Animal models of pulmonary arterial hypertension;Modèles animaux d'hypertension artérielle pulmonaire

Revue des Maladies Respiratoires

Volumn 24, Issue 4, 2007, Pages 481-496

  Naeije, R ^a,b   Dewachter, L ^a  

^a UNIVERSITÉ LIBRE DE BRUXELLES   (Belgium)

^b Erasme Campus ^*  (Belgium)

Author keywords

Animal models; Congenital heart disease; Hypoxia; Monocrotaline; Pulmonary hypertension

Indexed keywords

MONOCROTALINE;

ADVENTITIA; APOPTOSIS; DISEASE SEVERITY; GENETIC MANIPULATION; HEART VENTRICLE HYPERTROPHY; HYPOXIA; LAMB; LUNG EDEMA; LUNG VASCULAR RESISTANCE; NONHUMAN; PIGLET; PULMONARY HYPERTENSION; REVIEW; VASCULAR RESISTANCE; VASOSPASM;

EID: 34247899006     PISSN: 07618425     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0761-8425(07)91571-5     Document Type: Article

References (149)

1. McLaughlin V, Presberg KW, Doyle RL, Abman SH, McCrory DC, Fortin T, Ahearn G : Prognosis of Pulmonary Arterial Hypertension* ACCP Evidence-Based Clinical Practice Guidelines. Chest 2004 ; 126 : 78S-92S.
2. Provencher S, Sitbon O, Humbert M, Cabrol S, Jais X, Simonneau G : Long-term outcome with first-line bosentan therapy in idiopathic pulmonary arterial hypertension. Eur Heart J 2006 ; 27 : 589-95.
3. Heath D, Edwards JE : The pathology of pulmonary vascular disease: a description of six grades of structural changes in the pulmonary arteries, with special reference to congenital cardiac septal defects. Circulation 1958 ; 18 : 533-47.
4. Wagenvoort CA, Wagenvoort N : Primary pulmonary hypertension: a pathological study of the lung vessels in 156 clinically diagnosed cases. Circulation 1970 ; 42 : 1163-84.
5. Pietra GG, Capron F, Stewart S, Leone O, Humbert M, Robbins IM, Reid LM, Tuder RM : Pathologic assessment of vasculopathies in pulmonary arterial hypertension. J Am J Coll Cardiol 2004 ; 43 : 25S-32S.
6. Palevsky HI, Schloo BL, Pietra CG, Weber KT, Janicki JS, Rubin E, Fishman AP : Primary pulmonary hypertension: vascular structure, morphometry, and responsiveness to vasodilator agents. Circulation 1989 ; 80 : 1207-21.
7. Moser KM, Bloor CM : Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension. Chest 1993 ; 103 : 685-92.
8. Rich S, Dantzker DR, Ayres SM, Bergofsky EH, Brundage B, Detre K, Fishman AP, Goldring RM, Groves BM, Koerner SK : Primary pulmonary hypertension. A national prospective study. Ann Intern Med 1987 ; 107 : 216-23.
9. Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaici A, Weitzenblum E, Cordier JF, Chabot F, Dromer C, Pison C, Reynaud-Gaubert M, Haloun A, Laurent M, Hachulla E, Simonneau G : Pulmonary Arterial Hypertension in France Results from a National Registry. Am J Respir Crit Care Med 2006 ; 173 : 1023-30.
10. Farber HW, Loscalzo J : Pulmonary arterial hypertension. N Engl J Med 2004 ; 351 : 1655-65.
11. Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, Rabinovitch M : Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 2004 ; 43 : 13S-24S.
12. Atkinson C, Stewart S, Upton PD, Machado R, Thomson JR, Trembath RC, Morrell NW : Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation 2002 ; 105 : 1672-8.
13. Du L, Sullivan CC, Chu D, Cho AJ, Kido M, Wolf PL, Yuan JX, Deutsch R, Jamieson SW, Thistlethwaite PAI : Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med 2003 ; 348 : 500-9.
14. Sullivan CC, Du L, Chu D, Cho AJ, Kido M, Wolf PL, Jamieson SW, Thistlethwaite PA : Induction of pulmonary hypertension by an angiopoietin 1/TIE2/serotonin pathway. Proc Natl Acad Sci 2003 ; 100 : 12331-6.
15. Dewachter L, Adnot S, Fadel E, Humbert M, Maitre B, Barlier-Mur AM, Simonneau G, Hamon M, Naeije R, Eddahibi S : Angiopoietin/Tie2 Pathway Influences Smooth Muscle Hyperplasia in Idiopathic Pulmonary Hypertension. Am J Respir Crit Care Med 2006 ; 174 : 1025-33.
16. Grover RF, Wagner WW, McMurtry IF, Reeves JT : Pulmonary Circulation. In: handbook of Physiology. The Cardiovascular System. Peripheral Circulation and Organ Blood Flow. Bethesda MD: Am Physiol Soc, 1983, sect 2, vol III, part 1, Chap 4, pp 103-36.
