The Nitric Oxide/cGMP Signaling Pathway in Pulmonary Hypertension

Clinics in Chest Medicine

Volumn 28, Issue 1, 2007, Pages 143-167

  Klinger, James R ^a,b  

^a RHODE ISLAND HOSPITAL   (United States)

^b BROWN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (DIMETHYLAMINO)ETHYLPUTREANINE NITRIC OXIDE; AMINOPHYLLINE; AMRINONE; ARGININE; BOSENTAN; CALCIUM; CALCIUM CHANNEL BLOCKING AGENT; CYCLIC GMP; DIETHYLENETRIAMINE NITRIC OXIDE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ENDOTHELIUM DERIVED RELAXING FACTOR; ENOXIMONE; ETHYLPUTREANINE NITRIC OXIDE; GLYCERYL TRINITRATE; ILOPROST; INDUCIBLE NITRIC OXIDE SYNTHASE; MILRINONE; NITRATE; NITRIC OXIDE; NITRIC OXIDE DONOR; NITROPRUSSIDE SODIUM; PHOSPHODIESTERASE INHIBITOR; PHOSPHODIESTERASE V INHIBITOR; PLACEBO; PROSTACYCLIN; SILDENAFIL; TADALAFIL; THEOPHYLLINE; UNCLASSIFIED DRUG; VARDENAFIL; ZAPRINAST;

CALCIUM CELL LEVEL; CELL PROLIFERATION; CLINICAL TRIAL; DRUG DOSE INCREASE; ECHOCARDIOGRAPHY; ERECTILE DYSFUNCTION; HEART PRELOAD; HUMAN; HYPOTENSION; LUNG ARTERY PRESSURE; LUNG EDEMA; LUNG HEMODYNAMICS; LUNG VASCULAR RESISTANCE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOGENESIS; PRIORITY JOURNAL; PULMONARY HYPERTENSION; REBOUND PULMONARY HYPERTENSION; REVIEW; SCLERODERMA; SIGNAL TRANSDUCTION; TRANSGENICS; VASODILATATION;

ANIMALS; CELL PROLIFERATION; CYCLIC GMP; ENDOTHELIAL CELLS; HUMANS; HYPERTENSION, PULMONARY; NITRIC OXIDE; PIPERAZINES; PURINES; SIGNAL TRANSDUCTION; SULFONES; VASODILATION; VASODILATOR AGENTS;

EID: 33847410021     PISSN: 02725231     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ccm.2006.12.002     Document Type: Review

References (261)

1. Furchgott R.F., Davidson D., and Lin C.I. Conditions which determine whether muscarinic agonists contract or relax rabbit aortic rings and strips. Blood Vessels 16 4 (1979) 213-214
2. Furchgott R.F., and Zawadzki J.V. Relaxation of rabbit aortic smooth-muscle by acetylcholine. Pharmacologist 21 3 (1979) 271
3. Furchgott R.F. The pharmacology of vascular smooth muscle. Pharmacol Rev 7 2 (1955) 183-265
4. Furchgott R.F., and Zawadzki J.V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288 5789 (1980) 373-376
5. Chand N., and Altura B.M. Influence of primary prostaglandins on isolated canine renal arteries and veins. Prostaglandins Med 7 1 (1981) 49-62
6. Chand N., and Altura B.M. Acetylcholine and bradykinin relax intrapulmonary arteries by acting on endothelial cells: role in lung vascular diseases. Science 213 4514 (1981) 1376-1379
7. Palmer R.M., Ferrige A.G., and Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327 6122 (1987) 524-526
8. Ignarro L.J., Buga G.M., Wood K.S., et al. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A 84 24 (1987) 9265-9269
9. Koshland D.E. The molecule of the year. Science 258 5090 (1992) 1861
10. Marletta M.A. Nitric oxide synthase structure and mechanism. J Biol Chem 268 17 (1993) 12231-12234
11. McQuillan LP, Leung GK, Marsden PA, et al. Hypoxia inhibits expression of eNOS via transcriptional and posttranscriptional mechanisms. Am J Physiol 1994;267(5 Pt 2):H1921-7.
12. Liao J.K., Zulueta J.J., Yu F.S., et al. Regulation of bovine endothelial constitutive nitric oxide synthase by oxygen. J Clin Invest 96 6 (1995) 2661-2666
13. Davis M.E., Cai H., Drummond G.R., et al. Shear stress regulates endothelial nitric oxide synthase expression through c-Src by divergent signaling pathways. Circ Res 89 11 (2001) 1073-1080
14. Francis S.H., Blount M.A., Zoraghi R., et al. Molecular properties of mammalian proteins that interact with cGMP: protein kinases, cation channels, phosphodiesterases, and multi-drug anion transporters. Front Biosci 10 (2005) 2097-2117
15. Andriantsitohaina R., Lagaud G.J., Andre A., et al. Effects of cGMP on calcium handling in ATP-stimulated rat resistance arteries. Am J Physiol 268 3 Pt 2 (1995) H1223-H1231
16. Bkaily G., Peyrow M., Yamamoto T., et al. Macroscopic Ca2+ -Na+ and K+ currents in single heart and aortic cells. Mol Cell Biochem 80 1-2 (1988) 59-72
17. Archer S.L., Huang J.M., Hampl V., et al. Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc Natl Acad Sci U S A 91 16 (1994) 7583-7587
18. Furukawa K., Ohshima N., Tawada-Iwata Y., et al. Cyclic GMP stimulates Na+/Ca2+ exchange in vascular smooth muscle cells in primary culture. J Biol Chem 266 19 (1991) 12337-12341
19. Furukawa K., Tawada Y., and Shigekawa M. Regulation of the plasma membrane Ca2+ pump by cyclic nucleotides in cultured vascular smooth muscle cells. J Biol Chem 263 17 (1988) 8058-8065
20. Komalavilas P., and Lincoln T.M. Phosphorylation of the inositol 1,4,5-trisphosphate receptor by cyclic GMP-dependent protein kinase. J Biol Chem 269 12 (1994) 8701-8707
21. Surks H.K., Mochizuki N., Kasai Y., et al. Regulation of myosin phosphatase by a specific interaction with cGMP-dependent protein kinase I alpha. Science 286 5444 (1999) 1583-1587
22. Sauzeau V., Le Jeune H., Cario-Toumaniantz C., et al. Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular smooth muscle. J Biol Chem 275 28 (2000) 21722-21729
23. Patel H.J., Belvisi M.G., Donnelly L.E., et al. Constitutive expressions of type I NOS in human airway smooth muscle cells: evidence for an antiproliferative role. FASEB J 13 13 (1999) 1810-1816
24. Tanner F.C., Meier P., Greutert H., et al. Nitric oxide modulates expression of cell cycle regulatory proteins: a cytostatic strategy for inhibition of human vascular smooth muscle cell proliferation. Circulation 101 (2000) 1982-1989
25. Garg U.C., and Hassid A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 83 5 (1989) 1774-1777
26. Kolpakov V., Gordon D., and Kulik T.J. Nitric oxide-generating compounds inhibit total protein and collagen synthesis in cultured vascular smooth muscle cells. Circ Res 76 2 (1995) 305-309
27. Ambalavanan N., Mariani G., Bulger A., et al. Role of nitric oxide in regulating neonatal porcine pulmonary artery smooth muscle cell proliferation. Biol Neonate 76 5 (1999) 291-300
28. Jourdan K.B., Evans T.W., Lamb N.J., et al. Autocrine function of inducible nitric oxide synthase and cyclooxygenase-2 in proliferation of human and rat pulmonary artery smooth-muscle cells: species variation. Am J Respir Cell Mol Biol 21 1 (1999) 105-110
