Dual ETA/ETB vs. selective ETA endothelin receptor antagonism in patients with pulmonary hypertension

European Journal of Clinical Investigation

Volumn 36, Issue SUPPL. 3, 2006, Pages 1-9

  Opitz, C F ^a   Ewert, R ^b  

^a DRK KLINIKEN BERLIN WESTEND   (Germany)

^b UNIVERSITY OF GREIFSWALD   (Germany)

Author keywords

Bosentan; Endothelin; Pathophysiology; Pulmonary arterial hypertension; Receptor subtype specificity; Sitaxsentan

Indexed keywords

4 (1,3 BENZODIOXOL 5 YL) 1 [(2,6 DIETHYLPHENYL)CARBAMOYLMETHYL] 2 (4 PROPOXYPHENYL) 3 PYRROLIDINECARBOXYLIC ACID; AMBRISENTAN; ATRASENTAN; BLEOMYCIN; BOSENTAN; BSF 420627; CYCLO(DEXTRO TRYPTOPHYL DEXTRO ASPARTYLPROLYL DEXTRO VALYLLEUCYL); DARUSENTAN; ENDOTHELIN 1; ENDOTHELIN A RECEPTOR; ENDOTHELIN A RECEPTOR ANTAGONIST; ENDOTHELIN B RECEPTOR; ENDOTHELIN B RECEPTOR AGONIST; ENDOTHELIN B RECEPTOR ANTAGONIST; ENDOTHELIN RECEPTOR ANTAGONIST; LIVER ENZYME; N (2,6 DIMETHYLPIPERIDINOCARBONYL) 4 METHYLLEUCYL DEXTRO (1 METHOXYCARBONYLTRYPTOPHANYL) DEXTRO NORLEUCINE; SARAFOTOXIN; SITAXSENTAN; SUCCINYLENDOTHELIN 1 [8-21][9 GLUTAMIC ACID 11,15 ALANINE];

ABNORMALLY HIGH SUBSTRATE CONCENTRATION IN BLOOD; CELL PROLIFERATION; CELL PROTECTION; CLINICAL TRIAL; CONFERENCE PAPER; DATA ANALYSIS; DRUG CLEARANCE; DRUG EFFECT; DRUG MECHANISM; HUMAN; LIVER DYSFUNCTION; LUNG CIRCULATION; LUNG FIBROSIS; NONHUMAN; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RECEPTOR BLOCKING; SMOOTH MUSCLE FIBER; VASOCONSTRICTION; VASODILATATION;

ANTIHYPERTENSIVE AGENTS; CELL DIVISION; ENDOTHELIN-1; HUMANS; HYPERTENSION, PULMONARY; ISOXAZOLES; LUNG; PULMONARY FIBROSIS; RECEPTOR, ENDOTHELIN A; RECEPTOR, ENDOTHELIN B; RECEPTORS, ENDOTHELIN; SULFONAMIDES; THIOPHENES; VASOCONSTRICTION; VASODILATION;

EID: 33746860763     PISSN: 00142972     EISSN: 13652362     Source Type: Journal    
DOI: 10.1111/j.1365-2362.2006.01691.x     Document Type: Conference Paper

References (88)

