New perspectives for the treatment of pulmonary hypertension

British Journal of Pharmacology

Volumn 163, Issue 1, 2011, Pages 125-140

  Baliga, Reshma S ^a   MacAllister, Raymond J ^a   Hobbs, Adrian J ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

cyclic GMP; endothelin 1; growth factors; guanylate cyclase; ion channels; phosphodiesterase; prostacyclin; pulmonary hypertension; tyrosine kinase

Indexed keywords

ACETORPHAN; AMLODIPINE; ANGIOTENSIN CONVERTING ENZYME 2; BERAPROST; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BOSENTAN; CALCIUM CHANNEL BLOCKING AGENT; CAPTOPRIL; DILTIAZEM; ENDOTHELIN RECEPTOR ANTAGONIST; ESCITALOPRAM; GLEEVAC; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ILOPROST; IMATINIB; ION CHANNEL; IPTAKALIM; NATRIURETIC FACTOR; NIFEDIPINE; NITRIC OXIDE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PHOSPHODIESTERASE V INHIBITOR; PLACEBO; PROSTACYCLIN; PROSTACYCLIN DERIVATIVE; SEROTONIN; SILDENAFIL; SIMVASTATIN; TERGURIDE; UNCLASSIFIED DRUG; VASODILATOR AGENT;

CLINICAL TRIAL (TOPIC); DISEASE ASSOCIATION; DISEASE COURSE; DRUG ACTIVITY; DRUG COST; DRUG EFFICACY; DRUG TARGETING; ENDOTHELIAL DYSFUNCTION; GENE DELETION; HEART FAILURE; HUMAN; LUNG CIRCULATION; NONHUMAN; PERIPHERAL CIRCULATION; PHASE 3 CLINICAL TRIAL (TOPIC); PHENOTYPE; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SIGNAL TRANSDUCTION; SYSTOLIC HEART FAILURE;

ANIMALS; DRUG EVALUATION, PRECLINICAL; DRUG THERAPY, COMBINATION; HUMANS; HYPERTENSION, PULMONARY; MOLECULAR TARGETED THERAPY;

EID: 79953686516     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2010.01164.x     Document Type: Review

References (196)

1. Ahluwalia A, Hobbs AJ, (2005). Endothelium-derived C-type natriuretic peptide: more than just a hyperpolarizing factor. Trends Pharmacol Sci 26: 162-167. (Pubitemid 40313596)
2. Ahluwalia A, MacAllister RJ, Hobbs AJ, (2004). Vascular actions of natriuretic peptides. Cyclic GMP-dependent and -independent mechanisms. Basic Res Cardiol 99: 83-89. (Pubitemid 38325021)
3. Alexander SPH, Mathie A, Peters JA, (2009). Guide to receptors and channels (GRAC), 4th edn. Br J Pharmacol 158 (Suppl. 1): S1-S254.
4. Ali FY, Egan K, FitzGerald GA, Desvergne B, Wahli W, Bishop-Bailey D, et al,. (2006). Role of prostacyclin versus peroxisome proliferator-activated receptor beta receptors in prostacyclin sensing by lung fibroblasts. Am J Respir Cell Mol Biol 34: 242-246. (Pubitemid 43202472)
5. Alpert MA, Pressly TA, Mukerji V, Lambert CR, Mukerji B, (1992). Short- and long-term hemodynamic effects of captopril in patients with pulmonary hypertension and selected connective tissue disease. Chest 102: 1407-1412.
6. Amsallem E, Kasparian C, Haddour G, Boissel JP, Nony P, (2005). Phosphodiesterase III inhibitors for heart failure. Cochrane Database Syst Rev (1): CD002230.
7. Archer SL, Djaballah K, Humbert M, Weir KE, Fartoukh M, I'ava-Santucci J, et al,. (1998). Nitric oxide deficiency in fenfluramine- and dexfenfluramine-induced pulmonary hypertension. Am J Respir Crit Care Med 158: 1061-1067. (Pubitemid 28489002)
8. Atkinson C, Stewart S, Upton PD, Machado R, Thomson JR, Trembath RC, et al,. (2002). Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation 105: 1672-1678. (Pubitemid 34298611)
9. Badesch DB, McGoon MD, Barst RJ, Tapson VF, Rubin LJ, Wigley FM, et al,. (2009). Longterm survival among patients with scleroderma-associated pulmonary arterial hypertension treated with intravenous epoprostenol. J Rheumatol 36: 2244-2249.
10. Baliga RS, Zhao L, Madhani M, Lopez-Torondel B, Visintin C, Selwood D, et al,. (2008). Synergy between natriuretic peptides and phosphodiesterase 5 inhibitors ameliorates pulmonary arterial hypertension. Am J Respir Crit Care Med 178: 861-869.
11. Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, et al,. (1996). A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N Engl J Med 334: 296-302.
12. Barst RJ, Langleben D, Frost A, Horn EM, Oudiz R, Shapiro S, et al,. (2004). Sitaxsentan therapy for pulmonary arterial hypertension. Am J Respir Crit Care Med 169: 441-447. (Pubitemid 38187114)
13. Belik J, (2009). Riociguat, an oral soluble guanylate cyclase stimulator for the treatment of pulmonary hypertension. Curr Opin Investig Drugs 10: 971-979.
14. Bender AT, Beavo JA, (2006). Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 58: 488-520. (Pubitemid 44394910)
15. Black SM, Sanchez LS, Mata-Greenwood E, Bekker JM, Steinhorn RH, Fineman JR, (2001). sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 281: L1051-L1057.
16. Bogaard HJ, Natarajan R, Mizuno S, Abbate A, Chang PJ, Chau VQ, et al,. (2010). Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats. Am J Respir Crit Care Med 182: 652-660.
17. Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE, et al,. (1996). Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Circulation 94: 2807-2816. (Pubitemid 26411745)
18. Budhiraja R, Tuder RM, Hassoun PM, (2004). Endothelial dysfunction in pulmonary hypertension. Circulation 109: 159-165. (Pubitemid 38114133)
19. Cargill RI, Lipworth BJ, (1995). The role of the renin-angiotensin and natriuretic peptide systems in the pulmonary vasculature. Br J Clin Pharmacol 40: 11-18.
