New approaches to the treatment of pulmonary hypertension: From bench to bedside

Cardiology in Review

Volumn 18, Issue 2, 2010, Pages 76-84

  Murthy, Subramanyam N ^a   Nossaman, Bobby D ^a,b   Kadowitz, Philip J ^a  

^a TULANE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b OCHSNER MEDICAL CENTER   (United States)

Author keywords

Cardiovascular diseases; Fasudil; HA 1077; Inhibitors pharmacology; Pulmonary hypertension; rhoA rho kinase pathway; Riociguat; SB 772077 B; Smooth muscle; Soluble guanylate cyclase; Vascular; Y 27632

Indexed keywords

15 HYDROXY 11ALPHA,9ALPHA EPOXYMETHANOPROSTA 5,13 DIENOIC ACID; 4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; CALCIUM CHANNEL BLOCKING AGENT; FASUDIL; GUANYLATE CYCLASE ACTIVATOR; NANOCARRIER; PROSTACYCLIN; RHO KINASE INHIBITOR; RIOCIGUAT; SB 772077 B; UNCLASSIFIED DRUG;

ANTIHYPERTENSIVE ACTIVITY; ANTIHYPERTENSIVE THERAPY; ARTERIAL PRESSURE; CALCIUM SIGNALING; CLINICAL TRIAL; COMPARATIVE STUDY; CORONARY BLOOD VESSEL; CORONARY VASCULAR RESISTANCE; DRUG DELIVERY SYSTEM; DRUG EFFECT; DRUG POTENCY; DRUG SENSITIZATION; ENDOTHELIAL DYSFUNCTION; HEART INDEX; HEART OUTPUT; HUMAN; HYPOXIA; LUNG ARTERY PRESSURE; MUSCLE CONTRACTION; NONHUMAN; PULMONARY HYPERTENSION; PULMONARY VASCULAR DISEASE; REVIEW; SIGNAL TRANSDUCTION; SYSTOLIC BLOOD PRESSURE; UPREGULATION; VASCULAR SMOOTH MUSCLE; VASOCONSTRICTION; VASODILATATION;

AMIDES; ANIMALS; CALCIUM CHANNEL BLOCKERS; ENZYME INHIBITORS; EVIDENCE-BASED MEDICINE; GUANYLATE CYCLASE; HUMANS; HYPERTENSION, PULMONARY; IMIDAZOLES; MUSCLE CONTRACTION; MUSCLE, SMOOTH; OXADIAZOLES; PYRIDINES; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RHO-ASSOCIATED KINASES; VASODILATOR AGENTS;

EID: 77149165430     PISSN: 10615377     EISSN: None     Source Type: Journal    
DOI: 10.1097/CRD.0b013e3181cbcbf3     Document Type: Review

References (144)

