N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats

Respiratory Research

Volumn 15, Issue 1, 2014, Pages

  Chaumais, Marie Camille ^a,b,c   Ranchoux, Benoît ^a,b   Montani, David ^a,b,d   Dorfmüller, Peter ^a,b   Tu, Ly ^a,b   Lecerf, Florence ^a,b   Raymond, Nicolas ^a,b   Guignabert, Christophe ^a,b   Price, Laura ^e   Simonneau, Gérald ^a,b,d   Cohen Kaminsky, Sylvia ^a,b   Humbert, Marc ^a,b,d   Perros, Frédéric ^a,b  

^a UNIVERSITÉ PARIS SACLAY   (France)

^b Universite Paris Sud   (France)

^c HÔPITAL ANTOINE BÉCLÈRE   (France)

^d BICÊTRE HOSPITAL   (France)

^e ROYAL BROMPTON HOSPITAL   (United Kingdom)

Author keywords

Immunomodulation; Inflammation; N acetylcysteine; Pulmonary hypertension; Right heart function

Indexed keywords

ACETYLCYSTEINE; INTERLEUKIN 6; MONOCROTALINE; SODIUM CHLORIDE;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DENDRITIC CELL; DISEASE SEVERITY; DRUG EFFICACY; DRUG EXPOSURE; HEART FUNCTION; HEART MUSCLE CELL; HEART MUSCLE FIBROSIS; HEART OUTPUT; HEART RIGHT VENTRICLE FUNCTION; HEART RIGHT VENTRICLE HYPERTROPHY; HEART RIGHT VENTRICLE PRESSURE; HEART VENTRICLE HYPERTROPHY; HEMODYNAMIC PARAMETERS; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; INFLAMMATORY CELL; LUNG; LUNG ARTERY PRESSURE; LUNG VASCULAR RESISTANCE; MACROPHAGE; MALE; MONOCYTE; MORPHOMETRICS; NONHUMAN; PNEUMONIA; PROTEIN EXPRESSION; PULMONARY HYPERTENSION; RAT; SYSTOLIC BLOOD PRESSURE; ANIMAL; CELL CULTURE; CHEMICALLY INDUCED DISORDER; DRUG EFFECT; PATHOLOGY; SPRAGUE DAWLEY RAT; TREATMENT OUTCOME;

ACETYLCYSTEINE; ANIMALS; CELLS, CULTURED; HYPERTENSION, PULMONARY; MALE; MONOCROTALINE; MYOCYTES, CARDIAC; RATS; RATS, SPRAGUE-DAWLEY; TREATMENT OUTCOME;

EID: 84904694156     PISSN: 14659921     EISSN: 1465993X     Source Type: Journal    
DOI: 10.1186/1465-9921-15-65     Document Type: Article

References (49)

