1887
Volume 2014, Issue 3
  • ISSN: 2305-7823
  • E-ISSN:

ملخص

Phosphodiesterase inhibitors (PDE) can be used as therapeutic agents for various diseases such as dementia, depression, schizophrenia and erectile dysfunction in men, as well as congestive heart failure, chronic obstructive pulmonary disease, rheumatoid arthritis, other inflammatory diseases, diabetes and various other conditions. In this review we will concentrate on one type of PDE, mainly PDE5 and its role in pulmonary vascular diseases.

Loading

جارٍ تحميل قياسات المقالة...

/content/journals/10.5339/gcsp.2014.42
٢٠١٤-١١-٠١
٢٠٢٤-٠٥-١٨
Loading full text...

Full text loading...

/deliver/fulltext/gcsp/2014/3/gcsp.2014.42.html?itemId=/content/journals/10.5339/gcsp.2014.42&mimeType=html&fmt=ahah

References

  1. Liras S, Bell AS. Phosphodiesterases and Their Inhibitors. John Wiley & Sons Weinheim, Germany 2014:p.238.
    [Google الباحث العلمي]
  2. Amsallem E, Kasparian C, Haddour G, Boissel J-P, Nony P. Phosphodiesterase III inhibitors for heart failure. Cochrane Database Syst Rev. 2005; 1:CD002230. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002230.pub2/pdf/standard..
    [Google الباحث العلمي]
  3. Doherty AM. Phosphodiesterase 4 inhibitors as novel anti-inflammatory agents. Curr Opin Chem Biol. 1999; 3:4:466473.
    [Google الباحث العلمي]
  4. Huang Z, Ducharme Y, Macdonald D, Robichaud A. The next generation of PDE4 inhibitors. Curr Opin Chem Biol. 2001; 5:4:432438.
    [Google الباحث العلمي]
  5. Milani E, Nikfar S, Khorasani R, Zamani MJ, Abdollahi M. Reduction of diabetes-induced oxidative stress by phosphodiesterase inhibitors in rats. Comp Biochem Physiol Part C Toxicol Pharmacol. 2005; 140:2:251255.
    [Google الباحث العلمي]
  6. Conti M, Jin S-LC. The molecular biology of cyclic nucleotide phosphodiesterases. Prog Nucleic Acid Res Mol Biol. 1999; 63::138.
    [Google الباحث العلمي]
  7. Frumkin LR. The pharmacological treatment of pulmonary arterial hypertension. Pharmacol Rev. 2012; 64:3:583620.
    [Google الباحث العلمي]
  8. Rotella DP. Phosphodiesterase 5 inhibitors: Current status and potential applications. Nat Rev Drug Discov. 2002; 1:9:674682.
    [Google الباحث العلمي]
  9. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980; 288:5789:373376.
    [Google الباحث العلمي]
  10. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci. 1987; 84:24:92659269.
    [Google الباحث العلمي]
  11. Kuhn M. Endothelial actions of atrial and B-type natriuretic peptides. Br J Pharmacol. 2012; 166:2:522531.
    [Google الباحث العلمي]
  12. Tsai EJ, Kass DA. Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacol Ther. 2009; 122:3:216238.
    [Google الباحث العلمي]
  13. Francis SH, Busch JL, Corbin JD. cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev. 2010; 62:3:525563.
    [Google الباحث العلمي]
  14. Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation. 2004; 109:2:159165.
    [Google الباحث العلمي]
  15. Tuder R. Pathology of pulmonary arterial hypertension. Semin Respir Crit Care Med. 2009; 30:04:376385.
    [Google الباحث العلمي]
  16. Gao Y, Raj JU. Regulation of the pulmonary circulation in the fetus and newborn. Physiol Rev. 2010; 90:4:12911335.
    [Google الباحث العلمي]
  17. Murad F. Nitric oxide and cyclic GMP in cell signaling and drug development. N Engl J Med. 2006; 355:19:20032011.
    [Google الباحث العلمي]
  18. Chen C, Watson G, Zhao L. Cyclic guanosine monophosphate signalling pathway in pulmonary arterial hypertension. Vascul Pharmacol. 2013; 58:3:211218.
    [Google الباحث العلمي]
  19. Jeon YH, Heo YS, Kim CM, Hyun YL, Lee TG, Ro S, Cho JM. Phosphodiesterase: Overview of protein structures, potential therapeutic applications and recent progress in drug development. Cell Mol Life Sci. 2005; 62:11:11981220.
    [Google الباحث العلمي]
  20. Strada SJ, Uzunov P, Weiss B. Ontogenetic development of a phosphodiesterase activator and the multiple forms of cyclic amp phosphodiesterase of rat brain. J Neurochem. 1974; 23:6:10971103.
    [Google الباحث العلمي]
  21. Beavo J, Houslay MD. Cyclic Nucleotide Phosphodiesterases: Structure, Regulation, and Drug Action. John Wiley & Sons; San Francisco, CA USA 1990.
    [Google الباحث العلمي]
  22. Appleman MM, Thompson WJ, Russell TR. Cyclic nucleotide phosphodiesterases. Adv Cyclic Nucleotide Res. 1973; 3::6598.
    [Google الباحث العلمي]
  23. Wells JN, Hardman JG. Cyclic nucleotide phosphodiesterases. Adv Cyclic Nucleotide Res. 1976; 8::119143.
    [Google الباحث العلمي]
  24. Appleman MM, Thompson WJ. Multiple cyclic nucleotide phosphodiesterase activities from rat brain. Biochemistry (Mosc). 1971; 10:2:311316.
    [Google الباحث العلمي]
  25. Beavo JA. Cyclic nucleotide phosphodiesterases: Functional implications of multiple isoforms. Physiol Rev. 1995; 75:4:725748.
    [Google الباحث العلمي]
  26. Conti M. Phosphodiesterases and cyclic nucleotide signaling in endocrine cells. Mol Endocrinol. 2000; 14:9:13171327.
    [Google الباحث العلمي]
  27. Manganiello VC, Degerman E. Cyclic nucleotide phosphodiesterases (PDEs): Diverse regulators of cyclic nucleotide signals and inviting molecular targets for novel therapeutic agents. Thromb Haemost. 1999; 82:2:407411.
    [Google الباحث العلمي]
  28. Soderling SH, Bayuga SJ, Beavo JA. Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases. J Biol Chem. 1998; 273:25:1555315558.
    [Google الباحث العلمي]
  29. Surapisitchat J, Beavo JA. Chapter 173 – phosphodiesterase families. In: Bradshaw RADennis EA, eds. Handbook of Cell Signaling. 2nd ed. San Diego: Available from: http://www.sciencedirect.com/science/article/pii/B978012374145500173X  Academic Press 2010;:14091414.
    [Google الباحث العلمي]
  30. Francis SH, Colbran JL, McAllister-Lucas LM, Corbin JD. Zinc interactions and conserved motifs of the cGMP-binding cGMP-specific phosphodiesterase suggest that it is a zinc hydrolase. J Biol Chem. 1994; 269:36:2247722480.
    [Google الباحث العلمي]
  31. Sung BJ, Hwang KY, Jeon YH, Lee JI, Heo YS, Kim JH, Moon J, Yoon JM, Hyun YL, Kim E, Eum SJ, Park SY, Lee JO, Lee TG, Ro S, Cho JM. Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Nature. 2003; 425:6953:98102.
    [Google الباحث العلمي]
  32. Zhang KY, Card GL, Suzuki Y, Artis DR, Fong D, Gillette S, Hsieh D, Neiman J, West BL, Zhang C, Milburn MV, Kim SH, Schlessinger J, Bollag G. Glutamine switch mechanism for nucleotide selectivity by phosphodiesterases. Mol Cell. 2004; 15:2:279286.
    [Google الباحث العلمي]
  33. Corbin JD, Blount MA, Weeks JL 2nd, Beasley A, Kuhn KP, Ho YS, Saidi LF, Hurley JH, Kotera J, Francis SH. [3H]Sildenafil binding to phosphodiesterase-5 is specific, kinetically heterogeneous, and stimulated by cGMP. Mol Pharmacol. 2003; 63:6:13641372.
    [Google الباحث العلمي]
  34. Francis SH, Blount MA, Corbin JD. Mammalian cyclic nucleotide phosphodiesterases: Molecular mechanisms and physiological functions. Physiol Rev. 2011; 91:2:651690.
    [Google الباحث العلمي]
  35. Zoraghi R, Corbin JD, Francis SH. Properties and functions of GAF domains in cyclic nucleotide phosphodiesterases and other proteins. Mol Pharmacol. 2004; 65:2:267278.
    [Google الباحث العلمي]
  36. Rybalkin SD, Rybalkina IG, Shimizu-Albergine M, Tang X-B, Beavo JA. PDE5 is converted to an activated state upon cGMP binding to the GAF A domain. EMBO J. 2003; 22:3:469478.
    [Google الباحث العلمي]
  37. Corbin JD, Turko Be IV, asley A, Francis SH. Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities. Eur J Biochem. 2000; 267:9:27602767.
    [Google الباحث العلمي]
  38. Yanaka N, Kotera J, Ohtsuka A, Akatsuka H, Imai Y, Michibata H, Fujishige K, Kawai E, Takebayashi S, Okumura K, Omori K. Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene. Eur J Biochem. 1998; 255:2:391399.
    [Google الباحث العلمي]
  39. Lin C-S, Lau A, Tu R, Lue TF. Expression of three isoforms of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in human penile cavernosum. Biochem Biophys Res Commun. 2000; 268:2:628635.
    [Google الباحث العلمي]
  40. Loughney K, Hill TR, Florio VA, Uher L, Rosman GJ, Wolda SL, Jones BA, Howard ML, McAllister-Lucas LM, Sonnenburg WK, Francis SH, Corbin JD, Beavo JA, Ferguson K. Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3′,5′-cyclic nucleotide phosphodiesterase. Gene. 1998; 216:1:139147.
    [Google الباحث العلمي]
  41. Lin C-S. Tissue expression, distribution, and regulation of PDE5. Int J Impot Res. 2004; 16:S1:S810.
    [Google الباحث العلمي]
  42. Lin C-S, Lau A, Tu R, Lue TF. Identification of three alternative first exons and an intronic promoter of human PDE5A gene. Biochem Biophys Res Commun. 2000; 268:2:596602.
