toxicol 8:473-477, 1995
49. Szabó C, Zingarelli B, Salzman AL: Role of poly-ADP ribosyltransferase activation in the nitric oxideY and peroxynitrite-induced vascular failure. Circ Res 78:1051-1063, 1996
50. Zingarelli B, O'Connor M, Wong H, Salzman AL, Szabo C: Peroxynitrite-mediated DNA strand breakage activates poly-ADP ribosyl synthetase and causes cellular energy depletion in macrophages stimulated with bacterial lipopolysaccharide. J Immunol 156:350-358, 1996
51. Szabo C: Multiple pathways of peroxynitrite cytotoxicity. Toxicol Lett 140-141:105-112, 2003
52. Jagtap P, Szabo C: Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat Rev Drug Discov 4:421-440, 2005
53. Virag L, Szabo C: The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev 54:375-429, 2002
54. Du X, Matsumura T, Edelstein D, Rossetti L, Zsengellér Z, Szabó C, Brownlee M: Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. J Clin Invest 112:1049-1057, 2003
55. Devalaraja-Narashimha K, Padanilam BJ: PARP-1 inhibits glycolysis in ischemic kidneys. J Am Soc Nephrol 20:95-103, 2009
56. Bonfoco E, Krainc D, Ankarcrona M, Nicotera P, Lipton SA: Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with NMDA or nitric oxide/superoxide in cortical cell cultures. Proc Natl Acad Sci\USA 92:7162-7166, 1995
57. Estevez AG, Radi R, Barbeito L, Shin JT, Thompson JA, Beckman JS: Peroxynitrite-induced cytotoxicity in PC12 cells: evidence for an apoptotic mechanism differentially modulated by neurotropic factors. J Neurochem 65:1543-1550, 1995
58. Lin KT, Xue JY, Nomen M, Spur B, Wong PY: Peroxynitrite-induced apop-tosis in HL-60 cells. J Biol Chem 270:16487-16490, 1995
59. Salgo MG, Squadrito GL, Pryor WA: Peroxynitrite causes apoptosis in rat thymocytes. Biochem Biophys Res Commun 215:1111-1118, 1995
60. Shacka JJ, Sahawneh MA, Gonzalez JD, Ye YZ, D'Alessandro TL, Estevez AG: Two distinct signaling pathways regulate peroxynitrite-induced apoptosis in PC12 cells. Cell Death Differ 13:1506-1514, 2006
61. Virag L, Marmer DJ, Szabo C: Crucial role of apopain in the peroxynitrite-induced apoptotic DNA fragmentation. Free Radic Biol Med 25:1075-1082, 1998
62. Zhuang S, Simon G: Peroxynitrite-induced apoptosis involves activation of multiple caspases in HL-60 cells. Am J Physiol Cell Physiol 279:C341YC351, 2000
63. Kennedy M, Denenberg AG, Szabo C, Salzman AL: Poly(ADP-ribose) syn-thetase activation mediates increased permeability induced by peroxynitrite in Caco-2BBe cells. Gastroenterology 114:510-518, 1998
64. Khan AU, Delude RL, Han YY, Sappington PL, Han X, Carcillo JA, Fink MP: Liposomal NAD(+) prevents diminished O(2) consumption by immunostimu-lated Caco-2 cells. Am J Physiol Lung Cell Mol Physiol 282:L1082YL1091, 2002
65. Forstermann U, Munzel T: Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation 113:1708-1714, 2006
66. Goldstein S, Czapski G: Reactivity of peroxynitrite versus simultaneous generation of (*)NO and O(2)(*)(j) toward NADH. Chem Res Toxicol 13: 736-741, 2000
67. Kirsch M, de Groot H: Reaction of peroxynitrite with reduced nicotina-mide nucleotides, the formation of hydrogen peroxide. J Biol Chem 274: 24664-24670, 1999
68. Boczkowski J, Lisdero CL, Lanone S, Carreras MC, Aubier M, Poderoso JJ: Peroxynitrite-mediated mitochondrial dysfunction. Biol Signals Recept 10: 66-80, 2001
69. MacMillan-Crow LA, Crow JP, Kerby JD, Beckman JS, Thompson JA: Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts. Proc Natl Acad Sci\USA 93:11853-11858, 1996