1. Roden DM. An underrecognized challenge in evaluating postmarketing drug safety. Circulation 2005;111:246-8.
2. Channick RN, Sitbon O, Barst RJ, Manes A, Rubin LJ. Endothelin receptor antagonists in pulmonary arterial hypertension. J Am Coll Cardiol 2004;43 (Suppl. 12):62S-7.
3. Ito H, Hirata Y, Hiroe M, Tsujino M, Adachi S, Takamoto T et al. Endothelin-1 induces hypertrophy with enhanced expression of muscle-specific genes in cultured neonatal rat cardiomyocytes. Circ Res 1991;69:209-15.
4. Kahaleh MB. Endothelin, an endothelial-dependent vasoconstrictor in scleroderma. Enhanced production and profibrotic action. Arthritis Rheum 1991;34:978-83.
5. Shi-Wen X, Denton CP, Holmes A, Dashwood M, Abraham DJ, Black CM. Endothelins: effect on matrix biosynthesis and proliferation in normal and scleroderma fibroblasts. J Cardiovasc Pharmacol 1998;31 (Suppl. 1):S 360-3.
6. B receptors. Br J Pharmacol 1995;115:227-36.
7. Belloni AS, Rossi GP, Andreis PG, Neri G, Albertin G, Pessina AC et al. Endothelin adrenocortical secretagogue effect is mediated by the B receptor in rats. Hypertension 1996;27:1153-9.
8. Schiffrin EL, Touyz RM. Vascular biology of endothelin. J Cardiovasc Pharmacol 1998;32 (Suppl. 3):S2-13.
9. Nootens M, Kaufmann E, Rector T, Toher C, Judd D, Francis GS. Neurohormonal activation in patients with right ventricular failure from pulmonary hypertension: relation to hemodynamic variables and endothelin levels. J Am Coll Cardiol 1995;26:1581-5.
10. Galie N, Grigioni F, Bacchi-Reggiani L. Relation of endothelin-I to survival in patients with primary pulmonary hypertension. Eur J Clin Invest 1996;26 (Suppl. 1):273,A48.
11. Rubens C, Ewert R, Halank M, Wensel R, Orzechowski HD, Schultheiss HP et al. Big endothelin-1 and endothelin-1 plasma levels are correlated with the severity of primary pulmonary hypertension. Chest 2001;120 (5):1562-9.
12. Giaid A, Yanagisawa M, Langleben D, Michel RP, Levy R, Shennib H et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993;328 (24):1732-9.
13. Giaid A. Nitric oxide and endothelin-1 in pulmonary hypertension. Chest 1998;114 (Suppl. 3):208S-212S.
14. Galie N, Manes A, Branzi A. The endothelin system in pulmonary arterial hypertension. Cardiovasc Res 2004;61 (2):227-37.
15. Gregan B, Jurgensen J, Papsdorf G, Furkert J, Schaefer M, Beyermann M et al. Ligand-dependent differences in the internalization of endothelin A and endothelin B receptor heterodimers. J Biol Chem 2004;279 (26):27679-87.
16. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988;332:411-5.
17. A receptor antagonist, attenuates endothelin-1-induced vasoconstriction in rat pulmonary circulation. J Cardiovasc Pharmacol 1993;22:39-43.
18. A receptor antagonist BQ123 antagonizes endothelin-1-mediated mitogenesis. Eur J Pharmacol 1992;225:347-50.
19. Davie N, Haleen SJ, Upton PD, Polak JM, Yacoub MH, Morrell NW et al. ET (A) and ET (B) receptors modulate the proliferation of human pulmonary artery smooth muscle cells. Am J Respir Crit Care Med 2002;165:398-405.
20. Masaki T. Possible role of endothelin in endothelial regulation of vascular tone. Annu Rev Pharmacol Toxicol 1995;35:235-55.
21. Bagnall A, Webb D. Are selective endothelin A receptor antagonists better than mixed antagonists? J Cardiovasc Pharmacol 2001;38 (Suppl. 2):S43-6.
22. Clozel M, Ramuz H, Clozel JP, Breu V, Hess P, Loffler BM et al. Pharmacology of tezosentan, new endothelin receptor antagonist designed for parenteral use. J Pharmacol Exp Ther 1999;290:840-6.
23. B receptors mediating constriction and relaxation? J Cardiovasc Pharmacol 1995;26 (Suppl. 3):S262-4.
24. Fukuroda T, Ozaki S, Ihara M, Ishikawa K, Yano M, Nishikibe M. Synergistic inhibition by BQ-123 and BQ-788 of endothelin-1-induced contractions of the rabbit pulmonary artery. Br J Pharmacol 1994;113:336-8.
25. B receptor subtypes for antagonism of endothelin-1-induced contraction in human bronchi. Br J Pharmacol 1996;117:995-9.
