Emerging role for TNF-α in erectile dysfunction

Journal of Sexual Medicine

Volumn 7, Issue 12, 2010, Pages 3823-3834

  Carneiro, Fernando S ^a,b   Webb, Robert Clinton ^a   Tostes, Rita C ^a,b  

^a MEDICAL COLLEGE OF GEORGIA   (United States)

^b UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

Cardiovascular Disease; Coronary Artery Disease; Cytokines; Erectile Dysfunction; TNF

Indexed keywords

TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA RECEPTOR;

CORONARY ARTERY DISEASE; ERECTILE DYSFUNCTION; PENILE BLOOD VESSEL; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN SYNTHESIS; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION; SMOOTH MUSCLE CONTRACTION;

EID: 78649842236     PISSN: 17436095     EISSN: 17436109     Source Type: Journal    
DOI: 10.1111/j.1743-6109.2010.01762.x     Document Type: Review

References (138)

1. Burnett AL. Role of nitric oxide in the physiology of erection. Biol Reprod 1995;52:485-9.
2. Andersson KE. Pharmacology of penile erection. Pharmacol Rev 2001;53:417-50.
3. Andersson KE, Stief CG. Neurotransmission and the contraction and relaxation of penile erectile tissues. World J Urol 1997;15:14-20.
4. Ignarro LJ, Bush PA, Buga GM, Wood KS, Fukuto JM, Rajfer J. Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 1990;170:843-50.
5. Rajfer J, Aronson WJ, Bush PA, Dorey FJ, Ignarro LJ. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med 1992;326:90-4.
6. Burnett AL, Nelson RJ, Calvin DC, Liu JX, Demas GE, Klein SL, Kriegsfeld LJ, Dawson VL, Dawson TM, Snyder SH. Nitric oxide-dependent penile erection in mice lacking neuronal nitric oxide synthase. Mol Med 1996;2:288-96.
7. Alm P, Larsson B, Ekblad E, Sundler F, Andersson KE. Immunohistochemical localization of peripheral nitric oxide synthase-containing nerves using antibodies raised against synthesized C- and N-terminal fragments of a cloned enzyme from rat brain. Acta Physiol Scand 1993;148:421-9.
8. Burnett AL, Tillman SL, Chang TS, Epstein JI, Lowenstein CJ, Bredt DS, Snyder SH, Walsh PC. Immunohistochemical localization of nitric oxide synthase in the autonomic innervation of the human penis. J Urol 1993;150:73-6.
9. Dail WG, Barba V, Leyba L, Galindo R. Neural and endothelial nitric oxide synthase activity in rat penile erectile tissue. Cell Tissue Res 1995;282:109-16.
10. Leite R, Giachini FR, Carneiro FS, Nunes KP, Tostes RC, Webb RC. Targets for the treatment of erectile dysfunction: Is NO/cGMP still the answer? Recent Patents Cardiovasc Drug Discov 2007;2:119-32.
11. Priviero FB, Leite R, Webb RC, Teixeira CE. Neurophysiological basis of penile erection. Acta Pharmacol Sin 2007;28:751-5.
12. Chitaley K, Wingard CJ, Clinton Webb R, Branam H, Stopper VS, Lewis RW, Mills TM. Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway. Nat Med 2001;7:119-22.
13. 2+ sensitization in erectile function. J Biol Chem 2002;277:30614-21.
14. Chitaley K, Webb RC, Mills TM. Rho-kinase as a potential target for the treatment of erectile dysfunction. Drug News Perspect 2001;14:601-6.
15. Bivalacqua TJ, Champion HC, Usta MF, Cellek S, Chitaley K, Webb RC, Lewis RL, Mills TM, Hellstrom WJ, Kadowitz PJ. RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: A mechanism for diabetes-associated erectile dysfunction. Proc Natl Acad Sci U S A 2004;101:9121-6.
16. Rajasekaran M, White S, Baquir A, Wilkes N. Rho-kinase inhibition improves erectile function in aging male Brown-Norway rats. J Androl 2005;26:182-8.
