Therapeutics targeting of dysregulated redox equilibrium and endothelial dysfunction

Handbook of Experimental Pharmacology

Volumn 218, Issue , 2013, Pages 315-349

  Risbano, Michael G ^a   Gladwin, Mark T ^a  

^a UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

Author keywords

Endothelial dysfunction; Nitric oxide; Redox equilibrium

Indexed keywords

4 AMINO 5 CYCLOPROPYL 2 [1 (2 FLUOROBENZYL) 1H PYRAZOLO[3,4 B]PYRIDIN 3 YL]PYRIMIDINE; ARGINASE; ARGINASE 1; ARGINASE 2; ARGININE; ATACIGUAT; CINACIGUAT; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ENDOTHELIN 1; NITRATE; NITRIC OXIDE; NITRIC OXIDE DONOR; PROSTACYCLIN; REACTIVE OXYGEN METABOLITE; RIOCIGUAT; S NITROSOGLUTATHIONE; SILDENAFIL; TADALAFIL; TETRAHYDROBIOPTERIN; UNCLASSIFIED DRUG;

ARTICLE; BIOAVAILABILITY; CELL DAMAGE; CELL PROLIFERATION; DRUG APPROVAL; DRUG TARGETING; ENDOTHELIAL DYSFUNCTION; FOOD AND DRUG ADMINISTRATION; HEMOLYSIS; HOMEOSTASIS; HUMAN; INHALATION; MITOCHONDRION; NONHUMAN; OXIDATION REDUCTION STATE; OXIDATIVE PHOSPHORYLATION UNCOUPLING; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; PROTEIN TARGETING; PULMONARY HYPERTENSION; SCAVENGING SYSTEM; SIGNAL TRANSDUCTION; UPREGULATION; VASCULAR DISEASE; VASOCONSTRICTION; VASODILATATION;

ANIMALS; ENDOTHELIUM, VASCULAR; HUMANS; HYPERTENSION, PULMONARY; NADPH OXIDASE; NITRIC OXIDE; NITRIC OXIDE DONORS; NITRIC OXIDE SYNTHASE TYPE III; OXIDATION-REDUCTION; OXIDATIVE STRESS; PHOSPHODIESTERASE 5 INHIBITORS; REACTIVE OXYGEN SPECIES;

EID: 84893138988     PISSN: 01712004     EISSN: 18650325     Source Type: Book Series    
DOI: 10.1007/978-3-642-38664-0-13     Document Type: Article

References (232)

1. Agbani EO, Coats P et al (2011) Peroxynitrite stimulates pulmonary artery endothelial and smooth muscle cell proliferation: Involvement of ERK and PKC. Pulm Pharmacol Ther 24(1):100-109
2. Amaya Y, Yamazaki K et al (1990) Proteolytic conversion of xanthine dehydrogenase from the NAD-dependent type to the O2-dependent type. Amino acid sequence of rat liver xanthine dehydrogenase and identification of the cleavage sites of the enzyme protein during irreversible conversion by trypsin. J Biol Chem 265(24):14170-14175
3. Ameshima S, Golpon H et al (2003) Peroxisome proliferator-activated receptor gamma (PPARgamma) expression is decreased in pulmonary hypertension and affects endothelial cell growth. Circ Res 92(10):1162-1169
4. Archer SL, Marsboom G et al (2010) Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: A basis for excessive cell proliferation and a new therapeutic target. Circulation 121(24):2661-2671
5. Arnold WP, Mittal CK et al (1977) Nitric oxide activates guanylate cyclase and increases guanosine 30:50-cyclic monophosphate levels in various tissue preparations. Proc Natl Acad Sci USA 74(8):3203-3207
6. Artz JD, Schmidt B et al (2002) Effects of nitroglycerin on soluble guanylate cyclase: Implications for nitrate tolerance. J Biol Chem 277(21):18253-18256
7. Aslan M, Ryan TM et al (2001) Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease. Proc Natl Acad Sci USA 98(26):15215-15220
8. Ataga KI, Moore CG et al (2006) Pulmonary hypertension in patients with sickle cell disease: A longitudinal study. Br J Haematol 134(1):109-115
9. Atz AM, Wessel DL (1997) Inhaled nitric oxide in the neonate with cardiac disease. Semin Perinatol 21(5):441-455
10. Atz AM, Adatia I et al (1996) Rebound pulmonary hypertension after inhalation of nitric oxide. Ann Thorac Surg 62(6):1759-1764
11. Baliga RS, Milsom AB et al (2012) Dietary nitrate ameliorates pulmonary hypertension: Cytoprotective role for endothelial nitric oxide synthase and xanthine oxidoreductase. Circulation 125(23):2922-2932
12. Barst RJ, McGoon M et al (2004) Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol 43(12 Suppl S):40S-47S
13. Beckman JS, Koppenol WH (1996) Nitric oxide, superoxide, and peroxynitrite: The good, the bad, and ugly. Am J Physiol 271(5 Pt 1):C1424-C1437
14. Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology. Physiol Rev 87(1):245-313
15. Benhar M, Stamler JS (2005) A central role for S-nitrosylation in apoptosis. Nat Cell Biol 7(7):645-646
16. Bernatchez PN, Bauer PM et al (2005) Dissecting the molecular control of endothelial NO synthase by caveolin-1 using cell-permeable peptides. Proc Natl Acad Sci USA 102(3):761-766
17. Beyer J, Kolditz M et al (2008) L-arginine plasma levels and severity of idiopathic pulmonary arterial hypertension. Vasa 37(1):61-67
18. Biswas G, Anandatheerthavarada HK et al (2003) Mitochondria to nucleus stress signaling: A distinctive mechanism of NFkappaB/Rel activation through calcineurin-mediated inactivation of IkappaBbeta. J Cell Biol 161(3):507-519
19. Black SM, Heidersbach RS et al (1999) Inhaled nitric oxide inhibits NOS activity in lambs: Potential mechanism for rebound pulmonary hypertension. Am J Physiol 277(5 Pt 2): H1849-H1856