17. Weir EK, Archer SL : The mechanism of acute hypoxic pulmonary vasoconstriction: the tale of two channels. FASEB J 1995 ; 9 : 183-9.
18. Dorrington KL, Clar C, Young JD, Jonas M, Tansley JG, Robbins PA : Time course of the human pulmonary vascular response to 8 hours of isocapnic hypoxia. Am J Physiol 1997 ; 273 : H1126-34.
19. Maggiorini M, Melot C, Pierre S, Pfeiffer F, Greve I, Sartori C, Lepori M, Hauser M, Scherrer U, Naeije R : High-altitude pulmonary edema is initially caused by an increase in capillary pressure. Circulation 2001 ; 103 : 2078-83.
20. Groves BM, Reeves JT, Sutton JR, Wagner PD, Cymerman A, Malconian MK, Rock PB, Young PM, Houston CS : Operation Everest II: elevated high-altitude pulmonary resistance unresponsive to oxygen. J Appl Physiol 1987 ; 63 : 521-30.
21. Minamino T, Christou H, Hsieh CM, Liu Y, Dhawan V, Abraham NG, Perrella MA, Mitsialis SA, Kourembanas S : Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia. Proc Natl Acad Sci U S A 2001 ; 98 : 8798-803.
22. Madjdpour C, Jewell UR, Kneller S, Ziegler U, Schwendener R, Booy C, Klausli L, Pasch T, Schimmer RC, Beck-Schimmer B : Decreased alveolar oxygen tension induces lung inflammation. Am J Physiol Lung Cell Mol Physiol 2003 ; 284 : L360-7.
23. Maggiorini M, Brunner-La Rocca P, Peth S, Fischler M, Bohm T, Bernheim A, Kiencke S, Bloch KE, Dehnert C, Naeije R, Lehmann T, Bartsch P, Mairbaurl H : Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema: a randomized trial. Ann Intern Med 2006 ; 145 : 497-506.
24. Chen SJ, Chen IF, Meng QC, Durand J, Di Carlo VS, Oparil S : Endothelin-receptor antagonist bosentan prevents and reverses hypoxic pulmonary hypertension in rats. J Appl Physiol 1995 ; 79 : 2122-31.
25. Stenmark KR, Fasules J, Hyde DM, Voelkel NF, Henson J, Tucker A, Wilson H, Reeves JT : Severe pulmonary hypertension and arterial adventitial changes in newborn calves at 4300 m. J Appl Physiol 1987 ; 62 : 821-30.
26. Tucker A, Greenlees KJ, Wright ML, Migally N : Altered vascular responsiveness in isolated perfused lungs from aging rats. Exp Lung Res 1982 ; 3 : 29-35.
27. Sugita T, Stenmark KR, Wagner WW, Henson PM, Henson JE, Reeves JT : Abnormal alveolar cells in monocrotaline-induced pulmonary hypertension. Exp Lung Res 1983 ; 5 : 201-15.
28. Tucker A, Anderson KK, Babyak SD, White WL : Pulmonary hypertension and increased pulmonary vascular reactivity in rats at 10000 ft since birth. Chest 1988 ; 93 : 185S.
29. Peacock AJ, Pickett C, Morris K, Reeves JT: The relationship between rapid growth and pulmonary hemodynamics in the fast-growing broiler chicken. Am Rev Respir Dis 1989 ; 139 : 1524-30.
30. Julian RJ, Friars GW, French H, Quinton M : The relationship of right ventricular hypertrophy, right ventricular failure and ascites to weight gain in broiler and roaster chickens. Avian Dis 1987 ; 31 : 130-5.
31. Li H, Chen SJ, Chen YF, Meng QC, Durand J, Oparil S, Elton TS : Enhanced endothelin-1 and endothelin receptor gene expression in chronic hypoxia. J Appl Physiol 1994 ; 77 : 1451-9.
32. Soma S, Takahashi H, Muramatsu M, Oka M, Fukuchi Y : Localization and distribution of endothelin receptor subtypes in pulmonary vasculature of normal and hypoxia-exposed rats. Am J Respir Cell Mol Biol 1999 ; 20 : 620-30.
33. Tyler RC, Muramatsu M, Abman SH, Stelzner TJ, Rodman DM, Bloch KD, McMurtry IF : Variable expression of endothelial NO synthase in three forms of rat pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 1999 ; 276 : L297-303.
34. Blumberg FC, Lorenz C, Wolf K, Sandner P, Riegger GA, Pfeifer M : Increased pulmonary prostacyclin synthesis in rats with chronic pulmonary hypertension. Cardiovasc Res 2002 ; 55 : 171-7.
35. Eddahibi S, Fabre V, Boni C, Matres MP, Raffestin B, Hamon M, Adnot S : Induction of serotonin transporter by hypoxia in pulmonary artery smooth muscle cells. Relationship with the mitogenic action of serotonin. Circ Res 1999 ; 84 : 329-36.
36. Sebkhi A, Strange JW, Philips SC, Wharton J, Wilkins M : Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced pulmonary hyhpertension. Circulation 2003 ; 107 : 3230-5.
