Role of nitric oxide in the development of vascular contractile dysfunction in circulatory shock

Journal of Medical Sciences

Volumn 31, Issue 1, 2011, Pages 1-16

  Szabo, Csaba ^a   Wu, Chin Chen ^b  

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

^b NATIONAL DEFENSE MEDICAL CENTER   (Taiwan)

Author keywords

cGMP; Circulatory shock; Nitric oxide; Sepsis; Superoxide

Indexed keywords

BACTERIUM LIPOPOLYSACCHARIDE; CYCLIC GMP; GUANYLATE CYCLASE; METHYLENE BLUE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; NITRIC OXIDE; PEROXYNITRITE; POTASSIUM CHANNEL;

ARTICLE; ENZYME ACTIVITY; HUMAN; LIGATION; NITROSATIVE STRESS; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PATHOPHYSIOLOGY; PUNCTURE; SEPSIS; SHOCK; SMOOTH MUSCLE CONTRACTILITY; VASCULAR DISEASE; VASCULAR SMOOTH MUSCLE;

EID: 79952936147     PISSN: 10114564     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (204)

1. Vincent JL. Cardiovascular alterations in septic shock. J Antimicrob Chemother. 1998;41:S9-15.
2. Ruokonen E, Parviainen I, Uusaro A. Treatment of impaired perfusion in septic shock. Ann Med. 2002;34:590-597.
3. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348:1546-1554.
4. Assreuy J. Nitric oxide and cardiovascular dysfunction in sepsis. Endocr Metab Immune Disord Drug Targets. 2006;6:165-173.
5. Vincent JL. Clinical sepsis and septic shock definition, diagnosis and management principles. Langen-becks Arch Surg. 2008;393:817-24.
6. Myburgh JA. Catecholamines for shock: the quest for high quality evidence. Crit Care Resusc. 2007;9:352-356.
7. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buis-son C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36:296-327.
8. Leone M, Martin C. Vasopressor use in septic shock: an update. Curr Opin Anaesthesiol. 2008;21:141-147.
9. Russel JA. The current management of septic shock. Minerva Med. 2008;99:431-458.
10. Dünser MW, Hasibeder WR. Sympathetic overstimulation during critical illness: adverse effects of adrenergic stress. J Intensive Care Med. 2009;24:293-316.
11. Levy B, Dusang B, Annane D, Gibot S, Bollaert PE; College Interregional des Réanimateurs du Nord-Est. Cardiovascular response to dopamine and early prediction of outcome in septic shock: a prospective multiple-center study. Crit Care Med. 2005;33:2172-2177.
12. Micek ST, Shah P, Hollands JM, Shah RA, Shannon WD, Kollef MH. Addition of vasopressin to norepinephrine as independent predictor of mortality in patients with refractory septic shock: an observational study. Surg Infect (Larchmt). 2007;8:189-200.
13. Drexler H. Endothelial dysfunction: clinical implications. Prog Cardiovasc Dis. 1997;39:287-324.
14. Hein OV, Misterek K, Tessmann JP, van Dossow V, Krimphove M, Spies C. Time course of endothelial damage in septic shock: prediction of outcome. Crit Care. 2005;9:R323-330.
15. Grandel U, Grimminger F. Endothelial responses to bacterial toxins in sepsis. Crit Rev Immunol. 2003;23:267-299.
16. Matsuda N, Hattori Y. Vascular biology in sepsis: pathophysiological and therapeutic significance of vascular dysfunction. J Smooth Muscle Res. 2007;43:117-137.
17. Lucas R, Verin AD, Black SM, Catravas JD. Regulators of endothelial and epithelial barrier integrity and function in acute lung injury. Biochem Pharmacol. 2009;77:1763-1772
18. Gando S. Microvascular thrombosis and multiple organ dysfunction syndrome. Crit Care Med. 2010;38:S35-42.
19. Legrand M, Klijn E, Payen D, Ince C. The response of the host microcirculation to bacterial sepsis: does the pathogen matter? J Mol Med. 2010;88:127-133.
20. Szabó C, Módis K. Pathophysiological roles of peroxynitrite in circulatory shock. Shock, 2010 May 18. [Epub ahead of print]
21. Thiemermann C, Szabó C, Mitchell JA, Vane JR. Vascular hyporeactivity to vasoconstrictor agents and hemodynamic decompensation in hemorrhagic shock is mediated by nitric oxide. Proc Natl Acad Sci U S A. 1993;90:267-271.
22. De Kimpe SJ, Hunter ML, Bryant CE, Thiemermann C, Vane JR. Delayed circulatory failure due to the induction of nitric oxide synthase by lipoteichoic acid from Staphylococcus aureus in anaesthetized rats. Br J Pharmacol. 1995;114:1317-1323.
23. Cuzzocrea S, Filippelli A, Zingarelli B, Falciani M, Caputi AP, Rossi F. Role of nitric oxide in a nonseptic shock model induced by zymosan in the rat. Shock. 1997;7:351-357.
24. Zingarelli B, Ischiropoulos H, Salzman AL, Szabó C. Amelioration by mercaptoethylguanidine of the vascular and energetic failure in haemorrhagic shock in the anesthetised rat. Eur J Pharmacol. 1997;338:55-65.
25. Hattori Y, Kasai K, Nakanishi N, Gross SS, Thiemer-mann C. Induction of nitric oxide and tetrahydro-biopterin synthesis by lipoteichoic acid from Staphylococcus aureus in vascular smooth muscle cells. J Vasc Res. 1998;35:104-108.
26. Md S, Moochhala SM, Siew-Yang KL. The role of inducible nitric oxide synthase inhibitor on the arteriolar hyporesponsiveness in hemorrhagic-shocked rats. Life Sci. 2003;73:1825-1834.
27. Sigurdardottir T, Björck V, Herwald H, Mörgelin M, Rutardottir S, Törnebrant J, Bodelsson M. M1 protein from Streptococcus pyogenes induces nitric oxidemediated vascular hyporesponsiveness to phenylephrine: Involvement of toll-like receptor activation. Shock. 2009 Dec 7. [Epub ahead of print]
28. Furchgott RF, Zawadzki JW. The obligatory role of endothelial cells in the relaxation of vascular smooth muscle by acetylcholine. Nature 1980; 286:373-376.