20. Boveris A, Oshino N et al (1972) The cellular production of hydrogen peroxide. Biochem J 128(3):617-630
21. Brennan LA, Steinhorn RH et al (2003) Increased superoxide generation is associated with pulmonary hypertension in fetal lambs: A role for NADPH oxidase. Circ Res 92(6):683-691
22. Brown GC, Borutaite V (2006) Interactions between nitric oxide, oxygen, reactive oxygen species and reactive nitrogen species. Biochem Soc Trans 34(Pt 5):953-956
23. Burwell LS, Nadtochiy SM et al (2006) Direct evidence for S-nitrosation of mitochondrial complex I. Biochem J 394(Pt 3):627-634
24. Cannon RO 3rd, Schechter AN et al (2001) Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxide delivery. J Clin Invest 108(2):279-287
25. Chatterjee A, Black SM et al (2008) Endothelial nitric oxide (NO) and its pathophysiologic regulation. Vascul Pharmacol 49(4-6):134-140
26. Chen B, Calvert AE et al (2009) Hypoxia promotes human pulmonary artery smooth muscle cell proliferation through induction of arginase. Am J Physiol Lung Cell Mol Physiol 297(6): L1151-L1159
27. Christman BW, McPherson CD et al (1992) An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 327(2):70-75
28. Coggins MP, Bloch KD (2007) Nitric oxide in the pulmonary vasculature. Arterioscler Thromb Vasc Biol 27(9):1877-1885
29. Cosby K, Partovi KS et al (2003) Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med 9(12):1498-1505
30. Cote CG, Yu FS et al (1996) Regulation of intracellular xanthine oxidase by endothelial-derived nitric oxide. Am J Physiol 271(5 Pt 1):L869-L874
31. Crabtree MJ, Tatham AL et al (2009) Quantitative regulation of intracellular endothelial nitricoxide synthase (eNOS) coupling by both tetrahydrobiopterin-eNOS stoichiometry and biopterin redox status: Insights from cells with tet-regulated GTP cyclohydrolase I expression. J Biol Chem 284(2):1136-1144
32. Cross AR, Segal AW (2004) The NADPH oxidase of professional phagocytes-prototype of the NOX electron transport chain systems. Biochim Biophys Acta 1657(1):1-22
33. Cueto E, Lopez-Herce J et al (1997) Life-threatening effects of discontinuing inhaled nitric oxide in children. Acta Paediatr 86(12):1337-1339
34. Cunnington C, Channon KM (2010) Tetrahydrobiopterin: Pleiotropic roles in cardiovascular pathophysiology. Heart 96(23):1872-1877
35. D'Alecy LG, Billecke SS (2010) Massive quantities of asymmetric dimethylarginine (ADMA) are incorporated in red blood cell proteins and may be released by proteolysis following hemolytic stress. Blood Cells Mol Dis 45(1):40
36. Dahm CC, Moore K et al (2006) Persistent S-nitrosation of complex I and other mitochondrial membrane proteins by S-nitrosothiols but not nitric oxide or peroxynitrite: Implications for the interaction of nitric oxide with mitochondria. J Biol Chem 281(15):10056-10065
37. Dasgupta T, Fabry ME et al (2010) Antisickling property of fetal hemoglobin enhances nitric oxide bioavailability and ameliorates organ oxidative stress in transgenic-knockout sickle mice. Am J Physiol Regul Integr Comp Physiol 298(2):R394-R402
38. De Castro LM, Jonassaint JC et al (2008) Pulmonary hypertension associated with sickle cell disease: Clinical and laboratory endpoints and disease outcomes. Am J Hematol 83(1):19-25
39. de Man FS, Tu L et al (2012) Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension. Am J Respir Crit Care Med 186(8):780-789
40. Dejam A, Hunter CJ et al (2004) Emerging role of nitrite in human biology. Blood Cells Mol Dis 32(3):423-429
41. DeMarco VG, Habibi J et al (2008) Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat. Am J Physiol Heart Circ Physiol 294(6):H2659-H2668
42. DeMarco VG, Habibi J et al (2009) Rosuvastatin ameliorates the development of pulmonary arterial hypertension in the transgenic (mRen2)27 rat. Am J Physiol Heart Circ Physiol 297(3): H1128-H1139
43. Demoncheaux EA, Higenbottam TW et al (2005) Decreased whole body endogenous nitric oxide production in patients with primary pulmonary hypertension. J Vasc Res 42(2):133-136
44. Deruelle P, Grover TR et al (2005) Pulmonary vascular effects of nitric oxide-cGMP augmentation in a model of chronic pulmonary hypertension in fetal and neonatal sheep. Am J Physiol Lung Cell Mol Physiol 289(5):L798-L806
45. Doherty DH, Doyle MP et al (1998) Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin. Nat Biotechnol 16(7):672-676
46. Dou Y, Maillett DH et al (2002) Myoglobin as a model system for designing heme protein based blood substitutes. Biophys Chem 98(1-2):127-148
47. Eddahibi S, Adnot S et al (1992) L-arginine restores endothelium- dependent relaxation in pulmonary circulation of chronically hypoxic rats. Am J Physiol 263(2 Pt 1):L194-L200
48. Elkayam U (1991) Tolerance to organic nitrates: Evidence, mechanisms, clinical relevance, and strategies for prevention. Ann Intern Med 114(8):667-677
49. Erusalimsky JD, Moncada S (2007) Nitric oxide and mitochondrial signaling: From physiology to pathophysiology. Arterioscler Thromb Vasc Biol 27(12):2524-2531