37. Weir EK, Olschewski A : Role of ion channels in acute and chronic responses of the pulmonary vasculature to hypoxia. Cardiovasc Res 2006 ; 71 : 630-41.
38. Frid MG, Brunetti JA, Burke DL, Carpenter TC, Davie NJ, Reeves JT, Roedersheimer MT, van Rooijen N, Stenmark KR : Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/ macrophage lineage. Am J Pathol 2006 ; 168 : 659-69.
39. Takahasi H, Goto N, Kojima Y, Tsuda Y, Morio Y, Muramatsu M, Fukushi Y : Downregulation of type II bone morphogenetic protein receptor in hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2006 ; 290 : L450-8.
40. Kouyoumdjian C, Adnot S, Levame M, Eddahibi S, Bousbaa H, Raffestin B : Continuous inhalation of nitric oxide protects against development of pulmonary hypertension in chronically hypoxic rats. J Clin Invest 1994 ; 94 : 578-84.
41. Dumitrascu R, Weissmann N, Ghofrani HA, Dony E, Beuerlein K, Schmidt H, Stasch JP, Gnoth MJ, Seeger W, Grimminger F, Schermuly RT : Activation of soluble guanylate cyclase reverses experimental pulmonary hypertension and vascular remodeling. Circulation 2006 ; 113 : 286-95.
42. Eddahibi S, Raffestin B, Le Monier de Gouville AC, Adnot S : Effect of DMPPO, a phosphodiesterase type 5 inhibitor, on hypoxic pulmonary hypertension in rats. Br J Pharmacol 1998 ; 125 : 681-8.
43. Zhao L, Mason NA, Morrell NW, Kojonazarov B, Sadykov A, Maripov A, Mirrakhimov MM, Aldashev A, Wilkins MR : Sildenafil inhibits hypoxia-induced pulmonary hypertension. Circulation 2001 ; 104 : 424-8.
44. Abe Y, Tatsumi K, Sugito K, Ikeda Y, Kimura H, Kuriyama T : Effects of inhaled prostacyclin analogue on chronic hypoxic pulmonary hypertension. J Cardiovasc Pharmacol 2001 ; 37 : 239-51.
45. Geraci MW, Gao B, Shepherd DC, Moore MD, Westcott JY, Fagan KA, Alger LA, Tuder RM, Voelkel NF : Pulmonary prostacyclin synthase overexpression in transgenic mice protects against development of hypoxic pulmonary hypertension. J Clin Invest 1999 ; 103 : 1509-15.
46. Marcos E, Adnot S, Pham MH, Nosjean A, Raffestin B, Hamon M, Eddahibi S : Serotonin transporter inhibitors protect against hypoxic pulmonary hypertension. Am J Respir Crit Care Med 2003 ; 168 : 487-93.
47. Xie M, Wang H, Wang H, Hu G : Effects of iptakalim hydrochloride, a novel KATP channel opener, on pulmonary vascular remodeling in hypoxic rats. Life Sci 2004 ; 75 : 2065-76.
48. DiCarlo VS, Chen SJ, Meng QC, Durand J, Yano M, Chen YF, Oparil S : ETA-receptor antagonist prevents and reverses chronic hypoxia-induced pulmonary hypertension in rat. Am J Physiol 1995 ; 269 : L690-7.
49. Zaidi SH, You XM, Ciura S, Husain M, Rabinovitch M : Overexpression of the serine elastase inhibitor elafin protects transgenic mice from hypoxic pulmonary hypertension. Circulation 2002 ; 105 : 516-21.
50. Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, Grimminger F : Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 2005 ; 115 : 2811-21.
51. Vieillard-Baron A, Frisdal E, Eddahibi S, Deprez I, Baker AH, Newby AC, Berger, Levame M, Raffestin B, Adnot S, d'Ortho MP : Inhibition of matrix metalloproteinases by lung TIMP-1 gene transfer or doxycycline aggravates pulmonary hypertension in rats. Circ Res 2000 ; 87 : 418425.
52. Kay JM, Heath D : Crotalaria Spectabilis. The pulmonary hypertension plant. Springfield, Il, Thomas, 1969.
53. Kay JM, Heath D : Observations on the pulmonary arteries and heart weights of rats fed on crotalaria spectabilis seeds. J Pathol Bacteriol 1966 ; 92 : 385-94.
54. Kay JM, Harris P, Heath D : Pulmonary hypertension in rats produced by the ingestion of crotalaria spectabilis seeds. Thorax 1967 ; 22 : 176-85.
55. Plestina R, Stoner HB : Pulmonary edema in rats given monocrotaline pyrrole. J Pathol 1972 ; 106 : 235-49.
56. Sugita T, Hyers TM, Dauber IM, Wagner WW, MsMurtry IF, Reeves JT : Lung vessel leak precedes right ventricular hypertrophy in monocrotaline-treated rats. J A ppl Physiol 1983 ; 54 : 371-6.
57. Hilliker KS, Roth RA : Alteration of monocrotaline pyrrole-induced cardiopulmonary effects in rats by hydralazine, dexamethasone and sulphinpyrazone. Br J Pharmacol 1984 ; 82 : 375-80.
