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Volume 2014, Issue 2
  • ISSN: 2305-7823
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Abstract

Pulmonary arterial hypertension (PAH) is a rare but debilitating disease, which if left untreated rapidly progresses to right ventricular failure and eventually death. In the quest to understand the pathogenesis of this disease differences in the profile, expression and action of vasoactive substances released by the endothelium have been identified in patients with PAH. Of these, endothelin-1 (ET-1) is of particular interest since it is known to be an extremely powerful vasoconstrictor and also involved in vascular remodelling. Identification of ET-1 as a target for pharmacological intervention has lead to the discovery of a number of compounds that can block the receptors via which ET-1 mediates its effects. This review sets out the evidence in support of a role for ET-1 in the onset and progression of the disease and reviews the data from the various clinical trials of ET-1 receptor antagonists for the treatment of PAH.

© 2014 Chester, Yacoub, licensee Bloomsbury Qatar Foundation Journals.
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2014-09-01
2024-04-18
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References

  1. Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, Elliott CG, Gaine SP, Gladwin MT, Jing ZC, Krowka MJ, Langleben D, Nakanishi N, Souza R. Updated clinical classification of pulmonary hypertension. Journal of the American College of Cardiology. 2009; 54:1 Suppl:S43–S54.
     [Google Scholar]
  2. Peacock AJ, Murphy NF, McMurray JJ, Caballero L, Stewart S. An epidemiological study of pulmonary arterial hypertension. The European respiratory journal. 2007; 30:1:104–109.
     [Google Scholar]
  3. Sitbon O, Lascoux-Combe C, Delfraissy JF, Yeni PG, Raffi F, De Zuttere D, Gressin V, Clerson P, Sereni D, Simonneau G. Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era. American journal of respiratory and critical care medicine. 2008; 177:1:108–113.
     [Google Scholar]
  4. Channick RN, Simonneau G, Sitbon O, Robbins IM, Frost A, Tapson VF, Badesch DB, Roux S, Rainisio M, Bodin F, Rubin LJ. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001; 358:9288:1119–1123.
     [Google Scholar]
  5. Hachulla E, Gressin V, Guillevin L, Carpentier P, Diot E, Sibilia J, Kahan A, Cabane J, Francès C, Launay D, Mouthon L, Allanore Y, Tiev KP, Clerson P, de Groote P, Humbert M. Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis and rheumatism. 2005; 52:12:3792–3800.
     [Google Scholar]
  6. Mukerjee D, St George D, Coleiro B, Knight C, Denton CP, Davar J, Black CM, Coghlan JG. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Annals of the rheumatic diseases. 2003; 62:11:1088–1093.
     [Google Scholar]
  7. Machado RF, Gladwin MT. Pulmonary hypertension in hemolytic disorders: pulmonary vascular disease: the global perspective. Chest. 2010; 137:6 Suppl:30S–38S.
     [Google Scholar]
  8. Fonseca GH, Souza R, Salemi VM, Jardim CV, Gualandro SF. Pulmonary hypertension diagnosed by right heart catheterisation in sickle cell disease. The European respiratory journal. 2012; 39:1:112–118.
     [Google Scholar]
  9. Barst RJ. Pulmonary hypertension: past, present and future. Annals of thoracic medicine. 2008; 3:1:1–4.
     [Google Scholar]
  10. Tuder RM, Marecki JC, Richter A, Fijalkowska I, Flores S. Pathology of pulmonary hypertension. Clinics in chest medicine. 2007; 28:1:23–42, vii.
     [Google Scholar]
  11. Montani D, Günther S, Dorfmüller P, Perros F, Girerd B, Garcia G, Jaïs X, Savale L, Artaud-Macari E, Price LC, Humbert M, Simonneau G, Sitbon O. Pulmonary arterial hypertension. Orphanet journal of rare diseases. 2013; 8:1:97.
     [Google Scholar]
  12. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J. ACCF/AHA 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. Journal of the American College of Cardiology. 2009; 53:17:1573–1619.