50. Evgenov OV, Pacher P et al (2006) NO-independent stimulators and activators of soluble guanylate cyclase: Discovery and therapeutic potential. Nat Rev Drug Discov 5(9):755-768
51. Farrow KN, Groh BS et al (2008a) Hyperoxia increases phosphodiesterase 5 expression and activity in ovine fetal pulmonary artery smooth muscle cells. Circ Res 102(2):226-233
52. Farrow KN, Lakshminrusimha S et al (2008b) Superoxide dismutase restores eNOS expression and function in resistance pulmonary arteries from neonatal lambs with persistent pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 295(6):L979-L987
53. Fialkow L, Wang Y et al (2007) Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol Med 42(2):153-164
54. Fike CD, Slaughter JC et al (2008) Reactive oxygen species from NADPH oxidase contribute to altered pulmonary vascular responses in piglets with chronic hypoxia-induced pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 295(5):L881-L888
55. Flogel U, Godecke A et al (2004) Role of myoglobin in the antioxidant defense of the heart. FASEB J 18(10):1156-1158
56. Fonseca GH, Souza R et al (2012) Pulmonary hypertension diagnosed by right heart catheterisation in sickle cell disease. Eur Respir J 39(1):112-118
57. Forstermann U, Munzel T (2006) Endothelial nitric oxide synthase in vascular disease: From marvel to menace. Circulation 113(13):1708-1714
58. Foster MW, McMahon TJ et al (2003) S-nitrosylation in health and disease. Trends Mol Med 9 (4):160-168
59. Francis BN, Wilkins MR et al (2010) Tetrahydrobiopterin and the regulation of hypoxic pulmonary vasoconstriction. Eur Respir J 36(2):323-330
60. Frei AC, Guo Y et al (2008) Vascular dysfunction in a murine model of severe hemolysis. Blood 112(2):398-405
61. Fresquet F, Pourageaud F et al (2006) Role of reactive oxygen species and gp91phox in endothelial dysfunction of pulmonary arteries induced by chronic hypoxia. Br J Pharmacol 148 (5):714-723
62. Friebe A, Koesling D (2003) Regulation of nitric oxide-sensitive guanylyl cyclase. Circ Res 93 (2):96-105
63. Galie N, Ghofrani HA et al (2005) Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 353(20):2148-2157
64. Galie N, Brundage BH et al (2009) Tadalafil therapy for pulmonary arterial hypertension. Circulation 119(22):2894-2903
65. Garcia-Cardena G, Martasek P et al (1997) Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the nos caveolin binding domain in vivo. J Biol Chem 272(41):25437-25440
66. Gaston B, Reilly J et al (1993) Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proc Natl Acad Sci USA 90(23):10957-10961
67. Gaston B, Fry E et al (1998) Umbilical arterial S-nitrosothiols in stressed newborns: Role in perinatal circulatory transition. Biochem Biophys Res Commun 253(3):899-901
68. Gaston B, Singel D et al (2006) S-nitrosothiol signaling in respiratory biology. Am J Respir Crit Care Med 173(11):1186-1193
69. Ghofrani HA, Wiedemann R et al (2002) Sildenafil for treatment of lung fibrosis and pulmonary hypertension: A randomised controlled trial. Lancet 360(9337):895-900
70. Ghofrani HA, Hoeper MM et al (2010) Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: A phase II study. Eur Respir J 36(4):792-799
71. Giaid A, Yanagisawa M et al (1993) Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 328(24):1732-1739
72. Gielis JF, Lin JY et al (2011) Pathogenetic role of eNOS uncoupling in cardiopulmonary disorders. Free Radic Biol Med 50(7):765-776
73. Gladwin MT (2006) Deconstructing endothelial dysfunction: Soluble guanylyl cyclase oxidation and the NO resistance syndrome. J Clin Invest 116(9):2330-2332
74. Gladwin MT, Vichinsky E (2008) Pulmonary complications of sickle cell disease. N Engl J Med 359(21):2254-2265
75. Gladwin MT, Shelhamer JH et al (2000) Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans. Proc Natl Acad Sci USA 97(21):11482-11487
76. Gladwin MT, Sachdev V et al (2004) Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 350(9):886-895
77. Grimminger F, Weimann G et al (2009) First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension. Eur Respir J 33(4):785-792
78. Grobe AC, Wells SM et al (2006) Increased oxidative stress in lambs with increased pulmonary blood flow and pulmonary hypertension: Role of NADPH oxidase and endothelial NO synthase. Am J Physiol Lung Cell Mol Physiol 290(6):L1069-L1077
79. Hansmann G, Zamanian RT (2009) PPARgamma activation: A potential treatment for pulmonary hypertension. Sci Transl Med 1(12):12ps14
80. Harris CM, Massey V (1997) The oxidative half-reaction of xanthine dehydrogenase with NAD; reaction kinetics and steady-state mechanism. J Biol Chem 272(45):28335-28341
81. Hassoun PM, Mouthon L et al (2009) Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol 54(1 Suppl):S10-S19
82. Hattori Y, Nakanishi N et al (2003) HMG-CoA reductase inhibitor increases GTP cyclohydrolase I mRNA and tetrahydrobiopterin in vascular endothelial cells. Arterioscler Thromb Vasc Biol 23(2):176-182