1. Pietra GG, Capron F, Stewart S, Leone O, Humbert M, Robbins IM, Reid LM, Tuder RM. Pathologic assessment of vasculopathies in pulmonary hypertension. J Am Coll Cardiol 2004, 43:25S-32S. 10.1016/j.jacc.2004.02.033, 15194175.
2. Dorfmuller P, Perros F, Balabanian K, Humbert M. Inflammation in pulmonary arterial hypertension. Eur Respir J 2003, 22:358-363. 10.1183/09031936.03.00038903, 12952274.
3. Price LC, Wort SJ, Perros F, Dorfmuller P, Huertas A, Montani D, Cohen-Kaminsky S, Humbert M. Inflammation in pulmonary arterial hypertension. Chest 2012, 141:210-221. 10.1378/chest.11-0793, 22215829.
4. Huertas A, Tu L, Gambaryan N, Girerd B, Perros F, Montani D, Fabre D, Fadel E, Eddahibi S, Cohen-Kaminsky S, Guignabert C, Humbert M. Leptin and regulatory T-lymphocytes in idiopathic pulmonary arterial hypertension. Eur Respir J 2012, 40:895-904. 10.1183/09031936.00159911, 22362850.
5. Perros F, Dorfmuller P, Montani D, Hammad H, Waelput W, Girerd B, Raymond N, Mercier O, Mussot S, Cohen-Kaminsky S, Humbert M, Lambrecht BN. Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 2012, 185:311-321. 10.1164/rccm.201105-0927OC, 22108206.
6. Gambaryan N, Cohen-Kaminsky S, Montani D, Girerd B, Huertas A, Seferian A, Humbert M, Perros F. Circulating fibrocytes and pulmonary arterial hypertension. Eur Respir J 2012, 39:210-212. 10.1183/09031936.00039811, 22210811.
7. Yeager ME, Nguyen CM, Belchenko DD, Colvin KL, Takatsuki S, Ivy DD, Stenmark KR. Circulating fibrocytes are increased in children and young adults with pulmonary hypertension. Eur Respir J 2012, 39:104-111. 10.1183/09031936.00072311, 3319160, 21700605.
8. Dahal BK, Kosanovic D, Kaulen C, Cornitescu T, Savai R, Hoffmann J, Reiss I, Ghofrani HA, Weissmann N, Kuebler WM, Seeger W, Grimminger F, Schermuly RT. Involvement of mast cells in monocrotaline-induced pulmonary hypertension in rats. Respir Res 2011, 12:60. 10.1186/1465-9921-12-60, 3104382, 21535881.
9. Humbert M, Monti G, Brenot F, Sitbon O, Portier A, Grangeot-Keros L, Duroux P, Galanaud P, Simonneau G, Emilie D. Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am J Respir Crit Care Med 1995, 151:1628-1631. 10.1164/ajrccm.151.5.7735624, 7735624.
10. Bhargava A, Kumar A, Yuan N, Gewitz MH, Mathew R. Monocrotaline induces interleukin-6 mRNA expression in rat lungs. Heart Dis 1999, 1:126-132.
11. Gillespie MN, Goldblum SE, Cohen DA, McClain CJ. Interleukin 1 bioactivity in the lungs of rats with monocrotaline-induced pulmonary hypertension. Proc Soc Exp Biol Med 1988, 187:26-32. 10.3181/00379727-187-42632, 3124119.
12. Dorfmuller P, Zarka V, Durand-Gasselin I, Monti G, Balabanian K, Garcia G, Capron F, Coulomb-Lhermine A, Marfaing-Koka A, Simonneau G, Emilie D, Humbert M. Chemokine RANTES in severe pulmonary arterial hypertension. Am J Respir Crit Care Med 2002, 165:534-539. 10.1164/ajrccm.165.4.2012112, 11850348.
13. Sanchez O, Marcos E, Perros F, Fadel E, Tu L, Humbert M, Dartevelle P, Gerald S, Adnot S, Eddahibi S. Role of endothelium-derived CC chemokine ligand 2 in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 2007, 176:1041-1047. 10.1164/rccm.200610-1559OC, 17823354.
14. Balabanian K, Foussat A, Dorfmuller P, Durand-Gasselin I, Capel F, Bouchet-Delbos L, Portier A, Marfaing-Koka A, Krzysiek R, Rimaniol AC, Simonneau G, Emilie D, Humbert M. CX(3)C chemokine fractalkine in pulmonary arterial hypertension. Am J Respir Crit Care Med 2002, 165:1419-1425. 10.1164/rccm.2106007, 12016106.
15. Perros F, Dorfmuller P, Souza R, Durand-Gasselin I, Mussot S, Mazmanian M, Herve P, Emilie D, Simonneau G, Humbert M. Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension. Eur Respir J 2007, 29:462-468. 10.1183/09031936.00094706, 17107989.
16. Bogaard HJ, Abe K, Vonk Noordegraaf A, Voelkel NF. The right ventricle under pressure: cellular and molecular mechanisms of right-heart failure in pulmonary hypertension. Chest 2009, 135:794-804. 10.1378/chest.08-0492, 19265089.
17. Dorfmuller P, Chaumais MC, Giannakouli M, Durand-Gasselin I, Raymond N, Fadel E, Mercier O, Charlotte F, Montani D, Simonneau G, Humbert M, Perros F. Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension. Respir Res 2011, 12:119. 10.1186/1465-9921-12-119, 3189121, 21906276.