1. Rubin LJ, Badesch DB. Evaluation and management of the patient with pulmonary arterial hypertension. Ann Intern Med. 2005;1143:282-292.
2. Simonneau G, Galie N, Rubin LJ, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2004;43:5S-12S.
3. Widlitz A, Barst RJ. Pulmonary arterial hypertension in children. Eur Respir J. 2003;21:155-176.
4. Raiesdana A, Loscalzo J. Pulmonary arterial hypertension. Ann Med. 2006; 38:95-110.
5. Yang YY, Lin HC, Lee WC, et al. Portopulmonary hypertension: distinctive hemodynamic and clinical manifestations. J Gastroenterol. 2001;36:181-186.
6. Lai A, Frishman WH. Rho-kinase inhibition in the therapy of cardiovascular disease. Cardiol Rev. 2005;13:285-292.
7. Palevsky HI, Gurughagavatula I. Pulmonary hypertension in collagen vascular disease. Compr Ther. 1999;25:133-143.
8. Petitpretz P, Brenot F, Azarian R, et al. Pulmonary hypertension in patients with human immunodeficiency virus infection: comparison with primary pulmonary hypertension. Circulation. 1994;89:2722-2727.
9. Rich S, Levitsky S, Brundage BH. Pulmonary hypertension from chronic pulmonary thromboembolism. Ann Intern Med. 1988;108:425-434.
10. Rich S, Rubin L, Walker AM, et al. Anorexigens and pulmonary hypertension in the United States: results from the surveillance of North American pulmonary hypertension. Chest. 2000;117:870-874.
11. Abenhaim L, Humbert M. Pulmonary hypertension related to drugs and toxins. Curr Opin Cardiol. 1999;14:437-441.
12. Abu-Osba YK. Treatment of persistent pulmonary hypertension of the newborn: update. Arch Dis Child. 1991;66:74-77.
13. Lewis CS Jr, Samuels AJ, Daines MC, et al. Chronic lung disease, polycythemia and congestive heart failure; cardiorespiratory, vascular and renal adjustments in cor pulmonale. Circulation. 1952;6:874-887.
14. Ash R. Natural history of ventricular septal defects in childhood lesions with predominant arteriovenous shunts. J Pediatr. 1964;64:45-56.
15. Sackner MA, Akgun N, Kimbel P, et al. The pathophysiology of scleroderma involving the heart and respiratory system. Ann Intern Med. 1964; 60:611-630.
16. Brisbane JU, Howell DA, Bonkowsky HL. Pulmonary hypertension as a presentation of hepatocarcinoma. Report of a case and brief review of the literature. Am J Med. 1980;68:466-469.
17. Abramson SV, Burke JF, Kelly JJ Jr, et al. Pulmonary hypertension predicts mortality and morbidity in patients with dilated cardiomyopathy. Ann Intern Med. 1992;116:888-895.
18. Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary hypertension: a national prospective study. Ann Intern Med. 1987;107:216-223.
19. D'Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension: results from a national prospective registry. Ann Intern Med. 1991;115:343-349.
20. Haworth SG, Hislop AA. Treatment and survival in children with pulmonary arterial hypertension: the UK pulmonary hypertension service for children 2001-2006. Heart. 2009;95:312-317.
21. Toyoda Y, Thacker J, Santos R, et al. Long-term outcome of lung and heart-lung transplantation for idiopathic pulmonary arterial hypertension. Ann Thorac Surg. 2008;86:1116-1122.
22. Rubin LJ. Pulmonary arterial hypertension. Proc Am Thorac Soc. 2006;3: 111-115.
23. Galie N, Branzi A. Pulmonary arterial hypertension: therapeutic algorithm. Ital Heart J. 2005;6:856-860.
24. Nauser TD, Stites SW. Pulmonary hypertension: new perspectives. Congest Heart Fail. 2003;9:155-162.
25. Sitbon O, Humbert M, Simonneau G. Primary pulmonary hypertension: current therapy. Prog Cardiovasc Dis. 2002;45:115-128.
26. Franke UF, Wahlers T, Wittwer T, et al. Heart-lung transplantation is the method of choice in the treatment of patients with end-stage pulmonary hypertension. Transplant Proc. 2002;34:2181-2182.
27. Barst RJ. Recent advances in the treatment of pediatric pulmonary artery hypertension. Pediatr Clin North Am. 1999;46:331-345.
28. Stillwell PC, Mallory GB Jr. Pediatric lung transplantation. Clin Chest Med. 1997;18:405-414.