70. Cassina AM, Hodara R, Souza JM, Thomson L, Castro L, Ischiropoulos H, Freeman BA, Radi R: Cytochrome c nitration by peroxynitrite. J Biol Chem 275:21409-21415, 2000
71. Radi R, Cassina A, Hodara R, Quijano C, Castro L: Peroxynitrite reactions and formation in mitochondria. Free Radic Biol Med 33:1451-1464, 2002
72. Pacher P, Beckman JS, Liaudet L: Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87:315-424, 2007
73. Bagnasco P, MacMillan-Crow LA, Greendorfer JS, Young CJ, Andrews L, Thompson JA: Peroxynitrite modulates acidic fibroblast growth factor (FGF-1) activity. Arch Biochem Biophys 419:178-189, 2003
74. Zingarelli B, Salzman AL, Szabo C: Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion mole-cule-1 in myocardial ischemia/reperfusion injury. Circ Res 83:85-94, 1998
75. Zouki C, Zhang SL, Chan JS, Filep JG: Peroxynitrite induces integrin-dependent adhesion of human neutrophils to endothelial cells via activation of the Raf-1/MEK/Erk pathway. FASEB J 15:25-27, 2001
76. Knapp LT, Kanterewicz BI, Hayes EL, Klann E: Peroxynitrite-induced tyro-sine nitration and inhibition of protein kinase C. Biochem Biophys Res Com-mun 286:764-770, 2001
77. Bapat S, Verkleij A, Post JA: Peroxynitrite activates mitogen-activated protein kinase (MAPK) via a MEK-independent pathway: a role for protein kinase C. FEBS Lett 499:21-26, 2001
78. Mallozzi C, Di Stasi AM, Minetti M: Nitrotyrosine mimics phosphotyrosine binding to the SH2 domain of the src family tyrosine kinase lyn. FEBS Lett 503:189-195, 2001
79. Mallozzi C, Di Stasi MA, Minetti M: Peroxynitrite-dependent activation of src tyrosine kinases lyn and hck in erythrocytes is under mechanistically different pathways of redox control. Free Radic Biol Med 30:1108-1117, 2001
80. Ito K, Hanazawa T, Tomita K, Barnes PJ, Adcock IM: Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun 315:240-245, 2004
81. Zingarelli B, Day BJ, Crapo JD, Salzman AL, Szabo C: The potential role of peroxynitrite in the vascular contractile and cellular energetic failure in endo-toxic shock. Br J Pharmacol 120:259-267, 1997
82. Cuzzocrea S, Zingarelli B, Costantino G, Szabó A, Salzman AL, Caputi AP, Szabó C: Beneficial effects of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase in a rat model of splanchnic artery occlusion and reperfusion. Br J Pharmacol 121:1065-1074, 1997
83. Doursout MF, Oguchi T, Fischer UM, Liang Y, Chelly B, Hartley CJ, Chelly JE: Distribution of NOS isoforms in a porcine endotoxin shock model. Shock 29:692-702, 2008
84. Enkhbaatar P, Joncam C, Traber L, Nakano Y, Wang J, Lange M, Connelly R, Kulp G, Saunders F, Huda R, et al.: Novel ovine model of methicillin-resistant Staphylococcus aureusYinduced pneumonia and sepsis. Shock 29:642-649, 2008
85. Lehnert M, Arteel GE, Smutney OM, Conzelmann LO, Zhong Z, Thurman RG, Lemasters JJ: Dependence of liver injury after hemorrhage/resuscitation in mice on NADPH oxidaseYderived superoxide. Shock 19:345-351, 2003
86. Liaudet L, Soriano FG, Szabó E, Virág L, Mabley JG, Salzman AL, Szabo C: Protection against hemorrhagic shock in mice genetically deficient in poly(ADP-ribose)polymerase. Proc Natl Acad Sci\USA 97:10203-10208, 2000
87. Murakami K, Enkhbaatar P, Shimoda K, Cox RA, Burke AS, Hawkins HK, Traber LD, Schmalstieg FC, Salzman AL, Mabley JG, et al.: Inhibition of poly (ADP-ribose) polymerase attenuates acute lung injury in an ovine model of sepsis. Shock 21:126-133, 2004