29. Krick S., Platoshyn O., Sweeney M., et al. Nitric oxide induces apoptosis by activating K+ channels in pulmonary vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 282 1 (2002) H184-H193
30. Pollman M.J., Yamada T., Horiuchi M., et al. Vasoactive substances regulate vascular smooth muscle cell apoptosis: countervailing influences of nitric oxide and angiotensin II. Circ Res 79 (1996) 748-756
31. Smith J.D., McLean S.D., and Nakayama D.K. Nitric oxide causes apoptosis in pulmonary vascular smooth muscle cells. J Surg Res 79 (1998) 121-127
32. Thomae K.R., Nakayama D.K., Billiar T.R., et al. The effect of nitric oxide on fetal pulmonary artery smooth muscle growth. J Surg Res 59 3 (1995) 337-343
33. Tzeng E., Kim Y.M., Pitt B.R., et al. Adenoviral transfer of the inducible nitric oxide synthase gene blocks endothelial cell apoptosis. Surgery 122 2 (1997) 255-263
34. Zhao Y.D., Courtman D.W., Ng D.S., et al. Microvascular regeneration in established pulmonary hypertension by angiogenic gene transfer. Am J Respir Cell Mol Biol 35 2 (2006) 182-189
35. Babaei S., and Stewart D.J. Overexpression of endothelial NO synthase induces angiogenesis in a co-culture model. Cardiovasc Res 55 1 (2002) 190-200
36. Dubey R.K., Jackson E.K., and Luscher T.F. Nitric oxide inhibits angiotensin II-induced migration of rat aortic smooth muscle cell: role of cyclic-nucleotides and angiotensin 1 receptors. J Clin Invest 96 1 (1995) 141-149
37. Nakaki T., Nakayama M., and Kato R. Inhibition by nitric oxide and nitric oxide-producing vasodilators of DNA synthesis in vascular smooth muscle cells. Eur J Pharmacol 189 6 (1990) 347-353
38. Rosenkrantz J.G., Lynch F.P., and Vogel J.H. Hypoxic pulmonary hypertension: its modification by dipyridamole. J Surg Res 12 5 (1972) 330-333
39. Costa R.S., and Assreuy J. Multiple potassium channels mediate nitric oxide-induced inhibition of rat vascular smooth muscle cell proliferation. Nitric Oxide 13 2 (2005) 145-151
40. Hamad A.M., Johnson S.R., and Knox A.J. Antiproliferative effects of NO and ANP in cultured human airway smooth muscle. Am J Physiol 277 5 Pt 1 (1999) L910-L918
41. Boerth N.J., Dey N.B., Cornwell T.L., et al. Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell phenotype. J Vasc Res 34 4 (1997) 245-259
42. Yu S.M., Hung L.M., and Lin C.C. cGMP-elevating agents suppress proliferation of vascular smooth muscle cells by inhibiting the activation of epidermal growth factor signaling pathway. Circulation 95 5 (1997) 1269-1277
43. Wolfsgruber W., Feil S., Brummer S., et al. A proatherogenic role for cGMP-dependent protein kinase in vascular smooth muscle cells. Proc Natl Acad Sci U S A 100 23 (2003) 13519-13524
44. Fukuo K., Inoue T., Morimoto S., et al. Nitric oxide mediates cytotoxicity and basic fibroblast growth factor release in cultured vascular smooth muscle cells: a possible mechanism of neovascularization in atherosclerotic plaques. J Clin Invest 95 2 (1995) 669-676
45. Chiche J.D., Schlutsmeyer S.M., Bloch D.B., et al. Adenovirus-mediated gene transfer of cGMP-dependent protein kinase increases the sensitivity of cultured vascular smooth muscle cells to the antiproliferative and pro-apoptotic effects of nitric oxide/cGMP. J Biol Chem 273 51 (1998) 34263-34271
46. Klinger J.R., and Murray J.D. Atrial natriuretic peptide inhibits murine pulmonary vascular smooth muscle cell proliferation via natriuretic peptide receptor-A. Proc Am Thor Soc 3 (2006) A857
47. Kibbe M.R., Li J., Nie S., et al. Inducible nitric oxide synthase (iNOS) expression upregulates p21 and inhibits vascular smooth muscle cell proliferation through p42/44 mitogen-activated protein kinase activation and independent of p53 and cyclic guanosine monophosphate. J Vasc Surg 31 6 (2000) 1214-1228
48. Sandirasegarane L., Charles R., Bourbon N., et al. NO regulates PDGF-induced activation of PKB but not ERK in A7r5 cells: implications for vascular growth arrest. Am J Physiol Cell Physiol 279 1 (2000) C225-C235
49. Heller R., Polack T., Grabner R., et al. Nitric oxide inhibits proliferation of human endothelial cells via a mechanism independent of cGMP. Atherosclerosis 144 1 (1999) 49-57
50. Sarkar R., Meinberg E.G., Stanley J.C., et al. Nitric oxide reversibly inhibits the migration of cultured vascular smooth muscle cells. Circ Res 78 2 (1996) 225-230
51. Bauer P.M., Buga G.M., and Ignarro L.J. Role of p42/p44 mitogen-activated-protein kinase and p21waf1/cip1 in the regulation of vascular smooth muscle cell proliferation by nitric oxide. Proc Natl Acad Sci U S A 98 22 (2001) 12802-12807
52. Ignarro L.J., Buga G.M., Wei L.H., et al. Role of the arginine-nitric oxide pathway in the regulation of vascular smooth muscle cell proliferation. Proc Natl Acad Sci U S A 98 7 (2001) 4202-4208
53. Zuckerbraun B.S., Stoyanovsky D.A., Sengupta R., et al. Nitric oxide-induced inhibition of smooth muscle cell proliferation involves S-nitrosation and inactivation of RhoA. Am J Physiol Cell Physiol (2006) [Epub ahead of print]
54. Cornwell T.L., Arnold E., Boerth N.J., et al. Inhibition of smooth muscle cell growth by nitric oxide and activation of cAMP-dependent protein kinase by cGMP. Am J Physiol 267 5 Pt 1 (1994) C1405-C1413
55. D'Souza F.M., Sparks R.L., Chen H., et al. Mechanism of eNOS gene transfer inhibition of vascular smooth muscle cell proliferation. Am J Physiol Cell Physiol 284 1 (2003) C191-C199
56. Du M., Islam M., Lin L., et al. Promotion of proliferation of murine BALB/CT3 fibroblasts mediated by nitric oxide at lower concentrations. Biochem Mol Biol Int 41 (1997) 625-631
57. Ziche M., Parenti A., Ledda F., et al. Nitric oxide promotes proliferation and plasminogen activator production by coronary venular endothelium through endogenous bFGF. Circ Res 80 (1997) 845-852
58. Hassid A., Arabshahi H., Bourcier T., et al. Nitric oxide selectively amplifies FGF-2-induced mitogenesis in primary rat aortic smooth muscle cells. Am J Physiol Heart Circ Physiol 267 (1994) H1040-H1048