20. Channick RN, Simonneau G, Sitbon O, Robbins IM, Frost A, Tapson VF, et al,. (2001). Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 358: 1119-1123. (Pubitemid 32971843)
21. Chen YF, Feng JA, Li P, Xing D, Ambalavanan N, Oparil S, (2006). Atrial natriuretic peptide-dependent modulation of hypoxia-induced pulmonary vascular remodeling. Life Sci 79: 1357-1365. (Pubitemid 44215927)
22. Chester M, Tourneux P, Seedorf G, Grover TR, Gien J, Abman SH, (2009). Cinaciguat, a soluble guanylate cyclase activator, causes potent and sustained pulmonary vasodilation in the ovine fetus. Am J Physiol Lung Cell Mol Physiol 297: L318-L325.
23. Chhina MK, Nargues W, Grant GM, Nathan SD, (2010). Evaluation of imatinib mesylate in the treatment of pulmonary arterial hypertension. Future Cardiol 6: 19-35.
24. Christman BW, McPherson CD, Newman JH, King GA, Bernard GR, Groves BM, et al,. (1992). An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 327: 70-75.
25. Cool CD, Stewart JS, Werahera P, Miller GJ, Williams RL, Voelkel NF, et al,. (1999). Three-dimensional reconstruction of pulmonary arteries in plexiform pulmonary hypertension using cell-specific markers. Evidence for a dynamic and heterogeneous process of pulmonary endothelial cell growth. Am J Pathol 155: 411-419. (Pubitemid 29370391)
26. Crawley DE, Zhao L, Giembycz MA, Liu S, Barnes PJ, Winter RJ, et al,. (1992). Chronic hypoxia impairs soluble guanylyl cyclase-mediated pulmonary arterial relaxation in the rat. Am J Physiol 263: L325-L332.
27. Creagh-Brown BC, Griffiths MJ, Evans TW, (2009). Bench-to-bedside review: Inhaled nitric oxide therapy in adults. Crit Care 13: 221.
28. Crossno JT, Jr, Garat CV, Reusch JE, Morris KG, Dempsey EC, McMurtry IF, et al,. (2007). Rosiglitazone attenuates hypoxia-induced pulmonary arterial remodeling. Am J Physiol Lung Cell Mol Physiol 292: L885-L897. (Pubitemid 46608235)
29. Dempsie Y, Morecroft I, Welsh DJ, MacRitchie NA, Herold N, Loughlin L, et al,. (2008). Converging evidence in support of the 5-HT hypothesis of dexfenfluramine-induced pulmonary hypertension with novel transgenic mice. Circulation 117: 2928-2937. (Pubitemid 351787078)
30. Denton CP, Pope JE, Peter HH, Gabrielli A, Boonstra A, van den Hoogen FH, et al,. (2008). Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases. Ann Rheum Dis 67: 1222-1228.
31. Do e Z, Fukumoto Y, Takaki A, Tawara S, Ohashi J, Nakano M, et al,. (2009). Evidence for Rho-kinase activation in patients with pulmonary arterial hypertension. Circ J 73: 1731-1739.
32. Dony E, Lai YJ, Dumitrascu R, Pullamsetti SS, Savai R, Ghofrani HA, et al,. (2008). Partial reversal of experimental pulmonary hypertension by phosphodiesterase-3/4 inhibition. Eur Respir J 31: 599-610.
33. Dumitrascu R, Weissmann N, Ghofrani HA, Dony E, Beuerlein K, Schmidt H, et al,. (2006). Activation of soluble guanylate cyclase reverses experimental pulmonary hypertension and vascular remodeling. Circulation 113: 286-295.
34. Eddahibi S, Humbert M, Fadel E, Raffestin B, Darmon M, Capron F, et al,. (2001). 5-HT transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. J Clin Invest 108: 1141-1150. (Pubitemid 32995372)
35. Eddahibi S, Chaouat A, Morrell N, Fadel E, Fuhrman C, Bugnet AS, et al,. (2003). Polymorphism of the 5-HT transporter gene and pulmonary hypertension in chronic obstructive pulmonary disease. Circulation 108: 1839-1844. (Pubitemid 37296093)
36. Evgenov OV, Busch CJ, Evgenov NV, Liu R, Petersen B, Falkowski GE, et al,. (2006). Inhibition of phosphodiesterase 1 augments the pulmonary vasodilator response to inhaled nitric oxide in awake lambs with acute pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 290: L723-L729. (Pubitemid 43725077)
37. Evgenov OV, Kohane DS, Bloch KD, Stasch JP, Volpato GP, Bellas E, et al,. (2007). Inhaled agonists of soluble guanylate cyclase induce selective pulmonary vasodilation. Am J Respir Crit Care Med 176: 1138-1145. (Pubitemid 350223760)
38. Fadini GP, Avogaro A, Ferraccioli G, Agostini C, (2010). Endothelial progenitors in pulmonary hypertension: new pathophysiology and therapeutic implications. Eur Respir J 35: 418-425.
39. Fagan KA, Fouty BW, Tyler RC, Morris KG Jr, Hepler LK, Sato K, et al,. (1999). The pulmonary circulation of homozygous or heterozygous eNOS-null mice is hyperresponsive to mild hypoxia. J Clin Invest 103: 291-299. (Pubitemid 29053147)
40. Falcetti E, Hall SM, Phillips PG, Patel J, Morrell NW, Haworth SG, et al,. (2010). Smooth muscle proliferation and role of the prostacyclin (IP) receptor in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 182: 1161-1170.
41. Ferreira AJ, Shenoy V, Yamazato Y, Sriramula S, Francis J, Yuan L, et al,. (2009). Evidence for angiotensin-converting enzyme 2 as a therapeutic target for the prevention of pulmonary hypertension. Am J Respir Crit Care Med 179: 1048-1054.
42. Fowler MB, Lottes SR, Nelson JJ, Lukas MA, Gilbert EM, Greenberg B, et al,. (2007). Beta-blocker dosing in community-based treatment of heart failure. Am Heart J 153: 1029-1036. (Pubitemid 46809843)
43. Frantz S, Adamek A, Fraccarollo D, Tillmanns J, Widder JD, Dienesch C, et al,. (2009). The eNOS enhancer AVE 9488: a novel cardioprotectant against ischemia reperfusion injury. Basic Res Cardiol 104: 773-779.