     [Google Scholar]
  13. Luu TN, Chester AH, O'Neil GS, Tadjkarimi S, Yacoub MH. Effects of vasoactive neuropeptides on human saphenous vein. British heart journal. 1992; 67:6:474–477.
     [Google Scholar]
  14. Dzimiri N, Chester AH, Allen SP, Duran C, Yacoub MH. Vascular reactivity of arterial coronary artery bypass grafts – implications for their performance. Clinical cardiology. 1996; 19:3:165–171.
     [Google Scholar]
  15. Naeije R, Chesler N. Pulmonary circulation at exercise. Comprehensive Physiology. 2012; 2:1:711–741.
     [Google Scholar]
  16. McLaughlin VV, McGoon MD. Pulmonary arterial hypertension. Circulation. 2006; 114:13:1417–1431.
     [Google Scholar]
  17. Christman BW, McPherson CD, Newman JH, King GA, Bernard GR, Groves BM, Loyd JE. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. The New England journal of medicine. 1992; 327:2:70–75.
     [Google Scholar]
  18. Tuder RM, Cool CD, Geraci MW, Wang J, Abman SH, Wright L, Badesch D, Voelkel NF. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. American journal of respiratory and critical care medicine. 1999; 159:6:1925–1932.
     [Google Scholar]
  19. Mitchell JA, Ali F, Bailey L, Moreno L, Harrington LS. Role of nitric oxide and prostacyclin as vasoactive hormones released by the endothelium. Experimental physiology. 2008; 93:1:141–147.
     [Google Scholar]
  20. Ghofrani HA, Wiedemann R, Rose F, Olschewski H, Schermuly RT, Weissmann N, Seeger W, Grimminger F. Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Annals of internal medicine. 2002; 136:7:515–522.
     [Google Scholar]
  21. Galiè N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, Fleming T, Parpia T, Burgess G, Branzi A, Grimminger F, Kurzyna M, Simonneau G, Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group . Sildenafil citrate therapy for pulmonary arterial hypertension. The New England journal of medicine. 2005; 353:20:2148–2157.
     [Google Scholar]
  22. Galiè N, Brundage BH, Ghofrani HA, Oudiz RJ, Simonneau G, Safdar Z, Shapiro S, White RJ, Chan M, Beardsworth A, Frumkin L, Barst RJ, Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) Study Group . Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009; 119:22:2894–2903.
     [Google Scholar]
  23. Fraisse A, Wessel DL. Acute pulmonary hypertension in infants and children: cGMP-related drugs. Pediatric critical care medicine: a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2010; 11:2 Suppl:S37–S40.
     [Google Scholar]
  24. Mathew R. Pulmonary hypertension: current therapy and future prospects. Cardiovascular & hematological agents in medicinal chemistry. 2011; 9:3:165–182.
     [Google Scholar]
  25. Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, Masaki T. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proceedings of the National Academy of Sciences of the United States of America. 1989; 86:8:2863–2867.
     [Google Scholar]
  26. Luscher TF, Barton M. Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Circulation. 2000; 102:19:2434–2440.
     [Google Scholar]
  27. Masaki T. The discovery of endothelins. Cardiovascular research. 1998; 39:3:530–533.
     [Google Scholar]
  28. Benatti L, Fabbrini MS, Patrono C. Regulation of endothelin-1 biosynthesis. Annals of the New York Academy of Sciences. 1994; 714::109–121.
     [Google Scholar]
  29. Dorfman DM, Wilson DB, Bruns GA, Orkin SH. Human transcription factor GATA-2. Evidence for regulation of preproendothelin-1 gene expression in endothelial cells. The Journal of biological chemistry. 1992; 267:2:1279–1285.
     [Google Scholar]
  30. Morey AK, Razandi M, Pedram A, Hu RM, Prins BA, Levin ER. Oestrogen and progesterone inhibit the stimulated production of endothelin-1. The Biochemical journal. 1998; 330:Pt 3:1097–1105.
     [Google Scholar]
  31. Denault JB, Claing A, D'Orléans-Juste P, Sawamura T, Kido T, Masaki T, Leduc R. Processing of proendothelin-1 by human furin convertase. FEBS letters. 1995; 362:3:276–280.