59. Kawai N., Bloch D.B., Filippov G., et al. Constitutive endothelial nitric oxide synthase gene expression is regulated during lung development. Am J Physiol 268 4 Pt 1 (1995) L589-L595
60. North A.J., Star R.A., Brannon T.S., et al. Nitric oxide synthase type I and type III gene expression are developmentally regulated in rat lung. Am J Physiol 266 6 Pt 1 (1994) L635-L641
61. Parker T.A., le Cras T.D., Kinsella J.P., et al. Developmental changes in endothelial nitric oxide synthase expression and activity in ovine fetal lung. Am J Physiol Lung Cell Mol Physiol 278 1 (2000) L202-L208
62. Arrigoni F.I., Hislop A.A., Pollock J.S., et al. Birth upregulates nitric oxide synthase activity in the porcine lung. Life Sci 70 14 (2002) 1609-1620
63. Shaul P.W., Afshar S., Gibson L.L., et al. Developmental changes in nitric oxide synthase isoform expression and nitric oxide production in fetal baboon lung. Am J Physiol Lung Cell Mol Physiol 283 6 (2002) L1192-L1199
64. Shaul P.W., Yuhanna I.S., German Z., et al. Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension. Am J Physiol 272 5 Pt 1 (1997) L1005-L1012
65. North A.J., Moya F.R., Mysore M.R., et al. Pulmonary endothelial nitric oxide synthase gene expression is decreased in a rat model of congenital diaphragmatic hernia. Am J Respir Cell Mol Biol 13 6 (1995) 676-682
66. Davidson D., and Eldemerdash A. Endothelium-derived relaxing factor: evidence that it regulates pulmonary vascular resistance in the isolated neonatal guinea pig lung. Pediatr Res 29 6 (1991) 538-542
67. Fineman J.R., Heymann M.A., and Soifer S.J. N omega-nitro-L-arginine attenuates endothelium-dependent pulmonary vasodilation in lambs. Am J Physiol 260 4 Pt 2 (1991) H1299-H1306
68. Nelin L.D., and Dawson C.A. The effect of N omega-nitro-L-arginine methylester on hypoxic vasoconstriction in the neonatal pig lung. Pediatr Res 34 3 (1993) 349-353
69. Fineman J.R., Wong J., Morin III F.C., et al. Chronic nitric oxide inhibition in utero produces persistent pulmonary hypertension in newborn lambs. J Clin Invest 93 6 (1994) 2675-2683
70. Vosatka R.J., Kashyap S., and Trifiletti R.R. Arginine deficiency accompanies persistent pulmonary hypertension of the newborn. Biol Neonate 66 2-3 (1994) 65-70
71. Davidson D., Barefield E.S., Kattwinkel J., et al. Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: a randomized, double-masked, placebo-controlled, dose-response, multicenter study. The I-NO/PPHN Study Group. Pediatrics 101 3 Pt 1 (1998) 325-334
72. Roberts Jr. J.D., Fineman J.R., Morin III F.C., et al. Inhaled nitric oxide and persistent pulmonary hypertension of the newborn: the Inhaled Nitric Oxide Study Group. N Engl J Med 336 9 (1997) 605-610
73. Kobzik L., Bredt D.S., Lowenstein C.J., et al. Nitric oxide synthase in human and rat lung: immunocytochemical and histochemical localization. Am J Respir Cell Mol Biol 9 4 (1993) 371-377
74. Xue C., and Johns R.A. Endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 333 24 (1995) 1642-1644
75. Xue C., Rengasamy A., Le Cras T.D., et al. Distribution of NOS in normoxic vs. hypoxic rat lung: upregulation of NOS by chronic hypoxia. Am J Physiol 267 6 Pt 1 (1994) L667-L678
76. Giaid A., and Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 333 4 (1995) 214-221
77. Koizumi T., Gupta R., Banerjee M., et al. Changes in pulmonary vascular tone during exercise: effects of nitric oxide (NO) synthase inhibition, L-arginine infusion, and NO inhalation. J Clin Invest 94 6 (1994) 2275-2282
78. Jiang B.H., Maruyama J., Yokochi A., et al. Correlation of inhaled nitric-oxide induced reduction of pulmonary artery pressure and vascular changes. Eur Respir J 20 1 (2002) 52-58
79. Pison U., Lopez F.A., Heidelmeyer C.F., et al. Inhaled nitric oxide reverses hypoxic pulmonary vasoconstriction without impairing gas exchange. J Appl Physiol 74 3 (1993) 1287-1292
80. Hampl V., and Herget J. Role of nitric oxide in the pathogenesis of chronic pulmonary hypertension. Physiol Rev 80 4 (2000) 1337-1372
81. Hampl V., Weir E.K., and Archer S.L. Endothelilun-derived nitric oxide is less important for basal tone regulation in the pulmonary than the renal vessels of adult rat. Journal of Vascular Medicine and Biology 5 (1994) 22-30
82. Stamler J.S., Loh E., Roddy M.A., et al. Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans. Circulation 89 (1994) 2035-2040
83. Rich G.F., Roos C.M., Anderson S.M., et al. Inhaled nitric oxide: dose response and the effects of blood in the isolated rat lung. J Appl Physiol 75 3 (1993) 1278-1284
84. Frostell C.G., Blomqvist H., Hedenstierna G., et al. Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. Anesthesiology 78 3 (1993) 427-435
85. Fratacci M.D., Frostell C.G., Chen T.Y., et al. Inhaled nitric oxide: a selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep. Anesthesiology 75 6 (1991) 990-999
86. Weitzberg E., Rudehill A., and Lundberg J.M. Nitric oxide inhalation attenuates pulmonary hypertension and improves gas exchange in endotoxin shock. Eur J Pharmacol 233 1 (1993) 85-94
87. Bottiger B.W., Motsch J., Dorsam J., et al. Inhaled nitric oxide selectively decreases pulmonary artery pressure and pulmonary vascular resistance following acute massive pulmonary microembolism in piglets. Chest 110 4 (1996) 1041-1047
88. Rossaint R., Falke K.J., Lopez F., et al. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med 328 6 (1993) 399-405
89. Wanstall J.C., Hughes I.E., and O'Donnell S.R. Evidence that nitric oxide from the endothelium attenuates inherent tone in isolated pulmonary arteries from rats with hypoxic pulmonary hypertension. Br J Pharmacol 114 1 (1995) 109-114
90. Muramatsu M., Tyler R.C., Rodman D.M., et al. Thapsigargin stimulates increased NO activity in hypoxic hypertensive rat lungs and pulmonary arteries. J Appl Physiol 80 4 (1996) 1336-1344
91. Le Cras T.D., Xue C., Rengasamy A., et al. Chronic hypoxia upregulates endothelial and inducible NO synthase gene and protein expression in rat lung. Am J Physiol 270 1 Pt 1 (1996) L164-L170
92. Isaacson T.C., Hampl V., Weir E.K., et al. Increased endothelium-derived NO in hypertensive pulmonary circulation of chronically hypoxic rats. J Appl Physiol 76 2 (1994) 933-940