29. Furchgott RF: Studies in relaxation of rabbit aorta by sodium nitrate basis for the proposal that the acid activable component of the inhibitory factor from the retractor penis is the inorganic nitrate and the endothelium derived relaxing factor is nitric oxide. In "Mechanisms of Vasodilation" (PM Vanhoutte, ed.) pp. 401-414, 1988. Raven Press, New York.
30. Palmer RMJ, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium derived releasing factor. Nature 325:524-525,1987.
31. Julou-Schaeffer G, Gray GA, Fleming I, Schott C, Parratt JR, Stoclet JC. Loss of vascular responsiveness induced by endotoxin involves L-arginine pathway. Am J Physiol 1990;259: H1038-H1043.
32. Stoclet JC. The L-arginine-NO pathway and cyclic GMP in the vessel wall. Z Kardiol. 1991;80:S87-90.
33. Rees DD, Cellek S, Palmer RMJ, Moncada S. Dexamethasone prevents the induction by endotoxin of a nitric oxide synthase and the associated effects on vascular tone: and insight into endotoxin shock, Bio-chem Biophys Res Comm 1990;173:541-546.
34. Szabó C, Mitchell JA, Thiemermann C, Vane JR. Nitric oxidemediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in en-dotoxin shock. Br J Pharmacol. 1993;108:786-792.
35. Paya D, Maupoil V, Schott C, Rochette L, Stoclet JC. Temporal relationships between levels of circulating NO derivatives, vascular NO production and hypo-reactivity to noradrenaline induced by endotoxin in rats. Cardiovasc Res. 1995;30:952-959.
36. Huang KT, Kuo L, Liao JC. Lipopolysaccharide activates endothelial nitric oxide synthase through protein tyrosine kinase. Biochem Biophys Res Commun. 1998;245:33-37.
37. Scicluna JK, Mansart A, Ross JJ, Reilly CS, Brown NJ, Brookes ZL. Reduced vascular response to phenylephrine during exposure to lipopolysaccharide in vitro involves nitric oxide and endothelin 1. Shock. 2008;29:417-421.
38. Busse R, Mülsch A. Induction of nitric oxide by cytokines in vascular smooth muscle cells. FEBS Lett 1990;275:87-90.
39. Beasley D, Schwartz JH, Brenner JM. Interleukin-1 induces prolonged L-arginine-dependent cyclic guanosine monophosphate and nitrite production in rat vascular smooth muscle cells. J Clin Invest 1991;87:602-608.
40. Fleming I, Gray G, Stoclet JC. Influence of endothelium on induction of the L-arginine: nitric oxide path-way in rat aortas. Am J Physiol 1993;264:H1200-1207.
41. Szabó C: Alterations in the production of nitric oxide in various forms of circulatory shock. New Horizons 1995;3:3-32.
42. Gray GA, Schott C., Julou-Schaeffer G, Fleming I, Parratt JR, Stoclet JC. The effect of inhibitors of the L-arginine/nitric oxide pathway on endotoxininduced loss of vascular responsiveness in anaesthetized rats. Br J Pharmacol 1991;103:1218-1224.
43. Meyer J, Traber LD, Nelson S, Lentz CW, Nakazawa H, Herndon DN, Noda H, Traber DL. Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis. J Appl Physiol. 1992;73:324-328.
44. Yen MH, Chen SJ, Wu CC. Role of endothelium-derived relaxing factor on vascular reactivity in en-dotoxin-induced shock. Chin J Physiol. 1993;36:225-231.
45. Wu CC, Szabó C, Chen SJ, Thiemermann C, Vane JR. Activation of soluble guanylyl cyclase by a factor other than nitric oxide or carbon monoxide contributes to the vascular hyporeactivity to vasoconstrictor agents in the aorta of rats treated with endotoxin. Biochem Biophys Res Commun. 1994;201:436-442.
46. Southan GJ, Zingarelli B, O'Connor M, Salzman AL, Szabó C. Spontaneous rearrangement of aminoalky-lguanidines into mercaptoalkylguanidines - a novel class of nitric oxide synthase inhibitors with selectivity towards the inducible isoform. Br J. Pharmacol 1996;117:619-632.
47. Szabó C, Bryk R, Zingarelli B, Southan GJ, Gahman TC, Bhat V, Salzman AL, Wolff DJ. Pharmacological characterization of guanidinoethyldisulphide (GED), a novel inhibitor of nitric oxide synthase with selectivity towards the inducible isoform. Br J Pharmacol 1996;118:1659-1668.
48. Southan GJ, Szabó C. Selective pharmacological inhibition of distinct nitric oxide synthase isoforms. Biochem Pharmacol. 1996;51:383-394.
49. 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. 2006;319:73-81.
50. Wu CC, Chen SJ, Szabó C, Thiemermann C, Vane JR. Aminoguanidine attenuates the delayed circulatory failure and improves survival in rodent models of endotoxic shock. Br J Pharmacol. 1995;114:1666-1672.
51. Wu CC, Ruetten H, Thiemermann C. Comparison of the effects of aminoguanidine and N omega-nitro-L-arginine methyl ester on the multiple organ dysfunction caused by endotoxaemia in the rat. Eur J Pharmacol. 1996;300:99-104.
52. Wu CC, Yen MH. Combined effects of dexamethasone and aminoguanidine on rats with endotoxemia. Proc Natl Sci Counc Repub China B. 1998;22:39-45.
53. Alden KJ, Motew SJ, Sharma AC, Ferguson JL. Effect of aminoguanidine on plasma nitric oxide byproducts and blood flow during chronic peritoneal sepsis. Shock. 1998;9:289-295.
54. Scott JA, Mccormack DG. Selective in vivo inhibition of inducible nitric oxide synthase in a rat model of sepsis. J Appl Physiol. 1999;86:1739-1744.
55. Erol A, Kosay S. Effects of aminoguanidine administration on vascular hyporeactivity in thoracic aorta from endotoxaemic rats. Effects of aminoguanidine administration on vascular hyporeactivity in thoracic aorta from endotoxaemic rats. Eur J Pharmacol. 2000;408:175-181.
56. Boyle WA 3rd, Parvathaneni LS, Bourlier V, Sauter C, Laubach VE, Cobb JP. iNOS gene expression modulates microvascular responsiveness in endotoxin challenged mice. Circ Res. 2000;87:E18-24.