58. Langleben D, Reid LM: Effect of methylprednisoloneon monocrotaline- induced pulmonary vascular disease and right ventricular hypertrophy. Lab Invest 1985 ; 52 : 298-303.
59. Miyauchi T, Yorikane R, Sakai S, Sakurai T, Okada M, Nishikibe M, Yano M, Yamaguchi I, Sugishita Y, Goto K : Contribution of endogenous endothelin-1 to the progression of cardiopulmonary alterations in rats with monocrotaline- induced pulmonary hypertension. Circ Res 1993 ; 73 : 887-97.
60. Ono M, Sawa Y, Mizuno S, Fukushima N, Ichikawa H, Bessho K, Nakamura T, Matsuda H : Hepatocyte growth factor suppresses vascular medial hyperplasia and matrix accumulation in advanced pulmonary hypertension of rats. Circulation 2004 ; 110 : 2896-902.
61. Mathew R, Zeballos GA, Tun H, Gewitz MH : Role of nitric oxide and endothelin-1 in monocrotaline-induced pulmonary hypertension in rats. Cardiovasc Res 1995 ; 30 : 739-46.
62. Frasch HF, Marshall C, Marshall BE : Endothelin-1 is elevated in monocrotaline pulmonary hypertension. Am J Physiol 1999 ; 276 : L304-10.
63. Yorikane R, Miyauchi T, Sakai S, Sakurai T, Yamaguchi I, Sugishita Y, Goto K : Altered expression of ETB-receptor mRNA in the lung of rats with pulmonary hypertension. J Cardiovasc Pharmacol 1993 ; 22 Suppl 8 : S336-8.
64. Guignabert C, Raffestin B, Benferhat R, Raoul W, Zadigue P, Rideau D, Hamon M, Adnot S, Eddahibi S : Serotonin transporter inhibition prevents and reverses monocrotaline-induced pulmonary hypertension in rats. Circulation 2005 ; 111 : 2812-9.
65. McMurtry MS, Archer SL, Altieri DC, Bonnet S, Haromy A, Harry G, Bonnet S, Puttagunta L, Michelakis ED : Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. J Clin Invest 2005 ; 115 : 1479-91.
66. McMurtry MS, Bonnet S, Wu X, Dyck JR, Haromy A, Hashimoto K, Michelakis ED : Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res 2004 ; 95 : 830-40.
67. Voelkel NF, Tuder RM, Bridges J, Arend WP : Interleukin-1 receptor antagonist treatment reduces pulmonary hypertension generated in rats by monocrotaline. Am J Respir Cell Mol Biol 1994 ; 11 : 664-75.
68. Jones PL, Rabinovitch M : Tenascin-C is induced with progressive pulmonary vascular disease in rats and is functionally related to increased smooth muscle cell proliferation. Circ Res 1996 ; 79 : 1131-42.
69. Merklinger SL, Jones PL, Martinez EC, Rabinovitch M : Epidermal growth factor receptor blockade mediates smooth muscle cell apoptosis and improves survival in rats with pulmonary hypertension. Circulation 2005 ; 112 : 423-31.
70. Roberts JD Jr, Chiche JD, Weimann J, Steudel W, Zapol WM, Bloch KD : Nitric oxide inhalation decreases pulmonary artery remodeling in the injured lungs of rat pups. Circ Res 2000 ; 87 : 140-5.
71. McMurtry MS, Moudgil R, Hashimoto K, Bonnet S, Michelakis ED, Archer SL : Overexpression of human bone morphogenetic protein receptor II does not ameliorate monocrotaline pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 2006, sous presse.
72. Inoue M, Harada Y, Watanabe K, Mori C, Tanaka O : The effect of nifedipine on monocrotaline-induced pulmonary hypertension in rats. Acta Paediatr Jpn 1993 ; 35 : 273-7.
73. Ueno M, Miyauchi T, Sakai S, Goto K, Yamaguchi I : Endothelin-A-receptor antagonist and oral prostacyclin analog are comparably effective in ameliorating pulmonary hypertension and right ventricular hypertrophy in rats. J Cardiovasc Pharmacol 2000 ; 36 : S305-10.
74. Schermuly RT, Yilmaz H, Ghofrani HA, Woyda K, Pullamsetti S, Schulz A, Gessler T, Dimitrascu R, Weissmann N, Grimminger F, Seeger W: Inhaled iloprost reverses vascular remodeling in chronic experimental pulmonary hypertension. Am J Respir Crit Care Med 2005 ; 172 : 358-63.
75. Schermuly RT, Kreisselmeier KP, Ghofrani HA, Yilmaz H, Butrous G, Ermert L, Ermert M, Weissmann N, Rose F, Guenther A, Walmrath D, Seeger W, Grimminger F : Chronic sildenafil treatment inhibits monocrotaline-induced pulmonary hypertension in rats. Am J Respir Crit Care Med 2004 ; 169 : 39-45.