93. Xu W., Kaneko F.T., Zheng S., et al. Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension. FASEB J 18 14 (2004) 1746-1748
94. Archer S.L., Djaballah K., Humbert M., et al. Nitric oxide deficiency in fenfluramine- and dexfenfluramine-induced pulmonary hypertension. Am J Respir Crit Care Med 158 4 (1998) 1061-1067
95. Kharitonov S.A., Cailes J.B., Black C.M., et al. Decreased nitric oxide in the exhaled air of patients with systemic sclerosis with pulmonary hypertension. Thorax 52 12 (1997) 1051-1055
96. Mason N.A., Springall D.R., Burke M., et al. High expression of endothelial nitric oxide synthase in plexiform lesions of pulmonary hypertension. J Pathol 185 (1998) 313-318
97. Berger R.M., Geiger R., Hess J., et al. Altered arterial expression patterns of inducible and endothelial nitric oxide synthase in pulmonary plexogenic arteriopathy caused by congenital heart disease. Am J Respir Crit Care Med 163 6 (2001) 1493-1499
98. Kradin R., Matsubara O., and Mark E.J. Endothelial nitric oxide synthase expression in pulmonary capillary hemangiomatosis. Exp Mol Pathol 79 3 (2005) 194-197
99. Dweik R.A., Laskowski D., Ozkan M., et al. High levels of exhaled nitric oxide (NO) and NO synthase III expression in lesional smooth muscle in lymphangio-leiomyomatosis. Am J Respir Cell Mol Biol 24 4 (2001) 414-418
100. Steudel W., Ichinose F., Huang P.L., et al. Pulmonary vasoconstriction and hypertension in mice with targeted disruption of the endothelial nitric oxide synthase (NOS 3) gene. Circ Res 81 (1997) 34-41
101. Steudel W., Scherrer-Crosbie M., Bloch K.D., et al. Sustained pulmonary hypertension and right ventricular hypertrophy after chronic hypoxia in mice with congenital deficiency of nitric oxide synthase 3. J Clin Invest 101 11 (1998) 2468-2477
102. Fagan K.A., Fouty B.W., Tyler R.C., et al. The pulmonary circulation of homozygous or heterozygous eNOS-null mice is hyperresponsive to mild hypoxia. J Clin Invest 103 2 (1999) 291-299
103. Fagan K.A., Tyler R.C., Sato K., et al. Relative contributions of endothelial, inducible, and neuronal NOS to tone in the murine pulmonary circulation. Am J Physiol 277 3 Pt 1 (1999) L472-L478
104. Quinlan T.R., Li D., Laubach V.E., et al. eNOS-deficient mice show reduced pulmonary vascular proliferation and remodeling to chronic hypoxia. Am J Physiol Lung Cell Mol Physiol 279 4 (2000) L641-L650
105. Budts W., Pokreisz P., Nong Z., et al. Aerosol gene transfer with inducible nitric oxide synthase reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats. Circulation 102 23 (2000) 2880-2885
106. Campbell A.I., Kuliszewski M.A., and Stewart D.J. Cell-based gene transfer to the pulmonary vasculature: endothelial nitric oxide synthase overexpression inhibits monocrotaline-induced pulmonary hypertension. Am J Respir Cell Mol Biol 21 5 (1999) 567-575
107. 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 114 1 Suppl (2006) I181-I185
108. Kouyoumdjian C., Adnot S., Levame M., et al. Continuous inhalation of nitric oxide protects against development of pulmonary hypertension in chronically hypoxic rats. J Clin Invest 94 2 (1994) 578-584
109. Tod M.L., O'Donnel D.C., and Gordon J.B. Sites of inhaled NO-induced vasodilation during hypoxia and U-46619 infusion in isolated lamb lungs. Am J Physiol 268 4 Pt 2 (1995) H1422-H1427
110. Rimar S., and Gillis C.N. Selective pulmonary vasodilation by inhaled nitric oxide is due to hemoglobin inactivation. Circulation 88 6 (1993) 2884-2887
111. Dyar O., Young J.D., Xiong L., et al. Dose-response relationship for inhaled nitric oxide in experimental pulmonary hypertension in sheep. Br J Anaesth 71 5 (1993) 702-708
112. Gerlach H., Rossaint R., Pappert D., et al. Time-course and dose-response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in patients with adult respiratory distress syndrome. Eur J Clin Invest 23 8 (1993) 499-502
113. Puybasset L., Rouby J.J., Mourgeon E., et al. Inhaled nitric oxide in acute respiratory failure: dose-response curves. Intensive Care Med 20 5 (1994) 319-327
114. Sitbon O., Brenot F., Denjean A., et al. Inhaled nitric oxide as a screening vasodilator agent in primary pulmonary hypertension: a dose-response study and comparison with prostacyclin. Am J Respir Crit Care Med 151 2 Pt 1 (1995) 384-389
115. Jolliet P., Bulpa P., Thorens J.B., et al. Nitric oxide and prostacyclin as test agents of vasoreactivity in severe precapillary pulmonary hypertension: predictive ability and consequences on haemodynamics and gas exchange. Thorax 52 4 (1997) 369-372
116. Ricciardi M.J., Knight B.P., Martinez F.J., et al. Inhaled nitric oxide in primary pulmonary hypertension: a safe and effective agent for predicting response to nifedipine. J Am Coll Cardiol 32 4 (1998) 1068-1073
117. Sitbon O., Humbert M., Jagot J.L., et al. Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension. Eur Respir J 12 2 (1998) 265-270
118. Pepke-Zaba J., Higenbottam T.W., Dinh-Xuan A.T., et al. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet 338 8776 (1991) 1173-1174
119. Girard C., Lehot J.J., Pannetier J.C., et al. Inhaled nitric oxide after mitral valve replacement in patients with chronic pulmonary artery hypertension. Anesthesiology 77 5 (1992) 880-883
120. Foubert L., Latimer R., Oduro A., et al. Use of inhaled nitric oxide to reduce pulmonary hypertension after heart transplantation. J Cardiothorac Vasc Anesth 7 4 (1993) 506-507
121. Adnot S., Kouyoumdjian C., Defouilloy C., et al. Hemodynamic and gas exchange responses to infusion of acetylcholine and inhalation of nitric oxide in patients with chronic obstructive lung disease and pulmonary hypertension. Am Rev Respir Dis 148 2 (1993) 310-316
122. Moinard J., Manier G., Pillet O., et al. Effect of inhaled nitric oxide on hemodynamics and VA/Q inequalities in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 149 6 (1994) 1482-1487
123. Kinsella J.P., Neish S.R., Ivy D.D., et al. Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn with low doses of inhaled nitric oxide. J Pediatr 123 1 (1993) 103-108
