Therapeutic targets in neonatal pulmonary hypertension: Linking pathophysiology to clinical medicine

Expert Review of Respiratory Medicine

Volumn 2, Issue 1, 2008, Pages 85-96

  van der Horst, I W J M ^a   Reiss, I ^a   Tibboel, D ^a  

^a SOPHIA CHILDREN S HOSPITAL   (Netherlands)

Author keywords

Endothelin; Neonates; Nitric oxide; Pharmacotherapy; Phosphodiesterase; Prostaglandin; Pulmonary hypertension

Indexed keywords

4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; 4 AMINO 5 CYCLOPROPYL 2 [1 (2 FLUOROBENZYL) 1H PYRAZOLO[3,4 B]PYRIDIN 3 YL]PYRIMIDINE; AMBRISENTAN; ARTIFICIAL LUNG SURFACTANT; BERAPROST; BOSENTAN; BRAIN NATRIURETIC PEPTIDE; CYCLIC GMP; ENDOTHELIN 1; ENDOTHELIN RECEPTOR ANTAGONIST; FASUDIL; ILOPROST; MAGNESIUM SULFATE; MILRINONE; NESTRITIDE; NITRIC OXIDE; NITRIC OXIDE DONOR; PHOSPHODIESTERASE III; PHOSPHODIESTERASE INHIBITOR; PHOSPHODIESTERASE V; PROSTACYCLIN; RHO KINASE; SILDENAFIL; SITAXSENTAN; TADALAFIL; UNIPROST; VARDENAFIL; VASCULOTROPIN; VASCULOTROPIN INHIBITOR;

ARTIFICIAL VENTILATION; CLINICAL TRIAL; CONGENITAL HEART DISEASE; CONTROLLED CLINICAL TRIAL; DIAPHRAGM HERNIA; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; DRUG SAFETY; DRUG TARGETING; EXTRACORPOREAL OXYGENATION; HUMAN; INTENSIVE CARE; LIVER TOXICITY; LUNG VASCULAR RESISTANCE; LUNG VASOCONSTRICTION; LUNG VENTILATION; MECONIUM ASPIRATION; MORBIDITY; MORTALITY; NEONATAL RESPIRATORY DISTRESS SYNDROME; NEWBORN; NONHUMAN; PATHOPHYSIOLOGY; PROTEIN EXPRESSION; PULMONARY HYPERTENSION; RANDOMIZED CONTROLLED TRIAL; RECURRENT DISEASE; REVIEW; SMOOTH MUSCLE FIBER; VASODILATATION;

EID: 47649089232     PISSN: 17476348     EISSN: 17476356     Source Type: Journal    
DOI: 10.1586/17476348.2.1.85     Document Type: Review

References (124)

1. Walsh-Sukys MC, Tyson JE, Wright LL et al. Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes. Pediatrics 105(1 Pt 1), 14-20 (2000).
2. Tulloh RM. Congenital heart disease in relation to pulmonary hypertension in paediatric practice. Paediatr. Respir. Rev. 6(3), 174-180 (2005).
3. Leibovitch L, Matok I, Parer G. Therapeutic applications of sildenafil citrate in the management of paediatric pulmonary hypertension. Drugs 67(1), 57-73 (2007).
4. Rosenzweig EB, Widlitz AC, Barst RJ. Pulmonary arterial hypertension in children. Pediatr. Pulmonol. 38(1), 2-22 (2004).
5. Kumar VH, Hutchison AA, Lakshminrusimha S, Morin FC 3rd, Wynn RJ, Ryan RM. Characteristics of pulmonary hypertension in preterin neonates. J. Perinatol. 27(4), 214-219 (2007).
6. 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. 153(6), 1037-1047 (2007).
7. Hislop A. Developmental biology of the pulmonary circulation. Paediatr. Respir Rev. 6(1), 35-43 (2005).
8. Hislop AA, Pierce CM. Growth of the vascular tree. Paediatr. Respir. Rev. 1(4), 321-327 (2000).
9. Ghanayem NS, Gordon JB. Modulation of pulmonary vasomotor tone in the fetus and neonate. Respir. Res. 2(3), 139-144 (2001).