29. Kneussl MP, Lang IM, Brenot FP. Medical management of primary pulmonary hypertension. Eur Respir J. 1996;9:2401-2409.
30. Katz WE, Gasior TA, Quinlan JJ, et al. Immediate effects of lung transplantation on right ventricular morphology and function in patients with variable degrees of pulmonary hypertension. J Am Coll Cardiol. 1996;27: 384-391.
31. Rich S. Medical treatment of primary pulmonary hypertension: a bridge to transplantation? Am J Cardiol. 1995;75:63A-66A.
32. Rubin LJ. Primary pulmonary hypertension. Practical therapeutic recommendations. Drugs. 1992;43:37-43.
33. Pasque MK, Trulock EP, Kaiser LR, et al. Single-lung transplantation for pulmonary hypertension: three-month hemodynamic follow-up. Circulation. 1991;84:2275-2279.
34. Levine SM, Gibbons WJ, Bryan CL, et al. Single lung transplantation for primary pulmonary hypertension. Chest. 1990;98:1107-1115.
35. O'Meara N, Clarke R, Gearty G, et al. Primary pulmonary hypertension: treatment with heart-lung transplantation. Ir Med J. 1987;80:174-175.
36. Dranitsaris G, Mehta S. Oral therapies for the treatment of pulmonary arterial hypertension: a population-based cost-minimization analysis. Appl Health Econ Health Policy. 2009;7:43-59.
37. Mucke HA. Pulmonary arterial hypertension: on the way to a manageable disease. Curr Opin Investig Drugs. 2008;9:957-962.
38. LaRaia AV, Waxman AB: Pulmonary arterial hypertension: evaluation and management. South Med J. 2007;100:393-399.
39. Benza RL, Park MH, Keogh A, et al. Management of pulmonary arterial hypertension with a focus on combination therapies. J Heart Lung Transplant. 2007;26:437-446.
40. Kadowitz PJ, Hyman AL. Hydralazine and the treatment of primary pulmonary hypertension. N Engl J Med. 1982;306:1357-1359.
41. Li F, Xia W, Yuan S, et al. Acute inhibition of Rho-kinase attenuates pulmonary hypertension in patients with congenital heart disease. Pediatr Cardiol. 2009;30:363-366.
42. Ishikura K, Yamada N, Ito M, et al. Beneficial acute effects of rho-kinase inhibitor in patients with pulmonary arterial hypertension. Circ J. 2006;70: 174-178.
43. Fukumoto Y, Matoba T, Ito A, et al. Acute vasodilator effects of a Rho-kinase inhibitor, Fasudil, in patients with severe pulmonary hypertension. Heart. 2005;91:391-392.
44. Packer M. Vasodilator therapy for primary pulmonary hypertension. Limitations and hazards. Ann Intern Med. 1985;103:258-270.
45. McGoon MD, Vlietstra RE. Vasodilator therapy for primary pulmonary hypertension. Mayo Clin Proc. 1984;59:672-677.
46. Paramothayan NS, Lasserson TJ, Wells AU, et al. Prostacyclin for pulmonary hypertension in adults. Cochrane Database Syst Rev. 2005:CD002994.
47. Paramothayan NS, Lasserson TJ, Wells AU, et al. Prostacyclin for pulmonary hypertension. Cochrane Database Syst Rev. 2002:CD002994.
48. Hyman AL, Chapnick BM, Kadowitz PJ, et al. Unusual pulmonary vasodilator activity of 13,14-dehydroprostacyclin methyl ester: comparison with endoperoxides and other prostanoids. Proc Natl Acad Sci USA. 1977;74: 5711-5715.
49. Hyman AL, Kadowitz PJ. Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat. Circ Res. 1979;45:404-409.
50. Kadowitz PJ, Chapnick BM, Feigen LP, et al. Pulmonary and systemic vasodilator effects of the newly discovered prostaglandin, PGI2. J Appl Physiol. 1978;45:408-413.
51. Paramothayan NS, Lasserson TJ, Wells AU, et al. Prostacyclin for pulmonary hypertension. Cochrane Database Syst Rev. 2003:CD002994.
52. Szczeklik J, Dubiel JS, Mysik M, et al. Effects of prostaglandin E1 on pulmonary circulation in patients with pulmonary hypertension. Br Heart J. 1978;40:1397-1401.
53. Watkins WD, Peterson MB, Crone RK, et al. Prostacyclin and prostaglandin E1 for severe idiopathic pulmonary artery hypertension. Lancet. 1980;1: 1083.
54. McLaughlin VV, Genthner DE, Panella MM, et al. Compassionate use of continuous prostacyclin in the management of secondary pulmonary hypertension: a case series. Ann Intern Med. 1999;130:740-743.