    [Google الباحث العلمي]
  43. Wallis RM, Corbin JD, Francis SH, Ellis P. Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol. 1999; 83:5, Suppl 1:312.
    [Google الباحث العلمي]
  44. Sly MK, Eberhart RC, Prager MD. Anti-platelet action of nitric oxide and selective phosphodiesterase inhibitors. Shock. 1997; 8::115118.
    [Google الباحث العلمي]
  45. Berkels R, Klotz T, Sticht G, Englemann U, Klaus W. Modulation of human platelet aggregation by the phosphodiesterase type 5 inhibitor sildenafil. J Cardiovasc Pharmacol. 2001; 37:4:413421.
    [Google الباحث العلمي]
  46. Pannbacker RG, Fleischman DE, Reed DW. Cyclic nucleotide phosphodiesterase: High activity in a mammalian photoreceptor. Science. 1972; 175:4023:757758.
    [Google الباحث العلمي]
  47. Baehr W, Devlin MJ, Applebury ML. Isolation and characterization of cGMP phosphodiesterase from bovine rod outer segments. J Biol Chem. 1979; 254:22:1166911677.
    [Google الباحث العلمي]
  48. Lincoln TM, Hall CL, Park CR, Corbin JD. Guanosine 3′: 5′-cyclic monophosphate binding proteins in rat tissues. Proc Natl Acad Sci. 1976; 73:8:25592563.
    [Google الباحث العلمي]
  49. Coquil JF, Franks DJ, Wells JN, Dupuis M, Hamet P. Characteristics of a new binding protein distinct from the kinase for guanosine 3′:5′-monophosphate in rat platelets. Biochim Biophys Acta. 1980; 631:1:148165.
    [Google الباحث العلمي]
  50. Beavo JA, Hansen RS, Harrison SA, Hurwitz RL, Martins TJ, Mumby MC. Identification and properties of cyclic nucleotide phosphodiesterases. Mol Cell Endocrinol. 1982; 28:3:387410.
    [Google الباحث العلمي]
  51. Manganiello VC, Murata T, Taira M, Belfrage P, Degerman E. Diversity in cyclic nucleotide phosphodiesterase isoenzyme families. Arch Biochem Biophys. 1995; 322:1:113.
    [Google الباحث العلمي]
  52. Lin C-S, Lin G, Xin Z-C, Lue TF. Expression, distribution and regulation of phosphodiesterase 5. Curr Pharm Des. 2006; 12:27:34393457.
    [Google الباحث العلمي]
  53. Corbin JD, Beasley A, Blount MA, Francis SH. High lung PDE5: A strong basis for treating pulmonary hypertension with PDE5 inhibitors. Biochem Biophys Res Commun. 2005; 334:3:930938.
    [Google الباحث العلمي]
  54. Wharton J, Strange JW, Møller GM, Growcott EJ, Ren X, Franklyn AP, Phillips SC, Wilkins MR. Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am J Respir Crit Care Med. 2005; 172:1:105113.
    [Google الباحث العلمي]
  55. Nagendran J, Archer SL, Soliman D, Gurtu V, Moudgil R, Haromy A, St Aubin C, Webster L, Rebeyka IM, Ross DB, Light PE, Dyck JR, Michelakis ED. Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation. 2007; 116:3:238248.
    [Google الباحث العلمي]
  56. Pokreisz P, Vandenwijngaert S, Bito V, Van den Bergh A, Lenaerts I, Busch C, Marsboom G, Gheysens O, Vermeersch P, Biesmans L, Liu X, Gillijns H, Pellens M, Van Lommel A, Buys E, Schoonjans L, Vanhaecke J, Verbeken E, Sipido K, Herijgers P, Bloch KD, Janssens SP. Ventricular phosphodiesterase-5 expression is increased in patients with advanced heart failure and contributes to adverse ventricular remodeling after myocardial infarction in mice. Circulation. 2009; 119:3:408416.
    [Google الباحث العلمي]
  57. Shan X, Quaile MP, Monk JK, French B, Cappola TP, Margulies KB. Differential expression of PDE5 in failing and nonfailing human myocardium. Circ Heart Fail. 2012; 5:1:7986.
    [Google الباحث العلمي]
  58. Lu Z, Xu X, Hu X, Lee S, Traverse JH, Zhu G, Fassett J, Tao Y, Zhang P, dos Remedios C, Pritzker M, Hall JL, Garry DJ, Chen Y. Oxidative stress regulates left ventricular PDE5 expression in the failing heart. Circulation. 2010; 121:13:14741483.
    [Google الباحث العلمي]
  59. Gebska MA, Stevenson BK, Hemnes AR, Bivalacqua TJ, Haile A, Hesketh GG, Murray CI, Zaiman AL, Halushka MK, Krongkaew N, Strong TD, Cooke CA, El-Haddad H, Tuder RM, Berkowitz DE, Champion HC. Phosphodiesterase-5A (PDE5A) is localized to the endothelial caveolae and modulates NOS3 activity. Cardiovasc Res. 2011; 90:2:353363.
    [Google الباحث العلمي]
  60. Takimoto E, Champion HC, Belardi D, Moslehi J, Mongillo M, Mergia E, Montrose DC, Isoda T, Aufiero K, Zaccolo M, Dostmann WR, Smith CJ, Kass DA. cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation by NOS3-dependent mechanism. Circ Res. 2005; 96:1:100109.
    [Google الباحث العلمي]
  61. Takimoto E, Belardi D, Tocchetti CG, Vahebi S, Cormaci G, Ketner EA, Moens AL, Champion HC, Kass DA. Compartmentalization of cardiac β-adrenergic inotropy modulation by phosphodiesterase type 5. Circulation. 2007; 115:16:21592167.
    [Google الباحث العلمي]
  62. Mullershausen F, Friebe A, Feil R, Thompson WJ, Hofmann F, Koesling D. Direct activation of PDE5 by cGMP long-term effects within NO/cGMP signaling. J Cell Biol. 2003; 160:5:719727.
    [Google الباحث العلمي]
  63. Biswas KH, Visweswariah SS. Distinct allostery induced in the cyclic GMP-binding, cyclic GMP-specific phosphodiesterase (PDE5) by cyclic gmp, sildenafil, and metal ions. J Biol Chem. 2011; 286:10:85458554.
    [Google الباحث العلمي]
  64. Rybalkina IG, Tang X-B, Rybalkin SD. Multiple affinity states of cGMP-specific phosphodiesterase for sildenafil inhibition defined by cGMP-dependent and cGMP-independent mechanisms. Mol Pharmacol. 2010; 77:4:670677.
    [Google الباحث العلمي]
  65. Corbin JD, Zoraghi R, Francis SH. Allosteric-site and catalytic-site ligand effects on PDE5 functions are associated with distinct changes in physical form of the enzyme. Cell Signal. 2009; 21:12:17681774.
    [Google الباحث العلمي]
  66. Bessay EP, Zoraghi R, Blount MA, Grimes KA, Beasley A, Francis SH, Corbin JD. Phosphorylation of phosphodiesterase-5 is promoted by a conformational change induced by sildenafil, vardenafil, or tadalafil. Front Biosci. 2007; 12::18991910.
    [Google الباحث العلمي]
  67. Wang H, Liu Y, Huai Q, Cai J, Zoraghi R, Francis SH, Corbin JD, Robinson H, Xin Z, Lin G, Ke H. Multiple conformations of phosphodiesterase-5: Implications for enzyme function and drug development. J Biol Chem. 2006; 281:30:2146921479.
    [Google الباحث العلمي]
  68. Francis SH, Zoraghi R, Kotera J, Ke H, Bessay EP, Blount MA. Phosphodiesterase 5: Molecular characteristics relating to structure function and regulation. In: Beavo JAFrancis SHHouslay MD, eds. Cyclic Nucleotide Phosphodiesterases in Health and Disease. Boca Raton, FL: CRC Press 2006.
    [Google الباحث العلمي]
  69. Rybalkin SD, Rybalkina IG, Feil R, Hofmann F, Beavo JA. Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells. J Biol Chem. 2002; 277:5:33103317.
    [Google الباحث العلمي]
  70. Chaumais M-C, Perrin S, Sitbon O, Simonneau G, Humbert M, Montani D. Pharmacokinetic evaluation of sildenafil as a pulmonary hypertension treatment. Expert Opin Drug Metab Toxicol. 2013; 9:9:11931205.
    [Google الباحث العلمي]
  71. Broughton BJ, Chaplen P, Knowles P, Lunt E, Pain DL, Wooldridge KRH, Ford R, Marshall S, Walker JL, Maxwell DR. New inhibitor of reagin-mediated anaphylaxis. Nature. 1974; 251::650652, doi:10.1038/251650a0 .
    [Google الباحث العلمي]
  72. Kukovetz WR, Holzmann S, Wurm A, Pöch G. Evidence for cyclic GMP-mediated relaxant effects of nitro-compounds in coronary smooth muscle. Naunyn Schmiedebergs Arch Pharmacol. 1979; 310:2:129138.
    [Google الباحث العلمي]
  73. Gibson A. Phosphodiesterase 5 inhibitors and nitrergic transmission—from zaprinast to sildenafil. Eur J Pharmacol. 2001; 411:1-2:110.
    [Google الباحث العلمي]
  74. Bruzziches R, Francomano D, Gareri P, Lenzi A, Aversa A. An update on pharmacological treatment of erectile dysfunction with phosphodiesterase type 5 inhibitors. Expert Opin Pharmacother. 2013; 14:10:13331344.
    [Google الباحث العلمي]
  75. Bell AS, Brown D, Terrett NK. Pyrazolopyrimidinone antianginal agents. 1993;, US5250534 A.
    [Google الباحث العلمي]
  76. Campbell S. Science, art and drug discovery: A personal perspective. Clin Sci. 2000; 99::255260.
    [Google الباحث العلمي]
  77. Naylor AM. Endogenous neurotransmitters mediating penile erection. Br J Urol. 1998; 81:3:424431.
    [Google الباحث العلمي]
  78. Rotella DP. Tadalafil lilly ICOS. Curr Opin Investig Drugs Lond Engl. 2003; 4:1:6065.
    [Google الباحث العلمي]
  79. Coleman CI, Carabino JM, Vergara CM. Fei Wang.Vardenafil. Formulary. 2003; 38:3:131.
    [Google الباحث العلمي]
  80. Salem EA, Kendirci M, Hellstrom WJG. Udenafil, a long-acting PDE5 inhibitor for erectile dysfunction. Curr Opin Investig Drugs Lond Engl. 2006; 7:7:661669.