76. Jasmin JF, Lucas M, Cernacek P, Dupuis J : Effectiveness of a nonselective ET(A/B) and a selective ET(A) antagonist in rats with monocrotaline-induced pulmonary hypertension. Circulation 2001 ; 103 : 314-8.
77. Nishii Y, Gabazza EC, Fujimoto H, Nakahara H, Takagi T, Bruno N, D'Alessandro-Gabazza CN, Maruyama J, Maruyama K, Hayashi T, Adachi Y, Suzuki K, Taguchi O : Protective role of protein C inhibitor in monocrotaline-induced pulmonary hypertension. J Thromb Haemost 2006 ; 4 : 2331-9.
78. Ikeda Y, Yonemitsu Y, Kataoka C, Kitamoto S, Yamaoka T, Nishida K, Takeshita A, Egashira K, Sueishi K : Anti MCP1. Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary hypertension in rats. Am J Physiol Heart Circ Physiol 2002 ; 283 : H2021-8.
79. Cowan KN, Heilbut A, Humpl T, Lam C, Ito S, Rabinovitch M : Complete reversal of fatal pulmonary hypertension in rats by a serine elastase inhibitor. Nat Med 2000 ; 6 : 698-702.
80. Baber SR, Deng W, Master RG, Bunnell BA, Taylor BK, Murthy SN, Hyman AL, Kadowitz PJ : Intratracheal Mesenchymal Stem Cell Administration Attenuates Monocrotaline-Induced Pulmonary Hypertension and Endothelial Dysfunction. Am J Physiol Heart Circ Physiol 2006, sous presse.
81. Zhao YD, Courtman DW, Deng Y, Kugathasan L, Zhang Q, Stewart DJ : Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease. Circ Res 2005 ; 96 : 442-50.
82. Nishida M, Eshiro K, Okada Y, Takaoka M, Matsumura Y : Roles of endothelin ETA and ETB receptors in the pathogenesis of monocrotaline-induced pulmonary hypertension. J Cardiovasc Pharmacol 2004 ; 44 : 187-91.
83. Zhao YD, Campbell AIM, Robb M, Ng D, Stewart DJ : Protective role of angiopoietin-1 in experimental pulmonary hypertension. Circ Res 2003 ; 92 : 984-91.
84. Rudge JS, Thurston G, Yancopoulos GD : Angiopoietin-1 and pulmonary hypertension. Cause or cure? Circ Res 2003 ; 92 : 947-9.
85. Hoffman JI, Rudolph AM, Heymann MA : Pulmonary vascular disease with congenital heart lesions: pathologic features and causes. Circulation 1981 ; 64 : 873-7.
86. Eisenmenger V : Die angeborenens Defect der Kammerscheidewand des Herzen. Z Klin Med Suppl 1897 ; 32 : 1-28.
87. Wood P : The Eisenmenger syndrome or pulmonary hypertension with reversal shunt (The Croonian Lectures). Br Med J 1958 ; 2 : 701-9, 755-62.
88. Rendas A, Lennox S, Reid L : Aorta-pulmonary shunts in growing pigs. Functional and structural assessment of the changes in the pulmonary circulation. J Thorac Cardiovasc Surg 1979 ; 77 : 109-18.
89. De Canniere D, Stefanidis C, Brimioulle S, Naeije R : Effects of a chronic aortopulmonary shunt on pulmonary hemodynamics in piglets. J Appl Physiol 1994 ; 77 : 1591-6.
90. Wauthy P, Abdel Kafi AS, Mooi WJ, Brimioulle S, Naeije R : Effects of nitric oxide and prostacyclin in an over-circulation model of pulmonary hypertension. J Thorac Cardiovasc Surg 2003 126 : 1434-41.
91. Rondelet B, Kerbaul F, Motte S, van Beneden R, Remmelink M, Brimioulle S, McEntee K, Wauthy P, Salmon I, Ketelslegers JM, Naeije R : Bosentan for the prevention of overcirculation-induced experimental pulmonary arterial hypertension. Circulation 2003 ; 107 : 1329-35.
92. Rosenkrantz JG, Carlisle JH, Lynch FP, Vogel JH : Ligation of a single pulmonary artery in the pig: a model of chronic pulmonary hypertension. J Surg Res 1973 ; 15 : 67-73.
93. Garcia R, Diebold S : Simple, rapid and effective method of producing aortocaval shunts in the rat. Cardiovasc Res 1990 ; 24 : 430-2.
94. Reddy VM, Meyrick B, Wong J, Khoor A, Liddicoat JR, Hanley FL, Fineman JR : In utero placement of aortopulmonary shunts. A model of postnatal pulmonary hypertension with increased pulmonary blood flow in lambs. Circulation 1995 ; 92 : 606-13.
95. van Albada ME, van Veghel R, Cromme-Dijkhuis AH, Schoemaker RG, Berger RM : Treprostinil in advanced experimental pulmonary hypertension: beneficial outcome without reversed pulmonary vascular remodeling. J Cardiovasc Pharmacol 2006 ; 48 : 249-54.
96. Silove ED, Tavernor WD, Berry CL : Reactive pulmonary arterial hypertension after pulmonary venous constriction in the calf. Cardiovasc Res 1972 ; 6 : 36-44.