10. Haworth SG. Pulmonary hypertension in the young. Heart 88(6), 658-664 (2002).
11. Geggel RL, Reid LM. The structural basis of PPHN. Clin. Perinatol. 11 (3), 525-549 (1984).
12. Michalsky MP, Arca MJ, Groenman F, Hammond S, Tibboel D, Caniano DA. Alveolar capillary dysplasia: a logical approach to a fatal disease. J. Pediatr. Surg. 40(7), 1100-1105 (2005).
13. Gelband CH, Katovich MJ, Raizada MK. Current perspectives on the use of gene therapy for hypertension. Circ. Res. 87(12), 1118-1122 (2000).
14. van Haaften T, Thebaud B. Adult bone marrow-derived stem cells for the lung: implications for pediatric lung diseases. Pediatr. Res. 59(4 Pt 2), R94-R99 (2006).
15. Deprest J, Jani J, Gratacos E et al. Fetal intervention for congenital diaphragmatic hernia: the European experience. Semin. Perinatol. 29(2), 94-103 (2005).
16. Tuder RM, Cool CD, Yeager M, Tarasevidene-Stewart L, Bull TM, Voelkel NF. The pathobiology of pulmonary hypertension. Endothelium. Clin. Chest Med. 22(3),405-418 (2001).
17. Zamanian RT Haddad F, Doyle RL, Weinacker AB. Management strategies for patients with pulmonary hypertension in the intensive care unit. Crit. Care Med. 35(9), 2037-2050 (2007).
18. Rabinovitch M, Haworth SG, Castaneda AR, Nadas AS, Reid LM. Lung biopsy in congenital heart disease: a morphometric approach to pulmonary vascular disease. Circulation 58(6), 1107-1122 (1978).
19. Jones PL, Cowan KN, Rabinovitch M. Tenascin-C. Proliferation and subendothelial fibronectin in progressive pulmonary vascular disease. Am J. Pathol. 150(4), 1349-1360 (1997).
20. Dakshinamurti S. Pathophysiologic mechanisms of persistent pulmonary hypertension of the newborn. Pediatr. Pulmonol. 39(6),492-503 (2005).
21. Thebaud B. Angiogenesis in lung development, injury and repair implications for chronic lung disease of prematurity. Neonatology 91(4), 291-297 (2007).
22. Weir EK, Lopez-Barneo J, Buckler KJ, Archer SL. Acute oxygen-sensing mechanisms. N. Engl. J. Med. 353(19), 2042-2055 (2005).
23. Abu-Osba M Galal O, Manasra K, Rejjal A. Treatment of severe persistent pulmonary hypertension of the newborn with magnesium sulphate. Arch. Dis. Child. 67 (1 Spec No), 31-35 (1992).
24. Tolsa JF, Cotting J, Sekarski N, Payot M, Micheli JL, Calame A. Magnesium sulphate as an alternative and safe treatment for severe persistent pulmonary hypertension of the newborn. Arch. Dis. Chili Fetal Neonatal & 72(3), F184-F187 (1995).
25. Villamor E, Perez-Vacaino F, Ruiz T, Tamargo J, Moro M. In vitro effects of magnesium sulfate in isolated intrapulmonary and mesenteric arteries of piglets. Pediatr. Res. 39(6), 1107-1112 (1996).
26. Wu TJ, Teng RJ, Tsou KI. Persistent pulmonary hypertension of the newborn treated with magnesium sulfate in premature neonates. Pediatrics 96(3 Pt 1), 472-474 (1995).
27. Patole SK, Finer NN. Experimental and clinical effects of magnesium milision in the treatment of neonatal pulmonary hypertension. Magnes. Res. 8(4), 373-388 (1995).
28. Chandran S, Haqueb ME, Wickramasinghe HT, Wint Z. Use of magnesium sulphate in severe persistent pulmonary hypertension of the newborn. J. Trop. Pediatr. 50(4), 219-223 (2004).