    [Google الباحث العلمي]
  81. Burke RM, Evans JD. Avanafil for treatment of erectile dysfunction: Review of its potential. Vasc Health Risk Manag. 2012; 8::517523.
    [Google الباحث العلمي]
  82. Paick JS, Ahn TY, Choi HK, Chung WS, Kim JJ, Kim SC, Kim SW, Lee SW, Min KS, Moon KH, Park JK, Park K, Park NC, Suh JK, Yang DY, Jung HG. Efficacy and safety of mirodenafil, a new oral phosphodiesterase type 5 inhibitor, for treatment of erectile dysfunction. J Sex Med. 2008; 5:11:26722680.
    [Google الباحث العلمي]
  83. Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, Gingell C. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res. 1996; 8:2:4752.
    [Google الباحث العلمي]
  84. Jeremy JY, Ballard SA, Naylor AM, Miller MAW, Angelini GD. Effects of sildenafil, a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum in vitro. Br J Urol. 1997; 79:6:958963.
    [Google الباحث العلمي]
  85. Shamloul R, Ghanem H. Erectile dysfunction. The Lancet. 2013; 381:9861:153165.
    [Google الباحث العلمي]
  86. Blount MA, Beasley A, Zoraghi R, Sekhar KR, Bessay EP, Francis SH, Corbin JD. Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation. Mol Pharmacol. 2004; 66:1:144152.
    [Google الباحث العلمي]
  87. Gresser U, Gleiter CH. Erectile dysfunction: Comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil–review of the literature. Eur J Med Res. 2002; 7:10:435446.
    [Google الباحث العلمي]
  88. Saenz de Tejada I, Angulo J, Cuevas P, Fernández A, Moncada I, Allona A, Lledó E, Körschen HG, Niewöhner U, Haning H, Pages E, Bischoff E. The phosphodiesterase inhibitory selectivity and the in vitro and in vivo potency of the new PDE5 inhibitor vardenafil. Int J Impot Res. 2001; 13:5:282290.
    [Google الباحث العلمي]
  89. Schwartz BG, Kloner RA. Drug interactions with phosphodiesterase-5 inhibitors used for the treatment of erectile dysfunction or pulmonary hypertension. Circulation. 2010; 122:1:8895.
    [Google الباحث العلمي]
  90. Burgess G, Hoogkamer H, Collings L, Dingemanse J. Mutual pharmacokinetic interactions between steady-state bosentan and sildenafil. Eur J Clin Pharmacol. 2008; 64:1:4350.
    [Google الباحث العلمي]
  91. Wrishko RE, Dingemanse J, Yu A, Darstein C, Phillips DL, Mitchell MI. Pharmacokinetic interaction between tadalafil and bosentan in healthy male subjects. J Clin Pharmacol. 2008; 48:5:610618.
    [Google الباحث العلمي]
  92. Muirhead GJ, Wulff MB, Fielding A, Kleinermans D, Buss N. Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir. Br J Clin Pharmacol. 2000; 50:2:99107.
    [Google الباحث العلمي]
  93. Garraffo R, Lavrut T, Ferrando S, Durant J, Rouyrre N, MacGregor TR, Sabo JP, Dellamonica P. Effect of tipranavir/ritonavir combination on the pharmacokinetics of tadalafil in healthy volunteers. J Clin Pharmacol. 2011; 51:7:10711078.
    [Google الباحث العلمي]
  94. Loulergue P, Gaillard R, Mir O. Interaction involving tadalafil and CYP3A4 inhibition by ritonavir. Scand J Infect Dis. 2011; 43:3:239240.
    [Google الباحث العلمي]
  95. LEVITRA [Internet]. Available from: http://www.levitra.com/..
  96. CIALIS [Internet]. Available from: http://pi.lilly.com/us/cialis-pi.pdf..
  97. Chinello P, Cicalini S, Pichini S, Pacifici R, Tempestilli M, Petrosillo N. Sildenafil plasma concentrations in two HIV patients with pulmonary hypertension treated with ritonavir-boosted protease inhibitors. Curr HIV Res. 2012; 10:2:162164.
    [Google الباحث العلمي]
  98. Prickaerts J, Steinbusch HWM, Smits JFM, de Vente J. Possible role of nitric oxide-cyclic GMP pathway in object recognition memory: Effects of 7-nitroindazole and zaprinast. Eur J Pharmacol. 1997; 337:2-3:125136.
    [Google الباحث العلمي]
  99. Evgenov OV, Ichinose F, Evgenov NV, Gnoth MJ, Falkowski GE, Chang Y, Bloch KD, Zapol WM. Soluble guanylate cyclase activator reverses acute pulmonary hypertension and augments the pulmonary vasodilator response to inhaled nitric oxide in awake lambs. Circulation. 2004; 110:15:22532259.
    [Google الباحث العلمي]
  100. Ichinose F, Adrie C, Hurford WE, Zapol WM. Prolonged pulmonary vasodilator action of inhaled nitric oxide by zaprinast in awake lambs. J Appl Physiol. 1995; 78:4:12881295.
    [Google الباحث العلمي]
  101. Thusu KG, Morin FC 3rd, Russell JA, Steinhorn RH. The cGMP phosphodiesterase inhibitor zaprinast enhances the effect of nitric oxide. Am J Respir Crit Care Med. 1995; 152:5 Pt 1:16051610.
    [Google الباحث العلمي]
  102. Ziegler JW, Ivy DD, Wiggins JW, Kinsella JP, Clarke WR, Abman SH. Effects of dipyridamole and inhaled nitric oxide in pediatric patients with pulmonary hypertension. Am J Respir Crit Care Med. 1998; 158:5 Pt 1:13881395.
    [Google الباحث العلمي]
  103. Zhao L, Mason NA, Morrell NW, Kojonazarov B, Sadykov A, Maripov A, Mirrakhimov MM, Aldashev A, Wilkins MR. Sildenafil inhibits hypoxia-induced pulmonary hypertension. Circulation. 2001; 104:4:424428.
    [Google الباحث العلمي]
  104. Sylvester JT, Shimoda LA, Aaronson PI, Ward JPT. Hypoxic pulmonary vasoconstriction. Physiol Rev. 2012; 92:1:367520.
    [Google الباحث العلمي]
  105. Euler USv, Liljestrand G. Observations on the pulmonary arterial blood pressure in the cat. Acta Physiol Scand. 1946; 12:4:301320.
    [Google الباحث العلمي]
  106. Rabinovitch M, Gamble W, Nadas AS, Miettinen OS, Reid L. Rat pulmonary circulation after chronic hypoxia: Hemodynamic and structural features. Am J Physiol. 1979; 236:6:H818H827.
    [Google الباحث العلمي]
  107. Alexander AF. The bovine lung: Normal vascular histology and vascular lesions in high mountain disease. Respiration. 1962; 19:6:528542.
    [Google الباحث العلمي]
  108. Sebkhi A, Strange JW, Phillips SC, Wharton J, Wilkins MR. Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced pulmonary hypertension. Circulation. 2003; 107:25:32303235.
    [Google الباحث العلمي]
  109. Maclean MR, Johnston ED, Mcculloch KM, Pooley L, Houslay MD, Sweeney G. Phosphodiesterase isoforms in the pulmonary arterial circulation of the rat: Changes in pulmonary hypertension. J Pharmacol Exp Ther. 1997; 283:2:619624.
    [Google الباحث العلمي]
  110. Hanasato N, Oka M, Muramatsu M, Nishino M, Adachi H, Fukuchi Y. E-4010, a selective phosphodiesterase 5 inhibitor, attenuates hypoxic pulmonary hypertension in rats. Am J Physiol-Lung Cell Mol Physiol. 1999; 277:2:L225L232.
    [Google الباحث العلمي]
  111. Weimann J, Ullrich R, Hromi J, Fujino Y, Clark MW, Bloch KD, Zapol WM. Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension. Anesthesiology. 2000; 92:6:17021712.
    [Google الباحث العلمي]
  112. Ichinose F, Adrie C, Hurford WE, Bloch KD, Zapol WM. Selective pulmonary vasodilation induced by aerosolized zaprinast. Anesthesiology. 1998; 88:2:410416.
    [Google الباحث العلمي]
  113. McMAHON TJ, Ignarro LJ, Kadowitz PJ. Influence of zaprinast on vascular tone and vasodilator responses in the cat pulmonary vascular bed. J Appl Physiol. 1993; 74::17041711.
    [Google الباحث العلمي]
  114. Kouyoumdjian C, Adnot S, Levame M, Eddahibi S, Bousbaa H, Raffestin B. Continuous inhalation of nitric oxide protects against development of pulmonary hypertension in chronically hypoxic rats. J Clin Invest. 1994; 94:2:578.
    [Google الباحث العلمي]
  115. Kirsch M, Kemp-Harper B, Weissmann N, Grimminger F, Schmidt HHHW. Sildenafil in hypoxic pulmonary hypertension potentiates a compensatory up-regulation of NO-cGMP signaling. FASEB J. 2008; 22:1:3040.
    [Google الباحث العلمي]
  116. Sauzeau V, Rolli-Derkinderen M, Lehoux S, Loirand G, Pacaud P. Sildenafil prevents change in RhoA expression induced by chronic hypoxia in rat pulmonary artery. Circ Res. 2003; 93:7:630637.
    [Google الباحث العلمي]
  117. Guilluy C, Sauzeau V, Rolli-Derkinderen M, Guérin P, Sagan C, Pacaud P, Loirand G. Inhibition of RhoA/Rho kinase pathway is involved in the beneficial effect of sildenafil on pulmonary hypertension. Br J Pharmacol. 2005; 146:7:10101018.
    [Google الباحث العلمي]
  118. Pauvert O, Bonnet S, Rousseau E, Marthan R, Savineau JP. Sildenafil alters calcium signaling and vascular tone in pulmonary arteries from chronically hypoxic rats. Am J Physiol – Lung Cell Mol Physiol. 2004; 287:3:L577L583.
    [Google الباحث العلمي]
  119. Schermuly RT, Kreisselmeier KP, Ghofrani HA, Yilmaz H, Butrous G, Ermert L, Ermert M, Weissmann N, Rose F, Guenther A, Walmrath D, Seeger W, Grimminger F. Chronic sildenafil treatment inhibits monocrotaline-induced pulmonary hypertension in rats. Am J Respir Crit Care Med. 2004; 169:1:3945.