97. Heath D, Donald DE, Edwards JE : Pulmonary vascular changes in a dog after aortopulmonary anastomosis for four years. Br Heart J 1959 ; 21 : 187-96.
98. Esterly JA, Glagov S, Ferguson DJ : Morphogenesis of intimal obliterative hyperplasia of small pulmonary arteries in experimental pulmonary hypertension. An ultrastructural study on the role of smooth muscle cells. Am J Pathol 1968 ; 52 : 325-47.
99. Rondelet B, Van Beneden R, Kerbaul F, Motte S, Fesler P, McEntee K, Brimioulle S, Ketelslegers JM, Naeije R : Expression of the serotonin 1B receptor in experimental pulmonary hypertension. Eur Respir J 2003 ; 22 : 408-12.
100. Rondelet B, Kerbaul F, Van Beneden R, Motte S, Fesler P, Hubloue I, Remmelink M, Brimioulle S, Salmon I, Ketelslegers JM, Naeije R : Signaling molecules in overcirculation-induced pulmonary hypertension in piglets: effects of sildenafil therapy. Circulation 2004 ; 110 : 2220-5.
101. Rondelet B, Kerbaul F, Van Beneden R, Hubloue I, Huez S, Fesler P, Remmelink M, Brimioulle S, Salmon I, Naeije R : Partial prevention of pulmonary vascular remodeling and of decreased BMPR-2 expression by losartan therapy in shunt-induced pulmonary hypertension Am J Physiol Heart Circ Physiol 2005 ; 289 : H2319-24.
102. Rondelet B, Kerbaul F, Van Beneden R, Hubloue I, Huez S, Fesler P, Remmelink M, Brimioulle S, Salmon I, Naeije R : Sitaxsentan for the prevention of experimental shunt-induced pulmonary hypertension in piglets. Pediatr Res sous presse.
103. Ovadia B, Reinhartz O, Fitzgerald R, Bekker JM, Johengen MJ, Azakie A, Thelitz S, Black SM, Fineman JR : Alterations in ET-1, not nitric oxide, in 1-week-old lambs with increased pulmonary blood flow. Am J Physiol Heart Circ Physiol 2003 ; 284 : H480-90.
104. Black SM, Bekker JM, Johengen MJ, Parry AJ, Soifer SJ, Fineman JR : Altered regulation of the ET-1 cascade in lambs with increased pulmonary blood flow and pulmonary hypertension. Pediatr Res 2000 ; 47 : 97-106.
105. Black SM, Mata-Greenwood E, Dettman RW, Ovadia B, Fitzgerald RK, Reinhartz O, Thelitz S, Steinhorn RH, Gerrets R, Hendricks-Munoz K, Ross GA, Bekker JM, Johengen MJ, Fineman JR : Emergence of smooth muscle cell endothelin B-mediated vasoconstriction in lambs with experimental congenital heart disease and increased pulmonary blood flow. Circulation 2003 ; 108 : 1646-54.
106. Mata-Greenwood E, Meyrick B, Soifer SJ, Fineman JR, Black SM : Expression of VEGF and its receptors Flt-1 and Flk-1/KDR is altered in lambs with increased pulmonary blood flow and pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2003 ; 285 : L222-31.
107. Mata-Greenwood E, Meyrick B, Steinhorn RH, Fineman JR, Black SM : Alterations in TGF-beta1 expression in lambs with increased pulmonary blood flow and pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2003 ; 285 : L209-21.
108. Black SM, Sanchez LS, Mata-Greenwood E, Bekker JM, Steinhorn RH, Fineman JR : sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2001 ; 281 : L1051-7.
109. Cornfield DN, Resnik ER, Herron JM, Reinhartz O, Fineman JR : Pulmonary vascular K+ channel expression and vasoreactivity in a model of congenital heart disease. Am J Physiol Lung Cell Mol Physiol 2002 ; 283 : L1210-9.
110. Everett A, Le Cras TD, Xue C, Johns RA : ENOS expression is not altered in pulmonary vascular remodelling due to increased pulmonary blood flow. Am J Physiol Lung Cell Mol Physiol 1998 ; 274 : L1058-65.
111. Fratz S, Meyrick B, Ovadia B, Johengen MJ, Reinhartz O, Azakie A, Ross G, Fitzgerald R, Oishi P, Hess J, Black SM, Fineman JR : Chronic endothelin A receptor blockade in lambs with increased pulmonary blood flow and pressure. Am J Physiol Lung Cell Mol Physiol 2004 ; 287 : L592-7.
112. Van Albada ME, van Veghel R, Cromme-Dijkhuis AH, Scoemaker RG, Berger RM : Treprostinil in advanced experimental pulmonary hypertension: beneficial outcome without reversed pulmonary vascular remodeling. J Cardiovasc Pharmacol 2006 ; 48 : 249-54.
113. Fitzgerald RK, Oishi P, Ovadia B, Ross GA, Reinharz O, Johengen MJ, Fineman JR : Tezosentan, a combined parenteral endothelin receptor antagonist, produces pulmonary vasodilation in lambs with acute and chronic pulmonary hypertension. Pediatr Crit Care Med 2004 ; 5 : 571-7.