26. B blockade on ET-1-induced constriction in perfused rat lungs. Am J Physiol 1995;269:L668-72.
27. Davenport AP. International Union of Pharmacology. XXIX. Update on endothelin receptor nomenclature. Pharmacol Rev 2002;54 (2):219-26.
28. Luscher TF, Enseleit F, Pacher R, Mitrovic V, Schulze MR, Willenbrock R et al. Heart Failure ET(A) Receptor Blockade Trial. Hemodynamic and neurohumoral effects of selective endothelin A (ET(A)) receptor blockade in chronic heart failure: the Heart Failure ET(A) Receptor Blockade Trial (HEAT). Circulation 2002;106 (21):2666-72.
29. Givertz MM, Colucci WS, LeJemtel TH, Gottlieb SS, Hare JM, Slawsky MT et al. Acute endothelin A receptor blockade causes selective pulmonary vasodilation in patients with chronic heart failure. Circulation 2000;101 (25):2922-7.
30. McCulloch KM, Docherty CC, Morecroft I, MacLean MR. Endothelin B receptor-mediated contraction in human pulmonary resistance arteries. Br J Pharmacol 1996;119 (6):1125-30.
31. Ivy D, McMurtry IF, Yanagisawa M, Gariepy CE, Le Cras TD, Gebb SA et al. Endothelin B receptor deficiency potentiates ET-1 and hypoxic pulmonary vasoconstriction. Am J Physiol Lung Cell Mol Physiol 2001;280 (5):L1040-8.
32. Ivy DD, Parker TA, Abman SH. Prolonged endothelin B receptor blockade causes pulmonary hypertension in the ovine fetus. Am J Physiol Lung Cell Mol Physiol 2000;279 (4):L758-65.
33. Eddahibi S, Raffestin B, Clozel M, Levame M, Adnot S. Protection from pulmonary hypertension with an orally active endothelin receptor antagonist in hypoxic rats. Am J Physiol 1995;268 (2 Part 2):H828-35.
34. Tilton RG, Munsch CL, Sherwood SJ, Chen SJ, Chen YF, Wu C et al. Attenuation of pulmonary vascular hypertension and cardiac hypertrophy with sitaxsentan sodium, an orally active ET (A) receptor antagonist. Pulm Pharmacol Ther 2000;13 (2):87-97.
35. Chen SJ, Chen YF, Meng QC, Durand J, Dicarlo VS, Oparil S. Endothelin-receptor antagonist bosentan prevents and reverses hypoxic pulmonary hypertension in rats. J Appl Physiol 1995;79 (6):2122-31.
36. Chen SJ, Chen YF, Opgenorth TJ, Wessale JL, Meng QC, Durand J et al. The orally active nonpeptide endothelin A-receptor antagonist A-127722 prevents and reverses hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling in Sprague-Dawley rats. J Cardiovasc Pharmacol 1997;29 (6):713-25.
37. Stewart DJ, Levy RD, Cernacek P, Langleben D. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann Intern Med 1991;114:464-9.
38. Dupuis J, Cernacek P, Tardif JC, Stewart DJ, Gosselin G, Dyrda I et al. Reduced pulmonary clearance of endothelin-1 in pulmonary hypertension. Am Heart J 1998;135 (4):614-20.
39. Iwasa S, Fan J, Shimokama T, Nagata M, Watanabe T. Increased immunoreactivity of endothelin-1 and endothelin B receptor in human atherosclerotic lesions. A possible role in atherogenesis. Atherosclerosis 1999;146:93-100.
40. Hasdai D, Mathew V, Schwartz RS, Smith LA, Holmes DR, Jr., Katusic ZS et al. Enhanced endothelin-B-receptor-mediated vasoconstriction of small porcine coronary arteries in diet-induced hypercholesterolemia. Arterioscler Thromb Vasc Biol 1997;17:2737-43.
41. B receptor antagonism using BQ-123 and SB 209670. J Cardiovasc Pharmacol 1995;26 (Suppl. 3):S186-9.
42. Kakoki M, Hirata Y, Hayakawa H, Tojo A, Nagata D, Suzuki E et al. Effects of hypertension, diabetes mellitus, and hypercholesterolemia on endothelin type B receptor-mediated nitric oxide release from rat kidney. Circulation 1999;99:1242-8.
43. Ruetten H, Zabel U, Linz W, Schmidt HH. Downregulation of soluble guanylyl cyclase in young and aging spontaneously hypertensive rats. Circ Res 1999;85:534-41.
44. Takayanagi R, Kitazumi K, Takasaki C, Ohnaka K, Aimoto S, Tasaka K et al. Presence of non-selective type of endothelin receptor on vascular endothelium and its linkage to vasodilation. FEBS Lett 1991;282:103-6.