44. de Frutos S, Nitta CH, Caldwell E, Friedman J, Gonzalez Bosc LV, (2009). Regulation of soluble guanylyl cyclase-alpha1 expression in chronic hypoxia-induced pulmonary hypertension: role of NFATc3 and HuR. Am J Physiol Lung Cell Mol Physiol 297: L475-L486.
45. Fujita H, Fukumoto Y, Saji K, Sugimura K, Demachi J, Nawata J, et al,. (2010). Acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, in patients with pulmonary arterial hypertension. Heart Vessels 25: 144-149.
46. Galie N, Badesch D, Oudiz R, Simonneau G, McGoon MD, Keogh AM, et al,. (2005a). Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol 46: 529-535. (Pubitemid 41040298)
47. Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, et al,. (2005b). Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 353: 2148-2157. (Pubitemid 41653106)
48. Galie N, Brundage BH, Ghofrani HA, Oudiz RJ, Simonneau G, Safdar Z, et al,. (2009a). Tadalafil therapy for pulmonary arterial hypertension. Circulation 119: 2894-2903.
49. Galie N, Manes A, Negro L, Palazzini M, Bacchi-Reggiani ML, Branzi A, (2009b). A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J 30: 394-403.
50. Ghofrani HA, Wiedemann R, Rose F, Olschewski H, Schermuly RT, Weissmann N, et al,. (2002). Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann Intern Med 136: 515-522. (Pubitemid 34252285)
51. Ghofrani HA, Seeger W, Grimminger F, (2005). Imatinib for the treatment of pulmonary arterial hypertension. N Engl J Med 353: 1412-1413. (Pubitemid 41362714)
52. Ghofrani HA, Hoeper MM, Halank M, Meyer FJ, Staehler G, Behr J, et al,. (2010). Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study. Eur Respir J 36: 792-799.
53. Giaid A, Saleh D, (1995). Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 333: 214-221.
54. Girgis RE, Li D, Zhan X, Garcia JG, Tuder RM, Hassoun PM, et al,. (2003). Attenuation of chronic hypoxic pulmonary hypertension by simvastatin. Am J Physiol Heart Circ Physiol 285: H938-H945. (Pubitemid 37048146)
55. Gomberg-Maitland M, Maitland ML, Barst RJ, Sugeng L, Coslet S, Perrino TJ, et al,. (2010). A dosing/cross-development study of the multikinase inhibitor sorafenib in patients with pulmonary arterial hypertension. Clin Pharmacol Ther 87: 303-310.
56. Goyal P, Kiran U, Chauhan S, Juneja R, Choudhary M, (2006). Efficacy of nitroglycerin inhalation in reducing pulmonary arterial hypertension in children with congenital heart disease. Br J Anaesth 97: 208-214. (Pubitemid 44295707)
57. Grimminger F, Weimann G, Frey R, Voswinckel R, Thamm M, Bolkow D, et al,. (2009). BAY 63-2521, an oral soluble guanylate cyclase stimulator, has a favourable safety profile, improves cardiopulmonary haemodynamics and has therapeutic potential in pulmonary hypertension.
58. Guignabert C, Raffestin B, Benferhat R, Raoul W, Zadigue P, Rideau D, et al,. (2005). 5-HT transporter inhibition prevents and reverses monocrotaline-induced pulmonary hypertension in rats. Circulation 111: 2812-2819. (Pubitemid 40791554)
59. Guignabert C, Alvira CM, Alastalo TP, Sawada H, Hansmann G, Zhao M, et al,. (2009). Tie2-mediated loss of peroxisome proliferator-activated receptor-gamma in mice causes PDGF receptor-beta-dependent pulmonary arterial muscularization. Am J Physiol Lung Cell Mol Physiol 297: L1082-L1090.
60. Gunaydin S, Imai Y, Takanashi Y, Seo K, Hagino I, Chang D, et al,. (2002). The effects of vasoactive intestinal peptide on monocrotaline induced pulmonary hypertensive rabbits following cardiopulmonary bypass: a comparative study with isoproteronol and nitroglycerine. Cardiovasc Surg 10: 138-145. (Pubitemid 34219061)
61. Hampl V, Tristani-Firouzi M, Hutsell TC, Archer SL, (1996). Nebulized nitric oxide/nucleophile adduct reduces chronic pulmonary hypertension. Cardiovasc Res 31: 55-62. (Pubitemid 26093056)
62. Hansmann G, Zamanian RT, (2009). PPARgamma activation: a potential treatment for pulmonary hypertension. Sci Transl Med 1: 12ps14.
63. Hansmann G, Wagner RA, Schellong S, Perez VA, Urashima T, Wang L, et al,. (2007). Pulmonary arterial hypertension is linked to insulin resistance and reversed by peroxisome proliferator-activated receptor-gamma activation. Circulation 115: 1275-1284. (Pubitemid 46594772)
64. Hansmann G, de Jesus Perez VA, Alastalo TP, Alvira CM, Guignabert C, Bekker JM, et al,. (2008). An antiproliferative BMP-2/PPARgamma/apoE axis in human and murine SMCs and its role in pulmonary hypertension. J Clin Invest 118: 1846-1857. (Pubitemid 351632387)
65. Harrington LS, Moreno L, Reed A, Wort SJ, Desvergne B, Garland C, et al,. (2010). The PPARbeta/delta agonist GW0742 relaxes pulmonary vessels and limits right heart hypertrophy in rats with hypoxia-induced pulmonary hypertension. PloS One 5: e9526.
66. Hassoun PM, (2009). Pulmonary arterial hypertension complicating connective tissue diseases. Semin Respir Crit Care Med 30: 429-439.