88. Wu L, Mayeux PR: Effects of the inducible nitric-oxide synthase inhibitor L-N(6)-(1-iminoethyl)-lysine on microcirculation and reactive nitrogen species generation in the kidney following lipopolysaccharide administration in mice. J Pharmacol Exp Ther 320:1061-1067, 2007
89. Eiserich JP, Hristova M, Cross CE, Jones AD, Freeman BA, Halliwell B, van der Vliet A: Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature 391:393-397, 1998
90. Pfeiffer S, Lass A, Schmidt K, Mayer B: Protein tyrosine nitration in cytokine-activated murine macrophages. Involvement of a peroxidase/nitrite pathway rather than peroxynitrite. J Biol Chem 276:34051-34058, 2001
91. Brovkovych V, Gao XP, Ong E, Brovkovych S, Brennan ML, Su X, Hazen SL, Malik AB, Skidgel RA: Augmented inducible nitric oxide synthase expression and increased NO production reduce sepsis-induced lung injury and mortality in myeloperoxidase-null mice. Am J Physiol Lung Cell Mol Physiol 295:L96YL103, 2008
92. Zhang R, Brennan ML, Shen Z, MacPherson JC, Schmitt D, Molenda CE, Hazen SL: Myeloperoxidase functions as a major enzymatic catalyst for initiation of lipid peroxidation at sites of inflammation. J Biol Chem 277: 46116-46122, 2002
93. Ohya M, Marukawa S, Inoue T, Ueno N, Hosohara K, Terada N, Kosaka H: Plasma nitrotyrosine concentration relates to prognosis in human septic shock. Shock 18:116-118, 2002
94. Strand OA, Leone A, Giercksky KE, Kirkeboen KA: Nitric oxide indices in human septic shock. Crit Care Med 28:2779-2785, 2000
95. Kooy NW, Royall JA, Ye YZ, Kelly DR, Beckman JS: Evidence for in vivo peroxynitrite production in human acute lung injury. Am J Respir Crit Care Med 151:1250-1254, 1995
96. Fukuyama N, Takebayashi Y, Hida M, Ishida H, Ichimori K, Nakazawa H: Clinical evidence of peroxynitrite formation in chronic renal failure patients with septic shock. Free Radic Biol Med 22:771-774, 1997
97. Capasso M, Di Muzio A, Pandolfi A, Pace M, Di Tomo P, Ragno M, Uncini A: Possible role for nitric oxide dysregulation in critical illness myopathy. Muscle Nerve 37:196-202, 2008
98. Kooy NW, Lewis SJ, Royall JA, Ye YZ, Kelly DR, Beckman JS: Extensive tyrosine nitration in human myocardial inflammation: evidence for the presence of peroxynitrite. Crit Care Med 25:812-819, 1997
99. Lanone S, Manivet P, Callebert J, Launay JM, Payen D, Aubier M, Boczkowski J, Mebazaa A: Inducible nitric oxide synthase (NOS2) expressed in septic patients is nitrated on selected tyrosine residues: implications for enzymic activity. Biochem J 366:399-404, 2002
100. Lanone S, Mebazaa A, Heymes C, Henin D, Poderoso JJ, Panis Y, Zedda C, Billiar T, Payen D, Aubier M, et al.: Muscular contractile failure in septic patients: role of the inducible nitric oxide synthase pathway. Am J Respir Crit Care Med 162:2308-2315, 2000
101. Rossi MA, Celes MR, Prado CM, Saggioro FP: Myocardial structural changes in long-term human severe sepsis/septic shock may be responsible for cardiac dysfunction. Shock 27:10-18, 2007
102. Hecker M, Cattaruzza M, Wagner AH: Regulation of inducible nitric oxide synthase gene expression in vascular smooth muscle cells. Gen Pharmacol 32:9-16, 1999
103. Szabo C: Alterations in nitric oxide production in various forms of circulatory shock. New Horizons 3:2-32, 1995
104. Kilbourn RG, Traber DL, Szabo C: Nitric oxide and shock. Dis Mon 43: 277-348, 1997
105. Howes LG, Brillante DG: Expert opinion on tilarginine in the treatment of shock. Expert Opin Investig Drugs 17:1573-1580, 2008