57. Piepot HA, Groeneveld AB, van Lambalgen AA, Sip-kema P. The role of inducible nitric oxide synthase in lipopolysaccharide-mediated hyporeactivity to vasoconstrictors differs among isolated rat arteries. Clin Sci (Lond). 2002;102:297-305.
58. Lorente JA, Tejedor C, Delgado MA, Fernández-Segoviano P, Jara N, Tobalina R, Rodríguez-Corcos A, Moscoso A, Esteban A. Hemodynamic, biochemical and morphological changes induced by aminoguanidine in normal and septic sheep. Intensive Care Med. 2000;26:1670-1680.
59. Szabó C, Southan GJ, Thiemermann C. Beneficial effects and improved survival in rodent models of septic shock with S-methylisothiourea sulfate, a potent and selective inhibitor of inducible nitric oxide synthase. Proc Natl Acad Sci U S A. 1994;91:12472-12476.
60. Southan GJ, Szabó C, Thiemermann C. Isothioureas: potent inhibitors of nitric oxide synthases with variable isoform selectivity. Br J Pharmacol. 1995;114:510-516.
61. Southan GJ, Szabó C, Connor MP, Salzman AL, Thiemermann C. Amidines are potent inhibitors of nitric oxide synthases: preferential inhibition of the inducible isoform. Eur J Pharmacol. 1995;291:311-318.
62. Vromen A, Szabó C, Southan GJ, Salzman AL. Effects of S-isopropyl isothiourea, a potent inhibitor of nitric oxide synthase, in severe hemorrhagic shock. J Appl Physiol. 1996;81:707-715.
63. Booke M, Hinder F, Traber LD, McGuire R, Traber DL. S-ethylisothiourea, a nonamino acid inhibitor of nitric oxide synthase, reverses septic vasodilation in sheep. Shock. 1995;4:274-281.
64. Seo HG, Fujiwara N, Kaneto H, Asahi M, Fujii J, Taniguchi N. Effect of a nitric oxide synthase inhibitor, S-ethylisothiourea, on cultured cells and cardiovascular functions of normal and lipopolysaccharide-treated rabbits. J Biochem. 1996;119:553-558.
65. Mclntyre RC Jr, Sheridan B, Agrafojo J, Fullerton DA. Selective inhibition of receptor-mediated pulmonary vasorelaxation in endotoxin-induced acute lung injury. Shock. 1997;7:36-41.
66. Saetre T, Gundersen Y, Thiemermann C, Lilleaasen P, Aasen AO. Aminoethyl-isothiourea, a selective inhibitor of inducible nitric oxide synthase activity, improves liver circulation and oxygen metabolism in a porcine model of endotoxemia. Shock. 1998;9:109-115.
67. Rosselet A, Feihl F, Markert M, Gnaegi A, Perret C, Liaudet L. Selective iNOS inhibition is superior to norepinephrine in the treatment of rat endotoxic shock. Am J Respir Crit Care Med. 1998;157:162-170.
68. Wang D, Wei J, Hsu K, Jau J, Lieu MW, Chao TJ, Chen HI. Effects of nitric oxide synthase inhibitors on systemic hypotension, cytokines and inducible nitric oxide synthase expression and lung injury following endotoxin administration in rats. J Biomed Sci. 1999;6:28-35.
69. Hollenberg SM, Easington CR, Osman J, Broussard M, Parrillo JE. Effects of nitric oxide synthase inhibition on microvascular reactivity in septic mice. Shock. 1999;12:262-267.
70. Saetre T, Höiby EA, Aspelin T, Lermark G, Egeland T, Lyberg T. Aminoethyl-isothiourea, a nitric oxide synthase inhibitor and oxygen radical scavenger, improves survival and counteracts hemodynamic deterioration in a porcine model of streptococcal shock. Crit Care Med. 2000;28:2697-2706.
71. Soejima K, McGuire R, Snyder N 4th, Uchida T, Szabó C, Salzman A, Traber LD, Traber DL. The effect of inducible nitric oxide synthase (iNOS) inhibition on smoke inhalation injury in sheep. Shock. 2000;13:261-266.
72. Cohen RI, Shapir Y, Davis A, Loona R, Scharf SM. Comparison between selective and nonselective nitric oxide synthase inhibition and phenylephrine in normal and endotoxic swine. Crit Care Med. 2000; 28:3257-3267.
73. Ploner F, Radermacher P, Theisen M, Tugtekin IF, Matejovic M, Stehr A, Szabó C, Southan GJ, Georgi-eff M, Bruckner UB, Träger K. Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs. Shock. 2001;16:130-136.
74. Shi EY, Jiang XJ, Bai H, Gu TX, Yoshiki N. Effect of inducible nitric oxide synthase on intestinal micro-circulation in endotoxic shock. Sheng Li Xue Bao. 2005;57:39-44.
75. Cai M, Sakamoto A, Ogawa R. Inhibition of nitric oxide formation with L-canavanine attenuates endo-toxin-induced vascular hyporeactivity in the rat. Eur J Pharmacol. 1996;295:215-220.
76. Ichinose F, Hataishi R, Wu JC, Kawai N, Rodrigues AC, Mallari C, Post JM, Parkinson JF, Picard MH, Bloch KD, Zapol WM. A selective inducible NOS dimerization inhibitor prevents systemic, cardiac, and pulmonary hemodynamic dysfunction in en-dotoxemic mice. Am J Physiol Heart Circ Physiol. 2003;285:H2524-2530.
77. Mansart A, Bollaert PE, Giummelly P, Capdeville-At-kinson C, Atkinson J. Effects of dexamethasone and L-canavanine on the intracellular calcium-contraction relation of the rat tail artery during septic shock. Am J Physiol Heart Circ Physiol. 2006;291:H1177-1182.
78. Bachetti T, Pasini E, Suzuki H, Ferrari R. Species-specific modulation of the nitric oxide pathway after acute experimentally induced endotoxemia. Crit Care Med. 2003;31:1509-1514.
79. Levy B, Vallée C, Lauzier F, Plante GE, Mansart A, Mallie JP, Lesur O. Comparative effects of vasopressin, norepinephrine, and L-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock. Am J Physiol Heart Circ Physiol. 2004;287:H209-215.