17. Seftel A. RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: A mechanism for diabetes-associated erectile dysfunction. J Urol 2005;173:928-9.
18. Jin L, Liu T, Lagoda GA, Champion HC, Bivalacqua TJ, Burnett AL. Elevated RhoA/Rho-kinase activity in the aged rat penis: Mechanism for age-associated erectile dysfunction. FASEB J 2006;20:536-8.
19. Park K, Kim SW, Rhu KS, Paick JS. Chronic administration of an oral Rho kinase inhibitor prevents the development of vasculogenic erectile dysfunction in a rat model. J Sex Med 2006;3:996-1003.
20. Kobayashi N, Nakano S, Mita S, Kobayashi T, Honda T, Tsubokou Y, Matsuoka H. Involvement of Rho-kinase pathway for angiotensin II-induced plasminogen activator inhibitor-1 gene expression and cardiovascular remodeling in hypertensive rats. J Pharmacol Exp Ther 2002;301:459-66.
21. Loirand G, Rolli-Derkinderen M, Pacaud P. RhoA and resistance artery remodeling. Am J Physiol Heart Circ Physiol 2005;288:H1051-6.
22. Nakano S, Kobayashi N, Yoshida K, Ohno T, Matsuoka H. Cardioprotective mechanisms of spironolactone associated with the angiotensin-converting enzyme/epidermal growth factor receptor/extracellular signal-regulated kinases, NAD(P)H oxidase/lectin-like oxidized low-density lipoprotein receptor-1, and Rho-kinase pathways in aldosterone/salt-induced hypertensive rats. Hypertens Res 2005;28:925-36.
23. Ohtsu H, Mifune M, Frank GD, Saito S, Inagami T, Kim-Mitsuyama S, Takuwa Y, Sasaki T, Rothstein JD, Suzuki H, Nakashima H, Woolfolk EA, Motley ED, Eguchi S. Signal-crosstalk between Rho/ROCK and c-Jun NH2-terminal kinase mediates migration of vascular smooth muscle cells stimulated by angiotensin II. Arterioscler Thromb Vasc Biol 2005;25:1831-6.
24. Tayal V, Kalra BS. Cytokines and anti-cytokines as therapeutics-An update. Eur J Pharmacol 2008;579:1-12.
25. Kelso A. Cytokines: Principles and prospects. Immunol Cell Biol 1998;76:300-17.
26. O'Shea JJ, Murray PJ. Cytokine signaling modules in inflammatory responses. Immunity 2008;28:477-87.
27. Cotran RS, Pober JS. Cytokine-endothelial interactions in inflammation, immunity, and vascular injury. J Am Soc Nephrol 1990;1:225-35.
28. Cotran RS, Pober JS. Effects of cytokines on vascular endothelium: Their role in vascular and immune injury. Kidney Int 1989;35:969-75.
29. Zhang C. The role of inflammatory cytokines in endothelial dysfunction. Basic Res Cardiol 2008;103:398-406.
30. Glembot TM, Britt LD, Hill MA. Endotoxin interacts with tumor necrosis factor-alpha to induce vasodilation of isolated rat skeletal muscle arterioles. Shock 1996;5:251-7.
31. Minghini A, Britt LD, Hill MA. Interleukin-1 and interleukin-6 mediated skeletal muscle arteriolar vasodilation: In vitro versus in vivo studies. Shock 1998;9:210-5.
32. Vila E, Salaices M. Cytokines and vascular reactivity in resistance arteries. Am J Physiol Heart Circ Physiol 2005;288:H1016-21.
33. Zhang C, Xu X, Potter BJ, Wang W, Kuo L, Michael L, Bagby GJ, Chilian WM. TNF-alpha contributes to endothelial dysfunction in ischemia/reperfusion injury. Arterioscler Thromb Vasc Biol 2006;26:475-80.
34. Vlachopoulos C, Aznaouridis K, Ioakeimidis N, Rokkas K, Vasiliadou C, Alexopoulos N, Stefanadi E, Askitis A, Stefanadis C. Unfavourable endothelial and inflammatory state in erectile dysfunction patients with or without coronary artery disease. Eur Heart J 2006;27:2640-8.
35. Zhang H, Park Y, Wu J, Chen X, Lee S, Yang J, Dellsperger KC, Zhang C. Role of TNF-alpha in vascular dysfunction. Clin Sci (Lond) 2009;116:219-30.
36. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A 1975;72:3666-70.
37. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: Integrating mammalian biology. Cell 2001;104:487-501.
38. Baud V, Karin M. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 2001;11:372-7.
39. Giroir BP, Johnson JH, Brown T, Allen GL, Beutler B. The tissue distribution of tumor necrosis factor biosynthesis during endotoxemia. J Clin Invest 1992;90:693-8.
40. Kapadia S, Lee J, Torre-Amione G, Birdsall HH, Ma TS, Mann DL. Tumor necrosis factor-alpha gene and protein expression in adult feline myocardium after endotoxin administration. J Clin Invest 1995;96:1042-52.
41. Shakhov AN, Collart MA, Vassalli P, Nedospasov SA, Jongeneel CV. Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages. J Exp Med 1990;171:35-47.
42. Bazzoni F, Beutler B. The tumor necrosis factor ligand and receptor families. N Engl J Med 1996;334:1717-25.
43. Ruddle NH, Waksman BH. Cytotoxic effect of lymphocyte-antigen interaction in delayed hypersensitivity. Science 1967;157:1060-2.
44. Baker SJ, Reddy EP. Transducers of life and death: TNF receptor superfamily and associated proteins. Oncogene 1996;12:1-9.
45. Gaeta ML, Johnson DR, Kluger MS, Pober JS. The death domain of tumor necrosis factor receptor 1 is necessary but not sufficient for Golgi retention of the receptor and mediates receptor desensitization. Lab Invest 2000;80:1185-94.
46. Amrani Y, Ammit AJ, Panettieri RA Jr. Tumor necrosis factor receptor (TNFR) 1, but not TNFR2, mediates tumor necrosis factor-alpha-induced interleukin-6 and RANTES in human airway smooth muscle cells: Role of p38 and p42/44 mitogen-activated protein kinases. Mol Pharmacol 2001;60:646-55.
47. 2+ transients. FEBS Lett 1995;376:24-30.
48. Torre-Amione G, Kapadia S, Lee J, Bies RD, Lebovitz R, Mann DL. Expression and functional significance of tumor necrosis factor receptors in human myocardium. Circulation 1995;92:1487-93.
49. Carneiro FS, Zemse S, Giachini FR, Carneiro ZN, Lima VV, Webb RC, Tostes RC. TNF-alpha infusion impairs corpora cavernosa reactivity. J Sex Med 2009;6(3 suppl):311-9.
50. Hsu H, Shu HB, Pan MG, Goeddel DV. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 1996;84:299-308.
51. Rothe M, Sarma V, Dixit VM, Goeddel DV. TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40. Science 1995;269:1424-7.
52. Bradley JR, Pober JS. Tumor necrosis factor receptor-associated factors (TRAFs). Oncogene 2001;20:6482-91.
53. Stanger BZ, Leder P, Lee TH, Kim E, Seed B. RIP: A novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell 1995;81:513-23.
54. Park YC, Ye H, Hsia C, Segal D, Rich RL, Liou HC, Myszka DG, Wu H. A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction. Cell 2000;101:777-87.
55. Madge LA, Pober JS. TNF signaling in vascular endothelial cells. Exp Mol Pathol 2001;70:317-25.
56. Baldwin AS Jr. The NF-kappa B and I kappa B proteins: New discoveries and insights. Annu Rev Immunol 1996;14:649-83.
57. Pfizenmaier K, Wajant H, Grell M. Tumor necrosis factors in 1996. Cytokine Growth Factor Rev 1996;7:271-7.
58. Chen G, Goeddel DV. TNF-R1 signaling: A beautiful pathway. Science 2002;296:1634-5.
59. Ihnatko R, Kubes M. TNF signaling: Early events and phosphorylation. Gen Physiol Biophys 2007;26:159-67.
60. Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ 2003;10:45-65.
61. Ferrari R. Tumor necrosis factor in CHF: A double facet cytokine. Cardiovasc Res 1998;37:554-9.
