Gene and stem cell therapy in the treatment of erectile dysfunction and pulmonary hypertension; Potential treatments for the common problem of endothelial dysfunction

Current Gene Therapy

Volumn 7, Issue 2, 2007, Pages 131-153

  Nossaman, Bobby D ^a,b   Gur, Serap ^b   Kadowitz, Philip J ^b  

^a OCHSNER CLINIC FOUNDATION   (United States)

^b TULANE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

Author keywords

Adult; Aging pa; Aging ph; Cardiovascular diseases dt; Endothelium; Gene therapy mt; Impotence et; Male; Pulmonary hypertension dt; Risk factors; Vascular pp

Indexed keywords

ADENOVIRUS VECTOR; ANDROGEN; ANGIOPOIETIN; ANTIHYPERTENSIVE AGENT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BONE MORPHOGENETIC PROTEIN RECEPTOR 2; CALCITONIN GENE RELATED PEPTIDE; CALCIUM ANTAGONIST; CALCIUM CHANNEL BLOCKING AGENT; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; LARGE CONDUCTANCE CALCIUM ACTIVATED POTASSIUM CHANNEL; NEUROTROPHIN 3; NITRIC OXIDE SYNTHASE; PHOSPHODIESTERASE V INHIBITOR; POTASSIUM CHANNEL KV1.5; PROSTACYCLIN SYNTHASE; PROTEINASE INHIBITOR; RHO KINASE; SCATTER FACTOR; SEROTONIN UPTAKE INHIBITOR; SILDENAFIL; SUPEROXIDE DISMUTASE; SURVIVIN; TADALAFIL; TESTOSTERONE; UNINDEXED DRUG; VARDENAFIL; VASCULOTROPIN; VASOACTIVE INTESTINAL POLYPEPTIDE;

ALCOHOL ABSTINENCE; ANDROGEN BLOOD LEVEL; APOPTOSIS; BLOOD FLOW; BLOOD VESSEL TONE; BLOOD VESSEL WALL; BONE MARROW TRANSPLANTATION; CLINICAL ASSESSMENT; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CONTROLLED CLINICAL TRIAL; CORONARY ARTERY DISEASE; COUNSELING; DIABETES MELLITUS; DISEASE ASSOCIATION; DRUG CONTRAINDICATION; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; ENDOTHELIAL DYSFUNCTION; ERECTILE DYSFUNCTION; GENE MUTATION; GENE OVEREXPRESSION; GENE TRANSFER; HOMEOSTASIS; HORMONE SUBSTITUTION; HUMAN; HYPERTENSION; INCIDENCE; INFLAMMATION; KINESIOTHERAPY; LUNG TRANSPLANTATION; MESENCHYMAL STEM CELL TRANSPLANTATION; MONOTHERAPY; NONHUMAN; PATHOPHYSIOLOGY; PROGNOSIS; PULMONARY HYPERTENSION; RANDOMIZED CONTROLLED TRIAL; REVIEW; RISK FACTOR; SMOKING CESSATION; STEM CELL GENE THERAPY; STEM CELL MOBILIZATION; THROMBOGENICITY; UPREGULATION; VASCULAR ENDOTHELIUM; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY;

ENDOTHELIUM, VASCULAR; GENE THERAPY; HUMANS; HYPERTENSION, PULMONARY; IMPOTENCE; MALE; STEM CELL TRANSPLANTATION; TISSUE THERAPY;

EID: 34247877794     PISSN: 15665232     EISSN: None     Source Type: Journal    
DOI: 10.2174/156652307780363161     Document Type: Review

References (306)

1. Adnot, S. (2005) Lessons learned from cancer may help in the treatment of pulmonary hypertension.[comment]. J. Clin. Invest., 115: 1461-1463.
2. Ahn, H. S., Foster, M., Cable, M., Pitts, B. J. and Sybertz, E. J. (1991) Ca/cam-stimulated and cgmp-specific phosphodiesterases in vascular and non-vascular tissues. Adv. Exp. Med. Biol., 308: 191-197.
3. Aldashev, A. A., Kojonazarov, B. K., Amatov, T. A., Sooronbaev, T. M., Mirrakhimov, M. M., Morrell, N. W., Wharton, J. and Wilkins, M. R. (2005) Phosphodiesterase type 5 and high altitude pulmonary hypertension. Thorax, 60: 683-687.
4. Alessandri, G., Emanueli, C. and Madeddu, P. (2004) Genetically engineered stem cell therapy for tissue regeneration. Ann. N. Y. Acad. Sci., 1015: 271-284.
5. Ambrose, J. A. and Barua, R. S. (2004) The pathophysiology of cigarette smoking and cardiovascular disease: An update. J. Am. Coll. Cardiol., 43: 1731-1737.
6. Archer, S. L. (2002) Potassium channels and erectile dysfunction. Vascular Pharmacology, 38: 61-71.
7. Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G. and Isner, J. M. (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science, 275: 964-966.
8. Assmus, B., Honold, J., Schachinger, V., Britten, M. B., Fischer-Rasokat, U., Lehmann, R., Teupe, C., Pistorius, K., Martin, H., Abolmaali, N. D., Tonn, T., Dimmeler, S. and Zeiher, A. M. (2006) Transcoronary transplantation of progenitor cells after myocardial infarction. N. Engl. J. Med., 355:1222-1232.
9. Azadzoi, K. M. (2006) Vasculogenic erectile dysfunction: Beyond the haemodynamic changes. BJU Int., 97: 11-16.
10. Azadzoi, K. M. and Goldstein, I. (1992) Erectile dysfunction due to atherosclerotic vascular disease: The development of an animal model. J. Urol., 147: 1675-1681.
11. Azadzoi, K. M., Goldstein, I., Siroky, M. B., Traish, A. M., Krane, R. J. and Saenz de Tejada, I. (1998) Mechanisms of ischemia-induced cavernosal smooth muscle relaxation impairment in a rabbit model of vasculogenic erectile dysfunction. J. Urol., 160: 2216-2222.
12. Azadzoi, K. M. and Saenz de Tejada, I. (1991) Hypercholesterolemia impairs endothelium-dependent relaxation of rabbit corpus cavemosum smooth muscle. J. Urol., 146: 238-240.
13. Azadzoi, K. M., Siroky, M. B. and Goldstein, I. (1996) Study of etiologic relationship of arterial atherosclerosis to corporal veno-occlusive dys-function in the rabbit. J. Urol., 155: 1795-1800.
14. Azevedo, L. C., Janiszewski, M., Soriano, F. G. and Laurindo, F. R. (2006) Redox mechanisms of vascular cell dysfunction in sepsis. Endoc. Metab. Imm. Disord. Drug Targets, 6: 159-164.
15. Baber, S. R., Deng, W., Master, R. G., Bunnell, B. A., Taylor, B. K., Murthy, S. N., Hyman, A. L. and Kadowitz, P. J. (2006) Intratracheal mesenchymal stem cell administration attenuates monocrotaline-induced pulmonary hypertension and endothelial dysfunction. Am. J. Physiol. Heart Circ. Physiol., 00173.02006.
16. Bakker, E. N. T. P., van der Meulen, E. T., van den Berg, B. M., Everts, V., Spaan, J. A. E. and VanBavel, E. (2002) Inward remodeling follows chronic vasoconstriction in isolated resistance arteries. J. Vasc. Res., 39: 12-20.
17. Ballas, S. K. and Marcolina, M. J. (2006) Hyperhemolysis during the evolution of uncomplicated acute painful episodes in patients with sickle cell anemia. Transfusion (Paris)., 46: 105-110.
18. Barber, C. L. and Iruela-Arispe, M. L. (2006) The ever-elusive endothelial progenitor cell: Identities, functions and clinical implications. Pediatr. Res., 59: 26R-32.
19. Barst, R. J., McGoon, M., Torbicki, A., Sitbon, O., Krowka, M. J., Olschewski, H. and Gaine, S. (2004) Diagnosis and differential assessment of pulmonary arterial hypertension. J. Am. Coll. Cardiol., 43: 40S-47S.
20. Basar, M. M., Sargon, M. F., Basar, H., Atam, A., Ak, F., Celik, H. H., Basar, R. and Akalin, Z. (1998) Comparative study between corpus cavernosum-electromyography findings and electron microscopy of cavernosal muscle biopsies in erectile dysfunction patients. Int. J. Urol., 5: 252-255.
21. Bauersachs, J. and Schafer, A. (2004) Heart failure, platelet activation and inhibition of the renin-angiotensin-aldosterone system. Arch. Mal. Coeur Vaiss., 97: 889-893.
22. Beavo, J. A. (1995) Cyclic nucleotide phosphodiesterases: Functional implications of multiple isoforms. Physiol. Rev., 75: 725-748.
23. Beck, C., Uramoto, H., Boren, J. and Akyurek, L. M. (2004) Tissue-specific targeting for cardiovascular gene transfer. Potential vectors and future challenges. Curr. Gene Ther., 4: 457-467.
24. Bednarz, B., Jaxa-Chamiec, T., Gebalska, J., Herbaczynska-Cedro, K. and Ceremuzynski, L. (2004) L-arginine supplementation prolongs exercise capacity in congestive heart failure. Kardiol. Pol., 60: 348-353.
25. Bella, A. J. and Brock G. B. (2004) Intracavernous pharmacotherapy for erectile dysfunction. Endocrine, 23: 149-155.
26. Bennett, N. E., Kim, J., H., Wolfe, D. P., Sasaki, K., Yoshimura, N., Goins, W. F., Huang, S., Nelson, J. B., de Groat, W. C., Glorioso, J. C. and Chancellor, M. B. (2005) Improvement in erectile dysfunction after neurotrophic factor gene therapy in diabetic rats. J. Urol., 173: 1820-1824.
27. Billups, K. L. (2005) Erectile dysfunction as an early sign of cardiovascular disease. Int. J. Impot. Res., 17 Suppl 1: S19-24.