45. Shetty SS, Okada T, De Webb RLI, Grande D, Lappe RW. Functionally distinct endothelin B receptors in vascular endothelium and smooth muscle. Biochem Biophys Res Commun 1993;191:459-64.
46. Harrison VJ, Randriantsoa A, Schoeffter P. Heterogeneity of endothelin-sarafotoxin receptors mediating contraction of pig coronary artery. Br J Pharmacol 1992;105:511-3.
47. Gray GA, Loffler BM, Clozel M. Characterization of endothelin receptors mediating contraction of rabbit saphenous vein. Am J Physiol 1994;266:H959-66.
48. Bauer M, Wilkens H, Langer F, Schneider SO, Lausberg H, Schafers HJ. Selective upregulation of endothelin B receptor gene expression in severe pulmonary hypertension. Circulation 2002;105 (9):1034-6.
49. Dschietzig T, Bartsch C, Richter C, Laule M, Baumann G, Stangl K. Relaxin, a pregnancy hormone, is a functional endothelin-1 antagonist: attenuation of endothelin-1-mediated vasoconstriction by stimulation of endothelin type-B receptor expression via ERK-1/2 and nuclear factor-kappaB. Circ Res 2003;92 (1):32-40.
50. Conrad KP, Novak J. Emerging role of relaxin in renal and cardiovascular function. Am J Physiol Regul Integr Comp Physiol 2004;287 (2):R250-61.
51. Verhaar MC, Strachan FE, Newby DE, Cruden NL, Koomans HA, Rabelink TJ et al.Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B receptor blockade. Circulation 1998;97 (8):752-6.
52. B receptors mediate contraction to endothelin-1 in human blood vessels. Circulation 1994;89:1203-8.
53. B receptors cause vasoconstriction of human resistance and capacitance vessels in vivo. Circulation 1995;92:357-63.
54. Love MP, Ferro CJ, Haynes WG, Plumpton C, Davenport AP, Webb DJ et al. Endothelin receptor antagonism in patients with chronic heart failure. Cardiovasc Res 2000;47 (1):166-72.
55. Cowburn PJ, Cleland JG, McArthur JD, MacLean MR, McMurray JJ, Dargie HJ et al. Endothelin B receptors are functionally important in mediating vasoconstriction in the systemic circulation in patients with left ventricular systolic dysfunction. J Am Coll Cardiol 1999;33 (4):932-8.
56. A receptor blockade in chronic heart failure patients treated with ACE inhibitors. Circulation 1996;94:2131-7.
57. 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):1578-84.
58. Lepailleur-Enouf D, Egidy G, Philippe M, Louedec L, Henry J, Mulder P et al. Pulmonary endothelinergic system in experimental congestive heart failure. Cardiovasc Res 2001;49 (2):330-9.
59. Dupuis J, Moe GW, Cernacek P. Reduced pulmonary metabolism of endothelin-1 in canine tachycardia-induced heart failure. Cardiovasc Res 1998;39 (3):609-16.
60. Dupuis J, Rouleau JL, Cernacek P. Reduced pulmonary clearance of endothelin-1 contributes to the increase of circulating levels in heart failure secondary to myocardial infarction. Circulation 1998;98 (16):1684-7.
61. Weber C, Schmitt R, Birnboeck H, Hopfgartner G, van Marle SP, Peeters PA et al. Pharmacokinetics and pharmacodynamics of the endothelin-receptor antagonist bosentan in healthy human subjects. Clin Pharmacol Ther 1996;60 (2):124-37.
62. Williamson DJ, Wallman LL, Jones R, Keogh AM, Scroope F, Penny R et al. Hemodynamic effects of Bosentan, an endothelin receptor antagonist, in patients with pulmonary hypertension. Circulation 2000;102 (4):411-8.
63. Kiowski W, Sutsch G, Hunziker P, Muller P, Kim J, Oechslin E et al. Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure. Lancet 1995;346 (8977):732-6.
64. Goddard J, Johnston NR, Hand MF, Cumming AD, Rabelink TJ, Rankin AJ et al. Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure: a comparison of selective and combined endothelin receptor blockade. Circulation 2004;109 (9):1186-93.
65. Strachan FE, Spratt JC, Wilkinson IB, Johnston NR, Gray GA, Webb DJ. Systemic blockade of the endothelin-B receptor increases peripheral vascular resistance in healthy men. Hypertension 1999;33 (1 Part 2):581-5.