    [Google الباحث العلمي]
  120. Liu H, Liu Z, Guan Q. Oral sildenafil prevents and reverses the development of pulmonary hypertension in monocrotaline-treated rats. Interact Cardiovasc Thorac Surg. 2007; 6:5:608613.
    [Google الباحث العلمي]
  121. Sawamura F, Kato M, Fujita K, Nakazawa T, Beardsworth A. Tadalafil, a long-acting inhibitor of PDE5, improves pulmonary hemodynamics and survival rate of monocrotaline-induced pulmonary artery hypertension in rats. J Pharmacol Sci. 2009; 111:3:235243.
    [Google الباحث العلمي]
  122. Fan YF, Zhang R, Jiang X, Wen L, Wu DC, Liu D, Yuan P, Wang YL, Jing ZC. The phosphodiesterase-5 inhibitor vardenafil reduces oxidative stress while reversing pulmonary arterial hypertension. Cardiovasc Res. 2013; 99:3:395403.
    [Google الباحث العلمي]
  123. Yen CH, Leu S, Lin YC, Kao YH, Chang LT, Chua S, Fu M, Wu CJ, Sun CK, Yip HK. Sildenafil limits monocrotaline-induced pulmonary hypertension in rats through suppression of pulmonary vascular remodeling. J Cardiovasc Pharmacol. 2010; 55:6:574584.
    [Google الباحث العلمي]
  124. Bogdan S, Seferian A, Totoescu A, Dumitrache-Rujinski S, Ceausu M, Coman C, Ardelean CM, Dorobantu M, Bogdan M. Sildenafil reduces inflammation and prevents pulmonary arterial remodeling of the monocrotaline – induced disease in the wistar rats. Maedica (Buchar). 2012; 7:2:109116.
    [Google الباحث العلمي]
  125. Ghofrani HA, Osterloh IH, Grimminger F. Sildenafil: From angina to erectile dysfunction to pulmonary hypertension and beyond. Nat Rev Drug Discov. 2006; 5:8:689702.
    [Google الباحث العلمي]
  126. Prasad S, Wilkinson J, Gatzoulis MA. Sildenafil in primary pulmonary hypertension. N Engl J Med. 2000; 343:18:1342.
    [Google الباحث العلمي]
  127. Wilkens H, Guth A, König J, Forestier N, Cremers B, Hennen B, Böhm M, Sybrecht GW. Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation. 2001; 104:11:12181222.
    [Google الباحث العلمي]
  128. Ghofrani HA, Wiedemann R, Rose F, Olschewski H, Schermuly RT, Weissmann N, Seeger W, Grimminger F. Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann Intern Med. 2002; 136:7:515522.
    [Google الباحث العلمي]
  129. Ss K, B D. Chronic oral sildenafil therapy in severe pulmonary artery hypertension. Indian Heart J. 2001; 54:4:404409.
    [Google الباحث العلمي]
  130. Sastry BK, Narasimhan C, Reddy NK, Anand B, Prakash GS, Raju PR, Kumar DN. A study of clinical efficacy of sildenafil in patients with primary pulmonary hypertension. Indian Heart J. 2001; 54:4:410414.
    [Google الباحث العلمي]
  131. Sastry BKS, Narasimhan C, Reddy NK, Raju BS. Clinical efficacy of sildenafil in primary pulmonary hypertension: A randomized, placebo-controlled, double-blind, crossover study. J Am Coll Cardiol. 2004; 43:7:11491153.
    [Google الباحث العلمي]
  132. 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. 2002; 105:20:23982403.
    [Google الباحث العلمي]
  133. Michelakis ED, Tymchak W, Noga M, Webster L, Wu XC, Lien D, Wang SH, Modry D, Archer SL. Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Circulation. 2003; 108:17:20662069.
    [Google الباحث العلمي]
  134. Lepore JJ, Maroo A, Pereira NL, Ginns LC, Dec GW, Zapol WM, Bloch KD, Semigran MJ. Effect of sildenafil on the acute pulmonary vasodilator response to inhaled nitric oxide in adults with primary pulmonary hypertension. Am J Cardiol. 2002; 90:6:677680.
    [Google الباحث العلمي]
  135. Singh B, Gupta R, Punj V, Ghose T, Sapra R, Grover DN, Kaul U. Sildenafil in the management of primary pulmonary hypertension. Indian Heart J. 2002; 54:3:297300.
    [Google الباحث العلمي]
  136. Zimmermann GS, von Wulffen W, Huppmann P, Meis T, Ihle F, Geiseler J, Leuchte HH, Tufman A, Behr J, Neurohr C. Haemodynamic changes in pulmonary hypertension in patients with interstitial lung disease treated with PDE-5 inhibitors. Respirology. 2014; 19:5:700706.
    [Google الباحث العلمي]
  137. Watanabe H, Ohashi K, Takeuchi K, Yamashita K, Yokoyama T, Tran QK, Satoh H, Terada H, Ohashi H, Hayashi H. Sildenafil for primary and secondary pulmonary hypertension. Clin Pharmacol Ther. 2002; 71:5:398402.
    [Google الباحث العلمي]
  138. Galiè N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, Fleming T, Parpia T, Burgess G, Branzi A, Grimminger F, Kurzyna M, Simonneau G, Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group . Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005; 353:20:21482157.
    [Google الباحث العلمي]
  139. Moncada I, Jara J, Subirá D, Castaño I, Hernández C. Efficacy of sildenafil citrate at 12 hours after dosing: Re-exploring the therapeutic window. Eur Urol. 2004; 46:3:357361.
    [Google الباحث العلمي]
  140. Rubin LJ, Badesch DB, Fleming TR, Galiè N, Simonneau G, Ghofrani HA, Oakes M, Layton G, Serdarevic-Pehar M, McLaughlin VV, Barst RJ. SUPER-2 Study Group Long-term treatment with sildenafil citrate in pulmonary arterial hypertension: The SUPER-2 study. Chest. 2011; 140:5:12741283.
    [Google الباحث العلمي]
  141. Affuso F, Palmieri EA, Di Conza P, Guardasole V, Fazio S. Tadalafil improves quality of life and exercise tolerance in idiopathic pulmonary arterial hypertension. Int J Cardiol. 2006; 108:3:429431.
    [Google الباحث العلمي]
  142. Galiè N, Brundage BH, Ghofrani HA, Oudiz RJ, Simonneau G, Safdar Z, Shapiro S, White RJ, Chan M, Beardsworth A, Frumkin L, Barst RJ, Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) Study Group . Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009; 119:22:28942903.
    [Google الباحث العلمي]
  143. Oudiz RJ, Brundage BH, Galiè N, Ghofrani HA, Simonneau G, Botros FT, Chan M, Beardsworth A, Barst RJ, PHIRST Study Group . Tadalafil for the treatment of pulmonary arterial hypertension: A double-blind 52-week uncontrolled extension study. J Am Coll Cardiol. 2012; 60:8:768774.
    [Google الباحث العلمي]
  144. Frantz RP, Durst L, Burger CD, Oudiz RJ, Bourge RC, Franco V, Waxman AB, McDevitt S, Walker S. Conversion from sildenafil to tadalafil: Results from the sildenafil to tadalafil in pulmonary arterial hypertension (SITAR) study. J Cardiovasc Pharmacol Ther. 2014; 19:6:550557.
    [Google الباحث العلمي]
  145. Archer SL, Michelakis ED. An evidence-based approach to the management of pulmonary arterial hypertension. Curr Opin Cardiol. 2006; 21:4:385392.
    [Google الباحث العلمي]
  146. O'Callaghan D, Gaine SP. Combination therapy and new types of agents for pulmonary arterial hypertension. Clin Chest Med. 2007; 28:1:169185.
    [Google الباحث العلمي]
  147. Kawut SM, Horn EM, Berekashvili KK, Garofano RP, Goldsmith RL, Widlitz AC, Rosenzweig EB, Kerstein D, Barst RJ. New predictors of outcome in idiopathic pulmonary arterial hypertension. Am J Cardiol. 2005; 95:2:199203.
    [Google الباحث العلمي]
  148. Badesch DB, Abman SH, Simonneau G, Rubin LJ, McLaughlin VV. Medical therapy for pulmonary arterial hypertension: Updated accp evidence-based clinical practice guidelines. Chest. 2007; 131:6:19171928.
    [Google الباحث العلمي]
  149. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J, American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association . ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009; 53:17:15731619.
    [Google الباحث العلمي]
  150. Galiè N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G. ESC Committee for Practice Guidelines (CPG). Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J. 2009; 30:20:24932537.
    [Google الباحث العلمي]
  151. Galiè N, Negro L, Simonneau G. The use of combination therapy in pulmonary arterial hypertension: New developments. Eur Respir Rev. 2009; 18:113:148153.
    [Google الباحث العلمي]
  152. McGoon MD, Miller DP. REVEAL: A contemporary US pulmonary arterial hypertension registry. Eur Respir Rev. 2012; 21:123:818.
    [Google الباحث العلمي]
  153. Stiebellehner L, Petkov V, Vonbank K, Funk G, Schenk P, Ziesche R, Block LH. Long-term treatment with oral sildenafil in addition to continuous IV epoprostenol in patients with pulmonary arterial hypertension. Chest. 2003; 123:4:12931295.
    [Google الباحث العلمي]
  154. Hoeper M, Faulenbach C, Golpon H, Winkler J, Welte T, Niedermeyer J. Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension. Eur Respir J. 2004; 24:6:10071010.
    [Google الباحث العلمي]
  155. Mathai SC, Girgis RE, Fisher MR, Champion HC, Housten-Harris T, Zaiman A, Hassoun PM. Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension. Eur Respir J. 2007; 29:3:469475.
    [Google الباحث العلمي]
  156. Porhownik NR, Al-Sharif H, Bshouty Z. Addition of sildenafil in patients with pulmonary arterial hypertension with inadequate response to bosentan monotherapy. Can Respir J J Can Thorac Soc. 2008; 15:8:427430.
    [Google الباحث العلمي]
  157. Gruenig E, Michelakis E, Vachiéry JL, Vizza CD, Meyer FJ, Doelberg M, Bach D, Dingemanse J, Galiè N. Acute hemodynamic effects of single-dose sildenafil when added to established bosentan therapy in patients with pulmonary arterial hypertension: Results of the COMPASS-1 study. J Clin Pharmacol. 2009; 49:11:13431352.