     [Google Scholar]
  32. Valdenaire O, Lepailleur-Enouf D, Egidy G, Thouard A, Barret A, Vranckx R, Tougard C, Michel JB. A fourth isoform of endothelin-converting enzyme (ECE-1) is generated from an additional promoter molecular cloning and characterization. European journal of biochemistry/FEBS. 1999; 264:2:341–349.
     [Google Scholar]
  33. Galie N, Manes A, Branzi A. The endothelin system in pulmonary arterial hypertension. Cardiovascular research. 2004; 61:2:227–237.
     [Google Scholar]
  34. Frelin C, Guedin D. Why are circulating concentrations of endothelin-1 so low? Cardiovascular research. 1994; 28:11:1613–1622.
     [Google Scholar]
  35. Simonson MS. Endothelins: multifunctional renal peptides. Physiological reviews. 1993; 73:2:375–411.
     [Google Scholar]
  36. Sauvageau S, Thorin E, Caron A, Dupuis J. Evaluation of endothelin-1-induced pulmonary vasoconstriction following myocardial infarction. Experimental biology and medicine. 2006; 231:6:840–846.
     [Google Scholar]
  37. Thorin E, Clozel M. The cardiovascular physiology and pharmacology of endothelin-1. Advances in pharmacology. 2010; 60::1–26.
     [Google Scholar]
  38. Pollock DM, Keith TL, Highsmith RF. Endothelin receptors and calcium signaling. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 1995; 9:12:1196–1204.
     [Google Scholar]
  39. Ohlstein EH, Arleth A, Bryan H, Elliott JD, Sung CP. The selective endothelin ETA receptor antagonist BQ123 antagonizes endothelin-1-mediated mitogenesis. European journal of pharmacology. 1992; 225:4:347–350.
     [Google Scholar]
  40. Hirata Y, Emori T, Eguchi S, Kanno K, Imai T, Ohta K, Marumo F. Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. The Journal of clinical investigation. 1993; 91:4:1367–1373.
     [Google Scholar]
  41. Shichiri M, Kato H, Marumo F, Hirata Y. Endothelin-1 as an autocrine/paracrine apoptosis survival factor for endothelial cells. Hypertension. 1997; 30:5:1198–1203.
     [Google Scholar]
  42. Dupuis J, Goresky CA, Fournier A. Pulmonary clearance of circulating endothelin-1 in dogs in vivo: exclusive role of ETB receptors. Journal of applied physiology. 1996; 81:4:1510–1515.
     [Google Scholar]
  43. Dupuis J, Stewart DJ, Cernacek P, Gosselin G. Human pulmonary circulation is an important site for both clearance and production of endothelin-1. Circulation. 1996; 94:7:1578–1584.
     [Google Scholar]
  44. Matsumoto H, Suzuki N, Onda H, Fujino M. Abundance of endothelin-3 in rat intestine, pituitary gland and brain. Biochemical and biophysical research communications. 1989; 164:1:74–80.
     [Google Scholar]
  45. Lal H, Williams KI, Woodward B. Chronic hypoxia differentially alters the responses of pulmonary arteries and veins to endothelin-1 and other agents. European journal of pharmacology. 1999; 371:1:11–21.
     [Google Scholar]
  46. Kemp BK, Smolich JJ, Cocks TM. Evidence for specific regional patterns of responses to different vasoconstrictors and vasodilators in sheep isolated pulmonary arteries and veins. British journal of pharmacology. 1997; 121:3:441–450.
     [Google Scholar]
  47. Lambers C, Roth M, Zhong J, Campregher C, Binder P, Burian B, Petkov V, Block LH. The interaction of endothelin-1 and TGF-beta1 mediates vascular cell remodeling. PloS one. 2013; 8:8:e73399.
     [Google Scholar]
  48. Seccia TM, Belloni AS, Kreutz R, Paul M, Nussdorfer GG, Pessina AC, Rossi GP. Cardiac fibrosis occurs early and involves endothelin and AT-1 receptors in hypertension due to endogenous angiotensin II. Journal of the American College of Cardiology. 2003; 41:4:666–673.