124. Abman S.H., Kinsella J.P., Schaffer M.S., et al. Inhaled nitric oxide in the management of a premature newborn with severe respiratory distress and pulmonary hypertension. Pediatrics 92 4 (1993) 606-609
125. Allman K.G., Young J.D., Stevens J.E., et al. Nitric oxide treatment for fulminant pulmonary hypertension. Arch Dis Child 69 4 (1993) 449-450
126. Kinsella J.P., Toews W.H., Henry D., et al. Selective and sustained pulmonary vasodilation with inhalational nitric oxide therapy in a child with idiopathic pulmonary hypertension. J Pediatr 122 5 Pt 1 (1993) 803-806
127. Winberg P., Lundell B.P., and Gustafsson L.E. Effect of inhaled nitric oxide on raised pulmonary vascular resistance in children with congenital heart disease. Br Heart J 71 3 (1994) 282-286
128. Jolliet P., Thorens J.B., and Chevrolet J.C. Pulmonary vascular reactivity in severe pulmonary hypertension associated with mixed connective tissue disease. Thorax 50 1 (1995) 96-97
129. Williamson D.J., Hayward C., Rogers P., et al. Acute hemodynamic responses to inhaled nitric oxide in patients with limited scleroderma and isolated pulmonary hypertension. Circulation 94 3 (1996) 477-482
130. Channick R.N., Hoch R.C., Newhart J.W., et al. Improvement in pulmonary hypertension and hypoxemia during nitric oxide inhalation in a patient with end-stage pulmonary fibrosis. Am J Respir Crit Care Med 149 3 Pt 1 (1994) 811-814
131. Yoshida M., Taguchi O., Gabazza E.C., et al. The effect of low-dose inhalation of nitric oxide in patients with pulmonary fibrosis. Eur Respir J 10 9 (1997) 2051-2054
132. Preston I.R., Klinger J.R., Landzberg M.J., et al. Vasoresponsiveness of sarcoidosis-associated pulmonary hypertension. Chest 120 3 (2001) 866-872
133. Scherrer U., Vollenweider L., Delabays A., et al. Inhaled nitric oxide for high-altitude pulmonary edema. N Engl J Med 334 10 (1996) 624-629
134. Anand I.S., Prasad B.A., Chugh S.S., et al. Effects of inhaled nitric oxide and oxygen in high-altitude pulmonary edema. Circulation 98 22 (1998) 2441-2445
135. Preston I.R., Klinger J.R., Houtches J., et al. Acute and chronic effects of sildenafil in patients with pulmonary arterial hypertension. Respir Med 99 12 (2005) 1501-1510
136. Miller O.I., Celermajer D.S., Deanfield J.E., et al. Guidelines for the safe administration of inhaled nitric oxide. Arch Dis Child Fetal Neonatal Ed 70 1 (1994) F47-F49
137. Zapol W.M. Inhaled nitric oxide. Acta Anaesthesiol Scand Suppl 109 (1996) 81-83
138. Young J.D., and Dyar O.J. Delivery and monitoring of inhaled nitric oxide. Intensive Care Med 22 1 (1996) 77-86
139. Young J.D., Sear J.W., and Valvini E.M. Kinetics of methaemoglobin and serum nitrogen oxide production during inhalation of nitric oxide in volunteers. Br J Anaesth 76 5 (1996) 652-656
140. Occupational Safety and Health Administration. Regulations (Standards - 29 CFR), occupational safety and health standards. Subpart Z: toxic and hazardous substances, limits for air contaminants. 1910.1000 Table Z-1.
141. Klein W. Hemodynamic effects of aminophylline in primary pulmonary hypertension. Wien Klin Wochenschr 81 37 (1969) 651-653
142. Roberts Jr. J.D., Roberts C.T., Jones R.C., et al. Continuous nitric oxide inhalation reduces pulmonary arterial structural changes, right ventricular hypertrophy, and growth retardation in the hypoxic newborn rat. Circ Res 76 2 (1995) 215-222
143. Horstman D.J., Frank D.U., and Rich G.F. Prolonged inhaled NO attenuates hypoxic, but not monocrotaline-induced, pulmonary vascular remodeling in rats. Anesth Analg 86 1 (1998) 74-81
144. Parsons S., Celermajer D., Savidis E., et al. The effect of inhaled nitric oxide on 6-minute walk distance in patients with pulmonary hypertension. Chest 114 1 (1998) 70S-72S
145. Channick R.N., Newhart J.W., Johnson F.W., et al. Pulsed delivery of inhaled nitric oxide to patients with primary pulmonary hypertension: an ambulatory delivery system and initial clinical tests. Chest 109 6 (1996) 1545-1549
146. Roger N., Barbera J.A., Roca J., et al. Nitric oxide inhalation during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 156 3 Pt 1 (1997) 800-806
147. Miller O.I., Tang S.F., Keech A., et al. Rebound pulmonary hypertension on withdrawal from inhaled nitric oxide. Lancet 346 8966 (1995) 51-52
148. Lavoie A., Hall J.B., Olson D.M., et al. Life-threatening effects of discontinuing inhaled nitric oxide in severe respiratory failure. Am J Respir Crit Care Med 153 6 Pt 1 (1996) 1985-1987
149. Cueto E., Lopez-Herce J., Sanchez A., et al. Life-threatening effects of discontinuing inhaled nitric oxide in children. Acta Paediatr 86 12 (1997) 1337-1339
150. Scott W.S., and Nakayama D.K. Sustained nitric oxide exposure decreases soluble guanylate cyclase mRNA and enzyme activity in pulmonary artery smooth muscle. J Surg Res 79 1 (1998) 66-70
151. Sheehy A.M., Burson M.A., and Black S.M. Nitric oxide exposure inhibits endothelial NOS activity but not gene expression: a role for superoxide. Am J Physiol 274 5 Pt 1 (1998) L833-L841
152. Frank D.U., Horstman D.J., Morris G.N., et al. Regulation of the endogenous NO pathway by prolonged inhaled NO in rats. J Appl Physiol 85 3 (1998) 1070-1078
153. Loh E., Stamler J.S., Hare J.M., et al. Cardiovascular effects of inhaled nitric oxide in patients with left ventricular dysfunction. Circulation 90 6 (1994) 2780-2785
154. Preston I.R., Klinger J.R., Houtchens J., et al. Pulmonary edema caused by inhaled nitric oxide therapy in two patients with pulmonary hypertension associated with the CREST syndrome. Chest 121 2 (2002) 656-659
155. Pusch R., Habler O., Kleen M., et al. Inhaled sodium nitroprusside: non-selective reduction of thromboxane analogue-induced pulmonary vasoconstriction in healthy sheep. Eur J Med Res 1 3 (1995) 149-152
156. Vanderford P.A., Wong J., Chang R., et al. Diethylamine/nitric oxide (NO) adduct, an NO donor, produces potent pulmonary and systemic vasodilation in intact newborn lambs. J Cardiovasc Pharmacol 23 1 (1994) 113-119
157. Hampl V., Tristani-Firouzi M., Hutsell T.C., et al. Nebulized nitric oxide/nucleophile adduct reduces chronic pulmonary hypertension. Cardiovasc Res 31 1 (1996) 55-62