29. Daffa SH, Milaat WA. Role of magnesium sulphate in treatment of severe persistent pulmonary hypertension of the neoborn. Saudi Med. J. 23 (10), 1266-1269 (2002).
30. Ho JJ, Rasa G. Magnesium sulfate for persistent pulmonary hypertension of the newborn. Cochrane Database Syst. Rev. 3, CD005588 (2007).
31. Barrington KJ, Ryan CA, Finer NN. Effects of magnesium sulfate in a newborn piglet meconium aspiration model. J. Perinatol. 20(6), 373-378 (2000).
32. Velvis H, Moore P, Heymann MA. Prostaglandin inhibition prevents the fall in pulmonary vascular resistance as a result of rhythmic distension of the lungs in fetal lambs. Pediatt Res. 30(1), 62-68 (1991).
33. Gerarci MW, Gao B, Shepherd DC et al. Pulmonary prostacyclin synthase overexpression in transgenic mice protects against development of hypoxic pulmonary hypertension. J. Clin. Invest. 103(11), 1509-1515 (1999).
34. Sood BG, Delaney-Bla& V, Glibetic M, Aranda JV, Chen X Shankaran S. PGE2rM2 imbalance in neonatal hypoxemic respiratory failure. Acta Paediatr. 96(5), 669-673 (2007).
35. Galie N, Manes A, Branzi A. Medical therapy of pulmonary hypertension. The prostacyclins. Clin. Chest Med. 22(3), 529-537, (2001).
36. Hoeper MM, Olschewski H, Ghofrani HA et al. A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. German PPH study group. J Am. Coll. Cardiol. 35 (1), 176-182 (2000).
37. Chotigeat U, Jaratwashirakul S. Inhaled iloprost for severe persistent pulmonary hypertension of the newborn. J. Med. Assoc. Thai. 90(1), 167-170 (2007).
38. De Luca D, Zecca E, Piastra M, Romagnoli C. Iloprost as 'rescue' therapy for pulmonary hypertension of the neonate. Paediatr. Anaesth. 17(4), 394-395 (2007).
39. Ehlen M, Wiebe B. Iloprost in persistent pulmonary hypertension of the newborn. Cardiol. Young 13(4), 361-363 (2003).
40. Kelly LK, Porta NF, Goodman DM, Carroll CL, Steinhorn RH. Inhaled prostacydin for term infants with persistent pulmonary hypertension refractory to inhaled nitric oxide. J. Pediatr. 141(6), 830-832 (2002).
41. De Jaegere AP, van den Anker JN. Endotracheal instillation of prostacyclin in preterm infants with persistent pulmonary hypertension. Eur Respir. J. 12(4), 932-934 (1998).
42. Schermuly RT, Krupnik E, Tenor H et al. Coaerosolization of phosphodiesterase inhibitors markedly enhances the pulmonary vasodilatory response to inhaled iloprost in experimental pulmo nary hypertension. Maintenance of lung selectivity. Am. J. Respir. Crit. Care Med. 164(9), 1694-1700 (2001).
43. Kinsella JP, Neish SR, Shaffer E, Abman SH. Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 340(8823), 819-820 (1992).
44. Murad E Shattuck lecture. Nitric oxide and cyclic GMP in cell signaling and drug development. N. Engl. J. Med. 355(19), 2003-2011(2006).
45. Coggins MP, Bloch KD. Nitric oxide in the pulmonary vasculature. Arterioscler. Thromb. Vasc. Biol. 27(9), 1877-1885 (2007).
46. Clark RH, Kueser TJ, Walker MW et al. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group. N. Engl. J. Med. 342(7), 469-474(2000).
47. Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst. Rev. 4, CD000399 (2006).
48. Deruelle P, Grover TR, Abman SH. - Pulmonary vascular effects of nitric oxide-cGMP augmentation in a model of chronic pulmonary hypertension in fetal and neonatal sheep. Am. J. Physiol. Lung Cell. Mol. Physiol. 289(5), L798-L806 (2005).
49. Khoo JP, Zhao L, Alp NJ et al. Pivotal role for endothelial tetrahydrobiopterin in pulmonary hypertension. Circulatilation 111(16), 2126-2133 (2005).