67. Hobbs AJ, (1997). Soluble guanylate cyclase: the forgotten sibling. Trends Pharmacol Sci 18: 484-491.
68. Hoeper MM, Faulenbach C, Golpon H, Winkler J, Welte T, Niedermeyer J, (2004). Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension. Eur Respir J 24: 1007-1010. (Pubitemid 39642293)
69. Humbert M, Monti G, Fartoukh M, Magnan A, Brenot F, Rain B, et al,. (1998). Platelet-derived growth factor expression in primary pulmonary hypertension: comparison of HIV seropositive and HIV seronegative patients. Eur Respir J 11: 554-559. (Pubitemid 28194842)
70. Humbert M, Barst RJ, Robbins IM, Channick RN, Galie N, Boonstra A, et al,. (2004). Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J 24: 353-359. (Pubitemid 39232254)
71. Ichinose F, Roberts JD Jr, Zapol WM, (2004). Inhaled nitric oxide: a selective pulmonary vasodilator: current uses and therapeutic potential. Circulation 109: 3106-3111.
72. Ishikawa M, Sato N, Asai K, Takano T, Mizuno K, (2009). Effects of a pure alpha/beta-adrenergic receptor blocker on monocrotaline-induced pulmonary arterial hypertension with right ventricular hypertrophy in rats. Circ J 73: 2337-2341.
73. Ishikura K, Yamada N, Ito M, Ota S, Nakamura M, Isaka N, et al,. (2006). Beneficial acute effects of rho-kinase inhibitor in patients with pulmonary arterial hypertension. Circ J 70: 174-178. (Pubitemid 43170128)
74. Izikki M, Guignabert C, Fadel E, Humbert M, Tu L, Zadigue P, et al,. (2009). Endothelial-derived FGF2 contributes to the progression of pulmonary hypertension in humans and rodents. J Clin Invest 119: 512-523.
75. Jackson G, Benjamin N, Jackson N, Allen MJ, (1999). Effects of sildenafil citrate on human hemodynamics. Am J Cardiol 83: 13C-20C. (Pubitemid 29122753)
76. Jin H, Yang RH, Chen YF, Jackson RM, Oparil S, (1990). Atrial natriuretic peptide attenuates the development of pulmonary hypertension in rats adapted to chronic hypoxia. J Clin Invest 85: 115-120. (Pubitemid 20030298)
77. Jin H, Yang RH, Oparil S, (1992). Cicletanine blunts the pulmonary pressor response to acute hypoxia in rats. Am J Med Sci 304: 14-19.
78. Johnson SR, Mehta S, Granton JT, (2006). Anticoagulation in pulmonary arterial hypertension: a qualitative systematic review. Eur Respir J 28: 999-1004. (Pubitemid 46331971)
79. Kerkela R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C, et al,. (2006). Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 12: 908-916. (Pubitemid 44175142)
80. Khoo JP, Zhao L, Alp NJ, Bendall JK, Nicoli T, Rockett K, et al,. (2005). Pivotal role for endothelial tetrahydrobiopterin in pulmonary hypertension. Circulation 111: 2126-2133. (Pubitemid 40577909)
81. Klein M, Schermuly RT, Ellinghaus P, Milting H, Riedl B, Nikolova S, et al,. (2008). Combined tyrosine and serine/threonine kinase inhibition by sorafenib prevents progression of experimental pulmonary hypertension and myocardial remodeling. Circulation 118: 2081-2090.
82. Klinger JR, Petit RD, Warburton RR, Wrenn DS, Arnal F, Hill NS, (1993). Neutral endopeptidase inhibition attenuates development of hypoxic pulmonary hypertension in rats. J Appl Physiol 75: 1615-1623. (Pubitemid 23318208)
83. Klinger JR, Warburton RR, Pietras L, Hill NS, (1998). Brain natriuretic peptide inhibits hypoxic pulmonary hypertension in rats. J Appl Physiol 84: 1646-1652. (Pubitemid 28225903)
84. Klinger JR, Warburton RR, Pietras LA, Smithies O, Swift R, Hill NS, (1999). Genetic disruption of atrial natriuretic peptide causes pulmonary hypertension in normoxic and hypoxic mice. Am J Physiol 276: L868-L874. (Pubitemid 29249640)
85. Klinger JR, Thaker S, Houtchens J, Preston IR, Hill NS, Farber HW, (2006). Pulmonary hemodynamic responses to brain natriuretic peptide and sildenafil in patients with pulmonary arterial hypertension. Chest 129: 417-425. (Pubitemid 43289864)
86. Kuhn M, (2004). Molecular physiology of natriuretic peptide signalling. Basic Res Cardiol 99: 76-82. (Pubitemid 38325020)
87. Landmesser U, Dikalov S, Price SR, McCann L, Fukai T, Holland SM, et al,. (2003). Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest 111: 1201-1209. (Pubitemid 36519937)
88. Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA III, Loyd JE, et al,. (2000). Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet 26: 81-84.
89. Lapp H, Mitrovic V, Franz N, Heuer H, Buerke M, Wolfertz J, et al,. (2009). Cinaciguat (BAY 58-2667) improves cardiopulmonary hemodynamics in patients with acute decompensated heart failure. Circulation 119: 2781-2788.
90. Le Cras TD, Tyler RC, Horan MP, Morris KG, Tuder RM, McMurtry IF, et al,. (1998). Effects of chronic hypoxia and altered hemodynamics on endothelial nitric oxide synthase expression in the adult rat lung. J Clin Invest 101: 795-801. (Pubitemid 28096076)
91. Leiper J, Nandi M, Torondel B, Murray-Rust J, Malaki M, O'Hara B, et al,. (2007). Disruption of methylarginine metabolism impairs vascular homeostasis. Nat Med 13: 198-203.
92. Li P, Oparil S, Novak L, Cao X, Shi W, Lucas J, et al,. (2007). ANP signaling inhibits TGF-beta-induced Smad2 and Smad3 nuclear translocation and extracellular matrix expression in rat pulmonary arterial smooth muscle cells. J Appl Physiol 102: 390-398. (Pubitemid 46089790)
93. Long L, MacLean MR, Jeffery TK, Morecroft I, Yang X, Rudarakanchana N, et al,. (2006). 5-HT increases susceptibility to pulmonary hypertension in BMPR2-deficient mice. Circ Res 98: 818-827.
94. Lu W, Ran P, Zhang D, Peng G, Li B, Zhong N, et al,. (2010). Sildenafil inhibits chronically hypoxic upregulation of canonical transient receptor potential expression in rat pulmonary arterial smooth muscle. Am J Physiol Cell Physiol 298: C114-C123.