158. Brilli R.J., Krafte-Jacobs B., Smith D.J., et al. Aerosolization of novel nitric oxide donors selectively reduce pulmonary hypertension. Crit Care Med 26 8 (1998) 1390-1396
159. Brilli R.J., Krafte-Jacobs B., Smith D.J., et al. Intratracheal instillation of a novel NO/nucleophile adduct selectively reduces pulmonary hypertension. J Appl Physiol 83 6 (1997) 1968-1975
160. Lam C.F., van Heerden P.V., Sviri S., et al. The effects of inhalation of a novel nitric oxide donor, DETA/NO, in a patient with severe hypoxaemia due to acute respiratory distress syndrome. Anaesth Intensive Care 30 4 (2002) 472-476
161. McCaffrey M.J., Bose C.L., Reiter P.D., et al. Effect of L-arginine infusion on infants with persistent pulmonary hypertension of the newborn. Biol Neonate 67 4 (1995) 240-243
162. Block E.R., Herrera H., and Couch M. Hypoxia inhibits L-arginine uptake by pulmonary artery endothelial cells. Am J Physiol 269 (1995) L574-L580
163. Fike C.D., Kaplowitz M.R., Rehorst-Paea L.A., et al. L-arginine increases nitric oxide production in isolated lungs of chronically hypoxic newborn pigs. J Appl Physiol 88 5 (2000) 1797-1803
164. Morris C.R., Morris Jr. S.M., Hagar W., et al. Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease?. Am J Respir Crit Care Med 168 1 (2003) 63-69
165. Morris C.R., Kato G.J., Poljakovic M., et al. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA 294 1 (2005) 81-90
166. McNamara D.B., Bedi B., Aurora H., et al. L-arginine inhibits balloon catheter-induced intimal hyperplasia. Biochem Biophys Res Commun 193 1 (1993) 291-296
167. Taguchi J., Abe J., Okazaki H., et al. L-arginine inhibits neointimal formation following balloon injury. Life Sci 53 23 (1993) PL387-PL392
168. Holm A.M., Andersen C.B., Haunso S., et al. Effects of L-arginine on vascular smooth muscle cell proliferation and apoptosis after balloon injury. Scand Cardiovasc J 34 1 (2000) 28-32
169. Somoza B., Gonzalez C., Cachofeiro V., et al. Chronic l-arginine treatment reduces vascular smooth muscle cell hypertrophy through cell cycle modifications in spontaneously hypertensive rats. J Hypertens 22 4 (2004) 751-758
170. Tan X., Pan J.Q., Li J.C., et al. L-arginine inhibiting pulmonary vascular remodelling is associated with promotion of apoptosis in pulmonary arterioles smooth muscle cells in broilers. Res Vet Sci 79 3 (2005) 203-209
171. Fineman J.R., Chang R., and Soifer S.J. L-arginine, a precursor of EDRF in vitro, produces pulmonary vasodilation in lambs. Am J Physiol 261 5 Pt 2 (1991) H1563-H1569
172. Eddahibi S., Adnot S., Carville C., et al. L-arginine restores endothelium-dependent relaxation in pulmonary circulation of chronically hypoxic rats. Am J Physiol 263 2 Pt 1 (1992) L194-L200
173. Madden J.A., Keller P.A., Choy J.S., et al. L-arginine-related responses to pressure and vasoactive agents in monocrotaline-treated rat pulmonary arteries. J Appl Physiol 79 2 (1995) 589-593
174. Mitani Y., Maruyama K., and Sakurai M. Prolonged administration of L-arginine ameliorates chronic pulmonary hypertension and pulmonary vascular remodeling in rats. Circulation 96 2 (1997) 689-697
175. Bing W., Junbao D., Jianguang Q., et al. L-arginine impacts pulmonary vascular structure in rats with an aortocaval shunt. J Surg Res 108 1 (2002) 20-31
176. Souza-Costa D.C., Zerbini T., Palei A.C., et al. L-arginine attenuates acute pulmonary embolism-induced increases in lung matrix metalloproteinase-2 and matrix metalloproteinase-9. Chest 128 5 (2005) 3705-3710
177. Baudouin S.V., Bath P., Martin J.F., et al. L-arginine infusion has no effect on systemic haemodynamics in normal volunteers, or systemic and pulmonary haemodynamics in patients with elevated pulmonary vascular resistance. Br J Clin Pharmacol 36 1 (1993) 45-49
178. Surdacki A., Zmudka K., Bieron K., et al. Lack of beneficial effects of L-arginine infusion in primary pulmonary hypertension. Wien Klin Wochenschr 106 16 (1994) 521-526
179. Boger R.H., Mugge A., Bode-Boger S.M., et al. Differential systemic and pulmonary hemodynamic effects of L-arginine in patients with coronary artery disease or primary pulmonary hypertension. Int J Clin Pharmacol Ther 34 8 (1996) 323-328
180. Mehta S., Stewart D.J., Langleben D., et al. Short-term pulmonary vasodilation with L-arginine in pulmonary hypertension. Circulation 92 6 (1995) 1539-1545
181. Nagaya N., Uematsu M., Oya H., et al. Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension. Am J Respir Crit Care Med 163 4 (2001) 887-891
182. Lacassie H.J., Germain A.M., Valdes G., et al. Management of Eisenmenger syndrome in pregnancy with sildenafil and L-arginine. Obstet Gynecol 103 5 Pt 2 (2004) 1118-1120
183. Pritchard Jr. K.A., Shi Y., and Konduri G.G. Tetrahydrobiopterin in pulmonary hypertension: pulmonary hypertension in guanosine triphosphate-cyclohydrolase-deficient mice. Circulation 111 16 (2005) 2022-2024
184. Alp N.J., and Channon K.M. Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease. Arterioscler Thromb Vasc Biol 24 (2004) 413-420
185. Davydova M.P., Postnikov A.B., D'iakonov K.B., et al. Involvement of tetrahydrobiopterin in local change of endothelium-dependent vasorelaxation in pulmonary hypertension. Ross Fiziol Zh Im I M Sechenova 89 12 (2003) 1516-1522
186. Nandi M., Miller A., Stidwill R., et al. Pulmonary hypertension in a GTP-cyclohydrolase 1-deficient mouse. Circulation 111 16 (2005) 2086-2090
187. Khoo J.P., Zhao L., Alp N.J., et al. Pivotal role for endothelial tetrahydrobiopterin in pulmonary hypertension. Circulation 111 16 (2005) 2126-2133
188. Matsumoto T., Kobayashi T., and Kamata K. Phosphodiesterases in the vascular system. J Smooth Muscle Res 39 4 (2003) 67-86
189. Carson C.C. PDE5 inhibitors: are there differences?. Can J Urol 13 Suppl 1 (2006) 34-39
190. Maclean M.R., Johnston E.D., Mcculloch K.M., et al. Phosphodiesterase isoforms in the pulmonary arterial circulation of the rat: changes in pulmonary hypertension. J Pharmacol Exp Ther 283 2 (1997) 619-624
191. Hanson K.A., Ziegler J.W., Rybalkin S.D., et al. Chronic pulmonary hypertension increases fetal lung cGMP phosphodiesterase activity. Am J Physiol 275 5 Pt 1 (1998) L931-L941