55. Conte JV, Gaine SP, Orens JB, et al. The influence of continuous intravenous prostacyclin therapy for primary pulmonary hypertension on the timing and outcome of transplantation. J Heart Lung Transplant. 1998;17:679-685.
56. Okano Y, Senju S, Tsutsui Y, et al. Long-term continuous intravenous infusion of prostacyclin for severe primary pulmonary hypertension. Intern Med. 1997;36:794-798.
57. Barst RJ, Rubin LJ, McGoon MD, et al. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med. 1994;121:409-415.
58. Kramer MR, Fucks S, Simon Z, et al. Continuous therapy with intravenous prostacyclin for primary pulmonary hypertension: a bridge to heart-lung transplantation. Isr J Med Sci. 1993;29:613-616.
59. Scott JP, Higenbottam TW, Smyth RL, et al. Acute pulmonary hypertensive crisis in a patient with primary pulmonary hypertension treated by both epoprostenol (prostacyclin) and nitroprusside. Chest. 1991;99:1284-1285.
60. Macchia A, Marchioli R, Marfisi R, et al. A meta-analysis of trials of pulmonary hypertension: a clinical condition looking for drugs and research methodology. Am Heart J. 2007;153:1037-1047.
61. Archer-Chicko C. Continuous intravenous prostacyclin for advanced primary pulmonary hypertension. Dimens Crit Care Nurs. 2000;19:14-21.
62. Dahlem P. Combination of inhaled nitric oxide and intravenous prostacyclin for successful treatment of severe pulmonary hypertension in a patient with ARDS. Intensive Care Med. 1999;25:1474-1475.
63. Barst RJ. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin. Heart. 1997;77:299-301.
64. Rubin LJ, Mendoza J, Hood M, et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol): results of a randomized trial. Ann Intern Med. 1990;112:485-491.
65. Schenk P, Petkov V, Madl C, et al. Aerosolized iloprost therapy could not replace long-term IV epoprostenol (prostacyclin) administration in severe pulmonary hypertension. Chest. 2001;119:296-300.
66. Della Rocca G, Coccia C, Costa MG, et al. Inhaled aerosolized prostacyclin and pulmonary hypertension during anesthesia for lung transplantation. Transplant Proc. 2001;33:1634-1636.
67. Forrest IA, Small T, Corris PA. Effect of nebulized epoprostenol (prostacyclin) on exhaled nitric oxide in patients with pulmonary hypertension due to congenital heart disease and in normal controls. Clin Sci (Lond). 1999; 97:99-102.
68. Barry PW. Unsuccessful treatment of pulmonary hypertension by inhaled nitric oxide and aerosolized prostacyclin. Anaesth Intensive Care. 1999;27: 670-671.
69. Webb SA, Stott S, van Heerden PV. The use of inhaled aerosolized prostacyclin (IAP) in the treatment of pulmonary hypertension secondary to pulmonary embolism. Intensive Care Med. 1996;22:353-355.
70. Olschewski H, Walmrath D, Schermuly R, et al. Aerosolized prostacyclin and iloprost in severe pulmonary hypertension. Ann Intern Med. 1996;124: 820-824.
71. Shapiro S, Hill NS. Transition from IV to subcutaneous prostacyclin: premature withdrawal? Chest. 2007;132:741-743.
72. van Albada ME, van Veghel R, Cromme-Dijkhuis AH, et al. Treprostinil in advanced experimental pulmonary hypertension: beneficial outcome without reversed pulmonary vascular remodeling. J Cardiovasc Pharmacol. 2006; 48:249-254.
73. Simonneau G, Barst RJ, Galie N, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2002;165:800-804.
74. Lu H, Chen S, Wang H, et al. Role of adrenomedullin in congenital heart disease associated with pulmonary hypertension. J Huazhong Univ Sci Technolog Med Sci. 2003;23:275-277.
75. Nagaya N, Kyotani S, Uematsu M, et al. Effects of adrenomedullin inhalation on hemodynamics and exercise capacity in patients with idiopathic pulmonary arterial hypertension. Circulation. 2004;109:351-356.
76. Vijay P. Adrenomedullin in the treatment of pulmonary hypertension. Heart. 2000;84:575-576.
77. Champion HC, Bivalacqua TJ, Toyoda K, et al. In vivo gene transfer of prepro-calcitonin gene-related peptide to the lung attenuates chronic hypoxia-induced pulmonary hypertension in the mouse. Circulation. 2000;101: 923-930.