66. Kiowski W, Sutsch G, Oechslin E, Bertel O. Hemodynamic effects of bosentan in patients with chronic heart failure. Heart Fail Rev 2001;6 (4):325-34.
67. Clozel M, Salloukh H. Role of endothelin in fibrosis and anti-fibrotic potential of bosentan. Ann Med 2005;37 (1):2-12.
68. Hocher B, Schwarz A, Fagan KA, Thone-Reineke C, El-Hag K, Kusserow H et al. Pulmonary fibrosis and chronic lung inflammation in ET-1 transgenic mice. Am J Respir Cell Mol Biol 2000;23:19-26.
69. Du L, Sullivan CC, Chu D, Cho AJ, Kido M, Wolf PL et al. Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med 2003;348 (6):500-9.
70. A receptor via a rac/phosphoinositide 3-kinase/Akt-dependent pathway and is essential for the enhanced contractile phenotype of fibrotic fibroblasts. Mol Biol Cell 2004;15 (6):2707-19. Epub 2004 March 26.
71. Shi-Wen X, Denton CP, Dashwood MR, Holmes AM, Bou-Gharios G, Pearson JD et al. Fibroblast matrix gene expression and connective tissue remodeling: role of endothelin-1. J Invest Dermatol 2001;116:417-25.
72. Abraham DJ, Vancheeswaran R, Dashwood MR, Rajkumar VS, Pantelides P, Xu SW et al. Increased levels of endothelin-1 and differential endothelin type A and B receptor expression in scleroderma-associated fibrotic lung disease. Am J Pathol 1997;151 (3):831-41.
73. Mutsaers SE, Marshall RP, Goldsack NR, Laurent GJ, McAnulty RJ. Effect of endothelin receptor antagonists (BQ-485, Ro 47-0203) on collagen deposition during the development of bleomycin-induced pulmonary fibrosis in rats. Pulm Pharmacol Ther 1998;11 (2-3):221-5.
74. B receptor in the pathogenesis of monocrotaline-induced pulmonary hypertension in rats. Eur J Pharmacol 2004;496 (1-3):159-65.
75. Miyauchi T, Yorikane R, Sakai S, Sakurai T, Okada M, Nishikibe M et al. Contribution of endogenous endothelin-1 to the progression of cardiopulmonary alterations in rats with monocrotaline-induced pulmonary hypertension. Circ Res 1993;73 (5):887-97.
76. A receptor blockade. Clin Sci (Lond) 2003;105 (6):647-53.
77. 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.
78. Prie S, Leung TK, Cernacek P, Ryan JW, Dupuis J. The orally active ET (A) receptor antagonist (+)-(S)-2-(4,6-dimethoxypyrimidin-2-yloxy)-3-methoxy-3,3- diphe nyl-propionic acid (LU 135252) prevents the development of pulmonary hypertension and endothelial metabolic dysfunction in monocrotaline-treated rats. J Pharmacol Exp Ther 1997;282 (3):1312-8.
79. B receptors in the pathogenesis of monocrotaline-induced pulmonary hypertension. J Cardiovasc Pharmacol 2004;44 (2):187-91.
80. Channick RN, Simonneau G, Sitbon O, Robbins IM, Frost A, Tapson VF et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 2001;358:1119-23.
81. Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002;346:896-903.
82. McLaughlin VV, Sitbon O, Badesch DB, Barst RJ, Black C, Galie N et al. Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur Respir J 2005;25:244-9.
83. Barst RJ, Langleben D, Frost A, Horn EM, Oudiz R, Galie N et al. STRIDE-1 Study Group. Sitaxsentan therapy for pulmonary arterial hypertension. Am J Respir Crit Care Med 2004;169 (4):441-7.
84. Langleben D, Hirsch AM, Shalit E, Lesenko L, Barst RJ. Sustained symptomatic, functional, and hemodynamic benefit with the selective endothelin-A receptor antagonist, sitaxsentan, in patients with pulmonary arterial hypertension: a 1-year follow-up study. Chest 2004;126 (4):1377-81.
85. Galie N, Badesch D, Oudiz R, Simonneau G, McGoon MD, Keogh AM et al. Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2005;46 (3):529-35.
86. Hoeper MM. Drug treatment of pulmonary arterial hypertension: current and future agents. Drugs 2005;65 (10):1337-54.
87. Barst RJ, Langleben D, Badesch D, Frost A, Lawrence EC, Shapiro S et al. Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J Am Coll Cardiol 2006;47 (10):2049-56.
88. Encysiv Pharmaceuticals Inc. http://ir.encysive.com:9/14/2005: Encysive Pharmaceuticals Announces Interim Topline Data From STRIDE-2 Extension Trial.