50. Travadi JN, Patole SK. Phosphodiesterase inhibitors for persistent pulmonary hypertension of the newborn: a review. Pediatr. Pulmonol. 36(6), 529-535 (2003).
51. Saidy K, al-Alaiyan S. The use of 1-arginine [correction of F-arginine] and phosphodiesterase inhibitor (dipyridamole) to wean from inhaled nitric oxide. Indian J. Pediatr. 68(2), 175-177 (2001).
52. Konduri GG, Mital S. Adenosine and ATP cause nitric oxide-dependent pulmonary vasodilation in fetal lambs. Biol. Neonate 78(3), 220-229 (2000).
53. Lakshminrusimha S, Russell JA, Wedgwood S et al. Superoxide dismutase improves oxygenation and reduces oxidation in neonatal pulmonary hypertension. Am. J. Respir. Crit. Care Med. 174(12), 1370-1377 (2006).
54. Maurice DH, Palmer D, Tilley DG et al. Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system. Mol. Pharmacol. 64(3), 533-546 (2003).
55. Hanson KA, Burns F, Rybalkin SD, Miller JW, Beavo J, Clarke WR. Developmental changes in lung cGMP phosphodiesterase-5 activity, protein, and message. Am. J. Respir. Crit. Care Med. 158(1), 279-288 (1998).
56. Murray F, MacLean MR. Pyne NJ. 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(8), 1187-1194 (2002).
57. Wharton J, Strange JW, Mofler GM et al. Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am. J. Respir. Crit. Care Med. 172(1), 105-113 (2005).
58. Galic N, Ghofrani HA, Torbicki A et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N. Engl. J. Med. 353(20), 2148-2157 (2005).
59. Baquero H, Soliz A, Neira F, Venegas ME, Sola A. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study. Pediatrics 117(4), 1077-1083 (2006).
60. Michelakis E, Tymchak W Lien D, Webster L, Hashimoto K, Archer S. Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide. Circulation 105(20), 2398-2403 (2002).
61. Atz AM, Wessel DL. Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology 91(1), 307-310 (1999).
62. Kleinsasser A, Loeckinger A, Hoermann C et al. Sildenafil modulates hemodynamics and pulmonary gas exchange. Am. J. Respir. Crit. Care Med. 163(2), 339-343 (2001).
63. Haase E, Bigam. DL, Cravetchi O, Cheung PY. Dose response of intravenous sildenafil on systemic and regional hemodynamics in hypoxic neonatal piglets. Shock 26(1), 99-106 (2006).
64. Ghofrani HA, Voswinckel R, Reichenberger F et al. Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension: a randomized prospective study. J. Am. Cell Cardiol. 44(7), 1488-1496 (2004).
65. Ladha F, Bonnet S, Eaton F, Hashimoto K, Korbutt G, Thebaud B. Sildenafil improves alveolar growth and pulmonary hypertension in hyperoxia-induced lung injury. Am. J. Respir. Crit. Care Med. 172(6), 750-756 (2005).
66. Luong C, Eaton F, Thebaud B. Antenatal sildenafil attenuates features of persistent pulmonary hypertension of the newborn (PPHN) in rats with congenital diaphragmatic hernia (CDH). Presented at: 2006 PAS Annual Meeting, San Francisco, CA, USA, April 29-May 2, 2006.
67. Shah PS, Ohlsson A. Sildenafil for pulmonary hypertension in neonates. Cochrane Database Syst. Rev. 3, CD005494 (2007).
68. McNamara PJ, Laique F, Muang-In S, Whyte HE. Milrinone improves oxygenation in neonates with severe persistent pulmonary hypertension of the newborn. J Crit. Care 21(2), 217-222 (2006).
69. Bassler D, Choong K, McNamara P. Kirpalani H. Neonatal persistent pulmonary hypertension treated with milrinone: four case reports. Biol Neonate 89(1), 1-5 (2006).