80. Enkhbaatar P, Murakami K, Shimoda K, Mizutani A, Traber L, Phillips G, Parkinson J, Salsbury JR, Biondo N, Schmalstieg F, Burke A, Cox R, Hawkins H, Herndon D, Traber D. Inducible nitric oxide syn-thase dimerization inhibitor prevents cardiovascular and renal morbidity in sheep with combined burn and smoke inhalation injury. Am J Physiol Heart Circ Physiol. 2003;285:H2430-2436.
81. Enkhbaatar P, Murakami K, Traber LD, Cox R, Parkinson JF, Westphal M, Esechie A, Morita N, May-bauer MO, Maybauer DM, Burke AS, Schmalstieg FC, Hawkins HK, Herndon DN, Traber DL. The inhibition of inducible nitric oxide synthase in ovine sepsis model. Shock. 2006;25:522-527.
82. Matejovic M, Krouzecky A, Martinkova V, Rokyta R Jr, Kralova H, Treska V, Radermacher P, Novak I. Selective inducible nitric oxide synthase inhibition during long-term hyperdynamic porcine bacteremia. Shock. 2004;21:458-465.
83. Rosengarten B, Wolff S, Klatt S, Schermuly RT. Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model. Crit Care. 2009;13:R139.
84. Hoque AM, Papapetropoulos A, Venema RC, Catra-vas JD, Fuchs LC. Effects of antisense oligonucle-otide to iNOS on hemodynamic and vascular changes induced by LPS. Am J Physiol. 1998;275:H1078-1083.
85. Suzuki Y, Deitch EA, Mishima S, Duràn WN, Xu DZ. Endotoxin-induced mesenteric microvascular changes involve iNOS-derived nitric oxide: results from a study using iNOS knock out mice. Shock. 2000;13:397-403.
86. Pulido EJ, Shames BD, Fullerton DA, Sheridan BC, Selzman CH, Gamboni-Robertson F, Bensard DD, McIntyre RC Jr. Differential inducible nitric oxide synthase expression in systemic and pulmonary vessels after endotoxin. Am J Physiol Regul Integr Comp Physiol. 2000;278:R1232-1239.
87. Piepot HA, Groeneveld AB, van Lambalgen AA, Sipkema P. Endotoxin impairs endothelium-dependent vasodilation more in the coronary and renal arteries than in other arteries of the rat. J Surg Res. 2003;110:413-418.
88. Heesen BJ, Hotchkiss RS, Karl IE. Sepsis decreases phenylephrine- and KCl-induced aortic ring contraction and decreases the frequency of oscillations in active wall tension. Shock. 1994;2:106-112.
89. Fox GA, Paterson NA, McCormack DG. Effect of inhibition of NO synthase on vascular reactivity in a rat model of hyperdynamic sepsis. Am J Physiol. 1994;267:H1377-1382.
90. Chen SJ, Wu CC, Yen MH. Alterations of ex vivo vascular reactivity in intraperitoneal sepsis. J Cardio-vasc Pharmacol. 1994;24:786-793.
91. Yaghi A, Paterson NA, McCormack DG. Vascular reactivity in sepsis: importance of controls and role of nitric oxide. Am J Respir Crit Care Med. 1995;151:706-712.
92. Hauser GJ, Wasserloos K, Dayao EK, Pitt BR. Effect of sodium arsenite on iNOS expression and vascular hyporeactivity associated with cecal ligation and puncture in the rat. Shock. 2001;15:73-76.
93. Vromen A, Arkovitz MS, Zingarelli B, Salzman AL, Garcia VF, Szabó C. Low-level expression and limited role for the inducible isoform of nitric oxide synthase in the vascular hyporeactivity and mortality associated with cecal ligation and puncture in the rat. Shock. 1996;6:248-253.
94. Wang C, Mansard A, Giummelly P, Atkinson J. Decreased aortic smooth muscle contraction in a rat model of multibacterial sepsis. Fundam Clin Pharmacol. 2004;18:679-683.
95. Nussler AK, Billiar TR, Liu ZZ, Morris SM. Coin-duction of nitric oxide synthase and arginosuccinate synthetase in a murine macrophage cell line. J Biol Chem 1994;269:1257-1261.
96. Hattori Y, Campbell EB, Gross SS. Argininosuccinate synthetase mRNA and activity are induced by immunostimulants in vascular smooth muscle. Role in the regeneration or arginine for nitric oxide synthesis. J Biol Chem 1994;269:9405-9408.
97. + mediated L-arginine transport by an inflammatory agent. Surgery 1992;112:403-411.
98. Durante W, Liao L, Schafer AI. Differential regulation of L-arginine transport and inducible NOS in cultured vascular smooth muscle cells. Am J Physiol 1995;268:H1158-1164.
99. Gold ME, Wood KS, Buga GM, Byrns RE, Ignarro LJ. L-arginine causes whereas L-argininosuccinic acid inhibits endothelium-dependent vascular smooth muscle relaxation. Biochem Biophys Res Comm 1989;161:536-543.
100. Szabó C, Csáki C, Benyó Z, Reivich M, Kovách AGB. Role of the L-arginine nitric oxide pathway in the changes in cerebrovascular reactivity following hemorrhagic hypotension and retransfusion. Circ Shock 1992;37:307-316.
101. Schott CA, Gray GA, Stoclet JC. Dependence of endotoxin induced vascular hyporeactivity on extracellular L-arginine. Br J Pharmacol 1993;108:38-43.
102. Marcin N, Papapetropoulos A, Catravas JD. Tyrosine kinase inhibitors suppress endotoxinand IL-1beta induced NO synthesis in aortic smooth muscle cells. Am J Physiol 1993;265:H1014-1018.
103. Ehrentraut S, Frede S, Stapel H, Mengden T, Grohé C, Fandrey J, Meyer R, Baumgarten G. Antagonism of lipopolysaccharide induced blood pressure at-tenuation and vascular contractility. Arterioscler Thromb Vasc Biol. 2007;27:2170-2176.
104. Spink J, Cohen J, Evans TJ. The cytokine responsive vascular smooth muscle cell enhancer of inducible nitric oxide synthase. Activation by nuclear factor-kappa B. J Biol Chem. 1995;270:29541-29547.