    [Google الباحث العلمي]
  158. Bendayan D, Shitrit D, Kramer MR. Combination therapy with prostacyclin and tadalafil for severe pulmonary arterial hypertension: A pilot study. Respirology. 2008; 13:6:916918.
    [Google الباحث العلمي]
  159. Zhuang Y, Jiang B, Gao H, Zhao W. Randomized study of adding tadalafil to existing ambrisentan in pulmonary arterial hypertension. Hypertens Res. 2014; 37:6:507512.
    [Google الباحث العلمي]
  160. Hirashiki A, Kondo T, Murohara T. Combination therapy adding tadalafil to existing ambrisentan in patients with pulmonary arterial hypertension. Hypertens Res. 2014; 37:6:488489.
    [Google الباحث العلمي]
  161. Barst RJ, Oudiz RJ, Beardsworth A, Brundage BH, Simonneau G, Ghofrani HA, Sundin DP, Galiè N, Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) Study Group . Tadalafil monotherapy and as add-on to background bosentan in patients with pulmonary arterial hypertension. J Heart Lung Transplant. 2011; 30:6:632643.
    [Google الباحث العلمي]
  162. McLaughlin VV, Oudiz RJ, Frost A, Tapson VF, Murali S, Channick RN, Badesch DB, Barst RJ, Hsu HH, Rubin LJ. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2006; 174:11:12571263.
    [Google الباحث العلمي]
  163. Humbert M, Barst RJ, Robbins IM, Channick RN, Galiè N, Boonstra A, Rubin LJ, Horn EM, Manes A, Simonneau G. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J. 2004; 24:3:353359.
    [Google الباحث العلمي]
  164. Simonneau G, Rubin LJ, Galiè N, Barst RJ, Fleming TR, Frost AE, Engel PJ, Kramer MR, Burgess G, Collings L, Cossons N, Sitbon O, Badesch DB, PACES Study Group . Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: A randomized trial. Ann Intern Med. 2008; 149:8:521530.
    [Google الباحث العلمي]
  165. Simonneau G, Rubin LJ, Galiè N, Barst RJ, Fleming TR, Frost A, Engel P, Kramer MR, Serdarevic-Pehar M, Layton GR, Sitbon O, Badesch DB, PACES Study Group . Long-term sildenafil added to intravenous epoprostenol in patients with pulmonary arterial hypertension. J Heart Lung Transplant. 2014; 33:7:689697. Available from: http://www.sciencedirect.com/science/article/pii/S1053249814009978..
    [Google الباحث العلمي]
  166. Barst R. How has epoprostenol changed the outcome for patients with pulmonary arterial hypertension? Int J Clin Pract. 2010; 64::2332.
    [Google الباحث العلمي]
  167. Gomberg-Maitland M, McLaughlin V, Gulati M, Rich S. Efficacy and safety of sildenafil added to treprostinil in pulmonary hypertension. Am J Cardiol. 2005; 96:9:13341336.
    [Google الباحث العلمي]
  168. Buckley MS, Staib RL, Wicks LM. Combination therapy in the management of pulmonary arterial hypertension. Int J Clin Pract. 2013; 67::1323.
    [Google الباحث العلمي]
  169. Lunze K, Gilbert N, Mebus S, Miera O, Fehske W, Uhlemann F, Mühler EG, Ewert P, Lange PE, Berger F, Schulze-Neick I. First experience with an oral combination therapy using bosentan and sildenafil for pulmonary arterial hypertension. Eur J Clin Invest. 2006; 36::3238.
    [Google الباحث العلمي]
  170. Torres F, Gupta H, Soto F, Park M, Frey N, Murali S, Benza R. Safety and efficacy of bosentan in combination with sildenafil in pulmonary arterial hypertension: The COMPASS-3 study. Eur Respir J. 2011; 38:Suppl 55:409.
    [Google الباحث العلمي]
  171. Spence R, Mandagere A, Harrison B, Dufton C, Boinpally R. No clinically relevant pharmacokinetic and safety interactions of ambrisentan in combination with tadalafil in healthy volunteers. J Pharm Sci. 2009; 98:12:49624974.
    [Google الباحث العلمي]
  172. NIH. Study of ambrisentan and phosphodiesterase type-5 Inhibitor (PDE-5i) to treat pulmonary arterial hypertension [Internet]. Available from: www.clinicaltrials.gov/ct2/show/NCT00617305..
  173. AMBITION [Internet]. Available from: www.clinicaltrials.gov/ct2/show/NCT01178073..
  174. Kylhammar D, Persson L, Hesselstrand R, Rådegran G. Prognosis and response to first-line single and combination therapy in pulmonary arterial hypertension. Scand Cardiovasc J. 2014; 48:4:223233.
    [Google الباحث العلمي]
  175. Collins FS, Orringer EP. Pulmonary hypertension and cor pulmonale in the sickle hemoglobinopathies. Am J Med. 1982; 73:6:814821.
    [Google الباحث العلمي]
  176. Castro O, Hoque M, Brown BD. Pulmonary hypertension in sickle cell disease: Cardiac catheterization results and survival. Blood. 2003; 101:4:12571261.
    [Google الباحث العلمي]
  177. Fonseca GH, Souza R, Salemi VM, Jardim CV, Gualandro SF. Pulmonary hypertension diagnosed by right heart catheterisation in sickle cell disease. Eur Respir J. 2012; 39:1:112118.
    [Google الباحث العلمي]
  178. Simonneau G, Parent F. Pulmonary hypertension in patients with sickle cell disease: not so frequent but so different. Eur Respir J. 2012; 39:1:34.
    [Google الباحث العلمي]
  179. Aliyu ZY, Kato GJ, Taylor J 6th, Babadoko A, Mamman AI, Gordeuk VR, Gladwin MT. Sickle cell disease and pulmonary hypertension in Africa: A global perspective and review of epidemiology, pathophysiology, and management. Am J Hematol. 2008; 83:1:6370.
    [Google الباحث العلمي]
  180. Gladwin MT, Kato GJ. Cardiopulmonary complications of sickle cell disease: Role of nitric oxide and hemolytic anemia. Hematology Am Soc Hematol Educ Program. 2005;5157.
    [Google الباحث العلمي]
  181. Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, Brown B, Coles WA, Nichols JS, Ernst I, Hunter LA, Blackwelder WC, Schechter AN, Rodgers GP, Castro O, Ognibene FP. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004; 350:9:886895.
    [Google الباحث العلمي]
  182. Machado RF, Gladwin MT. Pulmonary hypertension in hemolytic disorders: Pulmonary vascular disease: The global perspective. Chest. 2010; 137:6_suppl:30S38S.
    [Google الباحث العلمي]
  183. Schnog JJ, Jager EH, van der Dijs FP, Duits AJ, Moshage H, Muskiet FD, Muskiet FA. Evidence for a metabolic shift of arginine metabolism in sickle cell disease. Ann Hematol. 2004; 83:6:371375.
    [Google الباحث العلمي]
  184. Reiter CD, Wang X, Tanus-Santos JE, Hogg N, Cannon RO 3rd, Schechter AN, Gladwin MT. Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med. 2002; 8:12:13831389.
    [Google الباحث العلمي]
  185. Morris CR, Kato GJ, Poljakovic M, Wang X, Blackwelder WC, Sachdev V, Hazen SL, Vichinsky EP, Morris SM Jr, Gladwin MT. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA. 2005; 294:1:8190.
    [Google الباحث العلمي]
  186. Bunn HF, Nathan DG, Dover GJ, Hebbel RP, Platt OS, Rosse WF, Ware RE. Pulmonary hypertension and nitric oxide depletion in sickle cell disease. Blood. 2010; 116:5:687692.
    [Google الباحث العلمي]
  187. Machado RF, Martyr S, Kato GJ, Barst RJ, Anthi A, Robinson MR, Hunter L, Coles W, Nichols J, Hunter C, Sachdev V, Castro O, Gladwin MT. Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension. Br J Haematol. 2005; 130:3:445453.
    [Google الباحث العلمي]
  188. Derchi G, Forni GL, Formisano F, Cappellini MD, Galanello R, D'Ascola G, Bina P, Magnano C, Lamagna M. Efficacy and safety of sildenafil in the treatment of severe pulmonary hypertension in patients with hemoglobinopathies. Haematologica. 2005; 90:4:452458.
    [Google الباحث العلمي]
  189. Mehari A, Gladwin MT, Tian X, Machado RF, Kato GJ. Mortality in adults with sickle cell disease and pulmonary hypertension. JAMA. 2012; 307:12:12541256.
    [Google الباحث العلمي]
  190. Mehari A, Alam S, Tian X, Cuttica MJ, Barnett CF, Miles G, Xu D, Seamon C, Adams-Graves P, Castro OL, Minniti CP, Sachdev V, Taylor JG 6th, Kato GJ, Machado RF. Hemodynamic predictors of mortality in adults with sickle cell disease. Am J Respir Crit Care Med. 2013; 187:8:840847.
    [Google الباحث العلمي]
  191. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, Gomez Sanchez MA, Krishna Kumar R, Landzberg M, Machado RF, Olschewski H, Robbins IM, Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013; 62:25:D34D41.
    [Google الباحث العلمي]
  192. Gladwin MT, Barst RJ, Gibbs JS, Hildesheim M, Sachdev V, Nouraie M, Hassell KL, Little JA, Schraufnagel DE, Krishnamurti L, Novelli E, Girgis RE, Morris CR, Berman Rosenzweig E, Badesch DB, Lanzkron S, Castro OL, Taylor JG 6th, Goldsmith JC, Kato GJ, Gordeuk VR, Machado RF, walk-PHaSST Investigators and Patients . Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom. PloS One. 2014; 9:7:e99489.
    [Google الباحث العلمي]
  193. Machado RF, Barst RJ, Yovetich NA, Hassell KL, Goldsmith JC, Woolson R, Gordeuk VR, Gibbs S, Little JA, Kato GJ, Schraufnagel DE, Krishnamurti L, Girgis R, Morris CR, Berman-Rosenzweig E, Badesch DB, Waclawiw MA, Gladwin MT. Evaluation of sildenafil therapy for patients with sickle cell disease and increased tricuspid regurgitant velocity: Preliminary results of the Walk-PHaSST trial. B16. Pulmonary Arterial Hypertension: From Assessing Risk to Therapeutic Results. 2010;A2514. doi:10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A2514..