28. Bivalacqua, T. J., Armstrong, J. S., Biggerstaff, J., Abdel-Mageed, A. B., Kadowitz, P. J. and Hellstrom, W. J. (2003) Gene transfer of extracellular sod to the penis reduces o2-[ast] and improves erectile function in aged rats. Am. J. Physiol. Heart Circ. Physiol., 284: H1408-H1421.
29. Bivalacqua, T. J., Champion, H. C., Abdel-Mageed, A. B., Kadowitz, P. J. and Hellstrom, W. J. (2001) Gene transfer of prepro-calcitonin generelated peptide restores erectile function in the aged rat. Biol. Reprod., 65: 1371-1377.
30. Bivalacqua, T. J., Champion, H. C., Mehta, Y. S., Abdel-Mageed, A. B., Sikka, S. C., Ignarro, L. J., Kadowitz, P. J. and Hellstrom, W. J. (2000) Adenoviral gene transfer of endothelial nitric oxide synthase (enos) to the penis improves age-related erectile dysfunction in the rat. Int. J. Impot. Res., 12 Suppl 3: S8-17.
31. Bivalacqua, T. J., Champion, H. C., Usta, M. F., Cellek, S., Chitaley, K., Webb, R. C., Lewis, R. L., Mills, T. M., Hellstrom, W. J. and Kadowitz, P. J. (2004) Rhoa/rho-kinase suppresses endothelial nitric oxide synthase in the penis: A mechanism for diabetes-associated erectile dysfunction.[see comment]. Proc. Natl. Acad. Sci. USA, 101: 9121-9126.
32. Bivalacqua, T. J., Deng, W., Kendirci, M., Usta, M. F., Robinson, C., Taylor, B. K., Murthy, S. N., Champion, H. C., Hellstrom, W. and Kadowitz, P. J. (2006) Mesenchymal stem cells alone or ex vivo gene-modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction. Am. J. Physiol. Heart Circ. Physiol., 00685. 02006.
33. Bivalacqua, T. J., Usta, M. F., Kendirci, M., Pradhan, L., Alvarez, X., Champion, H. C., Kadowitz, P. J. and Hellstrom, W. J. (2005) Superoxide anion production in the rat penis impairs erectile function in diabetes: Influence of in vivo extracellular superoxide dismutase gene therapy. J. Sex. Med. 2: 187-197; discussion 197-188.
34. Bonora, E. (2006) The metabolic syndrome and cardiovascular disease. Ann. Med., 38: 64-80.
35. Brett, S. J., Simon, J., Gibbs, R., Pepper, J. R. and Evans, T. W. (1996) Impairment of endothelium-dependent pulmonary vasodilation in patients with primary pulmonary hypertension. Thorax, 51: 89-91.
36. Britten, M. B., Abolmaali, N. D., Assmus, B., Lehmann, R., Honold, J., Schmitt, J., Vogl, T. J., Martin, H., Schachinger, V., Dimmeler, S. and Zeiher, A. M. (2003) Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (topcareami): Mechanistic insights from serial contrast-enhanced magnetic resonance imaging. Circulation, 108: 2212-2218.
37. Broekelmann, T. J., Limper, A. H., Colby, T. V. and McDonald, J. A. (1991) Transforming growth factor {beta} 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. PNAS, 88: 6642-6646.
38. Brown, N. J. (2005) Aldosterone and end-organ damage. Curr. Opin. Nephrol. Hypertens, 14: 235-241.
39. Brunner, H., Cockcroft, J. R., Deanfield, J., Donald, A., Ferrannini, E., Halcox, J., Kiowski, W., Luscher, T. F., Mancia, G., Natali, A., Oliver, J. J., Pessina, A. C., Rizzoni, D., Rossi, G. P., Salvetti, A., Spicker, L. E., Taddei, S., Webb, D. J. and Working Group on Endothelins and Endothelial Factors of the European Society of, H. (2005) Endothelial function and dysfunction. Part ii: Association with cardiovascular risk factors and diseases. A statement by the working group on endothelins and endothelial factors of the european society of hypertension. J. Hypertens, 23: 233-246.
40. Budts, W., Pokreisz, P., Nong, Z., Van Pelt, N., Gillijns, H., Gerard, R., Lyons, R., Collen, D., Bloch, K. D. and Janssens, S. (2000) Aerosol gene transfer with inducible nitric oxide synthase reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats. Circulation, 102: 2880-2885.
41. Bunnell, B. A., Deng, W., Robinson, C. M., Waldron, P. R., Bivalacqua, T. J., Baber, S. R., Hyman, A. L. and Kadowitz, P. J. (2005) Potential application for mesenchymal stem cells in the treatment of cardiovascular diseases. Can. J. Physiol. Pharmacol., 83: 529-539.
42. Burnett, A. L. (2006) Erectile dysfunction. J. Urol., 175: S25-31.
43. Burnett, A. L., Lowenstein, C. J., Bredt, D. S., Chang, T. S. and Snyder, S. H. (1992) Nitric oxide: A physiologic mediator of penile erection. Science, 257: 401-403.
44. Butany, J. W., Verma, S., Leask, R. L., Mohsen, B. and Asa, S. L. (2003) Genetic abnormalities of the endothelium. Microsc. Res. Tech., 60: 30-37.
45. Byrne, R. R., Henry, G. D., Rao, D. S., Huynh, T. T., Pippen, A. M., Annex, B. H., Hagen, P. O. and Donatucci, C. F. (2001) Vascular endothelial growth factor restores corporeal smooth muscle function in vitro. J. Urol., 165: 1310-1315.
46. Campbell, A. I., Zhao, Y., Sandhu, R. and Stewart, D. J. (2001) Cell-based gene transfer of vascular endothelial growth factor attenuates monocrotaline-induced pulmonary hypertension. Circulation, 104: 2242-2248.
47. Caretta, N., Ferlin, A., Palego, P. F. and Foresta, C. (2005) Erectile dysfunction in aging men: Testosterone role in therapeutic protocols. J. Endocrinol. Invest., 28: 108-111.
48. Carson, C. C., 3rd (2005) Cardiac safety in clinical trials of phosphodiesterase 5 inhibitors. Am. J. Cardiol., 96: 37M-41M.
49. Champion, H. C., Bivalacqua, T. J., D'Souza, F. M., Ortiz, L. A., Jeter, J. R., Toyoda, K., Heistad, D. D., Hyman, A. L. and Kadowitz, P. J. (1999a) Gene transfer of endothelial nitric oxide synthase to the lung of the mouse in vivo. Effect on agonist-induced and flow-mediated vascular responses. Circ. Res., 84: 1422-1432.
50. Champion, H. C., Bivalacqua, T. J., Greenberg, S. S., Giles, T. D., Hyman, A. L. and Kadowitz, P. J. (2002) Adenoviral gene transfer of endothelial nitric-oxide synthase (enos) partially restores normal pulmonary arterial pressure in enos-deficient mice. PNAS, 99: 13248-13253.
51. Champion, H. C., Bivalacqua, T. J., Hyman, A. L., Ignarro, L., Hellstrom, W. J. and Kadowitz, P. J. (1999b) Gene transfer of endothelial nitric oxide synthase to the penis augments erectile responses in the aged rat. Proc Natl Acad Sci USA 96: 11648-11652.
52. Champion, H. C., Bivalacqua, T. J., Toyoda, K., Heistad, D. D., Hyman, A. L. and Kadowitz, P. J. (2000) In vivo gene transfer of prepro-calcitonin gene-related peptide to the lung attenuates chronic hypoxia-induced pulmonary hypertension in the mouse.[see comment]. Circulation 101: 923-930.
53. Chancellor, M. B., Tirney, S., Mattes, C. E., Tzeng, E., Birder, L. A. and Kanai, A. (2003) Nitric oxide synthase gene transfer for erectile dysfunction in a rat model. BJU Int., 91: 691-696.
54. Chancellor, M. B., Yoshimura, N., Pruchnic, R. and Huard, J. (2001) Gene therapy strategies for urological dysfunction. Trends Mol. Med., 7: 301-306.
55. Channick, R. N., Sitbon, O., Barst, R. J., Manes, A. and Rubin, L. J. (2004) Endothelin receptor antagonists in pulmonary arterial hypertension. J. Am. Coll. Cardiol., 43: 62S-67S.
56. Chen, Y. F. and Oparil, S. (2000) Endothelial dysfunction in the pulmonary vascular bed. Am. J. Med. Sci., 320: 223-232.
57. Chicoine, L. G., Tzeng, E., Bryan, R., Saenz, S., Paffett, M. L., Jones, J., Lyons, C. R., Resta, T. C., Nelin, L. D. and Walker, B. R. (2004) Intratracheal adenoviral-mediated delivery of inos decreases pulmonary vasoconstrictor responses in rats. J. Appl. Physiol., 97: 1814-1822.
58. Chin, K. M., Kim, N. H. S. and Rubin, L. J. (2005) The right ventricle in pulmonary hypertension. Coron. Artery Dis., 16: 13-18.
59. Christ, G. J. (2003) Frontiers in gene therapy for erectile dysfunction. Int. J. Impot. Res., 15 Suppl 5: S33-40.
60. Christ, G. J. (2004) Gene therapy treatments for erectile and bladder dysfunction. Curr. Urol. Reports, 5: 52-60.
61. Christ, G. J., Day, N., Santizo, C., Sato, Y., Zhao, W., Sclafani, T., Bakal, R., Salman, M., Davies, K. and Melman, A. (2004) Intracorporal injection of hslo cdna restores erectile capacity in stz-diabetic f-344 rats in vivo. Am. J. Physiol.: Heart Circul. Physiol., 287: H1544-1553.
62. Cohen, R. A. (1993) Dysfunction of vascular endothelium in diabetes mellitus. Circulation, 87: V67-V76.
63. Cohn, J. N. and Colucci, W. (2006) Cardiovascular effects of aldosterone and post-acute myocardial infarction pathophysiology. Am. J. Cardiol., 97: 4F-12F.