     [Google Scholar]
  49. Shi-Wen X, Denton CP, Dashwood MR, Holmes AM, Bou-Gharios G, Pearson JD, Black CM, Abraham DJ. Fibroblast matrix gene expression and connective tissue remodeling: role of endothelin-1. The Journal of investigative dermatology. 2001; 116:3:417–425.
     [Google Scholar]
  50. Jozsef L, Khreiss T, Fournier A, Chan JS, Filep JG. Extracellular signal-regulated kinase plays an essential role in endothelin-1-induced homotypic adhesion of human neutrophil granulocytes. British journal of pharmacology. 2002; 135:5:1167–1174.
     [Google Scholar]
  51. Ishikawa T, Yanagisawa M, Kimura S, Goto K, Masaki T. Positive inotropic action of novel vasoconstrictor peptide endothelin on guinea pig atria. The American journal of physiology. 1988; 255:4 Pt 2:H970–H973.
     [Google Scholar]
  52. Ishikawa T, Yanagisawa M, Kimura S, Goto K, Masaki T. Positive chronotropic effects of endothelin, a novel endothelium-derived vasoconstrictor peptide. Pflugers Archiv: European journal of physiology. 1988; 413:1:108–110.
     [Google Scholar]
  53. Giaid A, Yanagisawa M, Langleben D, Michel RP, Levy R, Shennib H, Kimura S, Masaki T, Duguid WP, Stewart DJ. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. The New England journal of medicine. 1993; 328:24:1732–1739.
     [Google Scholar]
  54. Bressollette E, Dupuis J, Bonan R, Doucet S, Cernacek P, Tardif JC. Intravascular ultrasound assessment of pulmonary vascular disease in patients with pulmonary hypertension. Chest. 2001; 120:3:809–815.
     [Google Scholar]
  55. Stewart DJ, Levy RD, Cernacek P, Langleben D. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Annals of internal medicine. 1991; 114:6:464–469.
     [Google Scholar]
  56. Filep JG, Bodolay E, Sipka S, Gyimesi E, Csipo I, Szegedi G. Plasma endothelin correlates with antiendothelial antibodies in patients with mixed connective tissue disease. Circulation. 1995; 92:10:2969–2974.
     [Google Scholar]
  57. Uguccioni M, Pulsatelli L, Grigolo B, Facchini A, Fasano L, Cinti C, Fabbri M, Gasbarrini G, Meliconi R. Endothelin-1 in idiopathic pulmonary fibrosis. Journal of clinical pathology. 1995; 48:4:330–334.
     [Google Scholar]
  58. Giaid A, Michel RP, Stewart DJ, Sheppard M, Corrin B, Hamid Q. Expression of endothelin-1 in lungs of patients with cryptogenic fibrosing alveolitis. Lancet. 1993; 341:8860:1550–1554.
     [Google Scholar]
  59. Jia B, Zhang S, Chen Z, Li Z, Li X, Hui W, Ye M. Plasma endothelin 1 concentrations in children with congenital heart defects. Minerva pediatrica. 1998; 50:4:99–103.
     [Google Scholar]
  60. Gorenflo M, Bettendorf M, Brockmeier K, Ulmer HE. Pulmonary vasoreactivity and vasoactive mediators in children with pulmonary hypertension. Zeitschrift fur Kardiologie. 2000; 89:11:1000–1008.
     [Google Scholar]
  61. Thomson JR, Machado RD, Pauciulo MW, Morgan NV, Humbert M, Elliott GC, Ward K, Yacoub M, Mikhail G, Rogers P, Newman J, Wheeler L, Higenbottam T, Gibbs JS, Egan J, Crozier A, Peacock A, Allcock R, Corris P, Loyd JE, Trembath RC. Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family. Journal of medical genetics. 2000; 37:10:741–745.
     [Google Scholar]
  62. International PPHC, Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA 3rd, Loyd JE, Nichols WC, Trembath RC. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nature genetics. 2000; 26:1:81–84.