95. MacGregor JF, Wachter SB, Munger M, Stoddard G, Bristow MR, Gilbert EM, (2009). Carvedilol produces sustained long-term benefits: follow-up at 12 years. Congest Heart Fail 15: 5-8.
96. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, 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: 1573-1619.
97. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, 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: 2250-2294.
98. MacLean MR, Dempsie Y, (2009). 5-HT and pulmonary hypertension-from bench to bedside? Curr Opin Pharmacol 9: 281-286.
99. McMurtry MS, Archer SL, Altieri DC, Bonnet S, Haromy A, Harry G, et al,. (2005). Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. J Clin Invest 115: 1479-1491. (Pubitemid 40814657)
100. McMurtry MS, Moudgil R, Hashimoto K, Bonnet S, Michelakis ED, Archer SL, (2007). Overexpression of human bone morphogenetic protein receptor 2 does not ameliorate monocrotaline pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 292: L872-L878. (Pubitemid 46608233)
101. Machado RD, Koehler R, Glissmeyer E, Veal C, Suntharalingam J, Kim M, et al,. (2006). Genetic association of the 5-HT transporter in pulmonary arterial hypertension. Am J Respir Crit Care Med 173: 793-797.
102. Macrae DJ, Field D, Mercier JC, Moller J, Stiris T, Biban P, et al,. (2004). Inhaled nitric oxide therapy in neonates and children: reaching a European consensus. Intensive Care Med 30: 372-380. (Pubitemid 38375609)
103. Madhani M, Okorie M, Hobbs AJ, MacAllister RJ, (2006). Reciprocal regulation of human soluble and particulate guanylate cyclases in vivo. Br J Pharmacol 149: 797-801. (Pubitemid 44748072)
104. Mandegar M, Fung YC, Huang W, Remillard CV, Rubin LJ, Yuan JX, (2004). Cellular and molecular mechanisms of pulmonary vascular remodeling: role in the development of pulmonary hypertension. Microvasc Res 68: 75-103. (Pubitemid 39093882)
105. Matsui H, Shimosawa T, Itakura K, Guanqun X, Ando K, Fujita T, (2004). Adrenomedullin can protect against pulmonary vascular remodeling induced by hypoxia. Circulation 109: 2246-2251. (Pubitemid 38625404)
106. Merklinger SL, Jones PL, Martinez EC, Rabinovitch M, (2005). Epidermal growth factor receptor blockade mediates smooth muscle cell apoptosis and improves survival in rats with pulmonary hypertension. Circulation 112: 423-431. (Pubitemid 41022085)
107. Morrell NW, Yang X, Upton PD, Jourdan KB, Morgan N, Sheares KK, et al,. (2001). 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 104: 790-795. (Pubitemid 32762677)
108. Morty RE, Nejman B, Kwapiszewska G, Hecker M, Zakrzewicz A, Kouri FM, et al,. (2007). Dysregulated bone morphogenetic protein signaling in monocrotaline-induced pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol 27: 1072-1078. (Pubitemid 46641959)
109. Mouchaers KT, Schalij I, de Boer MA, Postmus PE, van Hinsbergh V, Van Nieuw Amerongen GP, et al,. (2010). Effective reduction of MCT-PAH by Fasudil. Comparison with bosentan and sildenafil. Eur Respir J 36: 800-807.
110. Murray F, MacLean MR, Pyne NJ, (2002). Increased expression of the cGMP-inhibited cAMP-specific (PDE3) and cGMP binding cGMP-specific (PDE5) phosphodiesterases in models of pulmonary hypertension. Br J Pharmacol 137: 1187-1194. (Pubitemid 36071735)
111. Murray F, Patel HH, Suda RY, Zhang S, Thistlethwaite PA, Yuan JX, et al,. (2007). Expression and activity of cAMP phosphodiesterase isoforms in pulmonary artery smooth muscle cells from patients with pulmonary hypertension: role for PDE1. Am J Physiol Lung Cell Mol Physiol 292: L294-L303. (Pubitemid 46103454)
112. Nandi M, Miller A, Stidwill R, Jacques TS, Lam AA, Haworth S, et al,. (2005). Pulmonary hypertension in a GTP-cyclohydrolase 1-deficient mouse. Circulation 111: 2086-2090. (Pubitemid 40577903)
113. Narumiya S, Sugimoto Y, Ushikubi F, (1999). Prostanoid receptors: structures, properties, and functions. Physiol Rev 79: 1193-1226. (Pubitemid 29473315)
114. National Pulmonary Hypertension Centres of the UK and Ireland (2008). Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Thorax 63: ii1-ii41.
115. Newman JH, Trembath RC, Morse JA, Grunig E, Loyd JE, Adnot S, et al,. (2004). Genetic basis of pulmonary arterial hypertension: current understanding and future directions. J Am Coll Cardiol 43: 33S-39S. (Pubitemid 38759715)
116. Newman JH, Phillips JA III, Loyd JE, (2008). Narrative review: the enigma of pulmonary arterial hypertension: new insights from genetic studies. Ann Intern Med 148: 278-283. (Pubitemid 351665488)
117. Nisbet RE, Sutliff RL, Hart CM, (2007). The role of peroxisome proliferator-activated receptors in pulmonary vascular disease. PPAR Res 2007: 18797.
118. Nishimura T, Faul JL, Berry GJ, Vaszar LT, Qiu D, Pearl RG, et al,. (2002). Simvastatin attenuates smooth muscle neointimal proliferation and pulmonary hypertension in rats. Am J Respir Crit Care Med 166: 1403-1408. (Pubitemid 35292709)
119. Oka M, Homma N, Taraseviciene-Stewart L, Morris KG, Kraskauskas D, Burns N, et al,. (2007a). Rho kinase-mediated vasoconstriction is important in severe occlusive pulmonary arterial hypertension in rats. Circ Res 100: 923-929. (Pubitemid 46555698)
120. Oka M, Karoor V, Homma N, Nagaoka T, Sakao E, Golembeski SM, et al,. (2007b). Dehydroepiandrosterone upregulates soluble guanylate cyclase and inhibits hypoxic pulmonary hypertension. Cardiovasc Res 74: 377-387. (Pubitemid 46693699)
121. Oka M, Fagan KA, Jones PL, McMurtry IF, (2008). Therapeutic potential of RhoA/Rho kinase inhibitors in pulmonary hypertension. Br J Pharmacol 155: 444-454.