83. He W, Barak Y et al (2003) Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle. Proc Natl Acad Sci USA 100(26):15712-15717
84. Hemnes AR, Zaiman A et al (2008) PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation. Am J Physiol Lung Cell Mol Physiol 294(1):L24-L33
85. Hendgen-Cotta UB, Merx MW et al (2008) Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury. Proc Natl Acad Sci USA 105(29):10256-10261
86. Hill A, Rother RP et al (2010) Effect of eculizumab on haemolysis-associated nitric oxide depletion, dyspnoea, and measures of pulmonary hypertension in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol 149(3):414-425
87. Hoshikawa Y, Ono S et al (2001) Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia. J Appl Physiol 90(4):1299-1306
88. Houston M, Estevez A et al (1999) Binding of xanthine oxidase to vascular endothelium. Kinetic characterization and oxidative impairment of nitric oxide-dependent signaling. J Biol Chem 274(8):4985-4994
89. Howell K, Costello CM et al (2009) L-Arginine promotes angiogenesis in the chronically hypoxic lung: A novel mechanism ameliorating pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 296(6):L1042-L1050
90. Hsu LL, Champion HC et al (2007) Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability. Blood 109(7):3088-3098
91. Huang KT, Keszler A et al (2005) The reaction between nitrite and deoxyhemoglobin. Reassessment of reaction kinetics and stoichiometry. J Biol Chem 280(35):31126-31131
92. Humbert M, Sitbon O et al (2006) Pulmonary arterial hypertension in France: Results from a national registry. Am J Respir Crit Care Med 173(9):1023-1030
93. Humbert M, Sitbon O, Yaci A, Montani D, O'Callaghan DS, Jas X, Parent F, Savale L, Natali D, Gunther S, Chaouat A, Chabot F, Cordier JF, Habib G, Gressin V, Jing ZC, Souza R, Simonneau G, French Pulmonary Arterial Hypertension Network (2010) Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur Respir J 36(3): 549-55. doi:10.1183/09031936.00057010, Epub 2010 Jun 18
94. Hunter CJ, Dejam A et al (2004) Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator. Nat Med 10(10):1122-1127
95. Ignarro LJ, Degnan JN et al (1982) Activation of purified guanylate cyclase by nitric oxide requires heme. Comparison of heme-deficient, heme-reconstituted and heme-containing forms of soluble enzyme from bovine lung. Biochim Biophys Acta 718(1):49-59
96. Ignarro LJ, Buga GM et al (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84(24):9265-9269
97. Ignarro LJ, Napoli C et al (2002) Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide: An overview. Circ Res 90(1):21-28
98. Imanishi T, Ikejima H et al (2008) Addition of eplerenone to an angiotensin-converting enzyme inhibitor effectively improves nitric oxide bioavailability. Hypertension 51(3):734-741
99. Ishii M, Shimizu S et al (2001) Stimulation of tetrahydrobiopterin synthesis induced by insulin: Possible involvement of phosphatidylinositol 3-kinase. Int J Biochem Cell Biol 33(1):65-73
100. Ivy DD, Parker TA et al (1997) Prolonged endothelin A receptor blockade attenuates chronic pulmonary hypertension in the ovine fetus. J Clin Invest 99(6):1179-1186
101. Jankov RP, Kantores C et al (2008) Contribution of xanthine oxidase-derived superoxide to chronic hypoxic pulmonary hypertension in neonatal rats. Am J Physiol Lung Cell Mol Physiol 294(2):L233-L245
102. Joppa P, Petrasova D et al (2007) Oxidative stress in patients with COPD and pulmonary hypertension. Wien Klin Wochenschr 119(13-14):428-434
103. Kanno S, Wu YJ et al (2001) Angiotensin-converting enzyme inhibitor preserves p21 and endothelial nitric oxide synthase expression in monocrotaline-induced pulmonary arterial hypertension in rats. Circulation 104(8):945-950
104. Karuppiah K, Druhan LJ et al (2011) Suppression of eNOS-derived superoxide by caveolin-1: A biopterin-dependent mechanism. Am J Physiol Heart Circ Physiol 301(3):H903-H911
105. Kato GJ, McGowan V et al (2006) Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood 107(6):2279-2285
106. Kato GJ, Wang Z et al (2009) Endogenous nitric oxide synthase inhibitors in sickle cell disease: Abnormal levels and correlations with pulmonary hypertension, desaturation, haemolysis, organ dysfunction and death. Br J Haematol 145(4):506-513
107. Kaul DK, Liu XD et al (2000) Impaired nitric oxide-mediated vasodilation in transgenic sickle mouse. Am J Physiol Heart Circ Physiol 278(6):H1799-H1806
108. Kaul DK, Liu XD et al (2004) Effect of fetal hemoglobin on microvascular regulation in sickle transgenic-knockout mice. J Clin Invest 114(8):1136-1145
109. Kelleher ZT, Matsumoto A et al (2007) NOS2 regulation of NF-kappaB by S-nitrosylation of p65. J Biol Chem 282(42):30667-30672
110. Kelley EE, Hock T et al (2006) Moderate hypoxia induces xanthine oxidoreductase activity in arterial endothelial cells. Free Radic Biol Med 40(6):952-959