    [Google الباحث العلمي]
  194. Machado RF, Barst RJ, Yovetich NA, Hassell KL, Kato GJ, Gordeuk VR, Gibbs JS, Little JA, Schraufnagel DE, Krishnamurti L, Girgis RE, Morris CR, Rosenzweig EB, Badesch DB, Lanzkron S, Onyekwere O, Castro OL, Sachdev V, Waclawiw MA, Woolson R, Goldsmith JC, Gladwin MT, walk-PHaSST Investigators and Patients . Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity. Blood. 2011; 118:4:855864.
    [Google الباحث العلمي]
  195. Zuber JP, Calmy A, Evison JM, Hasse B, Schiffer V, Wagels T, Nuesch R, Magenta L, Ledergerber B, Jenni R, Speich R, Opravil M, Swiss HIV Cohort Study Group . Pulmonary arterial hypertension related to HIV infection: Improved hemodynamics and survival associated with antiretroviral therapy. Clin Infect Dis. 2004; 38:8:11781185.
    [Google الباحث العلمي]
  196. Wong AR, Rasool AHG, Abidin NZ, Noor AR, Quah BS. Sildenafil as treatment for human immunodeficiency virus-related pulmonary hypertension in a child. J Paediatr Child Health. 2006; 42:3:147148.
    [Google الباحث العلمي]
  197. Degano B, Guillaume M, Savale L, Montani D, Jaïs X, Yaici A, Le Pavec J, Humbert M, Simonneau G, Sitbon O. HIV-associated pulmonary arterial hypertension: Survival and prognostic factors in the modern therapeutic era. AIDS. 2010; 24:1:6775.
    [Google الباحث العلمي]
  198. Degano B, Valmary S, Sitbon O, Humbert M. Pulmonary arterial hypertension and HIV and other viral infections. In: Humbert MSouza RSimonneau G, eds. Pulmonary Vascular Disorders. Prog Respir Res. Vol 41. Basel: Karger 2012;:105112Available from: http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstractBuch&ArtikelNr=334362&ProduktNr=255594.
    [Google الباحث العلمي]
  199. Sitbon O, Lascoux-Combe C, Delfraissy JF, Yeni PG, Raffi F, De Zuttere D, Gressin V, Clerson P, Sereni D, Simonneau G. Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era. Am J Respir Crit Care Med. 2008; 177:1:108113.
    [Google الباحث العلمي]
  200. Ghofrani HA, Distler O, Gerhardt F, Gorenflo M, Grünig E, Haefeli WE, Held M, Hoeper MM, Kähler CM, Kaemmerer H, Klose H, Köllner V, Kopp B, Mebus S, Meyer A, Miera O, Pittrow D, Riemekasten G, Rosenkranz S, Schranz D, Voswinckel R, Olschewski H. Treatment of pulmonary arterial hypertension (PAH): Updated recommendations of the cologne consensus conference 2011. Int J Cardiol. 2011; 154:Suppl 1:S20S33.
    [Google الباحث العلمي]
  201. Schumacher YO, Zdebik A, Huonker M, Kreisel W. Sildenafil in HIV-related pulmonary hypertension. AIDS. 2001; 15:13:17471748.
    [Google الباحث العلمي]
  202. D'Alto M, Romeo E, Argiento P, Sarubbi B, Santoro G, Grimaldi N, Correra A, Scognamiglio G, Russo MG, Calabrò R. Bosentan-sildenafil association in patients with congenital heart disease-related pulmonary arterial hypertension and Eisenmenger physiology. Int J Cardiol. 2012; 155:3:378382.
    [Google الباحث العلمي]
  203. Singh TP, Rohit M, Grover A, Malhotra S, Vijayvergiya R. A randomized, placebo-controlled, double-blind, crossover study to evaluate the efficacy of oral sildenafil therapy in severe pulmonary artery hypertension. Am Heart J. 2006; 151:4:851e1851e5.
    [Google الباحث العلمي]
  204. Mukhopadhyay S, Sharma M, Ramakrishnan S, Yusuf J, Gupta MD, Bhamri N, Trehan V, Tyagi S. Phosphodiesterase-5 inhibitor in eisenmenger syndrome: A preliminary observational study. Circulation. 2006; 114:17:18071810.
    [Google الباحث العلمي]
  205. Chau EMC, Fan KYY, Chow WH. Effects of chronic sildenafil in patients with Eisenmenger syndrome versus idiopathic pulmonary arterial hypertension. Int J Cardiol. 2007; 120:3:301305.
    [Google الباحث العلمي]
  206. Lu XL, Xiong CM, Shan GL, Zhu XY, Wu BX, Wu GH, Liu ZH, Ni XH, Cheng XS, Gu Q, Zhao ZH, Zhang DZ, Li WM, Zhang C, Tian HY, Guo YJ, Guo T, Liu HM, Zhang WJ, Gu H, Huang SA, Chen JY, Wu WF, Huang K, Li JJ, He JG. Impact of sildenafil therapy on pulmonary arterial hypertension in adults with congenital heart disease. Cardiovasc Ther. 2010; 28:6:350355.
    [Google الباحث العلمي]
  207. Sun YJ, Yang T, Zeng WJ, Gu Q, Ni XH, Zhao ZH, Liu ZH, Xiong CM, He JG. Impact of sildenafil on survival of patients with Eisenmenger syndrome. J Clin Pharmacol. 2013; 53:6:611618.
    [Google الباحث العلمي]
  208. Mukhopadhyay S, Nathani S, Yusuf J, Shrimal D, Tyagi S. Clinical efficacy of phosphodiesterase-5 inhibitor tadalafil in Eisenmenger syndrome-a randomized, placebo-controlled, double-blind crossover study. Congenit Heart Dis. 2011; 6:5:424431.
    [Google الباحث العلمي]
  209. Goldberg DJ, French B, McBride MG, Marino BS, Mirarchi N, Hanna BD, Wernovsky G, Paridon SM, Rychik J. Impact of oral sildenafil on exercise performance in children and young adults after the fontan operation: A randomized, double-blind, placebo-controlled, crossover trial. Circulation. 2011; 123:11:11851193.
    [Google الباحث العلمي]
  210. Manes A, Palazzini M, Leci E, Reggiani MLB, Branzi A, Galiè N. Current era survival of patients with pulmonary arterial hypertension associated with congenital heart disease: A comparison between clinical subgroups. Eur Heart J. 2014; 35:11:716724.
    [Google الباحث العلمي]
  211. Okyay K, Cemri M, Boyac B, Yalcn R, Cengel A. Use of long-term combined therapy with inhaled iloprost and oral sildenafil in an adult patient with Eisenmenger syndrome. Cardiol Rev. 2005; 13:6:312314.
    [Google الباحث العلمي]
  212. Iversen K, Jensen AS, Jensen TV, Vejlstrup NG, Søndergaard L. Combination therapy with bosentan and sildenafil in Eisenmenger syndrome: A randomized, placebo-controlled, double-blinded trial. Eur Heart J. 2010; 31:9:11241131.
    [Google الباحث العلمي]
  213. Fedullo P, Kerr KM, Kim NH, Auger WR. Chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med. 2011; 183:12:16051613.
    [Google الباحث العلمي]
  214. Fedullo PF, Auger WR, Kerr KM, Rubin LJ. Chronic thromboembolic pulmonary hypertension. N Engl J Med. 2001; 345:20:14651472.
    [Google الباحث العلمي]
  215. De Jesus Perez VA, Zamanian RT, Jais X, D'Armini AM, Jansa P. Chronic thromboembolic pulmonary hypertension. N Engl J Med. 2011; 2011:364:16771678.
    [Google الباحث العلمي]
  216. Hoeper MM, Mayer E, Simonneau G, Rubin LJ. Chronic thromboembolic pulmonary hypertension. Circulation. 2006; 113:16:20112020.
    [Google الباحث العلمي]
  217. Ghofrani HA, Schermuly RT, Rose F, Wiedemann R, Kohstall MG, Kreckel A, Olschewski H, Weissmann N, Enke B, Ghofrani S, Seeger W, Grimminger F. Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med. 2003; 167:8:11391141.
    [Google الباحث العلمي]
  218. Reichenberger F, Voswinckel R, Enke B, Rutsch M, El Fechtali E, Schmehl T, Olschewski H, Schermuly R, Weissmann N, Ghofrani HA, Grimminger F, Mayer E, Seeger W. Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension. Eur Respir J. 2007; 30:5:922927.
    [Google الباحث العلمي]
  219. Suntharalingam J, Treacy CM, Doughty NJ, Goldsmith K, Soon E, Toshner MR, Sheares KK, Hughes R, Morrell NW, Pepke-Zaba J. Long-term use of sildenafil in inoperable chronic thromboembolic pulmonary hypertension. Chest. 2008; 134:2:229236.
    [Google الباحث العلمي]
  220. Ghofrani HA, D'Armini AM, Grimminger F, Hoeper MM, Jansa P, Kim NH, Mayer E, Simonneau G, Wilkins MR, Fritsch A, Neuser D, Weimann G, Wang C, CHEST-1 Study Group . Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med. 2013; 369:4:319329.
    [Google الباحث العلمي]
  221. Hsu AR, Barnholt KE, Grundmann NK, Lin JH, McCallum SW, Friedlander AL. Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia. J Appl Physiol. 2006; 100:6:20312040.
    [Google الباحث العلمي]
  222. Richalet JP, Gratadour P, Robach P, Pham I, Déchaux M, Joncquiert-Latarjet A, Mollard P, Brugniaux J, Cornolo J. Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension. Am J Respir Crit Care Med. 2005; 171:3:275281.
    [Google الباحث العلمي]
  223. Aldashev AA, Kojonazarov BK, Amatov TA, Sooronbaev TM, Mirrakhimov MM, Morrell NW, Wharton J, Wilkins MR. Phosphodiesterase type 5 and high altitude pulmonary hypertension. Thorax. 2005; 60:8:683687.
    [Google الباحث العلمي]
  224. Ghofrani HA, Reichenberger F, Kohstall MG, Mrosek EH, Seeger T, Olschewski H, Seeger W, Grimminger F. Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: A randomized, double-blind, placebo-controlled crossover trial. Ann Intern Med. 2004; 141:3:169177.