70. Khazin V, Kaufman Y, Zabeeda D et al. Milrinone and nitric oxide: combined effect on pulmonary artery pressures after cardiopulmonary bypass in children. J. Cardiothorac. Vasc. Anesth. 18(2), 156-159 (2004).
71. Lobato EB, Beaver T, Muehlschlegel J, Kirby DS, Klodell C, Sidi A. Treatment with phosphodiesterase inhibitors type III and V: milrinone and sildenafil is an effective combination during thromboxane-induced acute pulmonary hypertension. Br. J. Anaesth. 96(3), 317-322 (2006).
72. Hentschel T. Yin N, Riad A et al. Inhalation of the phosphodiesterase-3 inhibitor milrinone attenuates pulmonary hypertension in a rat model of congestive heart failure. Anesthesiology 106(1), 124-131 (2007).
73. Tanaka H, Tajimi K, Moritsune O, Kobayashi K, Okada K. Effects of milrinone on pulmonary vasculature in normal dogs and in dogs with pulmonary hypertension. Crit. Care Med. 19(1), 68-74 (1991).
74. Buckley MS, Feldman JP. Nebulized milrinone use in a pulmonary hypertensive crisis. Pharmacotherapy 27(12), 1763-176 (2007).
75. Rashid N, Morin FC 3rd, Swartz DD et al. Effects of prostacyclin and milrinone on pulmonary hemodynamics in newborn lambs with persistent pulmonary hypertension induced by ductal ligation. Pediatr Res. 60(5), 624-629 (2006).
76. Thelitz S, Oishi P, Sanchez LS et al. Phosphodiesterase-3 inhibition prevents the increase in pulmonary vascular resistance following inhaled nitric oxide withdrawal lambs. Pediatr. Crit. Care Med. 5 (3), 234-239 (2004).
77. Buchan KW, Magnusson H, Rabe KF, Sumner MJ, Watts IS. Characterisation of the endothelin receptor mediating contraction of human pulmonary artery using BQ123 and Ro 46-2005. Eur J. Pharmacol. 260(2-3), 221-226 (1994).
78. Perreault T, Baribeau J. Characterization of endothelin receptors in newborn piglet lung. Am. J. Physiol. 268(4 Pt 1), L607-L614 (1995).
79. Ziegler JW, Ivy DD, Kinsella JP, Abman S The role of nitric oxide, endothelin, and Prostaglandins in the transition of the pulmonary circulation. Clin. Perinatol. 22(2), 387-403 (1995).
80. Perreault T, Coceani F. Endothelin in the perinatal circulation. Can. J. Physiol. Pharmacol. 81(6), 644-653 (2003).
81. Gosselin R, Gutkowska J, Baribeau J, Perreault T. Endothelin receptor changes hypoxia-induced pulmonary hypertension in the newborn piglet. Am J. Physiol. 2730(1 Pt 1), L72-L79 (1997).
82. Perreault T, Berkenbosch JW, Barrington KJ et al. TBC3711, an ET(A) receptor antagonist, reduces neonatal hypoxia-induced pulmonary hypertension in piglets. Pediatr. Res. 50(3), 374-383 (2001).
83. Okazaki T, Sharma HS, McCune SK, Tibboel D. Pulmonary vascular balance in congenital diaphragmatic hernia: enhance endothelin-1 gene expression as a possible cause of pulmonary vasoconstriction. J. Pediatr. Surg. 33(1), 81-84 (1998).
84. Rosenberg AA, Kennaugh J, Koppenhafer SL, Loomis M, Chatfield BA, Abman SH. Elevated immunoreactive endothelin-1 levels in newborn infants with persistent pulmonary hypertension. J. Pediatr. 123(1), 109-114 (1993).
85. Channick RN, Simonneau G, Sitbon O et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 358(9288), 1119-1123 (2001).
86. Rubin LJ. Primary pulmonary hypertension. N. Engl. J. Med. 336(2), 111-117 (1997).
87. Liu C, Chen J. Endothelin receptor antagonists for pulmonary arterial hypertension. Cochrane Database Syst. Rev. 3, CD004434 (2006).
88. Moffett BS, Chang AC. Future pharmacologic agents for treatment of heart failure in children. Pediatr. Cardiol. 27(5), 533-551 (2006).