     [Google Scholar]
  63. Machado RD, Pauciulo MW, Thomson JR, Lane KB, Morgan NV, Wheeler L, Phillips JA 3rd, Newman J, Williams D, Galiè N, Manes A, McNeil K, Yacoub M, Mikhail G, Rogers P, Corris P, Humbert M, Donnai D, Martensson G, Tranebjaerg L, Loyd JE. BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. American journal of human genetics. 2001; 68:1:92–102.
     [Google Scholar]
  64. Deng Z, Morse JH, Slager SL, Cuervo N, Moore KJ, Venetos G, Kalachikov S, Cayanis E, Fischer SG, Barst RJ, Hodge SE, Knowles JA. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. American journal of human genetics. 2000; 67:3:737–744.
     [Google Scholar]
  65. Rubin LJ, Roux S. Bosentan: a dual endothelin receptor antagonist. Expert opinion on investigational drugs. 2002; 11:7:991–1002.
     [Google Scholar]
  66. Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, Pulido T, Frost A, Roux S, Leconte I, Landzberg M, Simonneau G. Bosentan therapy for pulmonary arterial hypertension. The New England journal of medicine. 2002; 346:12:896–903.
     [Google Scholar]
  67. Weber C, Banken L, Birnboeck H, Schulz R. Effect of the endothelin-receptor antagonist bosentan on the pharmacokinetics and pharmacodynamics of warfarin. Journal of clinical pharmacology. 1999; 39:8:847–854.
     [Google Scholar]
  68. Humbert M, Nunes H, Sitbon O, Parent F, Herve P, Simonneau G. Risk factors for pulmonary arterial hypertension. Clinics in chest medicine. 2001; 22:3:459–475.
     [Google Scholar]
  69. Barst RJ, Ivy D, Dingemanse J, Widlitz A, Schmitt K, Doran A, Bingaman D, Nguyen N, Gaitonde M, van Giersbergen PL. Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. Clinical pharmacology and therapeutics. 2003; 73:4:372–382.
     [Google Scholar]
  70. Sitbon O, Gressin V, Speich R, Macdonald PS, Opravil M, Cooper DA, Fourme T, Humbert M, Delfraissy JF, Simonneau G. Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension. American journal of respiratory and critical care medicine. 2004; 170:11:1212–1217.
     [Google Scholar]
  71. Galie N, Beghetti M, Gatzoulis MA, Granton J, Berger RM, Lauer A, Chiossi E, Landzberg M. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation. 2006; 114:1:48–54.
     [Google Scholar]
  72. Wilkins MR, Paul GA, Strange JW, Tunariu N, Gin-Sing W, Banya WA, Westwood MA, Stefanidis A, Ng LL, Pennell DJ, Mohiaddin RH, Nihoyannopoulos P, Gibbs JS. Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study. American journal of respiratory and critical care medicine. 2005; 171:11:1292–1297.
     [Google Scholar]
  73. Barst RJ, Langleben D, Badesch D, Frost A, Lawrence EC, Shapiro S, Naeije R, Galie N, STRIDE-2 Study Group . Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. Journal of the American College of Cardiology. 2006; 47:10:2049–2056.
     [Google Scholar]
  74. Segal ES. Tracleer (bosentan) 2006;. Available from: http://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM153430.pdf .
     [Google Scholar]
  75. Dingemanse J, van Giersbergen PL. Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. Clinical pharmacokinetics. 2004; 43:15:1089–1115.
     [Google Scholar]
  76. Motte S, McEntee K, Naeije R. Endothelin receptor antagonists. Pharmacology & therapeutics. 2006; 110:3:386–414.
     [Google Scholar]
  77. Denton CP, Pope JE, Peter HH, Gabrielli A, Boonstra A, van den Hoogen FH, Riemekasten G, De Vita S, Morganti A, Dölberg M, Berkani O, Guillevin L, TRacleer Use in PAH associated with Scleroderma and Connective Tissue Diseases (TRUST) Investigators . Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases. Annals of the rheumatic diseases. 2008; 67:9:1222–1228.
     [Google Scholar]
  78. Valerio CJ, Coghlan JG. Bosentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient. Vascular health and risk management. 2009; 5::607–619.