64. Collados, M. T., Velazquez, B., Borbolla, J. R., Sandoval, J., Masso, F., Montano, L. F. and Guarner, V. (2003) Endothelin-1 and functional tissue factor: A possible relationship with severity in primary pulmonary hypertension. Heart Vessels, 18: 12-17.
65. Conraads, V. M., Bosmans, J. M., Claeys, M. J., Vrints, C. J., Snoeck, J. P., De Clerck, L. and Vermeire, P. A. (1994) Paradoxic pulmonary vasoconstriction in response to acetylcholine in patients with primary pulmonary hypertension. Chest, 106: 385-390.
66. Crilley, J. G., Dark, J. H. and Hall, J. A. (1998) Reversal of severe pulmonary hypertension with beta blockade in a patient with end stage left ventricular failure. Heart 80: 620-622.
67. Cuevas, A. M. and Germain, A. M. (2004) Diet and endothelial function. Biol. Res., 37: 225-230.
68. De Backer, T. L., Smedema, J. P. and Carlier, S. G. (2001) Current management of primary pulmonary hypertension. Biodrugs 15: 801-817.
69. de la Sierra, A. (2006) Angiotensin receptor blockers in hypertension and cardiovascular diseases. Cardiovas. Hematol. Agents Med. Chem., 4: 67-73.
70. De Meyer, G. R. Y. and Herman, A. G. (1997) Vascular endothelial dysfunction. Prog. Cardiovasc. Dis., 39: 325-342.
71. De Wet, C. J., Affleck, D. G., Jacobsohn, E., Avidan, M. S., Tymkew, H., Hill, L. L., Zanaboni, P. B., Moazami, N. and Smith, J. R. (2004) Inhaled prostacyclin is safe, effective, and affordable in patients with pulmonary hypertension, right heart dysfunction, and refractory hypoxemia after cardiothoracic surgery.[see comment]. J. Thorac. Cardiovasc. Surg., 127: 1058-1067.
72. Deng, W., St Hilaire, R.-C., Chattergoon, N. N., Jeter, J. R., Jr. and Kadowitz, P. J. (2006) Inhibition of vascular smooth muscle cell proliferation in vitro by genetically engineered marrow stromal cells secreting calcitonin gene-related peptide. Life Sci., 78: 1830-1838.
73. Dhawan, V., Handu, S. S., Nain, C. K. and Ganguly, N. K. (2005) Chronic l-arginine supplementation improves endothelial cell vasoactive functions in hypercholesterolemic and atherosclerotic monkeys. Mol. Cell. Biochem., 269: 1-11.
74. Dincer, H. E. and O'Neill, W. (2006) Deleterious effects of sleep-disordered breathing on the heart and vascular system. Respiration 73: 124-130.
75. Doumas, M. and Douma, S. (2006) The effect of antihypertensive drugs on erectile function: A proposed management algorithm. J. Clin. Hypertens., 8: 359-364.
76. Drexler, H. and Hornig, B. (1999) Endothelial dysfunction in human disease. J. Mol. Cell. Cardiol., 31: 51-60.
77. Dzau, V. J., Gnecchi, M., Pachori, A. S., Morello, F. and Melo, L. G. (2005) Therapeutic potential of endothelial progenitor cells in cardiovascular diseases. Hypertension, 46: 7-18.
78. Elesber, A. A., Solomon, H., Lennon, R. J., Mathew, V., Prasad, A., Pumper, G., Nelson, R. E., McConnell, J. P., Lerman, L. O. and Lerman, A. (2006) Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosis. Eur. Heart J., 27: 824-831.
79. Elrod, J. W., Duranski, M. R., Langston, W., Greer, J. J. M., Tan, L., Dugas, T. R., Kevil, C. G., Champion, H. C. and Lefer, D. J. (2006) Enos gene therapy exacerbates hepatic ischemia-reperfusion injury in diabetes: A role for enos uncoupling. Circ. Res., 99: 78-85.
80. Endemann, D. H. and Schiffrin, E. L. (2004) Endothelial dysfunction. J. Am. Soc. Nephrol., 15: 1983-1992.
81. Esposito, K., Marfella, R., Ciotola, M., Di Palo, C., Giugliano, F., Giugliano, G., D'Armiento, M., D'Andrea, F. and Giugliano, D. (2004) Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: A randomized trial.[see comment]. J. Am. Med. Assoc., 292: 1440-1446.
82. Fadini, G. P., Schiavon, M., Cantini, M., Baesso, I., Facco, M., Miorin, M., Tassinato, M., Kreutzenberg, S. V. d., Avogaro, A. and Agostini, C. (2006) Circulating progenitor cells are reduced in patients with severe lung disease. Stem Cells, 24: 1806-1813.
83. Fagan, K. A., Oka, M., Bauer, N. R., Gebb, S. A., Ivy, D. D., Morris, K. G. and McMurtry, I. F. (2004) Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of rho-kinase. Am. J. Physiol. Lung Cell Mol. Physiol., 287: L656-664.
84. Feldman, H. A., Goldstein, I., Hatzichristou, D. G., Krane, R. J. and McKinlay, J. B. (1994) Impotence and its medical and psychosocial correlates: Results of the massachusetts male aging study. J. Urol., 151: 54-61.
85. Ferrara, N. and Davis-Smyth, T. (1997) The biology of vascular endothelial growth factor. Endocr. Rev., 18: 4-25.
86. Ferroni, P., Basili, S., Paoletti, V. and Davi, G. (2006) Endothelial dysfunction and oxidative stress in arterial hypertension. Nutr. Metab. Cardiovas. Dis., 16: 222-233.
87. Finberg, J. P., Levy, S. and Vardi, Y. (1993) Inhibition of nerve stimulation-induced vasodilatation in corpora cavernosa of the pithed rat by blockade of nitric oxide synthase. Br. J. Pharmacol., 108: 1038-1042.
88. Foresta, C., Caretta, N., Lana, A., Cabrelle, A., Palu, G. and Ferlin, A. (2005) Circulating endothelial progenitor cells in subjects with erectile dysfunction.[see comment]. Int. J. Impot. Res., 17: 288-290.
89. Fortuno, A., Jose, G. S., Moreno, M. U., Diez, J. and Zalba, G. (2005) Oxidative stress and vascular remodelling. Exp. Physiol., 90: 457-462.
90. Frajese, G. V. and Pozzi, F. (2005) Phosphodiesterase type 5 inhibithors in older males. J. Endocrinol. Invest., 28: 112-115.
91. Francavilla, S., Bocchio, M., Pelliccione, F., Necozione, S. and Francavilla, F. (2005) Vascular aetiology of erectile dysfunction. Int. J. Androl., 28 Suppl 2: 35-39.
92. Fukuda, S. and Pelus, L. M. (2006) Survivin, a cancer target with an emerging role in normal adult tissues. Mol. Cancer Ther., 5: 1087-1098.
93. Fukumoto, Y., Matoba, T., Ito, A., Tanaka, H., Kishi, T., Hayashidani, S., Abe, K., Takeshita, A. and Shimokawa, H. (2005) Acute vasodilator effects of a rho-kinase inhibitor, fasudil, in patients with severe pulmonary hypertension. Heart 91: 391-392.
94. Galie, N., Ghofrani, H. A., Torbicki, A., Barst, R. J., Rubin, L. J., Badesch, D., Fleming, T., Parpia, T., Burgess, G., Branzi, A., Grimminger, F., Kurzyna, M., Simonneau, G. and Sildenafil Use in Pulmonary Arterial Hypertension Study, G. (2005) Sildenafil citrate therapy for pulmonary arterial hypertension. N. Engl. J. Med., 353: 2148-2157.
95. Garban, H., Marquez, D., Magee, T., Moody, J., Rajavashisth, T. and Rodriguez, J. A. (1997) Cloning of rat and human inducible penile nitric oxide synthase. Application for gene therapy of erectile dysfunction. Biol. Reprod., 56: 954-963.
96. Gautam, A., Waldrep, C. J. and Densmore, C. L. (2002) Delivery systems for pulmonary gene therapy. Am. J. Resp. Med., 1: 35-46.
97. Gautam, A., Waldrep, J. C. and Densmore, C. L. (2003) Aerosol gene therapy. Mol. Biotechnol., 23: 51-60.
98. Germana, A., del Valle, M. E., Laura, R., Ciriaco, E., Vega, J. A. and Germana, G. (2005) Effects of neurotrophin-3 gene mutation in the expression of neurocalcin. Ital. J. Anat. Embryol., 110: 37-47.
99. Ghalayini, I. F. (2004) Nitric oxide-cyclic gmp pathway with some emphasis on cavernosal contractility. Int. J. Impot. Res., 16: 459-469.
100. Ghofrani, H. A., Pepke-Zaba, J., Barbera, J. A., Channick, R., Keogh, A. M., Gomez-Sanchez, M. A., Kneussl, M. and Grimminger, F. (2004a) Nitric oxide pathway and phosphodiesterase inhibitors in pulmonary arterial hypertension. J. Am. Coll. Cardiol., 43: 68S-72S.
101. Ghofrani, H. A., Voswinckel, R., Reichenberger, F., Olschewski, H., Haredza, P., Karadas, B., Schermuly, R. T., Weissmann, N., Seeger, W. and Grimminger, F. (2004b) 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: 1488-1496.
102. Ghofrani, H. A., Wiedemann, R., Rose, F., Olschewski, H., Schermuly, R. T., Weissmann, N., Seeger, W. and Grimminger, F. (2002) Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann. Intern. Med., 136: 515-522.
103. Gholami, S. S., Rogers, R., Chang, J., Ho, H.-C., Grazziottin, T., Lin, C.-S. and Lue, T. F. (2003) The effect of vascular endothelial growth factor and adeno-associated virus mediated brain derived neurotrophic factor on neurogenic and vasculogenic erectile dysfunction induced by hyperlipidemia. J. Urol., 169: 1577-1581.
104. Gildea, T. R., Arroliga, A. C. and Minai, O. A. (2003) Treatments and strategies to optimize the comprehensive management of patients with pulmonary arterial hypertension. Cleve. Clin. J. Med., 70 Suppl 1: S18-27.