    [Google الباحث العلمي]
  225. Reichenberger F, Kohstall MG, Seeger T, Olschewski H, Grimminger F, Seeger W, Ghofrani HA. Effect of sildenafil on hypoxia-induced changes in pulmonary circulation and right ventricular function. Respir Physiol Neurobiol. 2007; 159:2:196201.
    [Google الباحث العلمي]
  226. Bates MG, Thompson AA, Baillie JK, Sutherland AI, Irving JB, Hirani N, Webb DJ. Sildenafil citrate for the prevention of high altitude hypoxic pulmonary hypertension: Double blind, randomized, placebo-controlled trial. High Alt Med Biol. 2011; 12:3:207214.
    [Google الباحث العلمي]
  227. Faoro V, Lamotte M, Deboeck G, Pavelescu A, Huez S, Guenard H, Martinot JB, Naeije R. Effects of sildenafil on exercise capacity in hypoxic normal subjects. High Alt Med Biol. 2007; 8:2:155163.
    [Google الباحث العلمي]
  228. Maggiorini M, Brunner-La Rocca HP, Peth S, Fischler M, Böhm T, Bernheim A, Kiencke S, Bloch KE, Dehnert C, Naeije R, Lehmann T, Bärtsch P, Mairbäurl H. Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema: A randomized trial. Ann Intern Med. 2006; 145:7:497506.
    [Google الباحث العلمي]
  229. Xu Y, Liu Y, Liu J, Qian G. Meta-analysis of clinical efficacy of sildenafil, a phosphodiesterase type-5 inhibitor on high altitude hypoxia and its complications. High Alt Med Biol. 2014; 15:1:4651.
    [Google الباحث العلمي]
  230. Travadi JN, Patole SK. Phosphodiesterase inhibitors for persistent pulmonary hypertension of the newborn: A review. Pediatr Pulmonol. 2003; 36:6:529535.
    [Google الباحث العلمي]
  231. Scipioni A, Giorgi M, Nuccetelli V, Stefanini S. Immunohistochemical localisation of PDE5 in rat lung during pre- and postnatal development. J Biomed Biotechnol. 2009; 2009::17.
    [Google الباحث العلمي]
  232. Jaillard S, Larrue B, Deruelle P, Delelis A, Rakza T, Butrous G, Storme L. Effects of phosphodiesterase 5 inhibitor on pulmonary vascular reactivity in the fetal lamb. Ann Thorac Surg. 2006; 81:3:935942.
    [Google الباحث العلمي]
  233. Larrue B, Jaillard S, Lorthioir M, Roubliova X, Butrous G, Rakza T, Warembourg H, Storme L. Pulmonary vascular effects of sildenafil on the development of chronic pulmonary hypertension in the ovine fetus. Am J Physiol Lung Cell Mol Physiol. 2005; 288:6:L1193L1200.
    [Google الباحث العلمي]
  234. Atz AM, Wessel DL. Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology. 1999; 91:1:307310.
    [Google الباحث العلمي]
  235. Bigatello LM, Hess D, Dennehy KC, Medoff BD, Hurford WE. Sildenafil can increase the response to inhaled nitric oxide. Anesthesiology. 2000; 92:6:1827.
    [Google الباحث العلمي]
  236. Miller OI, Tang SF, Keech A, Pigott NB, Beller E, Celermajer DS. Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: A randomised double-blind study. Lancet. 2000; 356:9240:14641469.
    [Google الباحث العلمي]
  237. Abrams D, Schulze-Neick I, Magee AG. Sildenafil as a selective pulmonary vasodilator in childhood primary pulmonary hypertension. Heart. 2000; 84:2:e4.
    [Google الباحث العلمي]
  238. 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. 2006; 117:4:10771083.
    [Google الباحث العلمي]
  239. Steinhorn RH, Kinsella JP, Pierce C, Butrous G, Dilleen M, Oakes M, Wessel DL. Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension. J Pediatr. 2009; 155:6:841847.
    [Google الباحث العلمي]
  240. Steinhorn RH, Kinsella JP, Butrous G, Dilleen M, Oakes M, Wessel DL. Abstract 2768: Open-Label, Multicentre, Pharmacokinetic Study of IV Sildenafil in the Treatment of Neonates With Persistent Pulmonary Hypertension of the Newborn (PPHN). Circulation. 2007; 116:16 Suppl:II_614.
    [Google الباحث العلمي]
  241. Schulze-Neick I, Hartenstein P, Li J, Stiller B, Nagdyman N, Hübler M, Butrous G, Petros A, Lange P, Redington AN. Intravenous sildenafil is a potent pulmonary vasodilator in children with congenital heart disease. Circulation. 2003; 108:10 suppl 1:II167II173.
    [Google الباحث العلمي]
  242. Fraisse A, Butrous G, Taylor M, Oakes M, Dilleen M, Wessel D. Intravenous sildenafil for postoperative pulmonary hypertension in children with congenital heart disease. Intensive Care Med. 2011; 37:3:502509.
    [Google الباحث العلمي]
  243. Tunks RD, Barker PCA, Benjamin DK, Cohen-Wolkowiez M, Fleming GA, Laughon M, Li JS, Hill KD. Sildenafil exposure and hemodynamic effect after fontan surgery. Pediatr Crit Care Med. 2014; 15:1:2834.
    [Google الباحث العلمي]
  244. Douwes JM, Roofthooft MTR, Loon RLEV, Ploegstra M-J, Bartelds B, Hillege HL, Berger RM. Sildenafil add-on therapy in paediatric pulmonary arterial hypertension, experiences of a national referral centre. Heart. 2014; 100:3:224230.
    [Google الباحث العلمي]
  245. van Loon RL, Roofthooft MT, van Osch-Gevers M, Delhaas T, Strengers JL, Blom NA, Backx A, Berger RM. Clinical characterization of pediatric pulmonary hypertension: Complex presentation and diagnosis. J Pediatr. 2009; 155:2:17682e1.
    [Google الباحث العلمي]
  246. Cerro MJ, Abman S, Diaz G, Freudenthal AH, Freudenthal F, Harikrishnan S, Haworth SG, Ivy D, Lopes AA, Raj JU, Sandoval J, Stenmark K, Adatia I. A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: Report from the PVRI pediatric taskforce. Panama Pulm Circ. 2011; 1:2:286298.
    [Google الباحث العلمي]
  247. Lammers AE, Adatia I, Cerro MJ, Diaz G, Freudenthal AH, Freudenthal F, Harikrishnan S, Ivy D, Lopes AA, Raj JU, Sandoval J, Stenmark K, Haworth SG. Functional classification of pulmonary hypertension in children: Report from the PVRI pediatric taskforce. Panama Pulm Circ. 2011; 1:2:280285.
    [Google الباحث العلمي]
  248. Barst RJ, Ertel SI, Beghetti M, Ivy DD. Pulmonary arterial hypertension: A comparison between children and adults. Eur Respir J. 2011; 37:3:665677.
    [Google الباحث العلمي]
  249. Humpl T, Reyes JT, Holtby H, Stephens D, Adatia I. Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension twelve-month clinical trial of a single-drug, open-label, pilot study. Circulation. 2005; 111:24:32743280.
    [Google الباحث العلمي]
  250. Barst RJ, Ivy DD, Gaitan G, Szatmari A, Rudzinski A, Garcia AE, Sastry BK, Pulido T, Layton GR, Serdarevic-Pehar M, Wessel DL. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation. 2012; 125:2:324334.
    [Google الباحث العلمي]
  251. Barst RJ, Beghetti M, Pulido T, Layton G, Konourina I, Zhang M, Ivy DD, STARTS-2 Investigators . STARTS-2: long-term survival with oral sildenafil monotherapy in treatment-naive pediatric pulmonary arterial hypertension. Circulation. 2014; 129:19:19141923.
    [Google الباحث العلمي]
  252. Abman SH, Kinsella JP, Rosenzweig EB, Krishnan U, Kulik T, Mullen M, Wessel DL, Steinhorn R, Adatia I, Hanna B, Feinstein J, Fineman J, Raj U, Humpl T, Pediatric Pulmonary Hypertension Network (PPHNet) . Implications of the U.S. food and drug administration warning against the use of sildenafil for the treatment of pediatric pulmonary hypertension. Am J Respir Crit Care Med. 2013; 187:6:572575.
    [Google الباحث العلمي]
  253. US Food and Drug Administration. FDA Drug Safety Communication: FDA recommends against use of Revatio (sildenafil) in children with pulmonary hypertension [Internet]. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm317123.htm.
  254. McElhinney DB. A new START for sildenafil in pediatric pulmonary hypertension: Reframing the dose-survival relationship in the STARTS-2 trial. Circulation. 2014; 129:19:19051908.
    [Google الباحث العلمي]
  255. Barst RJ, Beghetti M, Pulido T, Layton G, Konourina I, Zhang M, Ivy DD, STARTS-2 Investigators . STARTS-2: long-term survival with oral sildenafil monotherapy in treatment-naive pediatric pulmonary arterial hypertension. Circulation. 2014; 129:19:19141923.
    [Google الباحث العلمي]
  256. Kang KK, Ahn GJ, Sohn YS, Ahn BO, Kim WB. DA-8159, a new PDE5 inhibitor, attenuates the development of compensatory right ventricular hypertrophy in a rat model of pulmonary hypertension. J Int Med Res. 2003; 31:6:517528.
    [Google الباحث العلمي]
  257. Nagendran J, Sutendra G, Paterson I, Champion HC, Webster L, Chiu B, Haromy A, Rebeyka IM, Ross DB, Michelakis ED. Endothelin axis is upregulated in human and rat right ventricular hypertrophy. Circ Res. 2013; 112:2:347354.
    [Google الباحث العلمي]
  258. Xie Y-P, Chen B, Sanders P, Guo A, Li Y, Zimmerman K, Wang LC, Weiss RM, Grumbach IM, Anderson ME, Song LS. Sildenafil prevents and reverses transverse-tubule remodeling and Ca2+ handling dysfunction in right ventricle failure induced by pulmonary artery hypertension. Hypertension. 2012; 59:2:355362.
    [Google الباحث العلمي]
  259. Friedberg MK, Redington AN. Right versus left ventricular failure differences, similarities, and interactions. Circulation. 2014; 129:9:10331044.