78. Zhao Q, Liu Z, Wang Z, et al. Effect of prepro-calcitonin gene-related peptide-expressing endothelial progenitor cells on pulmonary hypertension. Ann Thorac Surg. 2007;84:544-552.
79. Haydar S, Sarti JF, Grisoni ER. Intravenous vasoactive intestinal polypeptide lowers pulmonary-to-systemic vascular resistance ratio in a neonatal piglet model of pulmonary arterial hypertension. J Pediatr Surg. 2007;42: 758-764.
80. Leuchte HH, Baezner C, Baumgartner RA, et al. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J. 2008;32:1289-1294.
81. Zeng C, Wang X, Hu X, et al. Autologous endothelial progenitor cells transplantation for the therapy of primary pulmonary hypertension. Med Hypotheses. 2007;68:1292-1295.
82. Wang XX, Zhang FR, Shang YP, et al. Transplantation of autologous endothelial progenitor cells may be beneficial in patients with idiopathic pulmonary arterial hypertension: a pilot randomized controlled trial. J Am Coll Cardiol. 2007;49:1566-1571.
83. Tamm M, Gratwohl A, Tichelli A, et al. Autologous haemopoietic stem cell transplantation in a patient with severe pulmonary hypertension complicating connective tissue disease. Ann Rheum Dis. 1996;55:779-780.
84. Zhao YD, Courtman DW, Deng Y, et al. Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease. Circ Res. 2005;96:442-450.
85. Kanki-Horimoto S, Horimoto H, Mieno S, et al. Implantation of mesenchymal stem cells overexpressing endothelial nitric oxide synthase improves right ventricular impairments caused by pulmonary hypertension. Circulation. 2006;114:I181-I185.
86. Takahashi M, Nakamura T, Toba T, et al. Transplantation of endothelial progenitor cells into the lung to alleviate pulmonary hypertension in dogs. Tissue Eng. 2004;10:771-779.
87. Otto C, Hein L, Brede M, et al. Pulmonary hypertension and right heart failure in pituitary adenylate cyclase-activating polypeptide type I receptor-deficient mice. Circulation. 2004;110:3245-3251.
88. Otsuka T, Ibuki C, Suzuki T, et al. Administration of the Rho-kinase inhibitor, Fasudil, following nitroglycerin additionally dilates the site of coronary spasm in patients with vasospastic angina. Coron Artery Dis. 2008;19:105-110.
89. Otsuka T, Ibuki C, Suzuki T, et al. Vasodilatory effect of subsequent administration of Fasudil, a rho-kinase inhibitor, surpasses that of nitroglycerin at the concentric coronary stenosis in patients with stable angina pectoris. Circ J. 2006;70:402-408.
90. Inokuchi K, Ito A, Fukumoto Y, et al. Usefulness of Fasudil, a Rho-kinase inhibitor, to treat intractable severe coronary spasm after coronary artery bypass surgery. J Cardiovasc Pharmacol. 2004;3:275-277.
91. Hiroki J, Fukumoto Y, Shimokawa H, et al. Inhibition of Rho-kinase by Fasudil preventing anginal attacks associated with spastic angina: a case report [in Japanese]. J Cardiol. 2004;4:161-164.
92. Mohri M, Shimokawa H, Hirakawa Y, et al. Rho-kinase inhibition with intracoronary Fasudil prevents myocardial ischemia in patients with coronary microvascular spasm. J Am Coll Cardiol. 2003;41:15-19.
93. Shimokawa H, Hiramori K, Iinuma H, et al. Anti-anginal effect of Fasudil, a Rho-kinase inhibitor, in patients with stable effort angina: a multicenter study. J Cardiovasc Pharmacol. 2002;40:751-761.
94. Masumoto A, Mohri M, Shimokawa H, et al. Suppression of coronary artery spasm by the Rho-kinase inhibitor Fasudil in patients with vasospastic angina. Circulation. 2002;105:1545-1547.
95. Chang J, Xie M, Shah VR, et al. Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis. Proc Natl Acad Sci USA. 2006;103:14495-14500.
96. Kishi T, Hirooka Y, Masumoto A, et al. Rho-kinase inhibitor improves increased vascular resistance and impaired vasodilation of the forearm in patients with heart failure. Circulation. 2005;111:2741-2747.
97. Schmitt M, Gunaruwan P, Payne N, et al. Effects of exogenous and endogenous natriuretic peptides on forearm vascular function in chronic heart failure. Arterioscler Thromb Vasc Biol. 2004;24:911-917.