18. Tabima DM, Frizzell S, Gladwin MT. Reactive oxygen and nitrogen species in pulmonary hypertension. Free Radic Biol Med 2012, 52:1970-1986. 10.1016/j.freeradbiomed.2012.02.041, 3856647, 22401856.
19. DeMarco VG, Habibi J, Whaley-Connell AT, Schneider RI, Heller RL, Bosanquet JP, Hayden MR, Delcour K, Cooper SA, Andresen BT, Sowers JR, Dellsperger KC. Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat. Am J Physiol Heart Circ Physiol 2008, 294:H2659-H2668. 10.1152/ajpheart.00953.2007, 18424632.
20. Hsu HH, Ko WJ, Hsu JY, Chen JS, Lee YC, Lai IR, Chen CF. Simvastatin ameliorates established pulmonary hypertension through a heme oxygenase-1 dependent pathway in rats. Respir Res 2009, 10:32. 10.1186/1465-9921-10-32, 2681458, 19409105.
21. Bowers R, Cool C, Murphy RC, Tuder RM, Hopken MW, Flores SC, Voelkel NF. Oxidative stress in severe pulmonary hypertension. Am J Respir Crit Care Med 2004, 169:764-769. 10.1164/rccm.200301-147OC, 14701708.
22. Cracowski JL, Degano B, Chabot F, Labarere J, Schwedhelm E, Monneret D, Iuliano L, Schwebel C, Chaouat A, Reynaud-Gaubert M, Faure P, Maas R, Renversez JC, Cracowski C, Sitbon O, Yaïci A, Simonneau G, Humbert M. Independent association of urinary F2-isoprostanes with survival in pulmonary arterial hypertension. Chest 2012, 142:869-876. 10.1378/chest.11-1267, 22406961.
23. Crosswhite P, Sun Z. Nitric oxide, oxidative stress and inflammation in pulmonary arterial hypertension. J Hypertens 2010, 28:201-212. 10.1097/HJH.0b013e328332bcdb, 2809140, 20051913.
24. Samuni Y, Goldstein S, Dean OM, Berk M. The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta 1830, 2013:4117-4129.
25. Cortijo J, Cerda-Nicolas M, Serrano A, Bioque G, Estrela JM, Santangelo F, Esteras A, Llombart-Bosch A, Morcillo EJ. Attenuation by oral N-acetylcysteine of bleomycin-induced lung injury in rats. Eur Respir J 2001, 17:1228-1235. 10.1183/09031936.01.00049701, 11491169.
26. Kharazmi A, Nielsen H, Schiotz PO. N-acetylcysteine inhibits human neutrophil and monocyte chemotaxis and oxidative metabolism. Int J Immunopharmacol 1988, 10:39-46.
27. Haleagrahara N, Julian V, Chakravarthi S. N-acetylcysteine offers cardioprotection by decreasing cardiac lipid hydroperoxides and 8-isoprostane level in isoproterenol-induced cardiotoxicity in rats. Cardiovasc Toxicol 2011, 11:373-381. 10.1007/s12012-011-9132-0, 21796404.
28. Foltz WU, Wagner M, Rudakova E, Volk T. N-acetylcysteine prevents electrical remodeling and attenuates cellular hypertrophy in epicardial myocytes of rats with ascending aortic stenosis. Basic Res Cardiol 2012, 107:290.
29. Handoko ML, Schalij I, Kramer K, Sebkhi A, Postmus PE, van der Laarse WJ, Paulus WJ, Vonk-Noordegraaf A. A refined radio-telemetry technique to monitor right ventricle or pulmonary artery pressures in rats: a useful tool in pulmonary hypertension research. Pflugers Arch 2008, 455:951-959. 10.1007/s00424-007-0334-z, 2137943, 17912547.
30. Price LC, Montani D, Tcherakian C, Dorfmuller P, Souza R, Gambaryan N, Chaumais MC, Shao DM, Simonneau G, Howard LS, Adcock IM, Wort SJ, Humbert M, Perros F. Dexamethasone reverses monocrotaline-induced pulmonary arterial hypertension in rats. Eur Respir J 2011, 37:813-822. 10.1183/09031936.00028310, 20693255.
31. Gomez-Arroyo JG, Farkas L, Alhussaini AA, Farkas D, Kraskauskas D, Voelkel NF, Bogaard HJ. The monocrotaline model of pulmonary hypertension in perspective. Am J Physiol Lung Cell Mol Physiol 2012, 302:L363-L369. 10.1152/ajplung.00212.2011, 21964406.
32. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, Gomez Sanchez MA, Krishna Kumar R, Landzberg M, Machado RF, Olschewski H, Robbins IM, Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013, 62:D34-D41. 10.1016/j.jacc.2013.10.029, 24355639.
33. Kabe Y, Ando K, Hirao S, Yoshida M, Handa H. Redox regulation of NF-kappaB activation: distinct redox regulation between the cytoplasm and the nucleus. Antioxid Redox Signal 2005, 7:395-403. 10.1089/ars.2005.7.395, 15706086.