89. Goissen C, Ghyselen L, Tourneux P et al. Persistent pulmonary hypertension of the newborn with transposition of the great arteries: successful treatment with bosentan. Eur. J. Pediatr. DOI: 10. 1007/sOO431-007-0531-y (2007) (Epub ahead of print).
90. Barst RJ, Langleben D, Badesch D et al. Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J Am. Coll. Cardiol. 47(10), 2049-2056 (2006).
91. Barst RJ. A review of pulmonary arterial hypertension: role of ambrisentan. Vasc. Health Risk Manag. 3 (1), 11-22 (2007).
92. Shehata SM, Tibboel D, Sharma HS, Mooi WJ. Impaired structural remodelling of pulmonary arteries in newborns with congenital diaphragmatic hernia: a histological study of 29 cases. J. Pathol. 189(1), 112-118 (1999).
93. Lotze A, Mitchell BR, Bulas DI, Zola EM, Shalwitz RA, Gunkel JH- Multicenter study of surfactant (beractant) use m the treatment of term infants with severe respiratory failure-Survanta in Term Infants Study Group. J. Pediatr. 132(1), 40-47 (1998).
94. Khush KK, De Marco T, Vakharia KT et a l. Nesiritide acutely increases pulmonary and systemic levels of nitric oxide in patients with pulmonary hypertension. J. Card. Fail. 12(7), 507-513 (2006).
95. Zhao L, Hughes JM, Winter RJ. Effects of natriuretic peptides and neutral endopeptidase 24.11 inhibition in isolated perfitsed rat lung. Am. Rev. Pespir. Dis. 146(5 Pt 1), 1198-1201 (1992).
96. Mathew B, Russell J, Steinhorn R et al. B-type natriuretic peptide (BNP) system in an ovine model of persistent pulmonary hypertension of the newborn (PPHN). Presented at: 2006 PAS Annual Meeting, San Fransisco, CA, USA, 29 April-2 May, 2006.
97. Reynolds EW, Ellington JG, Vranicar M, Bada HS. Brain-type natriuretic peptide in the diagnosis and management of persistent pulmonary hypertension of the newborn. Pediatrics 114(5), 1297-1304 (2004).
98. Investigators VMAC. Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 287(12), 1531-1540 (2002).
99. Reynolds EW, Conely ET, Vranicar M. Nesiritide for the treatment of pulmonary hypertension and cor pulmonale in an infant. Pediatr. Cardiol. 28(3), 229-233 (2007).
100. Mahle WT, Cuadrado AR, Kirshbom PM, Kanter KR, Simsic JM. Nesiritide in infants and children with congestive heart failure. Pediatn. Crit. Care Med. 6(5), 543-546 (2005).
101. Jefferies JL, Denfield SW, Price JF et al. A prospective evaluation of nesiritide in the treatment of pediatric heart failure. Pediatr. Cardiol. 27(4),402-407 (2006).
102. Jefferies JL, Price JF, Denfield SW et al. Safety and efficacy of nesiritide in pediatric heart failure. J. Card Fail. 13(7), 541-548 (2007).
103. El-Khuffash A, Molloy EJ. Are B-type natriuretic peptide (BNP) and N-terminal-pro-BNP useful in neonates? Arch. Dis. Child. Fetal Neonatal Ed. 92(4), F320-F324 (2007).
104. Somlyo AP, Wu X, Walker LA, Somlyo AV. Pharmacomechanical coupling: the role of calcium, G-proteins, kinases and phosphatases. Rev. Physiol. Biochem. Pharmacol. 134, 201-234 (1999).
105. Ward JP, Knock GA, Snetkov VA, Aaronson PI. Protein kinases in vascular smooth muscle tone - role in the pulmonary vasculature and hypoxic pulmonary vasoconstriction. Pharmacol. Ther. 104(3), 207-231 (2004).
106. de Caestecker M. Serotonin signaling in pulmonary hypertension. Circ. Res. 98(10), 1229-1231 (2006).