105. Gomberg-Maitland, M. (2006) Learning to pair therapies and the expanding matrix for pulmonary arterial hypertension: Is more better? Eur. Respir. J., 28: 683-686.
106. Gong, F., Tang, H., Lin, Y., Gu, W., Wang, W. and Kang, M. (2005) Gene transfer of vascular endothelial growth factor reduces bleomycin-induced pulmonary hypertension in immature rabbits. Pediatr. Int., 47: 242-247.
107. Gonzalez-Cadavid, N. F. and Rajfer, J. (2005) The pleiotropic effects of inducible nitric oxide synthase (inos) on the physiology and pathology of penile erection. Curr. Pharm. Des., 11: 4041-4046.
108. Guay, A. T. (2005) Relation of endothelial cell function to erectile dysfunction: Implications for treatment. Am. J. Cardiol., 96: 52M-56M.
109. Gunsilius, E., Duba, H.-C., Petzer, A. L., Kahler, C. M., Grunewald, K., Stockhammer, G., Gabl, C., Dirnhofer, S., Clausen, J. and Gastl, G. (2000) Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells. The Lancet 355: 1688-1691.
110. Hafez, E. S. and Hafez, S. D. (2005) Erectile dysfunction: Anatomical parameters, etiology, diagnosis, and therapy. Arch. Androl., 51: 15-31.
111. Hagl, C., Khaladj, N., Peters, T., Hoeper, M. M., Logemann, F., Haverich, A. and Macchiarini, P. (2003) Technical advances of pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. Eur. J. Cardiothorac. Surg., 23: 776-781; discussion 781.
112. Haj, R. M., Cinco, J. E. and Mazer, C. D. (2006) Treatment of pulmonary hypertension with selective pulmonary vasodilators. Curr. Opin. Anaesthesiol., 19: 88-95.
113. Harrison, R. E., Berger, R., Haworth, S. G., Tulloh, R., Mache, C. J., Morrell, N. W., Aldred, M. A. and Trembath, R. C. (2005) Transforming growth factor-beta receptor mutations and pulmonary arterial hypertension in childhood. Circulation, 111: 435-441.
114. Higenbottam, T. (1994) Pathophysiology of pulmonary hypertension. A role for endothelial dysfunction. Chest, 105: 7S-12S.
115. Higenbottam, T. W., Spiegelhalter, D., Scott, J. P., Foster, V., Dinh-Xuan, A. T., Caine, N. and Wallwork, J. (1993) Prostacyclin (epoprostenol) and heart-lung transplantation as treatments for severe pulmonary hypertension. Br. Heart J., 70: 366-370.
116. Hill, J. M., Zalos, G., Halcox, J. P. J., Schenke, W. H., Waclawiw, M. A., Quyyumi, A. A. and Finkel, T. (2003) Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N. Engl. J. Med., 348: 593-600.
117. Hingorani, A. D., Cross, J., Kharbanda, R. K., Mullen, M. J., Bhagat, K., Taylor, M., Donald, A. E., Palacios, M., Griffin, G. E., Deanfield, J. E., MacAllister, R. J. and Vallance, P. (2000) Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation, 102: 994-999.
118. Hoeper, M. M. (2005) Drug treatment of pulmonary arterial hypertension: Current and future agents. Drugs, 65: 1337-1354.
119. Hughes, R., Tong, J., Oates, C., Lordan, J. and Corris, P. A. (2005) Evidence for systemic endothelial dysfunction in patients and first-order relatives with pulmonary arterial hypertension. Chest, 128: 617S.
120. Humbert, M., Morrell, N. W., Archer, S. L., Stenmark, K. R., MacLean, M. R., Lang, I. M., Christman, B. W., Weir, E. K., Eickelberg, O., Voelkel, N. F. and Rabinovitch, M. (2004) Cellular and molecular pathobiology of pulmonary arterial hypertension. J. Am. Coll. Cardiol., 43: 13S-24S.
121. Hurlimann, D., Enseleit, F. and Ruschitzka, F. (2004) [rheumatoid arthritis, inflammation, and atherosclerosis]. Herz, 29: 760-768.
122. Hurlimann, D., Weber, R., Enseleit, F. and Luscher, T. F. (2005) [hiv infection, antiretroviral therapy, and endothelium]. Herz, 30: 472-480.
123. Hutter, A. M., Jr. (2004) Role of the cardiologist: Clinical aspects of managing erectile dysfunction. Clin. Cardiol., 27: 13-7.
124. Hyman, A. L., Chapnick, B. M., Kadowitz, P. J., Lands, W. E., Crawford, C. G., Fried, J. and Barton, J. (1977) Unusual pulmonary vasodilator activity of 13,14-dehydroprostacyclin methyl ester: Comparison with endoperoxides and other prostanoids. Proc. Natl. Acad. Sci. USA, 74: 5711-5715.
125. Hyman, A. L. and Kadowitz, P. J. (1979) Pulmonary vasodilator activity of prostacyclin (pgi2) in the cat. Circ. Res., 45: 404-409.
126. Hyvelin, J.-M., Howell, K., Nichol, A., Costello, C. M., Preston, R. J. and McLoughlin, P. (2005) Inhibition of rho-kinase attenuates hypoxia-induced angiogenesis in the pulmonary circulation. Circ. Res., 97: 185-191.
127. Ignarro, L. J., Bush, P. A., Buga, G. M., Wood, K. S., Fukuto, J. M. and Rajfer, J. (1990) Nitric oxide and cyclic gmp formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem. Biophys. Res. Commun., 170: 843-850.
128. Ingram, D. A., Caplice, N. M. and Yoder, M. C. (2005) Unresolved questions, changing definitions, and novel paradigms for defining endothelial progenitor cells. Blood, 106: 1525-1531.
129. Ishikura, K., Yamada, N., Ito, M., Ota, S., Nakamura, M., Isaka, N. and Nakano, T. (2006) Beneficial acute effects of rho-kinase inhibitor in patients with pulmonary arterial hypertension. Circ. J., 70: 174-178.
130. Ito, W., Kanehiro, A., Matsumoto, K., Hirano, A., Ono, K., Maruyama, H., Kataoka, M., Nakamura, T., Gelfand, E. W. and Tanimoto, M. (2005) Hepatocyte growth factor attenuates airway hyperresponsiveness, inflammation, and remodeling. Am. J. Respir. Cell Mol. Biol., 32: 268-280.
131. Jackson, G. (2004) Sexual dysfunction and diabetes. Int. J. Clin. Pract., 58: 358-362.
132. Jackson, G. (2005) Hemodynamic and exercise effects of phosphodiesterase 5 inhibitors. Am. J. Cardiol., 96: 32M-36M.
133. Jensen, J., Lendorf, A., Stimpel, H., Frost, J., Ibsen, H. and Rosenkilde, P. (1999) The prevalence and etiology of impotence in 101 male hypertensive outpatients. Am. J. Hypertens., 12: 271-275.
134. Jeremy, J. Y., Angelini, G. D., Khan, M., Mikhailidis, D. P., Morgan, R. J., Thompson, C. S., Bruckdorfer, K. R. and Naseem, K. M. (2000) Platelets, oxidant stress and erectile dysfunction: An hypothesis. Cardiovasc. Res., 46: 50-54.
135. Joffe, H. V. and Adler, G. K. (2005) Effect of aldosterone and mineralocorticoid receptor blockade on vascular inflammation. Heart Fail. Rev., 10: 31-37.
136. Jones, R. D., Hugh Jones, T. and Channer, K. S. (2004) The influence of testosterone upon vascular reactivity. Eur. J. Endocrinol., 151: 29-37.
137. Kadowitz, P. J., Chapnick, B. M., Feigen, L. P., Hyman, A. L., Nelson, P. K. and Spannhake, E. W. (1978) Pulmonary and systemic vasodilator effects of the newly discovered prostaglandin, pgi2. J. Appl. Physiol., 45: 408-413.
138. Kanki-Horimoto, S., Horimoto, H., Mieno, S., Kishida, K., Watanabe, F., Furuya, E. and Katsumata, T. (2006) Implantation of mesenchymal stem cells overexpressing endothelial nitric oxide synthase improves right ventricular impairments caused by pulmonary hypertension. Circulation 114: 1181-185.
139. Kawamoto, A., Gwon, H.-C., Iwaguro, H., Yamaguchi, J.-I., Uchida, S., Masuda, H., Silver, M., Ma, H., Kearney, M., Isner, J. M. and Asahara, T. (2001) Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation, 103: 634-637.
140. Keith, I. M. (2000) The role of endogenous lung neuropeptides in regulation of the pulmonary circulation. Physiol. Res., 49: 519-537.
141. Kendirci, Teloken, Champion, Hellstrom and Bivalacqua (2006) Gene therapy for erectile dysfunction: Fact or fiction? Eur. Urol., 50: 1208-1222.
142. Kendirci, M., Gur, S. and Sikka, S. C. (2005) Gene therapy for erectile dysfunction. Front. Biosci., 10: 2758-2769.
143. Khan, M. A., Morgan, R. J. and Mikhailidis, D. P. (2000) The molecular basis of penile erection. Curr. Med Res. Opin., 16 Suppl 1: s21-30.
144. Khan, M. A., Thompson, C. S., Jeremy, J. Y., Mumtaz, F. H., Mikhailidis, P. and Morgan, R. J. (2001) The effect of superoxide dismutase on nitric oxide-mediated and electrical field-stimulated diabetic rabbit cavernosal smooth muscle relaxation. BJU Int., 87: 98-103.
145. Kharbanda, R. K., Walton, B., Allen, M., Klein, N., Hingorani, A. D., MacAllister, R. J. and Vallance, P. (2002) Prevention of inflammation-induced endothelial dysfunction: A novel vasculo-protective action of aspirin. Circulation, 105: 2600-2604.
146. Khurana, R., Martin, J. F. and Zachary, I. (2001) Gene therapy for cardiovascular disease: A case for cautious optimism. Hypertension 38: 1210-1216.