106. Cuzzocrea S, Zingarelli B, O'Connor M, Salzman AL, Szabo C: Effect of L-buthionine-(S,R)-sulphoximine, an inhibitor of gamma-glutamylcysteine syn-thetase on peroxynitrite-and endotoxic shock-induced vascular failure. Br J Pharmacol 123:525-537, 1998
107. Nakamura M, Thourani VH, Ronson RS, Velez DA, Ma XL, Katzmark S, Robinson J, Schmarkey LS, Zhao ZQ, Wang NP, et al.: Glutathione reverses endothelial damage from peroxynitrite, the byproduct of nitric oxide degradation, in crystalloid cardioplegia. Circulation 102:III332-III338, 2000
108. Cuzzocrea S, Mazzon E, Di Paola R, Esposito E, Macarthur H, Matuschak GM, Salvemini D: A role for nitric oxide-mediated peroxynitrite formation in a model of endotoxin-induced shock. J Pharmacol Exp Ther 319:73-81, 2006
109. Mazzon E, De Sarro A, Caputi AP, Cuzzocrea S: Role of tight junction derangement in the endothelial dysfunction elicited by exogenous and endogenous peroxynitrite and poly(ADP-ribose) synthetase. Shock 18:434-439, 2002
110. Zhang Y, Zhao S, Gu Y, Lewis DF, Alexander JS, Wang Y: Effects of per-oxynitrite and superoxide radicals on endothelial monolayer permeability: potential role of peroxynitrite in preeclampsia. J Soc Gynecol Investig 12: 586-592, 2005
111. Wu F, Wilson JX: Peroxynitrite-dependent activation of protein phosphatase type 2A mediates microvascular endothelial barrier dysfunction. Cardiovasc Res 81:38-45, 2009
112. Maneen MJ, Cipolla MJ: Peroxynitrite diminishes myogenic tone in cerebral arteries: role of nitrotyrosine and F-actin. Am J Physiol Heart Circ Physiol 292:H1042YH1050, 2007
113. Pan BX, Zhao GL, Huang XL, Jin JQ, Zhao KS: Peroxynitrite induces arte-riolar smooth muscle cells membrane hyperpolarization with arteriolar hypo-reactivity in rats. Life Sci 74:1199-1210, 2004
114. Zhao KS, Liu J, Yang GY, Jin C, Huang Q, Huang X: Peroxynitrite leads to arteriolar smooth muscle cell membrane hyperpolarization and low vasoreactivity in severe shock. Clin Hemorheol Microcirc 23:259-267, 2000
115. Grover AK, Samson SE, Robinson S, Kwan CY: Effects of peroxynitrite on sarcoplasmic reticulum Ca2+ pump in pig coronary artery smooth muscle. Am J Physiol Cell Physiol 284:C294YC301, 2003
116. Walia M, Samson SE, Schmidt T, Best K, Kwan CY, Grover AK: Effects of peroxynitrite on pig coronary artery smooth muscle. Cell Calcium 34:69-74, 2003
117. Benkusky NA, Lewis SJ, Kooy NW: Peroxynitrite-mediated attenuation of alpha-and beta-adrenoceptor agonistYinduced vascular responses in vivo. Eur J Pharmacol 364:151-158, 1999
118. Lewis SJ, Hoque A, Sandock K, Robertson TP, Bates JN, Kooy NW: Differential effects of peroxynitrite on the function of arginine vasopressin V(1a) receptors and alpha(1)-adrenoceptors in vivo. Vascul Pharmacol 46:24-34, 2007
119. Shelkovnikov S, Merlic CA, Gonick HC: Influence of nitric oxide donors and peroxynitrite on the contractile effect and concentration of norepinephrine. Life Sci 74:2919-2928, 2004
120. Takakura K, Xiaohong W, Takeuchi K, Fukuda S: Peroxynitrite decreases dopamine's vasoconstrictive activity. Anesth Analg 97:1492-1496, 2003
121. Takakura K, Xiaohong W, Takeuchi K, Yasuda Y, Fukuda S: Deactivation of norepinephrine by peroxynitrite as a new pathogenesis in the hypotension of septic shock. Anesthesiology 98:928-934, 2003
122. Macarthur H, Westfall TC, Riley DP, Misko TP, Salvemini D: Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock. Proc Natl Acad Sci\USA 97:9753-9758, 2000
123. Schildknecht S, Ullrich V: Peroxynitrite as regulator of vascular prostanoid synthesis. Arch Biochem Biophys 484:183-189, 2009