    [Google الباحث العلمي]
  260. Senzaki H, Smith CJ, Juang GJ, Isoda T, Mayer SP, Ohler A, Paolocci N, Tomaselli GF, Hare JM, Kass DA. Cardiac phosphodiesterase 5 (cGMP-specific) modulates beta-adrenergic signaling in vivo and is down-regulated in heart failure. FASEB J. 2001; 15:10:17181726.
    [Google الباحث العلمي]
  261. Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER, Bedja D, Gabrielson KL, Wang Y, Kass DA. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med. 2005; 11:2:214222.
    [Google الباحث العلمي]
  262. Kukreja RC, Salloum F, Das A, Ockaili R, Yin C, Bremer YA, Fisher PW, Wittkamp M, Hawkins J, Chou E, Kukreja AK, Wang X, Marwaha VR, Xi L. Pharmacological preconditioning with sildenafil: Basic mechanisms and clinical implications. Vascul Pharmacol. 2005; 42:5-6:219232.
    [Google الباحث العلمي]
  263. Salloum F, Yin C, Xi L, Kukreja RC. Sildenafil induces delayed preconditioning through inducible nitric oxide synthase-dependent pathway in mouse heart. Circ Res. 2003; 92:6:595597.
    [Google الباحث العلمي]
  264. Das A, Xi L, Kukreja RC. Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling. J Biol Chem. 2005; 280:13:1294412955.
    [Google الباحث العلمي]
  265. Sahara M, Sata M, Morita T, Nakajima T, Hirata Y, Nagai R. A phosphodiesterase-5 inhibitor vardenafil enhances angiogenesis through a protein kinase G-dependent hypoxia-inducible factor-1/vascular endothelial growth factor pathway. Arterioscler Thromb Vasc Biol. 2010; 30:7:13151324.
    [Google الباحث العلمي]
  266. Lewis GD, Lachmann J, Camuso J, Lepore JJ, Shin J, Martinovic ME, Systrom DM, Bloch KD, Semigran MJ. Sildenafil improves exercise hemodynamics and oxygen uptake in patients with systolic heart failure. Circulation. 2007; 115:1:5966.
    [Google الباحث العلمي]
  267. Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J, Tawakol A, Gerszten RE, Systrom DM, Bloch KD, Semigran MJ. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation. 2007; 116:14:15551562.
    [Google الباحث العلمي]
  268. Guazzi M, Vicenzi M, Arena R, Guazzi MD. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail. 2011; 4:1:817.
    [Google الباحث العلمي]
  269. Redfield MM, Borlaug BA, Lewis GD, Mohammed SF, Semigran MJ, Lewinter MM, Deswal A, Hernandez AF, Lee KL, Braunwald E, Heart Failure Clinical Research Network . PhosphdiesteRasE-5 inhibition to improve clinical status and exercise capacity in diastolic heart failure (RELAX) trial: Rationale and design. Circ Heart Fail. 2012; 5:5:653659.
    [Google الباحث العلمي]
  270. Borlaug B, Lewis G, McNulty S, Semigran M, LeWinter M, Chen H, Lin G, Anstrom K, Velazquez E, Shah M, Margulies K, Redfield M. Diverging effects of sildenafil on ventricular-vascular function in HFPEF. J Am Coll Cardiol. 2014; 63:12_S, Available from: http://dx.doi.org/10.1016/S0735-1097(14)60759-2..
    [Google الباحث العلمي]
  271. Sharma K, Kass DA. Heart failure with preserved ejection fraction mechanisms, clinical features, and therapies. Circ Res. 2014; 115:1:7996.
    [Google الباحث العلمي]
  272. Melenovsky V, Hwang S-J, Lin G, Redfield MM, Borlaug BA. Right heart dysfunction in heart failure with preserved ejection fraction. Eur Heart J. pii: ehu193. [Epub ahead of print] 2014.
    [Google الباحث العلمي]
  273. Mohammed SF, Borlaug BA, McNulty S, Lewis GD, Lin G, Zakeri R, Semigran MJ, LeWinter M, Hernandez AF, Braunwald E, Redfield MM. Resting ventricular-vascular function and exercise capacity in heart failure with preserved ejection fraction: A RELAX trial ancillary study. Circ Heart Fail. 2014; 7:4:580589.
    [Google الباحث العلمي]
  274. Zakeri R, Borlaug BA, McNulty SE, Mohammed SF, Lewis GD, Semigran MJ, Deswal A, LeWinter M, Hernandez AF, Braunwald E, Redfield MM. Impact of atrial fibrillation on exercise capacity in heart failure with preserved ejection fraction A RELAX trial ancillary study. Circ Heart Fail. 2014; 7:1:123130.
    [Google الباحث العلمي]
  275. Minai OA, Chaouat A, Adnot S. Pulmonary hypertension in COPD: Epidemiology, significance, and management pulmonary vascular disease: The global perspective. Chest. 2010; 137:6_suppl:39S51S.
    [Google الباحث العلمي]
  276. Voelkel NF, Cool CD. Pulmonary vascular involvement in chronic obstructive pulmonary disease. Eur Respir J. 2003; 22:46 suppl:28s32s.
    [Google الباحث العلمي]
  277. Barberà JA. Chronic obstructive pulmonary disease: A Disease of the endothelium? Am J Respir Crit Care Med. 2013; 188:1:57.
    [Google الباحث العلمي]
  278. Goudie A, Hopkinson P, Anderson W, Lipworth B, Struthers A. The effects of sildenafil on lung function in COPD. Eur Respir J. 2012; 40:Suppl 56:P2188.
    [Google الباحث العلمي]
  279. Wang T, Liu Y, Chen L, Wang X, Hu XR, Feng YL, Liu DS, Xu D, Duan YP, Lin J, Ou XM, Wen FQ. Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats. Eur Respir J. 2009; 33:5:11221132.
    [Google الباحث العلمي]
  280. Ghofrani HA, Wiedemann R, Rose F, Schermuly RT, Olschewski H, Weissmann N, Gunther A, Walmrath D, Seeger W, Grimminger F. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: A randomised controlled trial. Lancet. 2002; 360:9337:895900.
    [Google الباحث العلمي]
  281. Amen EM, Becker E-M, Truebel H. Analysis of V/Q-matching—a safety biomarker in pulmonary drug development? Biomarkers. 2011; 16:S1:S510.
    [Google الباحث العلمي]
  282. Alp S, Skrygan M, Schmidt WE, Bastian A. Sildenafil improves hemodynamic parameters in COPD—an investigation of six patients. Pulm Pharmacol Ther. 2006; 19:6:386390.
    [Google الباحث العلمي]
  283. Madden BP, Allenby M, Loke T-K, Sheth A. A potential role for sildenafil in the management of pulmonary hypertension in patients with parenchymal lung disease. Vascul Pharmacol. 2006; 44:5:372376.
    [Google الباحث العلمي]
  284. Naeije R, Boerrigter BG. Pulmonary hypertension at exercise in COPD: Does it matter? Eur Respir J. 2013; 41:5:10021004.
    [Google الباحث العلمي]
  285. Naeije R. Pulmonary hypertension and right heart failure in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005; 2:1:2022.
    [Google الباحث العلمي]
  286. Blanco I, Santos S, Gea J, Güell R, Torres F, Gimeno-Santos E, Rodriguez DA, Vilaró J, Gómez B, Roca J, Barberà JA. Sildenafil to improve respiratory rehabilitation outcomes in COPD: A controlled trial. Eur Respir J. 2013; 42:4:982992.
    [Google الباحث العلمي]
  287. Goudie AR, Lipworth BJ, Hopkinson PJ, Wei L, Struthers AD. Tadalafil in patients with chronic obstructive pulmonary disease: A randomised, double-blind, parallel-group, placebo-controlled trial. Lancet Respir Med. 2014; 2:4:293300.
    [Google الباحث العلمي]
  288. Holverda S, Rietema H, Bogaard HJ, Westerhof N, Postmus PE, Boonstra A, Vonk-Noordegraaf A. Acute effects of sildenafil on exercise pulmonary hemodynamics and capacity in patients with COPD. Pulm Pharmacol Ther. 2008; 21:3:558564.
    [Google الباحث العلمي]
  289. Lederer DJ, Bartels MN, Schluger NW, Brogan F, Jellen P, Thomashow BM, Kawut SM. Sildenafil for chronic obstructive pulmonary disease: A randomized crossover trial. COPD. 2012; 9:3:268275.
    [Google الباحث العلمي]
  290. Maron BA, Goldstein RH, Rounds SI, Shapiro S, Jankowich M, Garshick E, Moy ML, Gagnon D, Choudhary G. Study design and rationale for investigating phosphodiesterase type 5 inhibition for the treatment of pulmonary hypertension due to chronic obstructive lung disease: The TADA-PHiLD (TADAlafil for pulmonary hypertension associated with chronic obstructive lung disease) trial. Pulm Circ. 2013; 3:4:889897.
    [Google الباحث العلمي]
  291. Hurdman J, Condliffe R, Elliot CA, Swift A, Rajaram S, Davies C, Hill C, Hamilton N, Armstrong IJ, Billings C, Pollard L, Wild JM, Lawrie A, Lawson R, Sabroe I, Kiely DG. Pulmonary hypertension in COPD: Results from the ASPIRE registry. Eur Respir J. 2013; 41:6:12921301.
    [Google الباحث العلمي]
  292. Collard HR, Anstrom KJ, Schwarz MI, Zisman DA. SIldenafil improves walk distance in idiopathic pulmonary fibrosis. Chest. 2007; 131:3:897899.
    [Google الباحث العلمي]
  293. Zisman DA, Schwarz M, Anstrom KJ, Collard HR, Flaherty KR, Hunninghake GW. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med. 2010; 363:7:620628.
    [Google الباحث العلمي]
  294. Nathan SD, King CS. Treatment of pulmonary hypertension in idiopathic pulmonary fibrosis: Shortfall in efficacy or trial design? Drug Des Devel Ther. 2014; 8::875885.
    [Google الباحث العلمي]
http://instance.metastore.ingenta.com/content/journals/10.5339/gcsp.2014.42
Loading
/content/journals/10.5339/gcsp.2014.42
Loading

جارٍ تحميل البيانات والوسائط...

  • نوع المستند: Research Article
الموضوعات الرئيسية pulmonary hypertensionpulmonary phosphodiesterase inhibitors and pulmonary vascular disease
هذه الخانة مطلوبة
يُرجى إدخال عنوان بريد إلكتروني صالح
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error