111. Kelley EE, Khoo NK et al (2010) Hydrogen peroxide is the major oxidant product of xanthine oxidase. Free Radic Biol Med 48(4):493-498
112. Khoo JP, Zhao L et al (2005) Pivotal role for endothelial tetrahydrobiopterin in pulmonary hypertension. Circulation 111(16):2126-2133
113. Kibbe MR, Li J et al (2000) Inducible nitric oxide synthase (iNOS) expression upregulates p21 and inhibits vascular smooth muscle cell proliferation through p42/44 mitogen-activated protein kinase activation and independent of p53 and cyclic guanosine monophosphate. J Vasc Surg 31(6):1214-1228
114. Krasuski RA, Devendra GP et al (2011) Response to inhaled nitric oxide predicts survival in patients with pulmonary hypertension. J Card Fail 17(4):265-271
115. Kunuthur SP, Milliken PH et al (2011) Tetrahydrobiopterin analogues with NO-dependent pulmonary vasodilator properties. Eur J Pharmacol 650(1):371-377
116. Kurz S, Hink U et al (1999) Evidence for a causal role of the renin-angiotensin system in nitrate tolerance. Circulation 99(24):3181-3187
117. Landburg PP, Teerlink T et al (2008) Plasma concentrations of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, are elevated in sickle cell patients but do not increase further during painful crisis. Am J Hematol 83(7):577-579
118. Landburg PP, Teerlink T et al (2010) Plasma asymmetric dimethylarginine concentrations in sickle cell disease are related to the hemolytic phenotype. Blood Cells Mol Dis 44(4):229-232
119. Langle F, Roth E et al (1995) Arginase release following liver reperfusion. Evidence of hemodynamic action of arginase infusions. Transplantation 59(11):1542-1549
120. Lavoie A, Hall JB et al (1996) Life-threatening effects of discontinuing inhaled nitric oxide in severe respiratory failure. Am J Respir Crit Care Med 153(6 Pt 1):1985-1987
121. Li H, Forstermann U (2000) Nitric oxide in the pathogenesis of vascular disease. J Pathol 190(3):244-254
122. Li D, Zhou N et al (1999) Soluble guanylate cyclase gene expression and localization in rat lung after exposure to hypoxia. Am J Physiol 277(4 Pt 1):L841-L847
123. List BM, Klosch B et al (1997) Characterization of bovine endothelial nitric oxide synthase as a homodimer with down-regulated uncoupled NADPH oxidase activity: Tetrahydrobiopterin binding kinetics and role of haem in dimerization. Biochem J 323(Pt 1):159-165
124. Liu L, Hausladen A et al (2001) A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans. Nature 410(6827):490-494
125. Liu L, Yan Y et al (2004) Essential roles of S-nitrosothiols in vascular homeostasis and endotoxic shock. Cell 116(4):617-628
126. Liu JQ, Zelko IN et al (2006) Hypoxic pulmonary hypertension: Role of superoxide and NADPH oxidase (gp91phox). Am J Physiol Lung Cell Mol Physiol 290(1):L2-L10
127. Liu X, Gai Y et al (2010) Trimetazidine inhibits pressure overload-induced cardiac fibrosis through NADPH oxidase-ROS-CTGF pathway. Cardiovasc Res 88(1):150-158
128. Lu X, Murphy TC et al (2010) PPAR{gamma} regulates hypoxia-induced Nox4 expression in human pulmonary artery smooth muscle cells through NF-{kappa}B. Am J Physiol Lung Cell Mol Physiol 299(4):L559-L566
129. Lundberg JO, Weitzberg E et al (2008) The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov 7(2):156-167
130. Lundberg JO, Gladwin MT et al (2009) Nitrate and nitrite in biology, nutrition and therapeutics. Nat Chem Biol 5(12):865-869
131. Machado RF, Anthi A et al (2006) N-terminal pro-brain natriuretic peptide levels and risk of death in sickle cell disease. JAMA 296(3):310-318
132. Machado RF, Hildescheim M et al (2009) NT-pro brain natriuretic peptide levels and the risk of stroke and death in the cooperative study of sickle cell disease. Blood 114:1541
133. Malhotra R, Hess D et al (2011) Vasoreactivity to inhaled nitric oxide with oxygen predicts longterm survival in pulmonary arterial hypertension. Pulm Circ 1(2):250-258
134. Markewitz BA, Michael JR (2000) Inhaled nitric oxide in adults with the acute respiratory distress syndrome. Respir Med 94(11):1023-1028
135. McLaughlin VV, Archer SL et al (2009a) ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol 53(17):1573-1619
136. McLaughlin VV, Archer SL et al (2009b) ACCF/AHA 2009 expert consensus document on pulmonary hypertension: A report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: Developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation 119(16):2250-2294
137. Mehari A, Gladwin MT et al (2012) Mortality in adults with sickle cell disease and pulmonary hypertension. JAMA 307(12):1254-1256
138. Mehta S, Stewart DJ et al (1995) Short-term pulmonary vasodilation with L-arginine in pulmonary hypertension. Circulation 92(6):1539-1545
139. Meyer C, Heiss C et al (2010) Hemodialysis-induced release of hemoglobin limits nitric oxide bioavailability and impairs vascular function. J Am Coll Cardiol 55(5):454-459
140. Miller OI, Tang SF et al (1995) Rebound pulmonary hypertension on withdrawal from inhaled nitric oxide. Lancet 346(8966):51-52