122. Okolicany J, McEnroe GA, Koh GY, Lewicki JA, Maack T, (1992). Clearance receptor and neutral endopeptidase-mediated metabolism of atrial natriuretic factor. Am J Physiol Renal Physiol 263: F546-F553.
123. Oliver PM, Fox JE, Kim R, Rockman HA, Kim HS, Reddick RL, et al,. (1997). Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A. Proc Natl Acad Sci USA 94: 14730-14735. (Pubitemid 28041442)
124. Paddenberg R, Stieger P, von Lilien AL, Faulhammer P, Goldenberg A, Tillmanns HH, et al,. (2007). Rapamycin attenuates hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy in mice. Respir Res 8: 15.
125. Patterson KC, Weissmann A, Ahmadi T, Farber HW, (2006). Imatinib mesylate in the treatment of refractory idiopathic pulmonary arterial hypertension. Ann Intern Med 145: 152-153. (Pubitemid 46780594)
126. Perros F, Montani D, Dorfmuller P, Durand-Gasselin I, Tcherakian C, Le PJ, et al,. (2008). Platelet-derived growth factor expression and function in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 178: 81-88. (Pubitemid 351919196)
127. Potter LR, Abbey-Hosch S, Dickey DM, (2006). Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Endocr Rev 27: 47-72. (Pubitemid 43228238)
128. Pozeg ZI, Michelakis ED, McMurtry MS, Thebaud B, Wu XC, Dyck JR, et al,. (2003). In vivo gene transfer of the O2-sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats. Circulation 107: 2037-2044. (Pubitemid 36506080)
129. Preston IR, Hill NS, Gambardella LS, Warburton RR, Klinger JR, (2004). Synergistic effects of ANP and sildenafil on cGMP levels and amelioration of acute hypoxic pulmonary hypertension. Exp Biol Med 229: 920-925. (Pubitemid 39539377)
130. Provencher S, Herve P, Jais X, Lebrec D, Humbert M, Simonneau G, et al,. (2006). Deleterious effects of beta-blockers on exercise capacity and hemodynamics in patients with portopulmonary hypertension. Gastroenterology 130: 120-126. (Pubitemid 43049842)
131. Qi JG, Ding YG, Tang CS, Du JB, (2007). Chronic administration of adrenomedullin attenuates hypoxic pulmonary vascular structural remodeling and inhibits proadrenomedullin N-terminal 20-peptide production in rats. Peptides 28: 910-919.
132. Raja SG, (2010). Macitentan, a tissue-targeting endothelin receptor antagonist for the potential oral treatment of pulmonary arterial hypertension and idiopathic pulmonary fibrosis. Curr Opin Investig Drugs 11: 1066-1073.
133. Reynolds AM, Xia W, Holmes MD, Hodge SJ, Danilov S, Curiel DT, et al,. (2007). Bone morphogenetic protein type 2 receptor gene therapy attenuates
134. Rich S, Brundage BH, (1987). High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation 76: 135-141. (Pubitemid 17093201)
135. Roberts JD, Polaner DM, Lang P, Zapol WM, (1992). Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 340: 818-819.
136. Roberts KE, Fallon MB, Krowka MJ, Benza RL, Knowles JA, Badesch DB, et al,. (2009). 5-HT transporter polymorphisms in patients with portopulmonary hypertension. Chest 135: 1470-1475.
137. Rubens C, Ewert R, Halank M, Wensel R, Orzechowski HD, Schultheiss HP, et al,. (2001). Big endothelin-1 and endothelin-1 plasma levels are correlated with the severity of primary pulmonary hypertension. Chest 120: 1562-1569. (Pubitemid 33078473)
138. Rubin LJ, Mendoza J, Hood M, McGoon M, Barst R, Williams WB, et al,. (1990). Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Ann Intern Med 112: 485-491. (Pubitemid 20100285)
139. Rybalkin SD, Rybalkina I, Beavo JA, Bornfeldt KE, (2002). Cyclic nucleotide phosphodiesterase 1C promotes human arterial smooth muscle cell proliferation. Circ Res 90: 151-157. (Pubitemid 34627083)
140. Saadjian A, Philip-Joet F, Paganelli F, Arnaud A, Levy S, (1998). Long-term effects of cicletanine on secondary pulmonary hypertension. J Cardiovasc Pharmacol 31: 364-371. (Pubitemid 28103615)
141. Said SI, Hamidi SA, Dickman KG, Szema AM, Lyubsky S, Lin RZ, et al,. (2007). Moderate pulmonary arterial hypertension in male mice lacking the vasoactive intestinal peptide gene. Circulation 115: 1260-1268. (Pubitemid 46594770)
142. Sasaki K, Heeschen C, Aicher A, Ziebart T, Honold J, Urbich C, et al,. (2006). Ex vivo pretreatment of bone marrow mononuclear cells with endothelial NO synthase enhancer AVE9488 enhances their functional activity for cell therapy. Proc Natl Acad Sci USA 103: 14537-14541. (Pubitemid 44484785)
143. Schermuly RT, Weissmann N, Enke B, Ghofrani HA, Forssmann WG, Grimminger F, et al,. (2001). Urodilatin, a natriuretic peptide stimulating particulate guanylate cyclase, and the phosphodiesterase 5 inhibitor dipyridamole attenuate experimental pulmonary hypertension: synergism upon coapplication. Am J Respir Cell Mol Biol 25: 219-225. (Pubitemid 32752448)
144. Schermuly RT, Kreisselmeier KP, Ghofrani HA, Samidurai A, Pullamsetti S, Weissmann N, et al,. (2004). Antiremodeling effects of iloprost and the dual-selective phosphodiesterase 3/4 inhibitor tolafentrine in chronic experimental pulmonary hypertension. Circ Res 94: 1101-1108. (Pubitemid 38579705)
145. Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, et al,. (2005). Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 115: 2811-2821. (Pubitemid 41434408)
146. Schermuly RT, Pullamsetti SS, Kwapiszewska G, Dumitrascu R, Tian X, Weissmann N, et al,. (2007). Phosphodiesterase 1 upregulation in pulmonary arterial hypertension: target for reverse-remodeling therapy. Circulation 115: 2331-2339. (Pubitemid 46685901)
147. Schermuly RT, Stasch JP, Pullamsetti SS, Middendorff R, Muller D, Schluter KD, et al,. (2008). Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J 32: 881-891.