62. Meldrum DR, Meng X, Dinarello CA, Ayala A, Cain BS, Shames BD, Ao L, Banerjee A, Harken AH. Human myocardial tissue TNF alpha expression following acute global ischemia in vivo. J Mol Cell Cardiol 1998;30:1683-9.
63. Berk BC, Abe JI, Min W, Surapisitchat J, Yan C. Endothelial atheroprotective and anti-inflammatory mechanisms. Ann N Y Acad Sci 2001;947:93-109; discussion 09-11.
64. Trepels T, Zeiher AM, Fichtlscherer S. The endothelium and inflammation. Endothelium 2006;13:423-9.
65. Chia S, Qadan M, Newton R, Ludlam CA, Fox KA, Newby DE. Intra-arterial tumor necrosis factor-alpha impairs endothelium-dependent vasodilatation and stimulates local tissue plasminogen activator release in humans. Arterioscler Thromb Vasc Biol 2003;23:695-701.
66. Anderson HD, Rahmutula D, Gardner DG. Tumor necrosis factor-alpha inhibits endothelial nitric-oxide synthase gene promoter activity in bovine aortic endothelial cells. J Biol Chem 2004;279:963-9.
67. Neumann P, Gertzberg N, Johnson A. TNF-alpha induces a decrease in eNOS promoter activity. Am J Physiol Lung Cell Mol Physiol 2004;286:L452-9.
68. Yoshizumi M, Perrella MA, Burnett JC Jr, Lee ME. Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life. Circ Res 1993;73:205-9.
69. Zhang L, Peppel K, Sivashanmugam P, Orman ES, Brian L, Exum ST, Freedman NJ. Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis. Arterioscler Thromb Vasc Biol 2007;27:1087-94.
70. Mong PY, Petrulio C, Kaufman HL, Wang Q. Activation of Rho kinase by TNF-alpha is required for JNK m activation in human pulmonary microvascular endothelial cells. J Immunol 2008;180:550-8.
71. Petrache I, Birukova A, Ramirez SI, Garcia JG, Verin AD. The role of the microtubules in tumor necrosis factor-alpha-induced endothelial cell permeability. Am J Respir Cell Mol Biol 2003;28:574-81.
72. McKenzie JA, Ridley AJ. Roles of Rho/ROCK and MLCK in TNF-alpha-induced changes in endothelial morphology and permeability. J Cell Physiol 2007;213:221-8.
73. Petrache I, Crow MT, Neuss M, Garcia JG. Central involvement of Rho family GTPases in TNF-alpha-mediated bovine pulmonary endothelial cell apoptosis. Biochem Biophys Res Commun 2003;306:244-9.
74. Hippenstiel S, Schmeck B, Seybold J, Krull M, Eichel-Streiber C, Suttorp N. Reduction of tumor necrosis factor-alpha (TNF-alpha) related nuclear factor-kappaB (NF-kappaB) translocation but not inhibitor kappa-B (Ikappa-B)-degradation by Rho protein inhibition in human endothelial cells. Biochem Pharmacol 2002;64:971-7.
75. 2+ sensitization of myosin light chain20 phosphorylation. Mol Pharmacol 2003;63:714-21.
76. Morin C, Sirois M, Echave V, Gomes MM, Rousseau E. EET displays anti-inflammatory effects in TNF-alpha stimulated human bronchi: Putative role of CPI-17. Am J Respir Cell Mol Biol 2008;38:192-201.
77. Doe C, Bentley R, Behm DJ, Lafferty R, Stavenger R, Jung D, Bamford M, Panchal T, Grygielko E, Wright LL, Smith GK, Chen Z, Webb C, Khandekar S, Yi T, Kirkpatrick R, Dul E, Jolivette L, Marino JP Jr, Willette R, Lee D, Hu E. Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther 2007;320:89-98.
78. Horton JW, Maass DL, Ballard-Croft C. Rho-associated kinase modulates myocardial inflammatory cytokine responses. Shock 2005;24:53-8.
79. Thorlacius K, Slotta JE, Laschke MW, Wang Y, Menger MD, Jeppsson B, Thorlacius H. Protective effect of fasudil, a Rho-kinase inhibitor, on chemokine expression, leukocyte recruitment, and hepatocellular apoptosis in septic liver injury. J Leukoc Biol 2006;79:923-31.