98. Hashiba Y, Tosaka M, Saito N, et al. Vasorelaxing effect of the Rho-kinase inhibitor, Y-27632, in isolated canine basilar arteries. Neurol Res. 2007;29: 485-489.
99. Chrissobolis S, Sobey CG. Recent evidence for an involvement of rho-kinase in cerebral vascular disease. Stroke. 2006;37:2174-2180.
100. 2+ is essential for the development of cerebral vasospasm. Curr Vasc Pharmacol. 2004;2: 13-21.
101. Sato M, Tani E, Fujikawa H, et al. Involvement of Rho-kinase-mediated phosphorylation of myosin light chain in enhancement of cerebral vasospasm. Circ Res. 2000;87:195-200.
102. Seasholtz TM, Wessel J, Rao F, et al. Rho kinase polymorphism influences blood pressure and systemic vascular resistance in human twins: role of heredity. Hypertension. 2006;47:937-947.
103. Masumoto A, Hirooka Y, Shimokawa H, et al. Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans. Hypertension. 2001;38:1307-1310.
104. Doe C, Bentley R, Behm DJ, et al. Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007; 320:89-98.
105. 2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev. 2003;83:1325-1358.
106. Guibert C, Ducret T, Savineau JP. Voltage-independent calcium influx in smooth muscle. Prog Biophys Mol Biol. 2008;98:10-23.
107. Salomonsson M, Sorensen CM, Arendshorst WJ, et al. Calcium handling in afferent arterioles. Acta Physiol Scand. 2004;181:421-429.
108. Nagaoka T, Fagan KA, Gebb SA, et al. Inhaled Rho kinase inhibitors are potent and selective vasodilators in rat pulmonary hypertension. Am J Respir Crit Care Med. 2005;171:494-499.
109. 2+ sensitivity in rabbit pulmonary artery smooth muscle. Pflugers Arch. 1990;417:21-28.
110. Liao JK, Seto M, Noma K. Rho kinase (ROCK) inhibitors. J Cardiovasc Pharmacol. 2007;50:17-24.
111. 2+ desensitization in pulmonary vascular smooth muscle through inhibition of RhoA/Rho kinase signaling. Am J Physiol Lung Cell Mol Physiol. 2004;287:L1220-L1229.
112. Robertson TP, Dipp M, Ward JP, et al. Inhibition of sustained hypoxic vasoconstriction by Y-27632 in isolated intrapulmonary arteries and perfused lung of the rat. Br J Pharmacol. 2000;131:5-9.
113. Wang Z, Jin N, Ganguli S, et al. Rho-kinase activation is involved in hypoxia-induced pulmonary vasoconstriction. Am J Respir Cell Mol Biol. 2001;25:628-635.
114. Abe K, Shimokawa H, Morikawa K, et al. Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats. Circ Res. 2004;94:385-393.
115. Jiang BH, Tawara S, Abe K, et al. Acute vasodilator effect of Fasudil, a Rho-kinase inhibitor, in monocrotaline-induced pulmonary hypertension in rats. J Cardiovasc Pharmacol. 2007;49:85-89.
116. Broughton BR, Walker BR, Resta TC. Chronic hypoxia induces Rho kinase-dependent myogenic tone in small pulmonary arteries. Am J Physiol Lung Cell Mol Physiol. 2008;294:L797-L806.
117. Nossaman BD, Kadowitz PJ. The role of the RhoA/rho-kinase pathway in pulmonary hypertension. Curr Drug Discov Technol. 2009;6:59-71.
118. Dhaliwal JS, Badejo AM Jr, Casey DB, et al. Analysis of pulmonary vasodilator responses to SB-772077-B [4-(7-((3-amino-1-pyrrolidinyl)carbonyl)-1- ethyl-1H-imidazo(4,5-c)pyridin- 2-yl)-1,2,5-oxadiazol-3-amine], a novel aminofurazan-based Rho kinase inhibitor. J Pharmacol Exp Ther. 2009;330:334-341.
119. Badejo AM Jr, Dhaliwal JS, Casey DB, et al. Analysis of pulmonary vasodilator responses to the Rho-kinase inhibitor Fasudil in the anesthetized rat. Am J Physiol Lung Cell Mol Physiol. 2008;295:L828-L836.
120. 2+ entry mediate increased pulmonary and systemic vascular resistance in L-NAME-treated rats. Am J Physiol Lung Cell Mol Physiol. 2007;293:L1306-L1313.
121. 2+ signaling in hypoxic pulmonary vasoconstriction: effects of myosin light chain and Rho kinase antagonists. Am J Physiol Lung Cell Mol Physiol. 2007;293:L674-L685.
122. Oka M, Homma N, Taraseviciene-Stewart L, et al. Rho kinase-mediated vasoconstriction is important in severe occlusive pulmonary arterial hypertension in rats. Circ Res. 2007;100:923-929.