141. Minneci PC, Deans KJ et al (2005) Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin. J Clin Invest 115(12):3409-3417
142. Minniti CP, Sable C et al (2009) Elevated tricuspid regurgitant jet velocity in children and adolescents with sickle cell disease: Association with hemolysis and hemoglobin oxygen desaturation. Haematologica 94(3):340-347
143. Mittal M, Roth M et al (2007) Hypoxia-dependent regulation of nonphagocytic NADPH oxidase subunit NOX4 in the pulmonary vasculature. Circ Res 101(3):258-267
144. Mittendorf J, Weigand S et al (2009) Discovery of riociguat (BAY 63-2521): A potent, oral stimulator of soluble guanylate cyclase for the treatment of pulmonary hypertension. ChemMedChem 4(5):853-865
145. Modin A, Bjorne H et al (2001) Nitrite-derived nitric oxide: A possible mediator of 'acidicmetabolic' vasodilation. Acta Physiol Scand 171(1):9-16
146. Morris CR, Morris SM Jr et al (2003) Arginine therapy: A new treatment for pulmonary hypertension in sickle cell disease Am J Respir Crit Care Med 168(1):63-69
147. Morris CR, Kato GJ et al (2005) Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA 294(1):81-90
148. Morris CR, Gladwin MT et al (2008) Nitric oxide and arginine dysregulation: A novel pathway to pulmonary hypertension in hemolytic disorders. Curr Mol Med 8(7):620-632
149. Moya MP, Gow AJ et al (2002) Inhaled ethyl nitrite gas for persistent pulmonary hypertension of the newborn. Lancet 360(9327):141-143
150. Munzel T, Giaid A et al (1995a) Evidence for a role of endothelin 1 and protein kinase C in nitroglycerin tolerance. Proc Natl Acad Sci USA 92(11):5244-5248
151. Munzel T, Sayegh H et al (1995b) Evidence for enhanced vascular superoxide anion production in nitrate tolerance. A novel mechanism underlying tolerance and cross-tolerance. J Clin Invest 95(1):187-194
152. Munzel T, Kurz S et al (1996) Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase. A new action for an old drug. J Clin Invest 98 (6):1465-1470
153. Nagaya N, Uematsu M et al (2001) Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension. Am J Respir Crit Care Med 163(4):887-891
154. Namachivayam P, Theilen U et al (2006) Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children. Am J Respir Crit Care Med 174(9):1042-1047
155. Nandi M, Miller A et al (2005) Pulmonary hypertension in a GTP-cyclohydrolase 1-deficient mouse. Circulation 111(16):2086-2090
156. Naoman SG, Nouraie M et al (2010) Echocardiographic findings in patients with sickle cell disease. Ann Hematol 89(1):61-66
157. Nisbet RE, Bland JM et al (2010) Rosiglitazone attenuates chronic hypoxia-induced pulmonary hypertension in a mouse model. Am J Respir Cell Mol Biol 42(4):482-490
158. Nisimoto Y, Motalebi S et al (1999) The p67(phox) activation domain regulates electron flow from NADPH to flavin in flavocytochrome b(558). J Biol Chem 274(33):22999-23005
159. Nolan VG, Wyszynski DF et al (2005) Hemolysis associated priapism in sickle cell disease. Blood 106(9):3264-3267
160. Nolan VG, Adewoye A et al (2006) Sickle cell leg ulcers: Associations with haemolysis and SNPs in Klotho, TEK and genes of the TGF-beta/BMP pathway. Br J Haematol 133(5):570-578
161. Nong Z, Stassen JM et al (1996) Inhibition of tissue angiotensin- converting enzyme with quinapril reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling. Circulation 94(8):1941-1947
162. Nozik-Grayck E, Suliman HB et al (2008) Lung EC-SOD overexpression attenuates hypoxic induction of Egr-1 and chronic hypoxic pulmonary vascular remodeling. Am J Physiol Lung Cell Mol Physiol 295(3):L422-L430
163. Oak JH, Cai H (2007) Attenuation of angiotensin II signaling recouples eNOS and inhibits nonendothelial NOX activity in diabetic mice. Diabetes 56(1):118-126
164. Onyekwere OC, Campbell A et al (2008) Pulmonary hypertension in children and adolescents with sickle cell disease. Pediatr Cardiol 29(2):309-312
165. Oudiz RJ, Brundage BH et al (2012) Tadalafil for the treatment of pulmonary arterial hypertension: A double-blind 52-week uncontrolled extension study. J Am Coll Cardiol 60(8):768-774
166. Ozaki M, Kawashima S et al (2002) Overexpression of endothelial nitric oxide synthase accelerates atherosclerotic lesion formation in apoE-deficient mice. J Clin Invest 110(3):331-340
167. Pagano PJ, Clark JK et al (1997) Localization of a constitutively active, phagocyte-like NADPH oxidase in rabbit aortic adventitia: Enhancement by angiotensin II. Proc Natl Acad Sci USA 94(26):14483-14488
168. Palmer RM, Ferrige AG et al (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327(6122):524-526
169. Palmer RM, Ashton DS et al (1988) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333(6174):664-666
170. Parent F, Bachir D et al (2011) A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med 365(1):44-53