80. Kawaguchi A, Ohmori M, Fujimura A. Partial protective effect of Y-27632, a Rho kinase inhibitor, against hepatic ischemia-reperfusion injury in rats. Eur J Pharmacol 2004;493:167-71.
81. Shiotani S, Shimada M, Suehiro T, Soejima Y, Yosizumi T, Shimokawa H, Maehara Y. Involvement of Rho-kinase in cold ischemia-reperfusion injury after liver transplantation in rats. Transplantation 2004;78:375-82.
82. Tasaka S, Koh H, Yamada W, Shimizu M, Ogawa Y, Hasegawa N, Yamaguchi K, Ishii Y, Richer SE, Doerschuk CM, Ishizaka A. Attenuation of endotoxin-induced acute lung injury by the Rho-associated kinase inhibitor, Y-27632. Am J Respir Cell Mol Biol 2005;32:504-10.
83. NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993;270:83-90.
84. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: Results of the Massachusetts Male Aging Study. J Urol 1994;151:54-61.
85. Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int 1999;84:50-6.
86. Shabsigh R, Fishman IJ, Schum C, Dunn JK. Cigarette smoking and other vascular risk factors in vasculogenic impotence. Urology 1991;38:227-31.
87. Feldman HA, Johannes CB, Derby CA, Kleinman KP, Mohr BA, Araujo AB, McKinlay JB. Erectile dysfunction and coronary risk factors: Prospective results from the Massachusetts male aging study. Prev Med 2000;30:328-38.
88. Hodges LD, Kirby M, Solanki J, O'Donnell J, Brodie DA. The temporal relationship between erectile dysfunction and cardiovascular disease. Int J Clin Pract 2007;61:2019-25.
89. Montorsi F, Briganti A, Salonia A, Rigatti P, Margonato A, Macchi A, Galli S, Ravagnani PM, Montorsi P. Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease. Eur Urol 2003;44:360-4; discussion 64-5.
90. Kloner RA, Mullin SH, Shook T, Matthews R, Mayeda G, Burstein S, Peled H, Pollick C, Choudhary R, Rosen R, Padma-Nathan H. Erectile dysfunction in the cardiac patient: How common and should we treat? J Urol 2003;170:S46-50; discussion S50.
91. Solomon H, Man JW, Wierzbicki AS, Jackson G. Relation of erectile dysfunction to angiographic coronary artery disease. Am J Cardiol 2003;91:230-1.
92. Akilli H, Gok H, Soylu A, Kayrak M. Severity of coronary artery disease and symptoms of erectile dysfunction in males with a positive exercise treadmill test. Int J Urol 2007;14:733-7.
93. Greenstein A, Chen J, Miller H, Matzkin H, Villa Y, Braf Z. Does severity of ischemic coronary disease correlate with erectile function? Int J Impot Res 1997;9:123-6.
94. Montorsi P, Ravagnani PM, Galli S, Rotatori F, Veglia F, Briganti A, Salonia A, Deho F, Rigatti P, Montorsi F, Fiorentini C. Association between erectile dysfunction and coronary artery disease. Role of coronary clinical presentation and extent of coronary vessels involvement: The COBRA trial. Eur Heart J 2006;27:2632-9.
95. Sullivan ME, Thompson CS, Dashwood MR, Khan MA, Jeremy JY, Morgan RJ, Mikhailidis DP. Nitric oxide and penile erection: Is erectile dysfunction another manifestation of vascular disease? Cardiovasc Res 1999;43:658-65.
96. Montorsi P, Montorsi F, Schulman CC. Is erectile dysfunction the "tip of the iceberg" of a systemic vascular disorder? Eur Urol 2003;44:352-4.
97. Kirby M, Jackson G, Simonsen U. Endothelial dysfunction links erectile dysfunction to heart disease. Int J Clin Pract 2005;59:225-9.
98. Billups KL, Bank AJ, Padma-Nathan H, Katz S, Williams R. Erectile dysfunction is a marker for cardiovascular disease: Results of the minority health institute expert advisory panel. J Sex Med 2005;2:40-50; discussion 50-2.