     [Google Scholar]
  79. Cheng JW. Ambrisentan for the management of pulmonary arterial hypertension. Clinical therapeutics. 2008; 30:5:825–833.
     [Google Scholar]
  80. Barst RJ. A review of pulmonary arterial hypertension: role of ambrisentan. Vascular health and risk management. 2007; 3:1:11–22.
     [Google Scholar]
  81. Galie N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA, Badesch DB, McGoon MD, McLaughlin VV, Roecker EB, Gerber MJ, Dufton C, Wiens BL, Rubin LJ, Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies (ARIES) Group . Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation. 2008; 117:23:3010–3019.
     [Google Scholar]
  82. Galie N, Badesch D, Oudiz R, Simonneau G, McGoon MD, Keogh AM, Frost AE, Zwicke D, Naeije R, Shapiro S, Olschewski H, Rubin LJ. Ambrisentan therapy for pulmonary arterial hypertension. Journal of the American College of Cardiology. 2005; 46:3:529–535.
     [Google Scholar]
  83. Opitz CF, Ewert R, Kirch W, Pittrow D. Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter? Eur Heart J. 2008; 29:16:1936–1948.
     [Google Scholar]
  84. Barst RJ, Langleben D, Frost A, Horn EM, Oudiz R, Shapiro S, McLaughlin V, Hill N, Tapson VF, Robbins IM, Zwicke D, Duncan B, Dixon RA, Frumkin LR, STRIDE-1 Study Group . Sitaxsentan therapy for pulmonary arterial hypertension. American journal of respiratory and critical care medicine. 2004; 169:4:441–447.
     [Google Scholar]
  85. Benza RL, Barst RJ, Galie N, Frost A, Girgis RE, Highland KB, Strange C, Black CM, Badesch DB, Rubin L, Fleming TR, Naeije R. Sitaxsentan for the treatment of pulmonary arterial hypertension: a 1-year, prospective, open-label observation of outcome and survival. Chest. 2008; 134:4:775–782.
     [Google Scholar]
  86. Langleben D, Cacoub P. A review of STRIDE-2 and STRIDE-2X: the case for selective endothelin receptor blockade. European journal of clinical investigation. 2009; 39 Suppl 2::27–31.
     [Google Scholar]
  87. Benza RL, Mehta S, Keogh A, Lawrence EC, Oudiz RJ, Barst RJ. Sitaxsentan treatment for patients with pulmonary arterial hypertension discontinuing bosentan. The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation. 2007; 26:1:63–69.
     [Google Scholar]
  88. Boniface S, Reynaud-Gaubert M. Endothelin receptor antagonists – their role in pulmonary medicine. Revue des maladies respiratoires. 2011; 28:8:e94–e107.
     [Google Scholar]
  89. Agency TEM. Thelin (sitaxentan) to be withdrawn due to cases of unpredictable serious liver injury 2010;. Available from: http://www.ema.europa.eu/ema/index.jsp?curl = pages/news_and_events/news/2010/12/news_detail_001161.jsp&mid = WC0b01ac058004d5c1
    [Google Scholar]
  90. Bolli MH, Boss C, Binkert C, Buchmann S, Bur D, Hess P, Iglarz M, Meyer S, Rein J, Rey M, Treiber A, Clozel M, Fischli W, Weller T. The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-p ropylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. Journal of medicinal chemistry. 2012; 55:17:7849–7861.
     [Google Scholar]
  91. Iglarz M, Binkert C, Morrison K, Fischli W, Gatfield J, Treiber A, Weller T, Bolli MH, Boss C, Buchmann S, Capeleto B, Hess P, Qiu C, Clozel M. Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist. The Journal of pharmacology and experimental therapeutics. 2008; 327:3:736–745.
     [Google Scholar]
  92. Sidharta PN, van Giersbergen PL, Halabi A, Dingemanse J. Macitentan: entry-into-humans study with a new endothelin receptor antagonist. European journal of clinical pharmacology. 2011; 67:10:977–984.