148. Schmidt HH, Schmidt PM, Stasch JP, (2009). NO- and Haem-independent soluble guanylate cyclase activators. Handb Exp Pharmacol 191: 309-339.
149. Sebkhi A, Strange JW, Phillips SC, Wharton J, Wilkins MR, (2003). Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced pulmonary hypertension. Circulation 107: 3230-3235. (Pubitemid 36793096)
150. Shaul PW, Yuhanna IS, German Z, Chen Z, Steinhorn RH, Morin FC, III, (1997). Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension. Am J Physiol 272: L1005-L1012.
151. Shenoy V, Ferreira AJ, Qi Y, Fraga-Silva RA, Díez-Freire C, Dooies A, et al,. (2010). The ACE2/Ang-(1-7)/Mas axis confers cardiopulmonary protection against lung fibrosis and pulmonary hypertension. Am J Respir Crit Care Med 182: 1065-L1072.
152. Shimokubo T, Sakata J, Kitamura K, Kangawa K, Matsuo H, Eto T, (1995). Augmented adrenomedullin concentrations in right ventricle and plasma of experimental pulmonary hypertension. Life Sci 57: 1771-1779.
153. Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, et al,. (2009). Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 54: S43-S54.
154. Sitbon O, Humbert M, Jais X, Ioos V, Hamid AM, Provencher S, et al,. (2005). Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 111: 3105-3111. (Pubitemid 40847788)
155. Sobolewski A, Rudarakanchana N, Upton PD, Yang J, Crilley TK, Trembath RC, et al,. (2008). Failure of bone morphogenetic protein receptor trafficking in pulmonary arterial hypertension: potential for rescue. Hum Mol Genet 17: 3180-3190.
156. Song Y, Jones JE, Beppu H, Keaney JF Jr, Loscalzo J, Zhang YY, (2005). Increased susceptibility to pulmonary hypertension in heterozygous BMPR2-mutant mice. Circulation 112: 553-562. (Pubitemid 41060796)
157. Souza R, Sitbon O, Parent F, Simonneau G, Humbert M, (2006). Long term imatinib treatment in pulmonary arterial hypertension. Thorax 61: 736. (Pubitemid 44211786)
158. Stasch JP, Hobbs AJ, (2009). NO-independent, haem-dependent soluble guanylate cyclase stimulators. Handb Exp Pharmacol 191: 277-308.
159. Stasch JP, Alonso-Alija C, Apeler H, Dembowsky K, Feurer A, Minuth T, et al,. (2002a). Pharmacological actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41-8543: in vitro studies. Br J Pharmacol 135: 333-343. (Pubitemid 34151165)
160. Stasch JP, Dembowsky K, Perzborn E, Stahl E, Schramm M, (2002b). Cardiovascular actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41-8543: in vivo studies. Br J Pharmacol 135: 344-355. (Pubitemid 34151166)
161. Steudel W, Ichinose F, Huang PL, Hurford WE, Jones RC, Bevan JA, et al,. (1997). Pulmonary vasoconstriction and hypertension in mice with targeted disruption of the endothelial nitric oxide synthase (NOS 3) gene. Circ Res 81: 34-41. (Pubitemid 27272980)
162. Stiebellehner L, Petkov V, Vonbank K, Funk G, Schenk P, Ziesche R, et al,. (2003). Long-term treatment with oral sildenafil in addition to continuous IV epoprostenol in patients with pulmonary arterial hypertension. Chest 123: 1293-1295. (Pubitemid 36444392)
163. Stocker C, Penny DJ, Brizard CP, Cochrane AD, Soto R, Shekerdemian LS, (2003). Intravenous sildenafil and inhaled nitric oxide: a randomised trial in infants after cardiac surgery. Intensive Care Med 29: 1996-2003. (Pubitemid 37487135)
164. Sun CK, Lee FY, Sheu JJ, Yuen CM, Chua S, Chung SY, et al,. (2009). Early combined treatment with cilostazol and bone marrow-derived endothelial progenitor cells markedly attenuates pulmonary arterial hypertension in rats. J Pharmacol Exp Ther 330: 718-726.
165. Tapper EB, Knowles D, Heffron T, Lawrence EC, Csete M, (2009). Portopulmonary hypertension: imatinib as a novel treatment and the Emory experience with this condition. Transplant Proc 41: 1969-1971.
166. Ten FH, Dumitrescu D, Bovenschulte H, Erdmann E, Rosenkranz S, (2009). Significant improvement of right ventricular function by imatinib mesylate in scleroderma-associated pulmonary arterial hypertension. Clin Res Cardiol 98: 265-267.
167. Thenappan T, Shah SJ, Rich S, Gomberg-Maitland M, (2007). A USA-based registry for pulmonary arterial hypertension: 1982-2006. Eur Respir J 30: 1103-1110. (Pubitemid 351194756)
168. Toshner M, Voswinckel R, Southwood M, Al-Lamki R, Howard LS, Marchesan D, et al,. (2009). Evidence of dysfunction of endothelial progenitors in pulmonary arterial hypertension. Am J Respir Crit Care Med 180: 780-787.
169. Tuder RM, Cool CD, Geraci MW, Wang J, Abman SH, Wright L, et al,. (1999). Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 159: 1925-1932. (Pubitemid 29275065)
170. Vanderford PA, Wong J, Chang R, Keefer LK, Soifer SJ, Fineman JR, (1994). Diethylamine/nitric oxide (NO) adduct, an NO donor, produces potent pulmonary and systemic vasodilation in intact newborn lambs. J Cardiovasc Pharmacol 23: 113-119. (Pubitemid 24016851)
171. Velez-Roa S, Ciarka A, Najem B, Vachiery JL, Naeije R, van de Borne P, (2004). Increased sympathetic nerve activity in pulmonary artery hypertension. Circulation 110: 1308-1312. (Pubitemid 39202350)
172. Vermeersch P, Buys E, Pokreisz P, Marsboom G, Ichinose F, Sips P, et al,. (2007). Soluble guanylate cyclase-alpha1 deficiency selectively inhibits the pulmonary vasodilator response to nitric oxide and increases the pulmonary vascular remodeling response to chronic hypoxia. Circulation 116: 936-943. (Pubitemid 47300918)
173. Voelkel NF, Quaife RA, Leinwand LA, Barst RJ, McGoon MD, Meldrum DR, et al,. (2006). Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation 114: 1883-1891. (Pubitemid 44673364)
174. Weissmann N, Hackemack S, Dahal BK, Pullamsetti SS, Savai R, Mittal M, et al,. (2009). The soluble guanylate cyclase activator HMR1766 reverses hypoxia-induced experimental pulmonary hypertension in mice. Am J Physiol Lung Cell Mol Physiol 297: L658-L665.