105. Hecker M. Preiss C. Schini-Kerth VB. Busse R. Antioxidants differentially affect nuclear factor kappa B-mediated nitric oxide synthase expression in vascular smooth muscle cells. FEBS Letters 1996;380:224-228.
106. Hirokawa K, O'Shaughnessy K, Moore K, Ramrakha P, Wilkins MR. Induction of nitric oxide synthase in cultured vascular smooth muscle cells: the role of cyclic AMP. Br J Pharmacol 1994;112:396-402.
107. Inoue T, Fukuo K, Nakahashi T, Hata S, Morimoto S, Ogihara T. cGMP upregulates nitric oxide synthase expression in vascular smooth muscle cells. Hypertension 1995;25:711-714.
108. Nakayama I, Kawahara Y, Tsuda T, Koide M, Yokoyama M. Cyclic AMP elevating agents synergize with inflammatory cytokines to induce an inducible type of nitric oxide synthase in cultured vascular smooth muscle cells. Ann NY Acad Sci 1995;748:586-589.
109. Paya D, Gray GA, Fleming I, Stoclet JC. Effect of dexamethaxone on the onset and persistence of vascular hyporeactivity induced by E. coli lipopolysac-charide in rats. Circ Shock 1993;41:103-112.
110. Szabó C, Mitchell JA, Gross, SS, Thiemermann C, Vane JR. Nifedipine inhibits endotoxin mediated nitric oxide synthase induction. J Pharmacol Exp Ther 1993;256:674-680.
111. Schini VB, Catovsky S, Schrayutz B, Busse R, Vanhoutte PM. Insulin-like growth factor I inhibits induction of nitric oxide synthase in vascular smooth muscle cells. Circ Res 1994; 74:24-32.
112. Geng YJ, Wu Q, Hansson GK. Protein kinase C activation inhibits cytokine-induced nitric oxide synthesis in vascular smooth muscle cells. Biochim Biophys Acta 1994;1223:125-132.
113. Szabó C, Haskó G, Zingarelli B, Németh ZH, Salz-man AL, Kvetan V, Pastores SM, Vizi ES. Isoproterenol regulates tumour necrosis factor, interleukin-10, interleukin-6 and nitric oxide production and protects against the development of vascular hypore-activity in endotoxaemia. Immunology. 1997;90:95-100.
114. Thiemermann C, Wu CC, Szabó C, Perretti, M, Vane JR. Tumour necrosis factor is an endogenous mediator of the induction of nitric oxide synthase in endotoxin shock in the rat. Br J Pharmacol 1993;110:177-182.
115. Szabó C, Wu CC, Gross, SS, Thiemermann C, Per-retti, M, Vane JR. Interleukin-1 contributes to the induction of nitric oxide synthase by endotoxin in vivo. Eur J Pharmacol, 1993;250:157-160.
116. Szabó C, Wu CC, Mitchell JA, Gross SS, Thiemer-mann C, Vane JR. Platelet-activating factor contributes to the induction of nitric oxide synthase by bacterial lipopolysaccharide. Circ Res. 1993;73:991-999.
117. Perrella MA, Hsieh CM, Lee WS, Shieh S, Tsai JC, Patterson C, Lowenstein CJ, Long NC, Haber E, Shore S, Lee ME: Arrest of endotoxin-induced hypotension by transforming growth. factor beta. Proc Natl Acad Sci USA 1996;93:2054-2059.
118. Vo PA, Lad B, Tomlinson JA, Francis S, Ahluwalia A. Autoregulatory role of endothelium derived nitric oxide (NO) on lipopolysaccharide induced vascular inducible NO synthase expression and function. J Biol Chem. 2005;280:7236-7243.
119. Connelly L, Madhani M, Hobbs AJ. Resistance to endotoxic shock in endothelial nitric-oxide synthase (eNOS) knock-out mice: a pro-inflammatory role for eNOS-derived no in vivo. J Biol Chem. 2005; 280:10040-10046.
120. Gocan NC, Scott JA, Tyml K. Nitric oxide produced via neuronal NOS may impair vasodilatation in septic rat skeletal muscle. Am J Physiol Heart Circ Physiol. 2000;278:H1480-1489.
121. McKinnon RL, Lidington D, Bolon M, Ouellette Y, Kidder GM, Tyml K. Reduced arteriolar conducted vasoconstriction in septic mouse cremaster muscle is mediated by nNOS-derived NO. Cardiovasc Res. 2006;69:236-244.
122. Enkhbaatar P, Lange M, Nakano Y, Hamahata A, Jonkam C, Wang J, Jaroch S, Traber L, Herndon D, Traber D. Role of neuronal nitric oxide synthase in ovine sepsis model. Shock. 2009;32:253-257.
123. Jia YX, Pan CS, Yang JH, Liu XH, Yuan WJ, Zhao J, Tang CS, Qi YF. Altered L-arginine/nitric oxide synthase/nitric oxide pathway in the vascular adven-titia of rats with sepsis. Clin Exp Pharmacol Physiol. 2006;33:1202-1208.
124. Kilbourn RG, Szabó C, Traber DL. Benefi cial versus detrimental effects of nitric oxide synthase inhibitors in circulatory shock: lessons learned from experimental and clinical studies. Shock. 1997;7:235-246.
125. Grover R, Zaccardelli D, Colice G, Guntupalli K, Watson D, Vincent JL. An open-label dose escalation study of the nitric oxide synthase inhibitor, N(G)-methyl-L-arginine hydrochloride (546C88), in patients with septic shock. Glaxo Wellcome International Septic Shock Study Group. Crit Care Med. 1999;27:913-922.
126. Broccard A, Hurni JM, Eckert P, Liaudet L, Schaller MD, Lazor R, Perret C, Feihl F. Tissue oxygenation and hemodynamic response to NO synthase inhibition in septic shock. Shock. 2000;14:35-40.
127. Cobb JP. Nitric oxide synthase inhibition as therapy for sepsis: a decade of promise. Surg Infect (Larch-mt). 2001;2:93-100.
128. Watson D, Grover R, Anzueto A, Lorente J, Smithies M, Bellomo R, Guntupalli K, Grossman S, Donaldson J, Le Gall JR. Cardiovascular effects of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride (546C88) in patients with septic shock: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002). Crit Care Med. 2004;32:13-20.