114. Morin FC : Ligating the ductus arteriosus before birth causes persistent pulmonary hypertension in the newborn lamb. Pediatr Res 1989 ; 25 : 245-50.
115. McQueston JA, Kinsella JP, Ivy DD, McMurtry IF, Abman SH : Chronic pulmonary hypertension in utero impairs endothelium-dependent vasodilation. Am J Physiol 1995 ; 268 : H288-94.
116. Villamor E, Le Cras TD, Horan MP, Halbower AC, Tuder RM, Abman SH : Chronic intrauterine pulmonary hypertension impairs endothelial nitric oxide synthase in the ovine fetus. Am J Physiol 1997 ; 272 : L1013-20.
117. rd. Disruption of cGMP production in pulmonary arteries isolated from fetal lambs with pulmonary hypertension. Am J Physiol 1995 ; 268 : H1483-9.
118. Hanson KA, Ziegler JW, Rybalkin SD, Miller JW, Abman SH, Clarke WR : Chronic pulmonary hypertension increases fetal lung cGMP phosphodiesterase activity. Am J Physiol 1998 ; 275 : L931-41.
119. Ivy DD, Le Cras TD, Horan MP, Abman SH : Increased lung prepro ET-1 and decreased ETB-receptor gene expression in fetal pulmonary circulation. Am JPphysiol 1998 ; 274 : L535-41.
120. Grover TR, Parker TA, Zenge JP, Markham NE, Kinsella JP, Abman SH : Intrauterine hypertension decreases lung VEGF expression and VEGF inhibition causes pulmonary hypertension in the ovine foetus. Am J Physiol Lung Cell Mol Physiol 2003 ; 284 : L508-17.
121. Resnick E, Herron J, Keck M, Sukovitch D, Linden B, Cornfield DN : Chronic intrauterine pulmonary hypertension selectively modifies pulmonary artery smooth muscle cell gene expression. Am J Physiol Lung Cell Mol Physiol 2006 ; 290 : L426-33.
122. Olschewski A, Hong Z, Linden BC, Porter VA, Weir EK, Cornfield DN : Contribution of the K(Ca) channel to membrane potential and oxygen sensitivity is decreased in an ovine PPHN model. Am J Physiol Lung Cell Physiol 2002 ; 283 : L1103-9.
123. Thebaut B, Petit T, De Lagousie P, Dall'Ava-Santucci J, Mercier JC, Dinh-Xuan AT : Altered guanylyl-cyclase activity in vitro of pulmonary arteries from fetal lambs with congenital diaphragmatic hernia. Am J Respir Cell Mol Biol 2002 ; 27 : 42-7.
124. Deruelle P, Grover TR, Abman SH : 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 2005 ; 289 : L798-806.
125. Thébaut B, de Lagausie P, Forgues D, Aigrain Y, Mercier JC, Dinh Xuan AT : ET(A) receptor blockade and ET(B)-receptor stimulation in experimental congenital diaphragmatic hernia. Am J Physiol Lung Cell Mol Physiol 2000 ; 278 : L923-32.
126. de Buys Roessingh AS, de Lagausie P, Barbet JP, Mercier JC, Aigrain Y, Dinh Xuan AT : Role of ATP-dependent potassium channels in pulmonary vascular tone of fetal lambs with congenital diaphragmatic hernia. Pediatr Res 2006 ; 60 : 537-42.
127. Chu D, Sullivan CC, Du L, Cho AJ, Kido M, Wolf PL, Weitzman MD, Jamieson SW, Thistlewaite PA : A new animal model for pulmonary hypertension based on the overexpression of a simple gene, angiopoietin-1 Ann Thorac Surg 2004 ; 77 : 449-56.
128. Kido M, Du L, Sullivan CC, Deutsch R, Jamieson SW, Thistlethwaite PA : Gene transfer of Tie2 receptor antagonist prevents pulmonary hypertension in rodents. J Thorac Cardiovasc Surg 2005 ; 129 : 268-76.
129. Eddahibi S, Hanoun N, Lanfumey L, Lesch KP, Raffestin B, Hamon M, Adnot S : Attenuated hypoxic pulmonary hypertension in mice lacking the 5-hydroxytryptamine transporter gene. J Clin Invest 2000 ; 105 : 1555-62.
130. Guignabert C, Izikki M, Tu LI, Li Z, Zadigue P, Barlier-Mur AM, Hanoun N, Rodman D, Hamon M, Adnot S, Eddahibi S : Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension. Circ Res 2006 ; 98 : 1323-30.
131. Long L, McLean MR, Jeffery TK, Morecroft I, Yang X, RudaraKanchana N, Southwood M, James V, Trembath RC, Morrell NW: Serotonin increases susceptibility to pulmonary hypertension in BMPR2-deficient mice. Circ Res 2006 ; 98 : 818-27.