124. Zou MH: Peroxynitrite and protein tyrosine nitration of prostacyclin synthase. Prostaglandins Other Lipid Mediat 82:119-127, 2007
125. Kennett EC, Davies MJ: Degradation of extracellular matrix by peroxynitrite/peroxynitrous acid. Free Radic Biol Med 45:716-725, 2008
126. Ishida H, Ichimori K, Hirota Y, Fukahori M, Nakazawa H: Peroxynitrite-induced cardiac myocyte injury. Free Radic Biol Med 20:343-350, 1996
127. Leon H, Baczko I, Sawicki G, Light PE, Schulz R: Inhibition of matrix met-alloproteinases prevents peroxynitrite-induced contractile dysfunction in the isolated cardiac myocyte. Br J Pharmacol 153:676-683, 2008
128. Digerness SB, Harris KD, Kirklin JW, Urthaler F, Viera L, Beckman JS, Darley-Usmar V: Peroxynitrite irreversibly decreases diastolic and systolic function in cardiac muscle. Free Radic Biol Med 27:1386-1392, 1999
129. Panas D, Khadour FH, Szabo C, Schulz R: Proinflammatory cytokines depress cardiac efficiency by a nitric oxide-dependent mechanism. Am J Physiol 275:H1016YH1023, 1998
130. Schulz R, Dodge KL, Lopaschuk GD, Clanachan AS: Peroxynitrite impairs cardiac contractile function by decreasing cardiac efficiency. Am J Physiol 272:H1212YH1219, 1997
131. Xie YW, Kaminski PM, Wolin MS: Inhibition of rat cardiac muscle contraction and mitochondrial respiration by endogenous peroxynitrite formation during posthypoxic reoxygenation. Circ Res 82:891-897, 1998
132. Ma XL, Lopez BL, Liu GL, Christopher TA, Ischiropoulos H: Peroxynitrite aggravates myocardial reperfusion injury in the isolated perfused rat heart. Cardiovasc Res 36:195-204, 1997
133. Mihm MJ, Bauer JA: Peroxynitrite-induced inhibition and nitration of cardiac myofibrillar creatine kinase. Biochimie 84:1013-1019, 2002
134. Borbély A, Tóth A, Edes I, Virág L, Papp JG, Varró A, Paulus WJ, van der Velden J, Stienen GJ, Papp Z: Peroxynitrite-induced alpha-actinin nitration and contractile alterations in isolated human myocardial cells. Cardiovasc Res 67:225-233, 2005
135. Snook JH, Li J, Helmke BP, Guilford WH: Peroxynitrite inhibits myofibrillar protein function in an in vitro assay of motility. Free Radic Biol Med 44:14-23, 2008
136. Gao CQ, Sawicki G, Suarez-Pinzon WL, Csont T, Wozniak M, Ferdinandy P, Schulz R: Matrix metalloproteinase-2 mediates cytokine-induced myocardial contractile dysfunction. Cardiovasc Res 57:426-433, 2003
137. Wang W, Sawicki G, Schulz R: Peroxynitrite-induced myocardial injury is mediated through matrix metalloproteinase-2. Cardiovasc Res 53:165-174, 2002
138. Pacher P, Cziraki A, Mabley JG, Liaudet L, Papp L, Szabo C: Role of pol-y(ADP-ribose) polymerase activation in endotoxin-induced cardiac collapse in rodents. Biochem Pharmacol 64:1785-1791, 2002
139. Pacher P, Liaudet L, Mabley JG, Cziraki A, Hasko G, Szabo C: Beneficial effects of a novel ultrapotent poly(ADP-ribose) polymerase inhibitor in mur-ine models of heart failure. Int J Mol Med 17:369-375, 2006
140. Gerö D, Módis K, Nagy N, Szoleczky P, Tóth ZD, Dormán G, Szabó C: Oxidant-induced cardiomyocyte injury: identification of the cytoprotective effect of a dopamine 1 receptor agonist using a cell-based high-throughput assay. Int J Mol Med 20:749-761, 2007
141. Khadour FH, Panas D, Ferdinandy P, Schulze C, Csont T, Lalu MM, Wildhirt SM, Schulz R: Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic rats. Am J Physiol Heart Circ Physiol 283:H1108YH1115, 2002