129. Bailey A, Pope TW, Moore SA, Campbell CL. The tragedy of TRIUMPH for nitric oxide synthesis inhibition in cardiogenic shock: where do we go from here? Am J Cardiovasc Drugs. 2007;7:337-345.
130. Howes LG, Brillante DG. Expert opinion on tilarginine in the treatment of shock. Expert Opin Investig Drugs. 2008;17:1573-1580.
131. Katsuki S, Arnold W, Mittal C, Murad F. Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. J Cylcic Nucleotide Res 1977;3:23-25.
132. Ignarro LJ. Signal transduction mechanisms involving nitric oxide. Biochem Pharmacol 1991;41:485-490.
133. 2+ by sarcoplasmic reticulum in vascular smooth muscle. Circ Res 1998;62:962-964.
134. Schmidt HHHW, Lohmann SM, Walter U: The nitric oxide and cGMP signal transduction system: regulation and mechanism of action. Biochem Bio-phys Acta 1993;1178:153-175.
135. Paya D, Gray GA, Stoclet JC. Effects of methylene blue on blood pressure and reactivity to norepineph-rine in endotoxemic rats. J Cardiovasc Pharmacol 1993;21:926-930.
136. Griffiths MJ, Liu S, Curzen NP, Messent M, Evans TW. In vivo treatment with endotoxin induces nitric oxide synthase in rat main pulmonary artery. Am J Physiol. 1995;268:L509-518.
137. Zingarelli B, Haskó G, Salzman AL, Szabó C. Effects of a novel guanylyl cyclase inhibitor on the vascular actions of nitric oxide and peroxynitrite in immunostimulated smooth muscle cells and in en-dotoxic shock. Crit Care Med. 1999;27:1701-1707.
138. Fernandes D, da Silva-Santos JE, Duma D, Villela CG, Barja-Fidalgo C, Assreuy J. Nitric oxide-dependent reduction in soluble guanylate cyclase functionality accounts for early lipopolysaccharide induced changes in vascular reactivity. Mol Pharmacol. 2006;69:983-990.
139. Fernandes D, Sordi R, Pacheco LK, Nardi GM, Heckert BT, Villela CG, Lobo AR, Barja-Fidalgo C, Assreuy J. Late, but not early, inhibition of soluble guanylate cyclase decreases mortality in a rat sepsis model. J Pharmacol Exp Ther. 2009;328:991-999.
140. Wu CC, Chen SJ, Yen MH. Nitric oxide-independent activation of soluble guanylyl cyclase contributes to endotoxin shock in rats. Am J Physiol. 1998;275:H1148-1157.
141. Da Silva-Santos JE, Terluk MR, Assreuy J. Differential involvement of guanylate cyclase and potassium channels in nitric oxide-induced hypore-sponsiveness to phenylephrine in endotoxemic rats. Shock. 2002;17:70-76.
142. Da Silva-Santos JE, Chiao CW, Leite R, Webb RC. The Rho-A/Rho-kinase pathway is up-regulated but remains inhibited by cyclic guanosine mono-phosphate-dependent mechanisms during endotoxemia in small mesenteric arteries. Crit Care Med. 2009;37:1716-1723.
143. Chen SJ, Chen KH, Wu CC. Nitric oxide-cyclic GMP contributes to abnormal activation of Na+-K+-ATPase in the aorta from rats with endotoxic shock. Shock. 2005; 23:179-185.
144. Mansart A, Bollaert PE, Levy B, Nicolas MB, Mallié JP. Comparative effects of dexamethasone and L-canavanine in experimental septic shock. Eur J Pharmacol. 2003;475:61-67.
145. Chen SJ, Li SY, Shih CC, Liao MH, Wu CC. Nitric oxide contributes to abnormal vascular calcium regulation and reactivity induced by peritonitis-associated spetic shock in rats. Shock, in press 2010.
146. Keaney JF Jr, Puyana JC, Francis S, Loscalzo J F, Stamler JS, Loscalzo J. Methylene blue reverses endotoxin-induced hypotension. Circ Res. 1994;74:1121-1125.
147. Marczin N, Tekeres M, Salzman AL, Szabó C. Methylene blue infusion in septic shock. Crit Care Med 1996;23:1936-1938.
148. Moro MA, Russel RJ, Cellek S, Lizasoain I, Su Y, Darley-Usmar VM, Radomski MW, Moncada S. cGMP mediates the vascular and platelet actions of nitric oxide: confi rmation using an inhibitor of the soluble guanylyl cyclase. Proc Natl Acad Sci USA 1996;93:1480-1485.
149. Zhang H, Rogiers P, Preiser JC, Spapen H, Manikis P, Metz G, Vincent JL. Effects of methylene blue on oxygen availability and regional blood flow during endotoxic shock Crit Care Med 1995;23:1711-1721.
150. Schneider F, Lutun P, Hasselmann M, Stoclet JC, Tempe JD. Methylene blue increases systemic vascular resistance in human septic shock. Preliminary observations. Int Care Med 1992;18:309-311.
151. Preiser JC, Lejeune P, Roman A, Carlier E, De Backer D, Leeman M, Kahn RJ, Vincent JL. Meth-ylene blue administration in septic shock: a clinical trial. Crit Care Med 1995;23:259-264.
152. Weingartner R, Oliveira E, Oliveira ES, Sant'Anna UL, Oliveira R P, Azambuja LA, Friedman G. Blockade of the action of nitric oxide in human septic shock increases systemic vascular resistance and has detrimental effects on pulmonary function after a short infusion of methylene blue. Braz J Med Biol Res. 1999;32:1505-1513.
153. Park BK, Shim TS, Lim CM, Lee SD, Kim WS, Kim DS, Kim WD, Koh Y. The effects of methylene blue on hemodynamic parameters and cytokine levels in refractory septic shock. Korean J Intern Med. 2005;20:123-128.
154. Juffermans NP, Vervloet MG, Daemen-Gubbels CR, Binnekade JM, de Jong M, Groeneveld AB. A dose finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock. Nitric Oxide. 2010;22:275-280.
155. Marcet-Palacios M, Graham K, Cass C, Befus AD, Mayers I, Radomski MW. Nitric oxide and cyclic GMP increase the expression of matrix metalloproteinase 9 in vascular smooth muscle. J Pharmacol Exp Ther. 2003;307:429-436.