175. Welsh DJ, Harnett M, MacLean M, Peacock AJ, (2004). Proliferation and signaling in fibroblasts: role of 5-hydroxytryptamine2A receptor and transporter. Am J Respir Crit Care Med 170: 252-259. (Pubitemid 38971409)
176. Westermann D, Riad A, Richter U, Jager S, Savvatis K, Schuchardt M, et al,. (2009). Enhancement of the endothelial NO synthase attenuates experimental diastolic heart failure. Basic Res Cardiol 104: 499-509.
177. Wharton J, Strange JW, Moller GM, Growcott EJ, Ren X, Franklyn AP, et al,. (2005). Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am J Respir Crit Care Med 172: 105-113. (Pubitemid 40923321)
178. Wilkens H, Guth A, Konig J, Forestier N, Cremers B, Hennen B, et al,. (2001). Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation 104: 1218-1222. (Pubitemid 32848108)
179. Wilkins MR, Ali O, Bradlow W, Wharton J, Taegtmeyer A, Rhodes CJ, et al,. (2010). Simvastatin as a treatment for pulmonary hypertension trial. Am J Respir Crit Care Med 181: 1106-1113.
180. Willers ED, Newman JH, Loyd JE, Robbins IM, Wheeler LA, Prince MA III, et al,. (2006). 5-HT transporter polymorphisms in familial and idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 173: 798-802.
181. Williamson DJ, Wallman LL, Jones R, Keogh AM, Scroope F, Penny R, et al,. (2000). Hemodynamic effects of Bosentan, an endothelin receptor antagonist, in patients with pulmonary hypertension. Circulation 102: 411-418. (Pubitemid 30490679)
182. Wohlfart P, Xu H, Endlich A, Habermeier A, Closs EI, Hubschle T, et al,. (2008). Antiatherosclerotic effects of small-molecular-weight compounds enhancing endothelial nitric-oxide synthase (eNOS) expression and preventing eNOS uncoupling. J Pharmacol Exp Ther 325: 370-379. (Pubitemid 351574784)
183. Xie W, Wang H, Wang H, Hu G, (2004). Effects of iptakalim hydrochloride, a novel KATP channel opener, on pulmonary vascular remodeling in hypoxic rats. Life Sci 75: 2065-2076. (Pubitemid 39106823)
184. Yang X, Long L, Southwood M, Rudarakanchana N, Upton PD, Jeffery TK, et al,. (2005). Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension. Circ Res 96: 1053-1063. (Pubitemid 40791377)
185. Yip HK, Chang LT, Sun CK, Sheu JJ, Chiang CH, Youssef AA, et al,. (2008). Autologous transplantation of bone marrow-derived endothelial progenitor cells attenuates monocrotaline-induced pulmonary arterial hypertension in rats. Crit Care Med 36: 873-880.
186. Yu Y, Fantozzi I, Remillard CV, Landsberg JW, Kunichika N, Platoshyn O, et al,. (2004). Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Proc Natl Acad Sci USA 101: 13861-13866. (Pubitemid 39298498)
187. Yu Y, Keller SH, Remillard CV, Safrina O, Nicholson A, Zhang SL, et al,. (2009). A functional single-nucleotide polymorphism in the TRPC6 gene promoter associated with idiopathic pulmonary arterial hypertension. Circulation 119: 2313-2322.
188. Yuan JX, Rubin LJ, (2005). Pathogenesis of pulmonary arterial hypertension: the need for multiple hits. Circulation 111: 534-538. (Pubitemid 40216478)
189. Yuan XJ, Wang J, Juhaszova M, Gaine SP, Rubin LJ, (1998). Attenuated K+ channel gene transcription in primary pulmonary hypertension. Lancet 351: 726-727. (Pubitemid 28105348)
190. Zhai FG, Zhang XH, Wang HL, (2009). Fluoxetine protects against monocrotaline-induced pulmonary arterial hypertension: potential roles of induction of apoptosis and upregulation of Kv1.5 channels in rats. Clin Exp Pharmacol Physiol 36: 850-856.
191. Zhao L, Hughes JM, Winter RJ, (1992). Effects of natriuretic peptides and neutral endopeptidase 24.11 inhibition in isolated perfused rat lung. Am Rev Respir Dis 146: 1198-1201.
192. Zhao L, Long L, Morrell NW, Wilkins MR, (1999). NPR-A-Deficient mice show increased susceptibility to hypoxia-induced pulmonary hypertension. Circulation 99: 605-607. (Pubitemid 29077357)
193. Zhao L, Mason NA, Strange JW, Walker H, Wilkins MR, (2003). Beneficial effects of phosphodiesterase 5 inhibition in pulmonary hypertension are influenced by natriuretic Peptide activity. Circulation 107: 234-237. (Pubitemid 36135217)
194. Zhao YY, Zhao YD, Mirza MK, Huang JH, Potula HH, Vogel SM, 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: 2009-2018.
195. Zhu Y, Zhang S, Xie W, Li Q, Zhou Y, Wang H, (2008). Iptakalim inhibited endothelin-1-induced proliferation of human pulmonary arterial smooth muscle cells through the activation of K(ATP) channel. Vascul Pharmacol 48: 92-99.
196. Zhu SP, Mao ZF, Huang J, Wang JY, (2009). Continuous fluoxetine administration prevents recurrence of pulmonary arterial hypertension and prolongs survival in rats. Clin Exp Pharmacol Physiol 36: e1-e5.