147. Kim, N., Azadzoi, K. M., Goldstein, I. and Saenz de Tejada, I. (1991) A nitric oxide-like factor mediates nonadrenergic-noncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle. J. Clin. Invest., 88: 112-118.
148. Kirby, M., Jackson, G. and Simonsen, U. (2005) Endothelial dysfuncfion links erectile dysfunction to heart disease. Int. J. Clin. Pract., 59: 225-229.
149. Kloner, R. and Padma-Nathan, H. (2005) Erectile dysfunction in patients with coronary artery disease. Int. J. Impot. Res., 17: 209-215.
150. Knudson, J. D., Dincer, U. D., Dick, G. M., Shibata, H., Akahane, R., Saito, M. and Tune, J. D. (2005) Leptin resistance extends to the coronary vasculature in prediabetic dogs and provides a protective adaptation against endothelial dysfunction. Am. J. Physiol. - Heart Circ. Physiol., 289: H1038-1046.
151. Kobayashi, H. and Lin, P. C. (2005) Angiopoietin/tie2 signaling, tumor angiogenesis and inflammatory diseases. Front. Biosci., 10: 666-674.
152. Koga, Y., Akita, Y., Junko, N., Yatsuga, S., Povalko, N., Fukiyama, R., Ishii, M. and Matsuishi, T. (2006) Endothelial dysfunction in melas improved by 1-arginine supplementation. Neurology 66: 1766-1769.
153. Kostis, J. B., Jackson, G., Rosen, R., Barrett-Connor, E., Billups, K., Burnett, A. L., Carson, C., 3rd, Cheitlin, M., Debusk, R., Fonseca, V., Ganz, P., Goldstein, I., Guay, A., Hatzichristou, D., Hollander, J. E., Hutter, A., Katz, S., Kloner, R. A., Mittleman, M., Montorsi, F., Montorsi, P., Nehra, A., Sadovsky, R. and Shabsigh, R. (2005) Sexual dysfunction and cardiac risk (the second princeton consensus conference). Am. J. Cardiol., 96: 313-321.
154. Kugathasan, L., Dutly, A. E., Zhao, Y. D., Deng, Y., Robb, M. J., Keshavjee, S. and Stewart, D. J. (2005) Role of angiopoietin-1 in experimental and human pulmonary arterial hypertension. Chest 128: 633S-642S.
155. Kurzyna, M., Dabrowski, M., Torbicki, A., Burakowski, J., Kuca, P., Fijalkowska, A. and Sikora, J. (2003) Atrial septostomy for severe primary pulmonary hypertension - report on two cases. Kardiol. Pol., 58: 27-33.
156. Landmesser, U., Hornig, B. and Drexler, H. (2004) Endothelial function: A critical determinant in atherosclerosis? Circulation, 109: II27-33.
157. Langleben, D., Dupuis, J., Langleben, I., Hirsch, A. M., Baron, M., Senecal, J.-L. and Giovinazzo, M. (2006) Etiology-specific endothelin-1 clearance in human precapillary pulmonary hypertension. Chest, 129: 689-695.
158. Lanner, M. C., Raper, M., Pratt, W. M. and Rhoades, R. A. (2005) Heterotrimeric g proteins and the platelet-derived growth factor receptor-beta contribute to hypoxic proliferation of smooth muscle cells. Am. J. Respir. Cell Mol. Biol., 33: 412-419.
159. Laties, A. and Sharlip, I. (2006) Ocular safety in patients using sildenafil citrate therapy for erectile dysfunction. J. Sex. Med., 3: 12-27.
160. Laumann, E. O., Paik, A. and Rosen, R. C. (1999) Sexual dysfunction in the united states: Prevalence and predictors.[see comment][erratum appears in jama 1999 apr 7;281(13):1174]. J. Am. Med. Assoc., 281: 537-544.
161. Lee, S. H. and Channick, R. N. (2005) Endothelin antagonism in pulmonary arterial hypertension. Semin. Respir. Crit. Care Med., 26: 402-408.
162. Lewis, R. W., Fugl-Meyer, K. S., Bosch, R., Fugl-Meyer, A. R., Laumann, E. O., Lizza, E. and Martin-Morales, A. (2004) Epidemiology/risk factors of sexual dysfunction. J. Sex. Med., 1: 35-39.
163. Liew, A., Barry, F. and O'Brien, T. (2006) Endothelial progenitor cells: Diagnostic and therapeutic considerations. Bioessays, 28: 261-270.
164. Liu, L., Liu, H., Visner, G. and Fletcher, B. S. (2006) Sleeping beauty-mediated enos gene therapy attenuates monocrotaline-induced pulmonary hypertension in rats. FASEB J., 20: 2594-2596.
165. Lopez-Candales, A., Dohi, K., Rajagopalan, N., Suffoletto, M., Murali, S., Gorcsan, J. and Edelman, K. (2005) Right ventricular dyssynchrony in patients with pulmonary hypertension is associated with disease severity and functional class. Cardiovas. Ultrasound, 3: 23.
166. Lue, T. F. (2000) Erectile dysfunction. N. Engl. J. Med., 342: 1802-1813.
167. Maas, R., Schwedhelm, E., Albsmeier, J. and Boger, R. H. (2002) The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function. Vasc. Med., 7: 213-225.
168. Magee, T. R., Ferrini, M., Garban, H. J., Vernet, D., Mitani, K., Rajfer, J. and Gonzalez-Cadavid, N. F. (2002) Gene therapy of erectile dysfunction in the rat with penile neuronal nitric oxide synthase.[republished from biol reprod., 2002 jul;67(1):20-8; pmid: 12079995]. Biol. Reprod., 67: 1033-1041.
169. McCrory, D. C. and Lewis, S. Z. (2004) Methodology and grading for pulmonary hypertension evidence review and guideline development. Chest 126: 11S-13S.
170. McLaughlin, V. V., Sitbon, O., Badesch, D. B., Barst, R. J., Black, C., Galie, N., Rainisio, M., Simonneau, G. and Rubin, L. J. (2005) Survival with first-line bosentan in patients with primary pulmonary hypertension. [see comment][erratum appears in eur respir j., 2005 may;25(5):942]. Eur. Respir. J., 25: 244-249.
171. McMahon, T. J., Ignarro, L. J. and Kadowitz, P. J. (1993) Influence of zaprinast on vascular tone and vasodilator responses in the cat pulmonary vascular bed. J. Appl. Physiol., 74: 1704-1711.
172. McMurtry, M. S., Archer, S. L., Altieri, D. C., Bonnet, S., Haromy, A., Harry, G., Bonnet, S., Puttagunta, L. and Michelakis, E. D. (2005) Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. J. Clin. Invest., 115: 1479-1491.
173. McMurtry, M. S., Moudgil, R., Hashimoto, K., Bonnet, S., Michelakis, E. D. and Archer, S. L. (2006) Overexpression of human bone morphogenetic protein receptor ii does not ameliorate monocrotaline pulmonary arterial hypertension. Am. J. Physiol. Lung Cell Mol. Physiol., 00309. 02006.
174. McVary, K. T., Carrier, S., Wessells, H. and Subcommittee on Smoking and Erectile Dysfunction Socioeconomic Committee, S. M. S. o. N. A. (2001) Smoking and erectile dysfunction: Evidence based analysis. J. Urol., 166: 1624-1632.
175. Melman, A. (2005) Gene transfer for the therapy of erectile dysfunction: Progress in the 21st century. Int. J. Impot. Res., 18: 19-25.
176. Melman, A., Bar-Chama, N., McCullough, A., Davies, K. and Christ, G. (2005) The first human trial for gene transfer therapy for the treatment of erectile dysfunction: Preliminary results. Eur. Urol., 48: 314-318.
177. Melo, L. G., Gnecchi, M., Pachori, A. S., Kong, D., Wang, K., Liu, X., Pratt, R. E. and Dzau, V. J. (2004) Endothelium-targeted gene and cell-based therapies for cardiovascular disease. Arterioscl. Thromb. Vas. Biol., 24: 1761-1774.
178. Michel, R. P., Langleben, D. and Dupuis, J. (2003) The endothelin system in pulmonary hypertension. Can. J. Physiol. Pharmacol., 81: 542-554.
179. Michelakis, E., Tymchak, W., Lien, D., Webster, L., Hashimoto, K. and Archer, S. (2002) Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: Comparison with inhaled nitric oxide. Circulation, 105: 2398-2403.
180. Michelakis, E. D. (2003) The role of the no axis and its therapeutic implications in pulmonary arterial hypertension. Heart Fail. Rev., 8: 5-21.
181. Michelakis, E. D., Dyck, J. R., McMurtry, M. S., Wang, S., Wu, X. C., Moudgil, R., Hashimoto, K., Puttagunta, L. and Archer, S. L. (2001) Gene transfer and metabolic modulators as new therapies for pulmonary hypertension. Increasing expression and activity of potassium channels in rat and human models. Adv. Exp. Med. Biol., 502: 401-418.
182. Michelakis, E. D. and Weir, E. K. (2001) The pathobiology of pulmonary hypertension. Smooth muscle cells and ion channels. Clin. Chest Med., 22: 419-432.
183. Miller, A. L. (2006) The effects of sustained-release-1-arginine formulation on blood pressure and vascular compliance in 29 healthy individuals. Altern. Med. Rev., 11: 23-29.
184. Montorsi, P., Ravagnani, P. M., Galli, S., Rotatori, F., Briganti, A., Salonia, A., Rigatti, P. and Montorsi, F. (2005) The artery size hypothesis: A macrovascular link between erectile dysfunction and coronary artery disease. Am. J. Cardiol., 96: 19-23.
185. Moreno, P. R. and Fuster, V. (2004) New aspects in the pathogenesis of diabetic atherothrombosis. J. Am. Coll. Cardiol., 44: 2293-2300.
186. Munzel, T., Daiber, A., Ullrich, V. and Mulsch, A. (2005) Vascular consequences of endothelial nitric oxide synthase uncoupling for the activity and expression of the soluble guanylyl cyclase and the cgmp-dependent protein kinase. Arteriosclerosis, Thrombosis Vas. Biol., 25: 1551-1557.