156. Cena JJ, Lalu MM, Cho WJ, Chow AK, Bagdan ML, Daniel EE, Castro MM, Schulz R. Inhibition of matrix metalloproteinase activity in vivo protects against vascular hyporeactivity in endotoxemia. Am J Physiol Heart Circ Physiol. 2010;298:H45-51.
157. Nathan C: Nitric oxide as a secretory product of mammalian cells. FASEB J 1992;6:3051-3064.
158. O'Connor M, Salzman AL, Szabó C. Role of per-oxynitrite in the protein oxidation and apoptotic DNA fragmentation in vascular smooth muscle cells stimulated with bacterial lipopolysaccharide and interferon-gamma. Shock. 1997;8:439-443.
159. Cuzzocrea S, Zingarelli B, O'Connor M, Salzman AL, Szabó C. Effect of L-buthionine-(S,R)-sulphoximine, an inhibitor of gamma-glutamyl-cysteine synthetase on peroxynitrite- and endotoxic shock-induced vascular failure. Br J Pharmacol. 1998;123:525-537.
160. Javesghani D, Hussain SN, Scheidel J, Quinn MT, Magder SA. Superoxide production in the vascu-lature of lipopolysaccharide-treated rats and pigs. Shock. 2003;19:486-493.
161. Cauwels A, Rogge E, Janssen B, Brouckaert P. Reactive oxygen species and small-conductance calcium-dependent potassium channels are key mediators of inflammation induced hypotension and shock. J Mol Med. May 25, 2010. [Epub ahead of print]
162. Szabó C, Salzman AL, Ischiropoulos H. Endotoxin triggers the expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in the rat aorta in vivo. FEBS Lett 1995;363:235-238.
163. Szabó 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 1995;372:229-232.
164. Szabó C: The role of peroxynitrite in the pathophys-iology of shock, infl ammation and ischemia reper fusion injury. Shock 1996;6:79-88.
165. Szabó C, Ischiropoulos H, Radi R. Peroxynitrite: biochemistry, pathophysiology and development of therapeutics. Nat Rev Drug Discov. 2007;6:662-680
166. Zingarelli B, Day BJ, Crapo JD, Salzman AL, Szab C. The potential role of peroxynitrite in the vascular contractile and cellular energetic failure in endo-toxic shock. Br J Pharmacol. 1997;120:259-267.
167. Cuzzocrea S, Misko TP, Costantino G, Mazzon E, Micali A, Caputi A P, Macarthur H, Salvemini D. Beneficial effects of peroxynitrite decomposition catalyst in a rat model of splanchnic artery occlusion and reperfusion. FASEB J. 2000;14:1061-1072.
168. Lehner MD, Marx D, Boer R, Strub A, Hesslinger C, Eltze M, Ulrich WR, Schwoebel F, Schermuly RT, Barsig J. In vivo characterization of the novel imida-zopyridine BYK191023 [2-[2-(4-methoxy-pyridin-2 -yl)-ethyl]-3H-imidazo[4,5-b]pyridine], a potent and highly selective inhibitor of inducible nitric-oxide synthase. J Pharmacol Exp Ther. 2006;317:181-187.
169. Maybauer DM, Maybauer MO, Szabó C, Cox RA, Westphal M, Kiss L, Horvath EM, Traber LD, Hawkins HK, Salzman AL, Southan GJ, Herndon DN, Traber DL. The peroxynitrite catalyst WW-85 improves pulmonary function in ovine septic shock. Shock. 2010 Jun 22. [Epub ahead of print]
170. Takakura K, Taniguchi T, Muramatsu I, Takeuchi K, Fukuda S. Modifi cation of alpha1 -adrenoceptors by peroxynitrite as a possible mechanism of systemic hypotension in sepsis. Crit Care Med. 2002;30:894-899.
171. Takakura K, Xiaohong W, Takeuchi K, Fukuda S. Peroxynitrite decreases dopamine's vasoconstrictive activity. Anesth Analg. 2003;97:1492-1496.
172. Takakura K, Xiaohong W, Takeuchi K, Yasuda Y, Fukuda S. Deactivation of norepinephrine by per-oxynitrite as a new pathogenesis in the hypotension of septic shock. Anesthesiology. 2003;98:928-934.
173. Jagtap P, Szabó C. Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat Rev Drug Discov. 2005;4:421-440.
174. Szabó C, Zingarelli B, O'Connor M, Salzman AL. DNA strand breakage, activation of poly (ADP-ribose) synthetase, and cellular energy depletion are involved in the cytotoxicity of macrophages and smooth muscle cells exposed to peroxynitrite. Proc Natl Acad Sci U S A. 1996;93:1753-1758.
175. Szabó C, Zingarelli B, Salzman AL. Role of poly-ADP ribosyltransferase activation in the vascular contractile and energetic failure elicited by exogenous and endogenous nitric oxide and peroxynitrite. Circ Res. 1996;78:1051-1063.
176. Zingarelli B, Salzman AL, Szabó C. Protective effects of nicotinamide against nitric oxide-mediated delayed vascular failure in endotoxic shock: potential involvement of polyADP ribosyl synthetase. Shock. 1996;5:258-264.
177. St John J, Barbee RW, Sonin N, Clemens MG, Watts JA. Inhibition of poly(ADP-ribose) synthetase improves vascular contractile responses following trauma-hemorrhage and resuscitation. Shock. 1999;12:188-95.
178. Liaudet L, Soriano FG, Szabó E, Virág L, Mab-ley JG, Salzman AL, Szabo C. Protection against hemorrhagic shock in mice genetically defi cient in poly(ADP-ribose)polymerase. Proc Natl Acad Sci U S A. 2000;97:10203-10208.
179. Jagtap P, Soriano FG, Virág L, Liaudet L, Mabley J, Szabó E, Haskó G, Marton A, Lorigados CB, Gallyas F Jr, Sümegi B, Hoyt DG, Baloglu E, Van-Duzer J, Salzman AL, Southan GJ, Szabó C. Novel phenanthridinone inhibitors of poly (adenosine 5'-diphosphate-ribose) synthetase: potent cytoprotec-tive and antishock agents. Crit Care Med. 2002; 30:1071-1082.