107. Chambers CD, Hernandez-Diaz S, Van Matter LJ et al. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N. Engl. J. Med. 354(6), 579-587 (2006).
108. Loirand G, Guerin P, Pacand P. Rho kinase, in cardiovascular physiology and pathophysiology. Circ. Res. 98(3), 322-334 (2006).
109. Parker TA, Roe G, Grover TF, Abman SH Rho kinase activation maintains high pulmonary vascular resistance in the ovine fetal lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 291(5), L976-L982 (2006).
110. McMurtry IF, Bauer NR, Fagan KA, Nagaoka T, Gebb SA, Oka M. Hypoxia an Rho/Rho-kinase signaling. Lung development versus hypoxic pulmonary hypertension. Adv. Exp. Med. Biol 543, 127-137 (2003).
111. Xing XQ Can Y, Wu SJ, Chen P Zhou R, Xiang XD. Rho-kinase as a potential therapeutic target for the treatment of pulmonary hypertension. Drug News Perspect. 19(9), 517-522 (2006).
112. Fukumoto Y, Matoba T, Ito A et al. Acute vasodilator effects of a Rho-kinase inhibitor, fasudil, in patients with severe pulmonary hypertension. Heart 91 (3), 391-392 (2005).
113. Ishikura K, Yamada N, Ito M et al. Beneficial acute effects of rho-kinase inhibitor in patients with pulmonary arterial hypertension. Circ. J. 70(2), 174-178 (2006).
114. Lahm T, Crisostomo PR, Markel TA, Wang M, Lillemoe KD, Meldrum DR. The critical role of vascular endothelial growth factor in pulmonary vascular remodeling after lung injury. Shock 28(1), 4-14 (2007).
115. Voelkel NF, Vandivier RW, Tuder RM. Vascular endothelial growth factor in the lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 290(2), L209-L221 (2006).
116. Le Cras TD, Markham NE, Tuder RM, Voetkel NF, Abman SH. Treatment of newborn rats with a VEGF receptor inhibitor causes pulmonary hypertension and abnormal lung structure. Am. J. Physiol. Lung Cell. Mol. Physiol. 283(3), L555-L562 (2002).
117. Tang JR, Markham NE, Lin YJ et al. Inhaled nitric oxide attenuates pulmonary hypertension and improves lung growth in infant rats after neonatal treatment with a VEGF receptor inhibitor. Am. J. Physiol. Lung Cell. Mol. Physiol. 287(2), L344-L351 (2004).
118. Balasubramaniam V, Tang JR, Maxey A, Plopper CG, Abman SH. Mild hypoxia impairs alveolarization in the endothelial nitric oxide synthase-deficient mouse. Am. J. Physiol. Lung Cell. Mol. Physiol. 284(6), L964-L971 (2003).
119. Nadeau S, Baribeau J, Janvier A, Perreault T. Changes in expression of vascular endothelial growth factor and its receptors in neonatal hypoxia-induced pulmonary hypertension. Pediatr Res. 58(2), 199-205 (2005).
120. Lassus P Turanlahti M, Heikkila P et al. Pulmonary vascular endothelial growth factor and Flt-1 in fetuses, in acute and chronic lung disease, and in persistent pulmonary hypertension of the newborn. Am. J. Respir. Crit. Care Med. 164(10 Pt 1), 1981-1987 (2001).
121. Shehata SM, Mooi WJ, Okazaki T, ElHBanna I, Sharma HS, Tibboel D. Enhanced expression of vascular endothetial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension. Thorax 54(5), 427-431 (1999).
122. Grover TR, Parker TA, Abman SH. Vascular endothefial growth factor improves pulmonary vascular reactivity and structure in an experimental moderof chronic pulmonary hypertension in fetal sheep. Chest 128(6 Suppl.), S614 (2005).
123. Thebaud B, Ladha F, Michelakis ED et al. Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization. Circulation 112(16), 2477-2486 (2005).
124. Papaioannou AI, Kostikas K, Kollia P, Gourgoulianis KI. Clinical implications for vascular endothelial growth factor in the lung: friend or foe? Respir Res. 7, 128 (2006).