187. Murakami, S., Kimura, H., Kangawa, K. and Nagaya, N. (2006) Physiological significance and therapeutic potential of adrenomedullin in pulmonary hypertension. Cardiovas. Hematolog. Disord. Drug Targ., 6: 125-132.
188. Murali, S. (2006) Pulmonary arterial hypertension. Curr. Opin. Crit. Care, 12: 228-234.
189. Naeije, R. and Vachiery, J. L. (2001) Medical therapy of pulmonary hypertension. Conventional therapies. Clin. Chest Med., 22: 517-527.
190. Nagaoka, T., Gebb, S. A., Karoor, V., Homma, N., Morris, K. G., McMurtry, I. F. and Oka, M. (2006) Involvement of rhoa/rho kinase signaling in pulmonary hypertension of the fawn-hooded rat. J. Appl. Physiol., 100: 996-1002.
191. Nagaya, N. (2004) Drug therapy of primary pulmonary hypertension. Am. J. Cardiovas. Drugs, 4: 75-85.
192. Nagaya, N., Kangawa, K., Kanda, M., Uematsu, M., Horio, T., Fukuyama, N., Hino, J., Harada-Shiba, M., Okumura, H., Tabata, Y., Mochizuki, N., Chiba, Y., Nishioka, K., Miyatake, K., Asahara, T., Hara, H. and Mori, H. (2003) Hybrid cell-gene therapy for pulmonary hypertension based on phagocytosing action of endothelial progenitor cells.[see comment]. Circulation, 108: 889-895.
193. Nagaya, N., Mori, H., Murakami, S., Kangawa, K. and Kitamura, S. (2005) Adrenomedullin: Angiogenesis and gene therapy. Am. J. Physiol. - Regulat. Integ. Comp. Physiol., 288: R1432-1437.
194. Nagaya, N., Yokoyama, C., Kyotani, S., Shimonishi, M., Morishita, R., Uematsu, M., Nishikimi, T., Nakanishi, N., Ogihara, T., Yamagishi, M., Miyatake, K., Kaneda, Y. and Tanabe, T. (2000) Gene transfer of human prostacyclin synthase ameliorates monocrotaline-induced pulmonary hypertension in rats. Circulation, 102: 2005-2010.
195. Nohria, A., Grunert, M. E., Rikitake, Y., Noma, K., Prsic, A., Ganz, P., Liao, J. K. and Creager, M. A. (2006) Rho kinase inhibition improves endothelial function in human subjects with coronary artery disease. Circ. Res., 99: 1426-1432.
196. Nossaman, B. D., Dabisch, P. A., Liles, J. T., Baber, S. R., Champion, H. C., Kaye, A. D., Feng, C. J., Anwar, M., Bivalacqua, T. J., Santiago, J. A., De Witt, B. J. and Kadowitz, P. J. (2004) Peroxynitrite does not impair pulmonary and systemic vascular responses. J. Appl. Physiol., 96: 455-462.
197. Nurnberg, H. G. and Duttagupta, S. (2004) Economic analysis of sildenafil citrate (viagra) add-on to treat erectile dysfunction associated with selective serotonin reuptake inhibitor use. Am. J. Ther., 11: 9-12.
198. O'Kane, P. D. and Jackson, G. (2001) Erectile dysfunction: Is there silent obstructive coronary artery disease? Int. J. Clin. Pract., 55: 219-220.
199. Ogita, H. and Liao, J. (2004) Endothelial function and oxidative stress. Endothelium: J. Endoth. Cell Res., 11: 123-132.
200. Okada, K., Bernstein, M. L., Zhang, W., Schuster, D. P. and Botney, M. D. (1998) Angiotensin-converting enzyme inhibition delays pulmonary vascular neointimal formation. Am. J. Respir. Crit. Care Med., 158: 939-950.
201. Ono, F., Nagaya, N., Kyotani, S., Oya, H., Nakanishi, N. and Miyatake, K. (2003a) Hemodynamic and hormonal effects of beraprost sodium, an orally active prostacyclin analogue, in patients with secondary precapillary pulmonary hypertension. Circ. J., 67: 375-378.
202. Ono, F., Nagaya, N., Okumura, H., Shimizu, Y., Kyotani, S., Nakanishi, N. and Miyatake, K. (2003b) Effect of orally active prostacyclin analogue on survival in patients with chronic thromboembolic pulmonary hypertension without major vessel obstruction. Chest, 123: 1583-1588.
203. Ono, M., Sawa, Y., Fukushima, N., Suhara, H., Nakamura, T., Yokoyama, C., Tanabe, T. and Matsuda, H. (2004a) Gene transfer of hepatocyte growth factor with prostacyclin synthase in severe pulmonary hypertension of rats. Eur. J. Cardiothorac. Surg., 26: 1092-1097.
204. Ono, M., Sawa, Y., Mizuno, S., Fukushima, N., Ichikawa, H., Bessho, K., Nakamura, T. and Matsuda, H. (2004b) Hepatocyte growth factor suppresses vascular medial hyperplasia and matrix accumulation in advanced pulmonary hypertension of rats. Circulation, 110: 2896-2902.
205. Orlic, D., Kajstura, J. A. N., Chimenti, S., Bodine, D. M., Leri, A. and Anversa, P. (2001) Transplanted adult bone marrow cells repair myocardial infarcts in mice. Ann. N.Y. Acad. Sci., 938: 221-230.
206. P. Sytze Van Dam, B. B. (1997) Oxidative stress and antioxidant treatment in diabetic neuropathy. Neurosci. Res. Commun., 21: 41-48.
207. Pacaud, P., Sauzeau, V. and Loirand, G. (2005) Rho proteins and vascular diseases. Arch. Mal. Coeur Vaiss., 98: 249-254.
208. Palevsky, H. I. M., Schloo, B. L. M., Pietra, G. G. M., Weber, K. T. M., Janicki, J. S. P., Rubin, E. M. and Fishman, A. P. M. (1989) Primary pulmonary hypertension: Vascular structure, morphometry, and responsiveness to vasodilator agents. Circulation, 80: 1207-1221.
209. Papatsoris, A. G. and Korantzopoulos, P. G. (2006) Hypertension, antihypertensive therapy, and erectile dysfunction. Angiology, 57: 47-52.
210. Parish, J. M. and Somers, V. K. (2004) Obstructive sleep apnea and cardiovascular disease. Mayo Clin. Proc., 79: 1036-1046.
211. Patel, M. D. and Katz, S. D. (2005) Phosphodiesterase 5 inhibition in chronic heart failure and pulmonary hypertension. Am. J. Cardiol., 96: 47M-51M.
212. Pepke-Zaba, J., Higenbottam, T. W., Dinh-Xuan, A. T., Stone, D. and Wallwork, J. (1991) Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet, 338: 1173-1174.
213. Peters, K., Unger, R. E., Brunner, J. and Kirkpatrick, C. J. (2003) Molecular basis of endothelial dysfunction in sepsis. Cardiovasc. Res., 60: 49-57.
214. Pietra, G. G. M., Edwards, W. D. M., Kay, J. M. M., Rich, S. M., Kernis, J. M., Betsy Schloo, MD, Ayres, S. M. M., Bergofsky, E. H. M., Brundage, B. H. M., Detre, K. M. M., DrPh, Fishman, A. P. M., Goldring, R. M. M., Groves, B. M. M., Levy, P. S. S., Reid, L. M. M., Vreim, C. E. P. and Williams, G. W. P. (1989) Histopathology of primary pulmonary hypertension: A qualitative and quantitative study of pulmonary blood vessels from 58 patients in the national heart, lung, and blood institute, primary pulmonary hypertension registry. Circulation, 80: 1198-1206.
215. Pomeranz, H. D. and Bhavsar, A. R. (2005) Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (viagra): A report of seven new cases. J. Neuroophthalmol., 25: 9-13.
216. Pozeg, Z. I., Michelakis, E. D., McMurtry, M. S., Thebaud, B., Wu, X.-C., Dyck, J. R. B., Hashimoto, K., Wang, S., Moudgil, R., Harry, G., Sultanian, R., Koshal, A. and Archer, S. L. (2003) In vivo gene transfer of the o2-sensitive potassium channel kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats. Circulation, 107: 2037-2044.
217. Quarck, R. and Holvoet, P. (2004) Gene therapy approaches for cardiovascular diseases. Curr. Gene Ther., 4: 207-223.
218. Rabinovitch, M. (2005) Cellular and molecular pathobiology of pulmonary hypertension conference summary. Chest, 128: 642S-646S.
219. Radomski, M. W. (1995) Nitric oxide: Biological mediator, modulator and effector. Ann. Med., 27: 321-329.
220. Rafii, S. (2000) Circulating endothelial precursors: Mystery, reality, and promise. J. Clin. Invest., 105: 17-19.
221. Raiesdana, A. and Loscalzo, J. (2006) Pulmonary arterial hypertension. Ann. Med., 38: 95-110.
222. Rajfer, J., Aronson, W. J., Bush, P. A., Dorey, F. J. and Ignarro, L. J. (1992) Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N. Eng. J. Med., 326: 90-94.
223. Rich, S. (1998) Clinical insights into the pathogenesis of primary pulmonary hypertension. Chest, 114: 237S-241S.
224. Rich, S., Rubin, L., Walker, A. M., Schneeweiss, S. and Abenhaim, L. (2000) Anorexigens and pulmonary hypertension in the united states*: Results from the surveillance of north american pulmonary hypertension. Chest, 117: 870-874.
225. Rolland, A. (2005) Gene medicines: The end of the beginning? Advanced Drug Deliv. Rev., 57: 669-673.
226. Ross, R. (1999) Atherosclerosis - an inflammatory disease. N. Engl. J. Med., 340: 115-126.
227. Rubin, L. J. and Galie, N. (2004) Pulmonary arterial hypertension: A look to the future. J. Am. Coll. Cardiol., 43: 89S-90S.