142. Lancel S, Tissier S, Mordon S, Marechal X, Depontieu F, Scherpereel A, Chopin C, Neviere R: Peroxynitrite decomposition catalysts prevent myo-cardial dysfunction and inflammation in endotoxemic rats. J Am Coll Cardiol 43:2348-2358, 2004
143. Soriano FG, Nogueira AC, Caldini EG, Lins MH, Teixeira AC, Cappi SB, Lotufo PA, Bernik MM, Zsengellér Z, Chen M, et al.: Potential role of poly(adenosine 5¶-diphosphate-ribose) polymerase activation in the pathogenesis of myocardial contractile dysfunction associated with human septic shock. Crit Care Med 34:1073-1079, 2006
144. Flesch M, Kilter H, Cremers B, Laufs U, Südkamp M, Ortmann M, Müller FU, Böhm M: Effects of endotoxin on human myocardial contractility involvement of nitric oxide and peroxynitrite. J Am Coll Cardiol 33:1062-1070, 1999
145. Alexander B: The role of nitric oxide in hepatic metabolism. Nutrition 14: 376-390, 1998
146. Spapen H: Liver perfusion in sepsis, septic shock, and multiorgan failure. Anat Rec (Hoboken) 291:714-720, 2008
147. D'Ambrosio SM, Gibson-D'Ambrosio RE, Brady T, Oberyszyn AS, Robertson FM: Mechanisms of nitric oxide-induced cytotoxicity in normal human he-patocytes. Environ Mol Mutagen 37:46-54, 2001
148. Watanabe N, Miura S, Zeki S, Ishii H: Hepatocellular oxidative DNA injury induced by macrophage-derived nitric oxide. Free Radic Biol Med 30: 1019-1028, 2001
149. Gero D, Szabo C: Role of the peroxynitrite-poly (ADP-ribose) polymerase pathway in the pathogenesis of liver injury. Curr Pharm Des 12:2903-2910, 2006
150. Shu Z, Jung M, Beger HG, Marzinzig M, Han F, Butzer U, Bruckner UB, Nussler AK: pH-dependent changes of nitric oxide, peroxynitrite, and reactive oxygen species in hepatocellular damage. Am J Physiol 273:G1118YG1126, 1997
151. Seven I, Türközkan N, Cimen B: The effects of nitric oxide synthesis on the Na+, K(+)-ATPase activity in guinea pig kidney exposed to lipopolysac-charides. Mol Cell Biochem 271:107-112, 2005
152. Cimen B, Türközkan N, Seven I, Unlü A, Karasu C: Impaired Na+,K+-ATPase activity as a mechanism of reactive nitrogen speciesYinduced cyto-toxicity in guinea pig liver exposed to lipopolysaccharides. Mol Cell Biochem 259:53-57, 2004
153. Yokozawa T, Rhyu DY, Cho EJ, Aoyagi K: Protective activity of (j)-epi-catechin 3-O-gallate against peroxynitrite-mediated renal damage. Free Radic Res 37:561-571, 2003
154. Yokozawa T, Rhyu DY, Cho EJ: (j)-Epicatechin 3-O-gallate ameliorates the damages related to peroxynitrite production by mechanisms distinct from those of other free radical inhibitors. J Pharm Pharmacol 56:231-239, 2004
155. Mota-Filipe H, McDonald MC, Cuzzocrea S, Thiemermann C: A membrane-permeable radical scavenger reduces the organ injury in hemorrhagic shock. Shock 12:255-261, 1999
156. Zacharowski K, Olbrich A, Cuzzocrea S, Foster SJ, Thiemermann C: Membrane-permeable radical scavenger, tempol, reduces multiple organ injury in a rodent model of gram-positive shock. Crit Care Med 28:1953-1961, 2000
157. Chatterjee PK, Cuzzocrea S, Brown PA, Zacharowski K, Stewart KN, Mota-Filipe H, Thiemermann C: Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated renal dysfunction and injury in the rat. Kidney Int 58:658-673, 2000
158. Di Paola R, Mazzon E, Muià C, Crisafulli C, Genovese T, Di Bella P, Esposito E, Menegazzi M, Meli R, Suzuki H, et al.: Protective effect of Hypericum perforatum in zymosan-induced multiple organ dysfunction syndrome: relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity. Nitric Oxide 16:118-130, 2007