192. Jernigan N.L., and Resta T.C. Chronic hypoxia attenuates cGMP-dependent pulmonary vasodilation. Am J Physiol Lung Cell Mol Physiol 282 (2002) L1366-L1375
193. Murray F., Patel H.H., Suda R.Y., et al. Expression and activity of cAMP phosphodiesterase isoforms in pulmonary artery smooth muscle cells from patients with pulmonary hypertension: role for PDE1. Am J Physiol Lung Cell Mol Physiol (2006) [Sept 15, Epub ahead of print]
194. Corbin J.D., Beasley A., Blount M.A., et al. High lung PDE5: a strong basis for treating pulmonary hypertension with PDE5 inhibitors. Biochem Biophys Res Commun 334 3 (2005) 930-938
195. Murray F., MacLean M.R., and Pyne N.J. 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 (2002) 1187-1194
196. Black S.M., Sanchez L.S., Mata-Greenwood E., et al. sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 281 5 (2001) L1051-L1057
197. Ingerman-Wojenski C.M., and Silver M.J. Model system to study interaction of platelets with damaged arterial wall. II: inhibition of smooth muscle cell proliferation by dipyridamole and AH-P719. Exp Mol Pathol 48 1 (1988) 116-134
198. Souness J.E., Hassall G.A., and Parrott D.P. Inhibition of pig aortic smooth muscle cell DNA synthesis by selective type III and type IV cyclic AMP phosphodiesterase inhibitors. Biochem Pharmacol 44 5 (1992) 857-866
199. Cohen A.H., Hanson K., Morris K., et al. Inhibition of cyclic 3′-5′-guanosine monophosphate-specific phosphodiesterase selectively vasodilates the pulmonary circulation in chronically hypoxic rats. J Clin Invest 97 (1996) 172-179
200. Tantini B., Manes A., Fiumana E., et al. Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells. Basic Res Cardiol 100 2 (2005) 131-138
201. Wharton J., Strange J.W., Moller G.M., et al. Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am J Respir Crit Care Med 172 1 (2005) 105-113
202. Zhao L., Mason N.A., Strange J.W., et al. Beneficial effects of phosphodiesterase 5 inhibition in pulmonary hypertension are influenced by natriuretic peptide activity. Circulation 107 2 (2003) 234-237
203. Zhao L., Mason N.A., Morrell N.W., et al. Sildenafil inhibits hypoxia-induced pulmonary hypertension. Circulation 104 4 (2001) 424-428
204. Cordes L., Danneel K.T., Hauch H.J., et al. Influence of chemotherapy on pulmonary hypertension with special regard to beta-hydroxypropyl theophylline. Z Kreislaufforsch 47 3-4 (1958) 118-132 [in German]
205. Klein W. Primary pulmonary hypertension: aminophylline. Wien Z Inn Med 50 10 (1969) 499-501
206. Bisgard G.E., and Will J.A. Glucagon and aminophylline as pulmonary vasodilators in the calf with hypoxic pulmonary hypertension. Chest 71 2 Suppl (1977) 263-265 [in German]
207. Panuccio P., Viroli L., Chelucci G., et al. Effects of theophylline-ethylendiamine on chronic pulmonary arterial hypertension secondary to chronic obstructive pulmonary disease. G Ital Cardiol 14 Suppl 1 (1984) 74-76
208. Hill N.S., and Rounds S. Amrinone dilates pulmonary vessels and blunts hypoxic vasoconstriction in isolated rat lungs. Proc Soc Exp Biol Med 173 2 (1983) 205-212
209. Tanaka H., Tajimi K., Moritsune O., et al. Effects of milrinone on pulmonary vasculature in normal dogs and in dogs with pulmonary hypertension. Crit Care Med 19 1 (1991) 68-74
210. Tanaka H., Tajimi K., Matsumoto A., et al. Vasodilatory effects of milrinone on pulmonary vasculature in dogs with pulmonary hypertension due to pulmonary embolism: a comparison with those of dopamine and dobutamine. Clin Exp Pharmacol Physiol 17 10 (1990) 681-690
211. Butt A.Y., Dinh-Xuan A.T., Pepke-Zaba J., et al. In vitro pulmonary vasorelaxant effect of the phosphodiesterase inhibitor enoximone. Angiology 44 4 (1993) 289-294
212. Chen E.P., Bittner H.B., Davis Jr. R.D., et al. Milrinone improves pulmonary hemodynamics and right ventricular function in chronic pulmonary hypertension. Ann Thorac Surg 63 3 (1997) 814-821
213. Burch G.H., Jensen L.R., Pappas J., et al. Growth factor expression and effects of amrinone in monocrotaline-induced pulmonary hypertension in rats. Biochem Mol Med 58 2 (1996) 204-210
214. Rich S., Ganz R., and Levy P.S. Comparative actions of hydralazine, nifedipine and amrinone in primary pulmonary hypertension. Am J Cardiol 52 8 (1983) 1104-1107
215. Hess W., Arnold B., and Veit S. The haemodynamic effects of amrinone in patients with mitral stenosis and pulmonary hypertension. Eur Heart J 7 9 (1986) 800-807
216. Hachenberg T., Mollhoff T., Holst D., et al. Cardiopulmonary effects of enoximone or dobutamine and nitroglycerin on mitral valve regurgitation and pulmonary venous hypertension. J Cardiothorac Vasc Anesth 11 4 (1997) 453-457
217. Tarr T.J., Jeffrey R.R., Kent A.P., et al. Use of enoximone in weaning from cardiopulmonary bypass following mitral valve surgery. Cardiology 77 Suppl 3 (1990) 51-57 [discussion: 62-7]
218. Leeman M., Lejeune P., Melot C., et al. Reduction in pulmonary hypertension and in airway resistances by enoximone (MDL 17,043) in decompensated COPD. Chest 91 5 (1987) 662-666
219. Doolan L.A., Jones E.F., Kalman J., et al. A placebo-controlled trial verifying the efficacy of milrinone in weaning high-risk patients from cardiopulmonary bypass. J Cardiothorac Vasc Anesth 11 1 (1997) 37-41
220. Hermiller J.B., Bambach D., Thompson M.J., et al. Vasodilators and prostaglandin inhibitors in primary pulmonary hypertension. Ann Intern Med 97 4 (1982) 480-489
221. Braner D.A., Fineman J.R., Chang R., et al. M&B 22948, a cGMP phosphodiesterase inhibitor, is a pulmonary vasodilator in lambs. Am J Physiol 264 1 Pt 2 (1993) H252-H258
222. Takahashi T., Kanda T., Inoue M., et al. A selective type V phosphodiesterase inhibitor, E4021, protects the development of right ventricular overload and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension. Life Sci 59 23 (1996) PL371-PL377
223. Eddahibi S., Raffestin B., Le Monnier de Gouville A.C., et al. Effect of DMPPO, a phosphodiesterase type 5 inhibitor, on hypoxic pulmonary hypertension in rats. Br J Pharmacol 125 4 (1998) 681-688