132. Keegan A, Morecroft I, Smillie D, Hicks MN, MacLean MR : Contribution of the 5-HT(1B) receptor to hypoxia-induced pulmonary hypertension: converging evidence using 5HT(1B)-receptor knockout mice and the 5-HT(1B/1D)-receptor antagonist GR127935. Circ Res 2001 ; 89 : 1231-9.
133. Morecroft I, Dempsie Y, Bader M, Walther DJ, Kotnik K, Loughlin L, Nilsen M, MacLean MR : Effect of tryptophan hydroxylase 1 deficiency on the development of hypoxia-induced pulmonary hypertension. Hypertension 2007 ; 49 : 232-6.
134. Fagan A, Fouty BW, Tyler RC, Morris KG Jr, Hepler LK, Sato K, LeCras TD, Abman SH, Weinberger HD, Huang PL, McMurtry IF, Rodman DM :The pulmonary circulation of homozygous or heterozygous eNOS-null mice is hyperresponsive to mild hypoxia. J Clin Invest 1999 ; 103 : 291-9.
135. Hamidi SA, Szema AM, Lyubsky S, Dickman KG, Degene A, Mathew SM, Waschek JA, Said SI : Clues to VIP function from knockout mice. Ann N Y Acad Sci 2006 ; 1070 : 5-9.
136. Matsui H, Shimosawa T, Itakura K, Guanqun X, Ando K, Fujita T : Adrenomedullin can protect against pulmonary vascular remodeling induced by hypoxia. Circulation 2004 ; 109 : 2246-51.
137. Hoshikawa Y, Voelkel NF, Gesell TL, Moore MD, Morris KG, Alger LA, Narumiya S, Geraci MW: Prostacyclin receptor-dependent modulation of pulmonary vascular remodeling. Am J Respir Crit Care Med 2001 ; 164 : 314-8.
138. Wanstall JC, Gambino A, Jeffery TK, Cahill MM, Bellomo D, Hayward NK, Kay GF : Vascular endothelial growth factor-B-deficient mice show impaired development of hypoxic pulmonary hypertension. Cardiovasc Res 2002 ; 55 : 361-8.
139. Budts W, Pokreisz P, Nong Z, Van Pelt N, Gillijns H, Gerard R, Lyons R, Collen D, Bloch KD, Janssens S : Aerosol gene transfer with inducible nitric oxide synthase reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats. Circulation 2000 ; 102 : 2880-5.
140. Nagaya N, Yokoyama C, Kyotani S, Shimonishi M, Morishita R, Uematsu M, Nishikimi T, Nakanishi N, Ogihara T, Yamagishi M, Miyatake K, Kaneda Y, Tanabe T : Gene transfer of human prostacyclin synthase ameliorates monocrotaline- induced pulmonary hypertension in rats. Circulation 2000 ; 102 : 2005-10.
141. Wharton J, Strange JW, Moller GMO, Growcott EJ, Ren X, Franklyn AP, Phillips SC, Wilkins MR : Anti-proliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am J Respir Crit Care Med 2005 ; 172 ; 105-13.
142. Clapp LH, Finney P, Turcato S, Tran S, Rubin LJ, Tinker A : Differential effects of stable prostacyclin analogs on smooth muscle proliferation and cyclic AMP generation in human pulmonary artery. Am J Respir Cell Mol Biol 2002 ; 26 : 194-201.
143. Morrell NW, Yang X, Upton PD, Jourdan KB, Morgan N, Sheares KK, Trembath RC : Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-beta(1) and bone morphogenetic proteins. Circulation 2001 ; 104 : 790-5.
144. Yang X, Long L, Southwood M, Rudarakanchana N, Upton PD, Jeffery TK, Atkinson C, Chen H, Trembath RC, Morrell NW : Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension. Circ Res 2006 ; 98 : 818-27.
145. Eddahibi S, Guignabert C, Barlier-Mur AM, Dewachter L, Fadel E, Dartevelle P, Humbert M, Simonneau G, Hanoun N, Saurini F, Hamon M, Adnot S :
146. Welsh DJ, Peacock AJ, MacLean M, Harnett M : Chronic hypoxia induces constitutive p38 mitogen-activated protein kinase activity that correlates with enhanced cellular proliferation in fibroblasts from rat pulmonary but not systemic arteries. Am J Respir Crit Care Med 2001 ; 164 : 282-9.
147. Welsh DJ, Harnett M, MacLean M, Peacock AJ : Proliferation and Signalling in Fibroblasts: Role of 5-Hydroxytryptamine2A Receptor and Transporter. Am J Respir Crit Care Med 2004 ; 170 : 252-9.
148. Wharton J, Strange JW, Moller GMO, Growcott EJ, Ren X, Franklyn AP, Phillips SC, Wilkins MR : Anti-proliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am J Respir Crit Care Med 2005 ; 172 ; 105-13.
149. Clapp LH, Finney P, Turcato S, Tran S, Rubin LJ, Tinker A : Differential effects of stable prostacyclin analogs on smooth muscle proliferation and cyclic AMP generation in human pulmonary artery. Am J Respir Cell Mol Biol 2002 ; 26 : 194-201