123. Guilluy C, Rolli-Derkinderen M, Tharaux PL, et al. Transglutaminase- dependent RhoA activation and depletion by serotonin in vascular smooth muscle cells. J Biol Chem. 2007;282:2918-2928.
124. Gao Y, Portugal AD, Negash S, et al. Role of Rho kinases in PKG-mediated relaxation of pulmonary arteries of fetal lambs exposed to chronic high altitude hypoxia. Am J Physiol Lung Cell Mol Physiol. 2007;292:L678-L684.
125. Nagaoka T, Morio Y, Casanova N, et al. Rho/Rho kinase signaling mediates increased basal pulmonary vascular tone in chronically hypoxic rats. Am J Physiol Lung Cell Mol Physiol. 2004;287:L665-L672.
126. Fagan KA, Oka M, Bauer NR, et al. Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho-kinase. Am J Physiol Lung Cell Mol Physiol. 2004;287:L656-L664.
127. Wang Z, Lanner MC, Jin N, et al. Hypoxia inhibits myosin phosphatase in pulmonary arterial smooth muscle cells: role of Rho-kinase. Am J Respir Cell Mol Biol. 2003;29:465-471.
128. McMurtry IF, Bauer NR, Fagan KA, et al. Hypoxia and Rho/Rho-kinase signaling: lung development versus hypoxic pulmonary hypertension. Adv Exp Med Biol. 2003;543:127-137.
129. Khan I, Oriowo MA, Chandrasekhar B, et al. Attenuated noradrenaline-induced contraction of pulmonary arteries from rats treated with monocrotaline: role of rho kinase. J Vasc Res. 2005;42:433-440.
130. Fukata Y, Amano M, Kaibuchi K. Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. Trends Pharmacol Sci. 2001;22:32-39.
131. Abe K, Tawara S, Oi K, et al. Long-term inhibition of Rho-kinase ameliorates hypoxia-induced pulmonary hypertension in mice. J Cardiovasc Pharmacol. 2006;48:280-285.
132. Janssen LJ, Lu-Chao H, Netherton S. Excitation-contraction coupling in pulmonary vascular smooth muscle involves tyrosine kinase and Rho kinase. Am J Physiol Lung Cell Mol Physiol. 2001;280:L666-L674.
133. Martin C, Göggel R, Ressmeyer AR, et al. Pressor responses to platelet-activating factor and thromboxane are mediated by Rho-kinase. Am J Physiol Lung Cell Mol Physiol. 2004;287:L250-L257.
134. Batchelor TJ, Sadaba JR, Ishola A, et al. Rho-kinase inhibitors prevent agonist-induced vasospasm in human internal mammary artery. Br J Pharmacol. 2001;132:302-308.
135. 2+ sensitivity in the bovine middle cerebral artery. Br J Pharmacol. 2003;140:871-880.
136. Baber SR, Deng W, Master RG, et al. Intratracheal mesenchymal stem cell administration attenuates monocrotaline-induced pulmonary hypertension and endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2007;292: H1120-H1128.
137. Kennedy TP, Michael JR, Summer W. Calcium channel blockers in hypoxic pulmonary hypertension. Am J Med. 1985;78:18-26.
138. Kennedy TP, Michael JR, Huang CK, et al. Nifedipine inhibits hypoxic pulmonary vasoconstriction during rest and exercise in patients with chronic obstructive pulmonary disease: a controlled double-blind study. Am Rev Respir Dis. 1984;129:544-551.
139. Michael JR, Kennedy TP, Buescher P, et al. Nitrendipine attenuates the pulmonary vascular remodeling and right ventricular hypertrophy caused by intermittent hypoxia in rats. Am Rev Respir Dis. 1986;133:375-379.
140. Chazova IE, Belenkov IuN, Mareev V, et al. The effect of Lomir (isradipine) on the tolerance for physical loading and on the gas exchange indices of patients with primary pulmonary hypertension [in Russian]. Ter Arkh. 1994;66:54-57.
141. Grimminger F, Weimann G, Frey R, et al. First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension. Eur Respir J. 2009;33:785-792.
142. Molecule of the month. Riociguat. Drug News Perspect. 2009;22:167.
143. Liu J, Gong T, Fu H, et al. Solid lipid nanoparticles for pulmonary delivery of insulin. Int J Pharm. 2008;356:333-344.
144. Grenha A, Remunan-Lopez C, Carvalho EL, et al. Microspheres containing lipid/chitosan nanoparticles complexes for pulmonary delivery of therapeutic proteins. Eur J Pharm Biopharm. 2008;69:83-93.