228. Rubin, L. J., Groves, B. M., Reeves, J. T., Frosolono, M., Handel, F. and Cato, A. E. (1982) Prostacyclin-induced acute pulmonary vasodilation in primary pulmonary hypertension. Circulation, 66: 334-338.
229. Rubin, L. J. M. and Badesch, D. B. M. (2005) Evaluation and management of the patient with pulmonary arterial hypertension. Ann. Intern. Med., 143: 282-292.
230. Ryu, J.-K., Cho, C.-H., Shin, H.-Y., Song, S. U., Oh, S.-M., Lee, M., Piao, S., Han, J.-Y., Kim, I.-H., Koh, G. Y. and Suh, J.-K. (2006) Combined angiopoietin-1 and vascular endothelial growth factor gene transfer restores cavernous angiogenesis and erectile function in a rat model of hypercholesterolemia. Mol. Ther.: J. Am. Soc. Gene Ther., 13: 705-715.
231. Saenz de Tejada, I., Angulo, J., Cellek, S., Gonzalez-Cadavid, N., Heaton, J., Pickard, R. and Simonsen, U. (2004) Physiology of erectile function. J. Sex. Med., 1: 254-265.
232. Saenz de Tejada, I., Angulo, J., Cellek, S., Gonzalez-Cadavid, N., Heaton, J., Pickard, R. and Simonsen, U. (2005) Pathophysiology of erectile dysfunction. J. Sex. Med., 2: 26-39.
233. Saenz de Tejada, I., Goldstein, I., Azadzoi, K., Krane, R. J. and Cohen, R. A. (1989) Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. N. Engl. J. Med., 320: 1025-1030.
234. Safar, M. E. (2005) Systolic hypertension in the elderly: Arterial wall mechanical properties and the renin-angiotensin-aldosterone system. J. Hypertens., 23: 673-681.
235. Satoh, K., Kagaya, Y., Nakano, M., Ito, Y., Ohta, J., Tada, H., Karibe, A., Minegishi, N., Suzuki, N., Yamamoto, M., Ono, M., Watanabe, J., Shirato, K., Ishii, N., Sugamura, K. and Shimokawa, H. (2006) Important role of endogenous erythropoietin system in recruitment of endothelial progenitor cells in hypoxia-induced pulmonary hypertension in mice. Circulation, 113: 1442-1450.
236. Sattar, N. (2004) Inflammation and endothelial dysfunction: Intimate companions in the pathogenesis of vascular disease?[comment]. Clin. Sci., 106: 443-445.
237. Savoia, C. and Schiffrin, E. L. (2006) Inflammation in hypertension. Curr. Opin. Nephrol. Hypertens., 15: 152-158.
238. Schermuly, R. T., Dony, E., Ghofrani, H. A., Pullamsetti, S., Savai, R., Roth, M., Sydykov, A., Lai, Y. J., Weissmann, N., Seeger, W. and Grimminger, F. (2005) Reversal of experimental pulmonary hypertension by pdgf inhibition.[see comment]. J. Clin. Invest., 115: 2811-2821.
239. Schiff, J. D. and Melman, A. (2006) Ion channel gene therapy for smooth muscle disorders: Relaxing smooth muscles to treat erectile dysfunction. Assay Drug Develop. Technol., 4: 89-95.
240. Schmieder, R. E. (2006) Endothelial dysfunction: How can one intervene at the beginning of the cardiovascular continuum? J. Hyperten. - Suppl., 24: S31-35.
241. Shamsuzzaman, A. S. M., Gersh, B. J. and Somers, V. K. (2003) Obstructive sleep apnea: Implications for cardiac and vascular disease.[see comment]. J. Am. Med. Assoc., 290: 1906-1914.
242. Shen, Z.-J., Wang, H., Lu, Y.-L., Zhou, X.-L., Chen, S.-W. and Chen, Z.-D. (2005) Gene transfer of vasoactive intestinal polypeptide into the penis improves erectile response in the diabetic rat. BJU Int., 95: 890-894.
243. Shigemura, N., Sawa, Y., Mizuno, S., Ono, M., Ohta, M., Nakamura, T., Kaneda, Y. and Matsuda, H. (2005) Amelioration of pulmonary emphysema by in vivo gene transfection with hepatocyte growth factor in rats. Circulation, 111: 1407-1414.
244. Shimokawa, H. (2002) Rho-kinase as a novel therapeutic target in treatment of cardiovascular diseases. J. Cardiovas. Pharmacol. Therap., 39: 319-327.
245. Simonneau, G., Barst, R. J., Galie, N., Naeije, R., Rich, S., Bourge, R. C., Keogh, A., Oudiz, R., Frost, A., Blackburn, S. D., Crow, J. W., Rubin, L. J. and Treprostinil Study, G. (2002) Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: A double-blind, randomized, placebo-controlled trial. Am. J. Respir. Crit. Care Med., 165: 800-804.
246. Simonneau, G., Galie, N., Rubin, L. J., Langleben, D., Seeger, W., Domenighetti, G., Gibbs, S., Lebrec, D., Speich, R., Beghetti, M., Rich, S. and Fishman, A. (2004) Clinical classification of pulmonary hypertension. J. Am. Coll. Cardiol., 43: 5S-12S.
247. Simonsen, U., Garcia-Sacristan, A. and Prieto, D. (2002) Penile arteries and erection. J. Vasc. Res., 39: 283-303.
248. Simonsen, U., Prieto, D., Delgado, J. A., Hernandez, M., Resel, L., Saenz de Tejada, I. and Garcia-Sacristan, A. (1997) Nitric oxide is involved in the inhibitory neurotransmission and endothelium-dependent relaxations of human small penile arteries. Clin. Sci., 92: 269-275.
249. Siobal, M. (2004) Aerosolized prostacyclins. Respir. Care, 49: 640-652.
250. Siroky, M. B. and Azadzoi, K. M. (2003) Vasculogenic erectile dysfunction: Newer therapeutic strategies. J. Urol., 170: S24-29; discussion S29-30.
251. Sommer, F. and Schulze, W. (2005) Treating erectile dysfunction by endothelial rehabilitation with phosphodiesterase 5 inhibitors. World J. Urol., 23: 385-392.
252. Stanley, K. P., Chicoine, L. G., Young, T. L., Reber, K. M., Lyons, C. R., Liu, Y. and Nelin, L. D. (2006) Gene transfer with inducible nitric oxide synthase decreases production of urea by arginase in pulmonary arterial endothelial cells. Am. J. Physiol. Lung Cell Mol. Physiol., 290: L298-306.
253. Steiner, M. K., Preston, I. R., Klinger, J. R. and Hill, N. S. (2005) Pulmonary hypertension: Inhaled nitric oxide, sildenafil and natriuretic peptides. Curr. Opin. Pharmacol., 5: 245-250.
254. Stewart, D. J. (1994) Endothelial dysfunction in pulmonary vascular disorders. Arzneimittelforschung, 44: 451-454.
255. Strange, J. W., Wharton, J., Phillips, P. G. and Wilkins, M. R. (2002) Recent insights into the pathogenesis and therapeutics of pulmonary hypertension. [see comment]. Clin. Sci., 102: 253-268.
256. Strehlow, K., Werner, N., Berweiler, J., Link, A., Dirnagl, U., Priller, J., Laufs, K., Ghaeni, L., Milosevic, M., Bohm, M. and Nickenig, G. (2003) Estrogen increases bone marrow-derived endothelial progenitor cell production and diminishes neointima formation. Circulation, 107: 3059-3065.
257. Struthers, A. D. and MacDonald, T. M. (2004) Review of aldosterone- and angiotensin ii-induced target organ damage and prevention. Cardiovasc. Res., 61: 663-670.
258. Suhara, H., Sawa, Y., Fukushima, N., Kagisaki, K., Yokoyama, C., Tanabe, T., Ohtake, S. and Matsuda, H. (2002) Gene transfer of human prostacyclin synthase into the liver is effective for the treatment of pulmonary hypertension in rats. J. Thorac. Cardiovasc. Surg., 123: 855-861.
259. Sullivan, M. E., Keoghane, S. R. and Miller, M. A. W. (2001) Vascular risk factors and erectile dysfunction. BJU Int., 87: 838-845.
260. Sullivan, M. E., Thompson, C. S., Dashwood, M. R., Khan, M. A., Jeremy, J. Y., Morgan, R. J. and Mikhailidis, D. P. (1999) Nitric oxide and penile erection: Is erectile dysfunction another manifestation of vascular disease? Cardiovasc. Res., 43: 658-665.
261. Sun, X. and Ku, D. D. (2006) Selective right, but not left, coronary endothelial dysfunction precedes development of pulmonary hypertension and right heart hypertrophy in rats. Am. J. Physiol. - Heart & Circul. Physiol., 290: H758-764.
262. Szocs, K. (2004) Endothelial dysfunction and reactive oxygen species production in ischemia/reperfusion and nitrate tolerance. Gen. Physiol. Biophys., 23: 265-295.
263. Tahara, N., Kai, H., Niiyama, H., Mori, T., Sugi, Y., Takayama, N., Yasukawa, H., Numaguchi, Y., Matsui, H., Okumura, K. and Imaizumi, T. (2004) Repeated gene transfer of naked prostacyclin synthase plasmid into skeletal muscles attenuates monocrotaline-induced pulmonary hypertension and prolongs survival in rats. Hum. Gene Ther., 15: 1270-1278.
264. Takahashi, M., Nakamura, T., Toba, T., Kajiwara, N., Kato, H. and Shimizu, Y. (2004) Transplantation of endothelial progenitor cells into the lung to alleviate pulmonary hypertension in dogs. Tissue Eng., 10: 771-779.
265. Takemoto, M., Sun, J., Hiroki, J., Shimokawa, H. and Liao, J. K. (2002) Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase. Circulation, 106: 57-62.