171. Pearson DL, Dawling S et al (2001) Neonatal pulmonary hypertension-urea-cycle intermediates, nitric oxide production, and carbamoyl-phosphate synthetase function. N Engl J Med 344 (24):1832-1838
172. Quyyumi AA, Dakak N et al (1995) Nitric oxide activity in the human coronary circulation. Impact of risk factors for coronary atherosclerosis. J Clin Invest 95(4):1747-1755
173. Rabinovitch M (2008) Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest 118(7):2372-2379
174. Rassaf T, Flogel U et al (2007) Nitrite reductase function of deoxymyoglobin: Oxygen sensor and regulator of cardiac energetics and function. Circ Res 100(12):1749-1754
175. Reiter CD, Wang X et al (2002) Cell-free hemoglobin limits nitric oxide bioavailability in sicklecell disease. Nat Med 8(12):1383-1389
176. Robbins IM, Hemnes AR et al (2011) Safety of sapropterin dihydrochloride (6r-bh4) in patients with pulmonary hypertension. Exp Lung Res 37(1):26-34
177. Roberts JD Jr, Fineman JR et al (1997) Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group. N Engl J Med 336(9):605-610
178. Rossaint R, Falke KJ et al (1993) Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med 328(6):399-405
179. Rother RP, Bell L et al (2005) The clinical sequelae of intravascular
180. Sachdev V, Kato GJ et al (2011) Echocardiographic markers of elevated pulmonary pressure and left ventricular diastolic dysfunction are associated with exercise intolerance in adults and adolescents with homozygous sickle cell anemia in the United States and United Kingdom. Circulation 124(13):1452-1460
181. Sanders KA, Hoidal JR (2007) The NOX on pulmonary hypertension. Circ Res 101(3):224-226
182. Sanghani PC, Davis WI et al (2009) Kinetic and cellular characterization of novel inhibitors of S-nitrosoglutathione reductase. J Biol Chem 284(36):24354-24362
183. Schnog JB, Teerlink T et al (2005) Plasma levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are elevated in sickle cell disease. Ann Hematol 84(5):282-286
184. Sharma S, Kumar S et al (2009) Alterations in lung arginine metabolism in lambs with pulmonary hypertension associated with increased pulmonary blood flow. Vascul Pharmacol 51(5-6):359-364
185. Shiva S, Gladwin MT (2009) Shining a light on tissue NO stores: Near infrared release of NO from nitrite and nitrosylated hemes. J Mol Cell Cardiol 46(1):1-3
186. Shiva S, Huang Z et al (2007) Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration. Circ Res 100(5):654-661
187. Sitbon O, Humbert M et al (1998) Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension. Eur Respir J 12(2):265-270
188. Sitbon O, Humbert M et al (2005) Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 111(23):3105-3111
189. Spiekermann S, Schenk K et al (2009) Increased xanthine oxidase activity in idiopathic pulmonary arterial hypertension. Eur Respir J 34(1):276
190. Stasch JP, Becker EM et al (2001) NO-independent regulatory site on soluble guanylate cyclase. Nature 410(6825):212-215
191. Stewart DJ, Levy RD et al (1991) Increased plasma endothelin-1 in pulmonary hypertension: Marker or mediator of disease Ann Intern Med 114(6):464-469
192. Sturrock A, Cahill B et al (2006) Transforming growth factor-beta1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 290(4):L661-L673
193. Sutendra G, Bonnet S et al (2010) Fatty acid oxidation and malonyl-CoA decarboxylase in the vascular remodeling of pulmonary hypertension. Sci Transl Med 2(44):44ra58
194. Sutliff RL, Kang BY et al (2010) PPARgamma as a potential therapeutic target in pulmonary hypertension. Ther Adv Respir Dis 4(3):143-160
195. Sydow K, Daiber A et al (2004) Central role of mitochondrial aldehyde dehydrogenase and reactive oxygen species in nitroglycerin tolerance and cross-tolerance. J Clin Invest 113(3):482-489
196. Tabima DM, Frizzell S et al (2012) Reactive oxygen and nitrogen species in pulmonary hypertension. Free Radic Biol Med 52(9):1970-1986
197. Takeya R, Sumimoto H (2003) Molecular mechanism for activation of superoxide-producing NADPH oxidases. Mol Cells 16(3):271-277
198. Teng RJ, Du J et al (2011) Sepiapterin improves angiogenesis of pulmonary artery endothelial cells with in utero pulmonary hypertension by recoupling endothelial nitric oxide synthase. Am J Physiol Lung Cell Mol Physiol 301(3):L334-L345
199. Tian J, Smith A et al (2009) Effect of PPARgamma inhibition on pulmonary endothelial cell gene expression: Gene profiling in pulmonary hypertension. Physiol Genomics 40(1):48-60
200. Tiso M, Tejero J et al (2011) Human neuroglobin functions as a redox-regulated nitrite reductase. J Biol Chem 286(20):18277-18289
201. Tofovic SP, Jackson EK et al (2009) Adenosine deaminase-adenosine pathway in hemolysisassociated pulmonary hypertension. Med Hypotheses 72(6):713-719
202. Tota B, Quintieri AM et al (2010) The emerging role of nitrite as an endogenous modulator and therapeutic agent of cardiovascular function. Curr Med Chem 17(18):1915-1925
203. Tuder RM, Groves B et al (1994) Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am J Pathol 144(2):275-285