159. Tsukada K, Hasegawa T, Tsutsumi S, Katoh H, Kuwano H, Miyazaki T, Yamamoto Y: Effect of uric acid on liver injury during hemorrhagic shock. Surgery 127:439-446, 2000
160. Ogetman Z, Dirlik M, Caglikulekci M, Canbaz H, Karabacak T, Yaylak F, Tamer L, Kanik A, Aydin S: The effect of aminoguanidine on blood and tissue lipid peroxidation in jaundiced rats with endotoxemia induced with LPS. J Invest Surg 19:19-30, 2006
161. Harrois A, Huet O, Duranteau J: Alterations of mitochondrial function in sepsis and critical illness. Curr Opin Anaesthesiol 22:143-149, 2009
162. Fink MP: Bench-to-bedside review: Cytopathic hypoxia. Crit Care 6:491-499, 2002
163. Rhyu DY, Kang KS, Sekiya M, Tanaka T, Park JC, Yokozawa T: Active compounds isolated from traditional Chinese prescription Wen-Pi-Tang protecting against peroxynitrite-induced LLC-PK(1) cell damage. Am J Chin Med 36:761-770, 2008
164. Paller MS, Weber K, Patten M: Nitric oxideYmediated renal epithelial cell injury during hypoxia and reoxygenation. Ren Fail 20:459-469, 1998
165. Jung JS, Park MY, Lee RH, Jun JS, Kim YK: Protection against hydrogen peroxide induced injury in renal proximal tubule cell lines by inhibition of poly(ADP-ribose) synthase. Kidney Blood Press Res 23:14-19, 2000
166. Filipovic DM, Meng X, Reeves WB: Inhibition of PARP prevents oxidant-induced necrosis but not apoptosis in LLC-PK1 cells. Am J Physiol 277: F428-F436, 1999
167. Tikoo K, Lau SS, Monks TJ: Histone H3 phosphorylation is coupled to poly-(ADP-ribosylation) during reactive oxygen speciesYinduced cell death in renal proximal tubular epithelial cells. Mol Pharmacol 60:394-402, 2001
168. Szabo C, Saunders C, O'Connor M, Salzman AL: Peroxynitrite causes energy depletion and increases permeability via activation of poly (ADP-ribose) syn-thetase in pulmonary epithelial cells. Am J Respir Cell Mol Biol 16:105-109, 1997
169. Janssen-Heininger YM, Persinger RL, Korn SH, Pantano C, McElhinney B, Reynaert NL, Langen RC, Ckless K, Shrivastava P, Poynter ME: Reactive nitrogen species and cell signaling: implications for death or survival of lung epithelium. Am J Respir Crit Care Med 166:S9YS16, 2002
170. Ho YS, Liou HB, Lin JK, Jeng JH, Pan MH, Lin YP, Guo HR, Ho SY, Lee CC, Wang YJ: Lipid peroxidation and cell death mechanisms in pulmonary epithelial cells induced by peroxynitrite and nitric oxide. Arch Toxicol 76:484-493, 2002
171. Lobo SM, Orrico SR, Queiroz MM, Cunrath GS, Chibeni GS, Contrin LM, Cury PM, Burdmann EA, de Oliveira Machado AM, Togni P, et al.: Pneumonia-induced sepsis and gut injury: effects of a poly-(ADP-ribose) poly-merase inhibitor. J Surg Res 129:292-297, 2005
172. Javeshghani D, Magder S: Presence of nitrotyrosine with minimal inducible nitric oxide synthase induction in lipopolysaccharide-treated pigs. Shock 16: 304-311, 2001
173. Naidu BV, Fraga C, Salzman AL, Szabo C, Verrier ED, Mulligan MS: Critical role of reactive nitrogen species in lung ischemia-reperfusion injury. J Heart Lung Transplant 22:784-793, 2003
174. Maybauer DM, Maybauer MO, Szabó C, Westphal M, Traber LD, Enkhbaatar P, Murthy KG, Nakano Y, Salzman AL, Herndon DN, et al.: Lung-protective effects of the metalloporphyrinic peroxynitrite decomposition catalyst WW-85 in interleukin-2 induced toxicity. Biochem Biophys Res Commun 377:786-791, 2008
175. Maybauer DM, Maybauer MO, Szabó C, Cox RA, Westphal M, Kiss L, Horvath EM, Traber LD, Hawkins HK, Salzman AL, et al.: The peroxy-nitrite catalyst WW-85 improves pulmonary function in ovine septic shock. Shock In press. 2010.