266. Task Force, m., Galie, N., Torbicki, A., Barst, R., Dartevelle, P., Haworth, S., Higenbottam, T., Olschewski, H., Peacock, A., Pietra, G., Rubin, L. J. and Simonneau, G. (2004) Guidelines on diagnosis and treatment of pulmonary arterial hypertension: The task force on diagnosis and treatment of pulmonary arterial hypertension of the european society of cardiology. Eur. Heart J., 25: 2243-2278.
267. Teichert-Kuliszewska, K., Kutryk, M. J., Kuliszewski, M. A., Karoubi, G., Courtman, D. W., Zucco, L., Granton, J. and Stewart, D. J. (2006) Bone morphogenetic protein receptor-2 signaling promotes pulmonary arterial endothelial cell survival: Implications for loss-of-function mutations in the pathogenesis of pulmonary hypertension.[see comment]. Circ. Res., 98: 209-217.
268. The Medical Letter (2002). Reprostinil (remodulin) for pulmonary hypertension. New Rochelle, The Medical Letter on Drugs and Therapeutics.
269. Thuillez, C. and Richard, V. (2005) Targeting endothelial dysfunction in hypertensive subjects. J. Hum. Hypertens., 19 Suppl 1: S21-25.
270. Tirney, S., Mattes, C. E., Yoshimura, N., Yokayama, T., Ozawa, H., Tzeng, E., Birder, L. A., Kanai, A. J., Huard, J., de Groat, W. C. and Chancellor, M. B. (2001) Nitric oxide synthase gene therapy for erectile dysfunction: Comparison of plasmid, adenovirus, and adenovirus-transduced myoblast vectors. Mol. Urology, 5: 37-43.
271. Tousoulis, D., Charakida, M. and Stefanadis, C. (2005) Inflammation and endothelial dysfunction as therapeutic targets in patients with heart failure. Int. J. Cardiol., 100: 347-353.
272. Touyz, R. M. (2004a) Reactive oxygen species and angiotensin ii signaling in vascular cells - implications in cardiovascular disease. Braz. J. Med. Biol. Res., 37: 1263-1273.
273. Touyz, R. M. (2004b) Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: What is the clinical significance? Hypertension, 44: 248-252.
274. Traish, A. and Kim, N. (2005) The physiological role of androgens in penile erection: Regulation of corpus cavernosum structure and function. J. Sex. Med., 2: 759-770.
275. Tuder, R. M., Cool, C. D., Geraci, M. W., Wang, J., Abman, S. H., Wright, L., Badesch, D. and Voelkel, N. F. (1999) Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am. J. Respir. Crit. Care Med., 159: 1925-1932.
276. Uslu, N., Eren, M., Gorgulu, S., Alper, A. T., Orhan, A. L., Yildirim, A., Nurkalem, Z. and Aksu, H. (2006a) Left ventricular diastolic function and endothelial function in patients with erectile dysfunction. Am. J. Cardiol., 97: 1785-1788.
277. Uslu, N., Gorgulu, S., Alper, A. T., Eren, M., Nurkalem, Z., Yildirim, A. and Ozer, O. (2006b) Erectile dysfunction as a generalized vascular dysfunction. J. Am. Soc. Echocardiogr., 19: 341-346.
278. van Zonneveld, A.-J. and Rabelink, T. J. (2006) Endothelial progenitor cells: Biology and therapeutic potential in hypertension. Curr. Opin. Nephrol. Hypertens., 15: 167-172.
279. VanBavel, E., Bakker, E. N. T. P., Pistea, A., Sorop, O. and Spaan, J. A. E. (2006) Mechanics of microvascular remodeling. Clin. Hemorheol. Microcirc., 34: 35-41.
280. Via, G. and Braschi, A. (2004) Pathophysiology of severe pulmonary hypertension in the critically ill patient. Minerva Anestesiol., 70: 233-237.
281. Vila, E. and Salaices, M. (2005) Cytokines and vascular reactivity in resistance arteries. Am. J. Physiol. - Heart & Circ. Physiol., 288: H1016-1021.
282. Virag, R., Bouilly, P. and Frydman, D. (1985) Is impotence an arterial disorder? A study of arterial risk factors in 440 impotent men. Lancet, 1: 181-184.
283. Virdis, A. and Schiffrin, E. L. (2003) Vascular inflammation: A role in vascular disease in hypertension? Curr. Opin. Nephrol. Hypertens., 12: 181-187.
284. Voetsch, B., Jin, R. C. and Loscalzo, J. (2004) Nitric oxide insufficiency and atherothrombosis. Histochem. Cell Biol., 122: 353-367.
285. Vogel, R. A. (2003) Heads and hearts: The endothelial connection. [comment]. Circulation, 107: 2766-2768.
286. Weir, E. K. (1978) Does normoxic pulmonary vasodilatation rather than hypoxic vasoconstriction account for the pulmonary pressor response to hypoxia? Lancet, 1: 476-477.
287. Werner, N. and Nickenig, G. (2006a) Clinical and therapeutical implications of epc biology in atherosclerosis. J. Cell Mol. Med., 10: 318-332.
288. Werner, N. and Nickenig, G. (2006b) Influence of cardiovascular risk factors on endothelial progenitor cells: Limitations for therapy? Arterioscler. Thromb. Vasc. Biol., 26: 257-266.
289. Werner, N. and Nickenig, G. (2006c) Influence of cardiovascular risk factors on endothetial progenitor cells: Limitations for therapy? Arteriosclerosis, Thrombosis Vasc. Biol., 26: 257-266.
290. Werner, N., Priller, J., Laufs, U., Endres, M., Bohm, M., Dirnagl, U. and Nickenig, G. (2002) Bone marrow-derived progenitor cells modulate vascular reendothelialization and neointimal formation: Effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition. Arterioscler. Thromb. Vasc. Biol., 22: 1567-1572.
291. Wessells, H., Teal, T. H., Luttrell, I. P. and Sullivan, C. J. (2006) Effect of endothelial cell-based inos gene transfer on cavernosal enos expression and mouse erectile responses. Int. J. Impot. Res., 18: 438-445.
292. Westphal, S., Taneva, E., Kastner, S., Martens-Lobenhoffer, J., Bode-Boger, S., Kropf, S., Dierkes, J. and Luley, C. (2006) Endothelial dysfunction induced by postprandial lipemia is neutralized by addition of proteins to the fatty meal. Atherosclerosis, 185: 313-319.
293. Wharton, J., Strange, J. W., Moller, G. M. O., Growcott, E. J., Ren, X., Franklyn, A. P., Phillips, S. C. and Wilkins, M. R. (2005) Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am. J. Respir. Crit. Care Med., 172: 105-113.
294. White, M., Ducharme, A., Ibrahim, R., Whittom, L., Lavoie, J., Guertin, M.-C., Racine, N., He, Y., Yao, G., Rouleau, J. L., Schiffrin, E. L. and Touyz, R. M. (2006) Increased systemic inflammation and oxidative stress in patients with worsening congestive heart failure: Improvement after short-term inotropic support. Clin. Sci., 110: 483-489.
295. Widlitz, A. and Barst, R. J. (2003) Pulmonary arterial hypertension in children. Eur. Respir. J., 21: 155-176.
296. Wilkens, H., Guth, A., Konig, J., Forestier, N., Cremers, B., Hennen, B., Bohm, M. and Sybrecht, G. W. (2001) Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation, 104: 1218-1222.
297. Woywodt, A., Bahlmann, F. H., De Groot, K., Haller, H. and Haubitz, M. (2002) Circulating endothelial cells: Life, death, detachment and repair of the endothelial cell layer. Nephrol. Dialy. Transplant., 17: 1728-1730.
298. Yamada, T., Hisanaga, M., Nakajima, Y., Mizuno, S., Matsumoto, K., Nakamura, T. and Nakano, H. (2000) Enhanced expression of hepatocyte growth factor by pulmonary ischemia-reperfusion injury in the rat. Am. J. Respir. Crit. Care Med., 162: 707-715.
299. Yamamoto, T., Wada, A., Tsutamoto, T., Ohnishi, M. and Horie, M. (2004) Long-term treatment with a phosphodiesterase type 5 inhibitor improves pulmonary hypertension secondary to heart failure through enhancing the natriuretic peptides-cgmp pathway. J. Cardiovasc. Pharmacol., 44: 596-600.
300. Yanagita, K., Matsumoto, K., Sekiguchi, K., Ishibashi, H., Niho, Y. and Nakamura, T. (1993) Hepatocyte growth factor may act as a pulmotrophic factor on lung regeneration after acute lung injury. J. Biol. Chem., 268: 21212-21217.
301. Yavuzgil, O., Altay, B., Zoghi, M., Gurgun, C., Kayikcioglu, M. and Kultursay, H. (2005) Endothelial function in patients with vasculogenic erectile dysfunction. Int. J. Cardiol., 103: 19-26.
302. Zhao, Y. D., Campbell, A. I. M., Robb, M., Ng, D. and Stewart, D. J. (2003) Protective role of angiopoietin-1 in experimental pulmonary hypertension. [see comment]. Circ. Res., 92: 984-991.
303. Zhao, Y. D., Courtman, D. W., Deng, Y., Kugathasan, L., Zhang, Q. and Stewart, D. J. (2005) Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: Efficacy of combined cell and enos gene therapy in established disease. Circ. Res., 96: 442-450.
304. Zhao, Y. D., Courtman, D. W., Ng, D. S., Robb, M. J., Deng, Y. P., Trogadis, J., Han, R. N. and Stewart, D. J. (2006) Microvascular regeneration in established pulmonary hypertension by angiogenic gene transfer. Am. J. Respir. Cell Mol. Biol., 35: 182-189.
305. Zimmermann, R., Kreuder, J., Michel-Behnke, I., Voelkel, N. F. and Schranz, D. (2006) Pulmonary flow reserve in children with idiopathic pulmonary arterial hypertension: Implications for diagnosis and therapy. Eur. J. Med. Res., 11: 208-213.
306. Zou, M.-H., Cohen, R. and Ullrich, V. (2004) Peroxynitrite and vascular endothelial dysfunction in diabetes mellittis. Endothelium: J. Endothel. Cell Res., 11: 89-97.