204. Vachiery JL, Huez S et al (2011) Safety, tolerability and pharmacokinetics of an intravenous bolus of sildenafil in patients with pulmonary arterial hypertension. Br J Clin Pharmacol 71(2):289-292
205. Venema VJ, Zou R et al (1997) Caveolin-1 detergent solubility and association with endothelial nitric oxide synthase is modulated by tyrosine phosphorylation. Biochem Biophys Res Commun 236(1):155-161
206. Vignais PV (2002) The superoxide-generating NADPH oxidase: Structural aspects and activation mechanism. Cell Mol Life Sci 59(9):1428-1459
207. Vosatka RJ, Kashyap S et al (1994) Arginine deficiency accompanies persistent pulmonary hypertension of the newborn. Biol Neonate 66(2-3):65-70
208. Voskaridou E, Christoulas D et al (2010) The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: Results of a 17-year, single-center trial (LaSHS). Blood 115(12):2354-2363
209. Wedgwood S, Black SM (2003) Role of reactive oxygen species in vascular remodeling associated with pulmonary hypertension. Antioxid Redox Signal 5(6):759-769
210. Wedgwood S, Bekker JM et al (2001) Shear stress regulation of endothelial NOS in fetal pulmonary arterial endothelial cells involves PKC. Am J Physiol Lung Cell Mol Physiol 281(2):L490-L498
211. Wedgwood S, Steinhorn RH et al (2005) Increased hydrogen peroxide downregulates soluble guanylate cyclase in the lungs of lambs with persistent pulmonary hypertension of the newborn. Am J Physiol Lung Cell Mol Physiol 289(4):L660-L666
212. Weerackody RP, Welsh DJ et al (2009) Inhibition of p38 MAPK reverses hypoxia-induced pulmonary artery endothelial dysfunction. Am J Physiol Heart Circ Physiol 296(5): H1312-H1320
213. Weinberger B, Laskin DL et al (2001) The toxicology of inhaled nitric oxide. Toxicol Sci 59(1):5-16
214. Wenzel P, Schulz E et al (2008) AT1-receptor blockade by telmisartan upregulates GTP-cyclohydrolase I and protects eNOS in diabetic rats. Free Radic Biol Med 45(5):619-626
215. Whalen EJ, Foster MW et al (2007) Regulation of beta-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2. Cell 129(3):511-522
216. Williamson JR, Chang K et al (1993) Hyperglycemic pseudohypoxia and diabetic complications. Diabetes 42(6):801-813
217. Wolin MS (2009) Reactive oxygen species and the control of vascular function. Am J Physiol Heart Circ Physiol 296(3):H539-H549
218. Wolin MS, Ahmad M et al (2005) The sources of oxidative stress in the vessel wall. Kidney Int 67(5):1659-1661
219. Wood KC, Hebbel RP et al (2005) Endothelial cell NADPH oxidase mediates the cerebral microvascular dysfunction in sickle cell transgenic mice. FASEB J 19(8):989-991
220. Wood KC, Hsu LL et al (2008) Sickle cell disease vasculopathy: A state of nitric oxide resistance. Free Radic Biol Med 44(8):1506-1528
221. Wu X, Du L et al (2010) Increased nitrosoglutathione reductase activity in hypoxic pulmonary hypertension in mice. J Pharmacol Sci 113(1):32-40
222. Wunderlich C, Schober K et al (2008) The adverse cardiopulmonary phenotype of caveolin-1 deficient mice is mediated by a dysfunctional endothelium. J Mol Cell Cardiol 44(5):938-947
223. Xu W, Kaneko FT et al (2004) Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension. FASEB J 18(14):1746-1748
224. Yeo TW, Lampah DA et al (2007) Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria. J Exp Med 204(11):2693-2704
225. Yeo TW, Lampah DA et al (2009) Relationship of cell-free hemoglobin to impaired endothelial nitric oxide bioavailability and perfusion in severe falciparum malaria. J Infect Dis 200 (10):1522-1529
226. Zhang J, Chen Z et al (2004) Role of mitochondrial aldehyde dehydrogenase in nitroglycerininduced vasodilation of coronary and systemic vessels: An intact canine model. Circulation 110(6):750-755
227. Zhao YY, Zhao YD et al (2009) Persistent eNOS activation secondary to caveolin-1 deficiency induces pulmonary hypertension in mice and humans through PKG nitration. J Clin Invest 119(7):2009-2018
228. Zisman DA, Schwarz M et al (2010) A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med 363(7):620-628
229. Zuckerbraun BS, Stoyanovsky DA et al (2007) Nitric oxide-induced inhibition of smooth muscle cell proliferation involves S-nitrosation and inactivation of RhoA. Am J Physiol Cell Physiol 292(2):C824-C831
230. Zuckerbraun BS, Shiva S et al (2010) Nitrite potently inhibits hypoxic and inflammatory pulmonary arterial hypertension and smooth muscle proliferation via xanthine oxidoreductasedependent nitric oxide generation. Circulation 121(1):98-109
231. Zuckerbraun BS, George P et al (2011) Nitrite in pulmonary arterial hypertension: Therapeutic avenues in the setting of dysregulated arginine/nitric oxide synthase signalling. Cardiovasc Res 89(3):542-552
232. Zulueta JJ, Sawhney R et al (2002) Modulation of inducible nitric oxide synthase by hypoxia in pulmonary artery endothelial cells. Am J Respir Cell Mol Biol 26(1):22-30