176. Mart́nez-Caro L, Lorente JA, Maŕn-Corral J, Sánchez-Rodŕguez C, Sánchez-Ferrer A, Nin N, Ferruelo A, de Paula M, Fernández-Segoviano P, Barreiro E, et al.: Role of free radicals in vascular dysfunction induced by high tidal volume ventilation. Intensive Care Med 35:1110-1119, 2009
177. Szabo C, Ferrer-Sueta G, Zingarelli B, Southan GJ, Salzman AL, Radi R: Mercaptoethylguanidine and guanidine inhibitors of nitric-oxide synthase react with peroxynitrite and protect against peroxynitrite-induced oxidative damage. J Biol Chem 272:9030-9036, 1997
178. Zingarelli B, Ischiropoulos H, Salzman AL, Szabo C: Amelioration by mer-captoethylguanidine of the vascular and energetic failure in haemorrhagic shock in the anesthetised rat. Eur J Pharmacol 338:55-65, 1997
179. Cuzzocrea S, Zingarelli B, Hake P, Salzman AL, Szabo C: Antiinflammatory effects of mercaptoethylguanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, in carrageenan-induced models of inflammation. Free Radic Biol Med 24:450-459, 1998
180. Szabo A, Hake P, Salzman AL, Szabo C: Beneficial effects of mercaptoe-thylguanidine, an inhibitor of the inducible isoform of nitric oxide synthase and a scavenger of peroxynitrite, in a porcine model of delayed hemorrhagic shock. Crit Care Med 27:1343-1350, 1999
181. Ploner F, Radermacher P, Theisen M, Tugtekin IF, Matejovic M, Stehr A, Szabó C, Southan GJ, Georgieff M, Bruckner UB, et al.: Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs. Shock 16:130-136, 2001
182. Liaudet L, Szabo A, Soriano FG, Zingarelli B, Szabo C, Salzman AL: Poly (ADP-ribose) synthetase mediates intestinal mucosal barrier dysfunction after mesenteric ischemia. Shock 14:134-141, 2000
183. Cuzzocrea S, Mazzon E, Dugo L, Serraino I, Centorrino T, Ciccolo A, Van de Loo FA, Britti D, Caputi AP, Thiemermann C: Inducible nitric oxide synthase-deficient mice exhibit resistance to the acute pancreatitis induced by cerulein. Shock 17:416-422, 2002
184. El-Dwairi Q, Comtois A, Guo Y, Hussain SN: Endotoxin-induced skeletal muscle contractile dysfunction: contribution of nitric oxide synthases. Am J Physiol 274:C770YC779, 1998
185. Alvarez S, Boveris A: Mitochondrial nitric oxide metabolism in rat muscle during endotoxemia. Free Radic Biol Med 37:1472-1478, 2004
186. Salvemini D, Riley DP, Lennon PJ, Wang ZQ, Currie MG, Macarthur H, Misko TP: Protective effects of a superoxide dismutase mimetic and peroxynitrite decomposition catalysts in endotoxin-induced intestinal damage. Br J Pharmacol 127:685-692, 1999
187. Stefanutti G, Pierro A, Smith VV, Klein NJ, Eaton S: Peroxynitrite decomposition catalyst FeTMPyP provides partial protection against intestinal ischemia and reperfusion injury in infant rats. Pediatr Res 62:43-48, 2007
188. Cuzzocrea S, Misko TP, Costantino G, Mazzon E, Micali A, Caputi AP, Macarthur H, Salvemini D: Beneficial effects of peroxynitrite decomposition catalyst in a rat model of splanchnic artery occlusion and reperfusion. FASEB J 14:1061-1072, 2000
189. Cuzzocrea S, Costantino G, Mazzon E, De Sarro A, Caputi AP: Beneficial effects of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a super-oxide dismutase mimetic, in zymosan-induced shock. Br J Pharmacol 128: 1241-1251, 1999
190. Nin N, Cassina A, Boggia J, Alfonso E, Botti H, Peluffo G, Trostchansky A, Batthyány C, Radi R, Rubbo H, et al.: Septic diaphragmatic dysfunction is prevented by Mn(III)porphyrin therapy and inducible nitric oxide synthase inhibition. Intensive Care Med 30:2271-2278, 2004