224. Hanasato N., Oka M., Muramatsu M., et al. E-4010, a selective phosphodiesterase 5 inhibitor, attenuates hypoxic pulmonary hypertension in rats. Am J Physiol 277 2 Pt 1 (1999) L225-L232
225. Kodama K., and Adachi H. Improvement of mortality by long-term E4010 treatment in monocrotaline-induced pulmonary hypertensive rats. J Pharmacol Exp Ther 290 2 (1999) 748-752
226. Ichinose F., Adrie C., Hurford W.E., et al. Selective pulmonary vasodilation induced by aerosolized zaprinast. Anesthesiology 88 2 (1998) 410-416
227. Ziegler J.W., Ivy D.D., Wiggins J.W., et al. Effects of dipyridamole and inhaled nitric oxide in pediatric patients with pulmonary hypertension. Am J Respir Crit Care Med 158 5 Pt 1 (1998) 1388-1395
228. Nagamine J., Hill L.L., and Pearl R.G. Combined therapy with zaprinast and inhaled nitric oxide abolishes hypoxic pulmonary hypertension. Crit Care Med 28 7 (2000) 2420-2424
229. Thusu K.G., Morin III F.C., Russell J.A., et al. The cGMP phosphodiesterase inhibitor zaprinast enhances the effect of nitric oxide. Am J Respir Crit Care Med 152 5 Pt 1 (1995) 1605-1610
230. Ichinose F., Adrie C., Hurford W.E., et al. Prolonged pulmonary vasodilator action of inhaled nitric oxide by zaprinast in awake lambs. J Appl Physiol 78 4 (1995) 1288-1295
231. Worwag S., Mulla H., Luyt D., et al. Dipyridamole in the treatment of a neonate with persistent pulmonary hypertension. J R Soc Med 93 2 (2000) 77-78
232. Abrams D., Schulze-Neick I., and Magee A.G. Sildenafil as a selective pulmonary vasodilator in childhood primary pulmonary hypertension. Heart 84 2 (2000) E4
233. Weimann J., Ullrich R., Hromi J., et al. Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension. Anesthesiology 92 6 (2000) 1702-1712
234. Prasad S., Wilkinson J., and Gatzoulis M.A. Sildenafil in primary pulmonary hypertension. N Engl J Med 343 (2000) 1342
235. Sayin T., and Zenci M. Sildenafil in primary pulmonary hypertension: is there a subset of patients who respond favourably?. Can J Cardiol 18 6 (2002) 676-678
236. Singh B., Gupta R., Punj V., et al. Sildenafil in the management of primary pulmonary hypertension. Indian Heart J 54 3 (2002) 297-300
237. Jackson G., and Chambers J. Sildenafil for primary pulmonary hypertension: short and long-term symptomatic benefit. Int J Clin Pract 56 5 (2002) 397-398
238. Littera R., La Nasa G., Derchi G., et al. Long-term treatment with sildenafil in a thalassemic patient with pulmonary hypertension. Blood 100 4 (2002) 1516-1517
239. Wilkens H., Guth A., Konig J., et al. Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation 104 11 (2001) 1218-1222
240. Ghofrani H.A., Wiedemann R., Rose F., et al. Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann Intern Med 136 7 (2002) 515-522
241. Michelakis E., Tymchak W., Lien D., et al. Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide. Circulation 105 20 (2002) 2398-2403
242. Ghofrani H.A., Wiedemann R., Rose F., et al. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet 360 9337 (2002) 895-900
243. Kang K.K., Ahn G.J., Sohn Y.S., et al. DA-8159, a potent cGMP phosphodiesterase inhibitor, attenuates monocrotaline-induced pulmonary hypertension in rats. Arch Pharm Res 26 8 (2003) 612-619
244. Schermuly R.T., Kreisselmeier K.P., Ghofrani H.A., et al. Chronic sildenafil treatment inhibits monocrotaline-induced pulmonary hypertension in rats. Am J Respir Crit Care Med 169 1 (2004) 39-45
245. Sebkhi A., Strange J.W., Phillips S.C., et al. Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced pulmonary hypertension. Circulation 107 25 (2003) 3230-3235 [Epub 2003 Jun 9]
246. Kothari S.S., and Duggal B. Chronic oral sildenafil therapy in severe pulmonary artery hypertension. Indian Heart J 54 4 (2002) 404-409
247. Sastry B.K., Narasimhan C., Reddy N.K., et al. A study of clinical efficacy of sildenafil in patients with primary pulmonary hypertension. Indian Heart J 54 4 (2002) 410-414
248. Michelakis E.D., Tymchak W., Noga M., et al. Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Circulation 108 17 (2003) 2066-2069
249. Mikhail G.W., Prasad S.K., Li W., et al. Clinical and haemodynamic effects of sildenafil in pulmonary hypertension: acute and mid-term effects. Eur Heart J 25 5 (2004) 431-436
250. Ghofrani H.A., Schermuly R.T., Rose F., et al. Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 167 8 (2003) 1139-1141
251. Bharani A., Mathew V., Sahu A., et al. The efficacy and tolerability of sildenafil in patients with moderate-to-severe pulmonary hypertension. Indian Heart J 55 1 (2003) 55-59
252. Sastry B.K., Narasimhan C., Reddy N.K., et al. Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study. J Am Coll Cardiol 43 7 (2004) 1149-1153
253. Singh T.P., Rohit M., Grover A., et al. A randomized, placebo-controlled, double-blind, crossover study to evaluate the efficacy of oral sildenafil therapy in severe pulmonary artery hypertension. Am Heart J 151 4 (2006) 851.e1-851.e5
254. Galie N., Ghofrani H.A., Torbicki A., et al. Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group: sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 353 20 (2005) 2148-2157
255. Kataoka M., Satoh T., Manabe T., et al. Oral sildenafil improves primary pulmonary hypertension refractory to epoprostenol. Circ J 69 4 (2005) 461-465
256. Wilkins M.R., Paul G.A., Strange J.W., et al. Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study. Am J Respir Crit Care Med 171 11 (2005) 1292-1297
257. Chockalingam A., Gnanavelu G., Venkatesan S., et al. Efficacy and optimal dose of sildenafil in primary pulmonary hypertension. Int J Cardiol 99 1 (2005) 91-95
258. Ghofrani H.A., 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 Coll Cardiol 44 7 (2004) 1488-1496
259. Palmieri E.A., Affuso F., Fazio S., et al. Tadalafil in primary pulmonary arterial hypertension. Ann Intern Med 141 9 (2004) 743-744
260. Affuso F., Palmieri E.A., Di Conza P., et al. Tadalafil improves quality of life and exercise tolerance in idiopathic pulmonary arterial hypertension. Int J Cardiol 108 3 (2006) 429-431
261. Aizawa K., Hanaoka T., Kasai H., et al. Long-term vardenafil therapy improves hemodynamics in patients with pulmonary hypertension. Hypertens Res 29 2 (2006) 123-128