180. Di Paola R, Genovese T, Caputi AP, Threadgill M, Thiemermann C, Cuzzocrea S. Beneficial effects of 5-aminoisoquinolinone, a novel, potent, water-soluble, inhibitor of poly (ADP-ribose) polymerase, in a rat model of splanchnic artery occlusion and reperfusion. Eur J Pharmacol. 2004;492:203-210.
181. Tasatargil A, Dalaklioglu S, Sadan G. Inhibition of poly(ADP-ribose) polymerase prevents vascular hy-poresponsiveness induced by lipopolysaccharide in isolated rat aorta. Pharmacol Res. 2005;51:581-586.
182. Zhou XW, Liu JC, Liao ZF, Wang LT, Liu LM. Effect of poly-adenosine diphosphate ribosyl-polymerase on vascular hyporeactivity in rats with hemorrhagic shock. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2008;20:148-150.
183. Salvemini D, Misko T P, Masferrer J, Seibert K, Currie MG, Needleman P. Nitric oxide activates cyclooxygenase enzymes. Proc Natl Acad Sci USA 1993;90:7240-7244.
184. Bolotina VM, Najibi S, Palacino JJ, Pagano PJ, Cohen RA. Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature 1994;368:850-883.
185. Pataricza J, Toth GK, Penke B, Hohn J, Papp JG. Effect of selective inhibition of potassium channels on vasorelaxing response to cromakalim, nitroglyc-erin and nitric oxide of canine coronary arteries. J Pharm Pharmacol. 1995;47:921-925.
186. Hall S, Turcato S, Clapp L. Abnormal activation of K+ channels underlies relaxation to bacterial li-popolysaccharide in rat aorta. Biochem Biophys Res Comm 1996;224:184-190.
187. Chen SJ, Wu CC, Yang SN, Lin CI, Yen MH. Abnormal activation of K(+) channels in aortic smooth muscle of rats with endotoxic shock: electrophysiological and functional evidence. Br J Pharmacol. 2000; 131:213-222.
188. Chen SJ, Wu CC, Yang SN, Lin CI, Yen MH. Hyperpolarization contributes to vascular hyporeactivity in rats with lipopolysaccharide-induced endotoxic shock. Life Sci. 2000;68:659-668.
189. Murphy ME, Brayden JE. Nitric oxide hyperpolarizes rabbit mesenteric arteries via ATP-sensitive potassium channels. J Physiol 1995;486:47-58.
190. Preiser JC, Zhang H, Debelle F, Fesler P, Kafi SA, Naeije R, Vincent JL. Hemodynamic effects of glib-enclamide during endotoxemia: contrasting findings in vitro versus in vivo. Shock. 2003;19:223-228.
191. O'Brien AJ, Thakur G, Buckley JF, Singer M, Clapp LH. The pore-forming subunit of the K(ATP) channel is an important molecular target for LPS-induced vascular hyporeactivity in vitro. Br J Pharmacol. 2005;144:367-375.
192. Zhou R, Liu LM, Hu D Y. Effect of nitric oxide-induced tyrosine phosphorylation of calcium-activated potassium channel alpha subunit on vascular hyporesponsiveness in rats. Chin J Traumatol. 2005;8:209-215.
193. Pickkers P, Dorresteijn MJ, Bouw MP, van der Hoeven JG, Smits P. In vivo evidence for nitric oxide mediated calcium-activated potassium channel activation during human endotoxemia. Circulation. 2006;114:414-421.
194. Kuo JH, Chen SJ, Shih CC, Lue WM, Wu CC. Abnormal activation of potassium channels in aortic smooth muscle of rats with peritonitis-induced septic shock. Shock. 2009;32:74-79.
195. Wu CC, Chen SJ, Garland CJ. NO and KATP channels underlie endotoxin-induced smooth muscle hyperpolarization in rat mesenteric resistance arteries. Br J Pharmacol. 2004;142:479-484.
196. Fatehi-Hassanabad Z, Burns H, Aughey EA, Paul A, Plevin R, Parratt JR, Furman BL. Effects of L-ca-navenine, an inhibitor of inducible nitric oxide synthase on endotoxin mediated shock in rats. Shock 1996;6:194-200.
197. Scott JA, Mehta S, Duggan M, Bihari A, McCor-Mack DG. Functional inhibition of constitutive nitric oxide synthase in a rat model of sepsis. Am J Respir Crit Care Med. 2002;165:1426-1432.
198. Chauhan SD, Seggara G, Vo PA, Macallister RJ, Hobbs AJ, Ahluwalia A. Protection against lipopoly-saccharide-induced endothelial dysfunction in resistance and conduit vasculature of iNOS knockout mice. FASEB J. 203;17:773-775.
199. Matejovic M, Krouzecky A, Radej J, Rokyta R Jr, Kralova H, Radermacher P, Novak I. Coagulation and endothelial dysfunction during longterm hyper-dynamic porcine bacteremia--effects of selective inducible nitric oxide synthase inhibition. Thromb Haemost. 2007;97:304-309.
200. Subramani J, Leo MD, Kathirvel K, Arunadevi R, Singh TU, Prakash VR, Mishra SK. Essential role of nitric oxide in sepsis-induced impairment of endothelium-derived hyperpolarizing factor-mediated relaxation in rat pulmonary artery. Eur J Pharmacol. 2010;630:84-91.
201. Stasch JP, Schmidt PM, Nedvetsky PI, Nedvetskaya TY, H S AK, Meurer S, Deile M, Taye A, Knorr A, Lapp H, Müller H, Turgay Y, Rothkegel C, Tersteegen A, Kemp-Harper B, Müller-Esterl W, Schmidt HH. Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. J Clin Invest. 2006;116:2552-2561.
202. Evgenov O V, Pacher P, Schmidt PM, Haskó G, Schmidt HH, Stasch JP. NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov. 2006;5:755-768.
203. Browner NC, Sellak H, Lincoln TM. Downregula-tion of cGMP-dependent protein kinase expression by infl ammatory cytokines in vascular smooth muscle cells. Am J Physiol Cell Physiol. 2004;287:C88-96.
204. Burgoyne JR, Madhani M, Cuello F, Charles RL, Brennan JP, Schröder E, Browning DD, Eaton P. Cysteine redox sensor in PKGIa enables oxidant-induced activation. Science. 2007;317:1393-1397.