     [Google Scholar]
  93. Sidharta PN, van Giersbergen PL, Dingemanse J. Safety, tolerability, pharmacokinetics, and pharmacodynamics of macitentan, an endothelin receptor antagonist, in an ascending multiple-dose study in healthy subjects. Journal of clinical pharmacology. 2013; 53:11:1131–1138.
     [Google Scholar]
  94. Sitbon O, Morrell N. Pathways in pulmonary arterial hypertension: the future is here. European respiratory review: an official journal of the European Respiratory Society. 2012; 21:126:321–327.
     [Google Scholar]
  95. Hatano M, Yao A, Kinugawa K, Hirata Y, Nagai R. Acute effect of sildenafil is maintained in pulmonary arterial hypertension patients chronically treated with bosentan. International heart journal. 2011; 52:4:233–239.
     [Google Scholar]
  96. Hoeper MM, Faulenbach C, Golpon H, Winkler J, Welte T, Niedermeyer J. Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension. The European respiratory journal. 2004; 24:6:1007–1010.
     [Google Scholar]
  97. Benza RL, Rayburn BK, Tallaj JA, Pamboukian SV, Bourge RC. Treprostinil-based therapy in the treatment of moderate-to-severe pulmonary arterial hypertension: long-term efficacy and combination with bosentan. Chest. 2008; 134:1:139–145.
     [Google Scholar]
  98. Akagi S, Matsubara H, Miyaji K, Ikeda E, Dan K, Tokunaga N, Hisamatsu K, Munemasa M, Fujimoto Y, Ohe T. Additional effects of bosentan in patients with idiopathic pulmonary arterial hypertension already treated with high-dose epoprostenol. Circulation journal: official journal of the Japanese Circulation Society. 2008; 72:7:1142–1146.
     [Google Scholar]
  99. Maki H, Yao A, Inaba T, Shiga T, Hatano M, Kinugawa K, Yamashita T, Aizawa T, Nagai R. Initial and programmed combination therapy with oral drugs for severe idiopathic pulmonary arterial hypertension. International heart journal. 2011; 52:5:323–326.
     [Google Scholar]
  100. Tapson VF, Torres F, Kermeen F, Keogh AM, Allen RP, Frantz RP, Badesch DB, Frost AE, Shapiro SM, Laliberte K, Sigman J, Arneson C, Galiè N. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial. Chest. 2012; 142:6:1383–1390.
     [Google Scholar]
  101. Jing ZC, Parikh K, Pulido T, Jerjes-Sanchez C, White RJ, Allen R, Torbicki A, Xu KF, Yehle D, Laliberte K, Arneson C, Rubin LJ. Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial. Circulation. 2013; 127:5:624–633.
     [Google Scholar]
  102. Seed A, Kuc RE, Maguire JJ, Hillier C, Johnston F, Essers H, de Voogd HJ, McMurray J, Davenport AP. The dual endothelin converting enzyme/neutral endopeptidase inhibitor SLV-306 (daglutril), inhibits systemic conversion of big endothelin-1 in humans. Life sciences. 2012; 91:13-14:743–748.
     [Google Scholar]
  103. Parvanova A, van der Meer IM, Iliev I, Perna A, Gaspari F, Trevisan R, Bossi A, Remuzzi G, Benigni A, Ruggenenti P, Daglutril in Diabetic Nephropathy Study Group . Effect on blood pressure of combined inhibition of endothelin-converting enzyme and neutral endopeptidase with daglutril in patients with type 2 diabetes who have albuminuria: a randomised, crossover, double-blind, placebo-controlled trial. The lancet Diabetes & endocrinology. 2013; 1:1:19–27.
     [Google Scholar]
  104. Kohan DE, Rossi NF, Inscho EW, Pollock DM. Regulation of blood pressure and salt homeostasis by endothelin. Physiological reviews. 2011; 91:1:1–77.
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.5339/gcsp.2014.29
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The role of endothelin-1 in pulmonary arterial hypertension
Global Cardiology Science and Practice 2014, 29 (2014); https://doi.org/10.5339/gcsp.2014.29
/content/journals/10.5339/gcsp.2014.29
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