34. Price LC, Caramori G, Perros F, Gambaryan N, Dorfmuller P, Montani D, Casolari P, Zhu J, Dimopoulos K, Shao D, Girerd B, Mumby S, Proudfoot A, Griffiths M, Papi A, Humbert M, Adcock IM, Wort SJ. Nuclear factor-kB is activated in the pulmonary vessels of patients with end-stage idiopathic pulmonary arterial hypertension. PLoS One 2013, in press.
35. Sawada H, Mitani Y, Maruyama J, Jiang BH, Ikeyama Y, Dida FA, Yamamoto H, Imanaka-Yoshida K, Shimpo H, Mizoguchi A, Maruyama K, Komada Y. A nuclear factor-kappaB inhibitor pyrrolidine dithiocarbamate ameliorates pulmonary hypertension in rats. Chest 2007, 132:1265-1274. 10.1378/chest.06-2243, 17934115.
36. Kimura S, Egashira K, Chen L, Nakano K, Iwata E, Miyagawa M, Tsujimoto H, Hara K, Morishita R, Sueishi K, Tominaga R, Sunagawa K. Nanoparticle-mediated delivery of nuclear factor kappaB decoy into lungs ameliorates monocrotaline-induced pulmonary arterial hypertension. Hypertension 2009, 53:877-883. 10.1161/HYPERTENSIONAHA.108.121418, 19307469.
37. de Man FS, Tu L, Handoko ML, Rain S, Ruiter G, Francois C, Schalij I, Dorfmuller P, Simonneau G, Fadel E, Perros F, Boonstra A, Postmus PE, van der Velden J, Vonk-Noordegraaf A, Humbert M, Eddahibi S, Guignabert C. Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension. Am J Respir Crit Care Med 2012, 186:780-789. 10.1164/rccm.201203-0411OC, 22859525.
38. Ullian ME, Gelasco AK, Fitzgibbon WR, Beck CN, Morinelli TA. N-acetylcysteine decreases angiotensin II receptor binding in vascular smooth muscle cells. J Am Soc Nephrol 2005, 16:2346-2353. 10.1681/ASN.2004060458, 15944340.
39. Han WQ, Zhu DL, Wu LY, Chen QZ, Guo SJ, Gao PJ. N-acetylcysteine-induced vasodilation involves voltage-gated potassium channels in rat aorta. Life Sci 2009, 84:732-737. 10.1016/j.lfs.2009.02.023, 19268479.
40. Probyn ME, Cock ML, Duncan JR, Tolcos M, Hale N, Shields A, Rees SM, Harding R. The anti-inflammatory agent N-acetyl cysteine exacerbates endotoxin-induced hypoxemia and hypotension and induces polycythemia in the ovine fetus. Neonatology 2010, 98:118-127. 10.1159/000280385, 20160461.
41. Voelkel NF, Bogaard HJ, Al Husseini A, Farkas L, Gomez-Arroyo J, Natarajan R. Antioxidants for the treatment of patients with severe angioproliferative pulmonary hypertension?. Antioxid Redox Signal 2013, 18:1810-1817. 10.1089/ars.2012.4828, 22870869.
42. Gomez-Arroyo J, Mizuno S, Szczepanek K, Van Tassell B, Natarajan R, dos Remedios CG, Drake JI, Farkas L, Kraskauskas D, Wijesinghe DS, Chalfant CE, Bigbee J, Abbate A, Lesnefsky EJ, Bogaard HJ, Voelkel NF. Metabolic gene remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy secondary to pulmonary arterial hypertension. Circ Heart Fail 2013, 6:136-144. 10.1161/CIRCHEARTFAILURE.111.966127, 3790960, 23152488.
43. Lowes BD, Minobe W, Abraham WT, Rizeq MN, Bohlmeyer TJ, Quaife RA, Roden RL, Dutcher DL, Robertson AD, Voelkel NF, Badesch DB, Groves BM, Gilbert EM, Bristow MR. Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium. J Clin Invest 1997, 100:2315-2324. 10.1172/JCI119770, 508428, 9410910.
44. Baicu CF, Stroud JD, Livesay VA, Hapke E, Holder J, Spinale FG, Zile MR. Changes in extracellular collagen matrix alter myocardial systolic performance. Am J Physiol Heart Circ Physiol 2003, 284:H122-H132.
45. Takimoto E, Kass DA. Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension 2007, 49:241-248. 10.1161/01.HYP.0000254415.31362.a7, 17190878.
46. Redout EM, Wagner MJ, Zuidwijk MJ, Boer C, Musters RJ, van Hardeveld C, Paulus WJ, Simonides WS. Right-ventricular failure is associated with increased mitochondrial complex II activity and production of reactive oxygen species. Cardiovasc Res 2007, 75:770-781. 10.1016/j.cardiores.2007.05.012, 17582388.
47. Giordano FJ. Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest 2005, 115:500-508. 10.1172/JCI200524408, 1052012, 15765131.
48. Voelkel NF, Gomez-Arroyo J, Abbate A, Bogaard HJ, Nicolls MR. Pathobiology of pulmonary arterial hypertension and right ventricular failure. Eur Respir J 2012, 40:1555-1565. 10.1183/09031936.00046612, 4019748, 22743666.
49. van Wolferen SA, Marcus JT, Boonstra A, Marques KM, Bronzwaer JG, Spreeuwenberg MD, Postmus PE, Vonk-Noordegraaf A. Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur Heart J 2007, 28:1250-1257. 10.1093/eurheartj/ehl477, 17242010.