99. Ponholzer A, Temml C, Obermayr R, Wehrberger C, Madersbacher S. Is erectile dysfunction an indicator for increased risk of coronary heart disease and stroke? Eur Urol 2005;48:512-8; discussion 17-8.
100. Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA. Erectile dysfunction and subsequent cardiovascular disease. JAMA 2005;294:2996-3002.
101. Grover SA, Lowensteyn I, Kaouache M, Marchand S, Coupal L, DeCarolis E, Zoccoli J, Defoy I. The prevalence of erectile dysfunction in the primary care setting: Importance of risk factors for diabetes and vascular disease. Arch Intern Med 2006;166:213-9.
102. Jackson G. The metabolic syndrome and erectile dysfunction: Multiple vascular risk factors and hypogonadism. Eur Urol 2006;50:426-7.
103. Heidler S, Temml C, Broessner C, Mock K, Rauchenwald M, Madersbacher S, Ponholzer A. Is the metabolic syndrome an independent risk factor for erectile dysfunction? J Urol 2007;177:651-4.
104. Savoia C, Schiffrin EL. Vascular inflammation in hypertension and diabetes: Molecular mechanisms and therapeutic interventions. Clin Sci (Lond) 2007;112:375-84.
105. Sullivan ME, Miller MA, Bell CR, Jagroop IA, Thompson CS, Khan MA, Morgan RJ, Mikhailidis DP. Fibrinogen, lipoprotein (a) and lipids in patients with erectile dysfunction. A preliminary study. Int Angiol 2001;20:195-9.
106. Billups KL, Kaiser DR, Kelly AS, Wetterling RA, Tsai MY, Hanson N, Bank AJ. Relation of C-reactive protein and other cardiovascular risk factors to penile vascular disease in men with erectile dysfunction. Int J Impot Res 2003;15:231-6.
107. Bocchio M, Desideri G, Scarpelli P, Necozione S, Properzi G, Spartera C, Francavilla F, Ferri C, Francavilla S. Endothelial cell activation in men with erectile dysfunction without cardiovascular risk factors and overt vascular damage. J Urol 2004;171:1601-4.
108. Giugliano F, Esposito K, Di Palo C, Ciotola M, Giugliano G, Marfella R, D'Armiento M, Giugliano D. Erectile dysfunction associates with endothelial dysfunction and raised proinflammatory cytokine levels in obese men. J Endocrinol Invest 2004;27:665-9.
109. Chiurlia E, D'Amico R, Ratti C, Granata AR, Romagnoli R, Modena MG. Subclinical coronary artery atherosclerosis in patients with erectile dysfunction. J Am Coll Cardiol 2005;46:1503-6.
110. Esposito K, Giugliano F, Martedi E, Feola G, Marfella R, D'Armiento M, Giugliano D. High proportions of erectile dysfunction in men with the metabolic syndrome. Diabetes Care 2005;28:1201-3.
111. Eaton CB, Liu YL, Mittleman MA, Miner M, Glasser DB, Rimm EB. A retrospective study of the relationship between biomarkers of atherosclerosis and erectile dysfunction in 988 men. Int J Impot Res 2007;19:218-25.
112. Vlachopoulos C, Rokkas K, Ioakeimidis N, Stefanadis C. Inflammation, metabolic syndrome, erectile dysfunction, and coronary artery disease: Common links. Eur Urol 2007;52:1590-600.
113. Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB. Incidence of erectile dysfunction in men 40-69 years old: Longitudinal results from the Massachusetts male aging study. J Urol 2000;163:460-3.
114. Paolisso G, Rizzo MR, Mazziotti G, Tagliamonte MR, Gambardella A, Rotondi M, Carella C, Giugliano D, Varricchio M, D'Onofrio F. Advancing age and insulin resistance: Role of plasma tumor necrosis factor-alpha. Am J Physiol 1998;275:E294-9.
115. Holm T, Aukrust P, Andreassen AK, Ueland T, Brosstad F, Froland SS, Simonsen S, Gullestad L. Peripheral endothelial dysfunction in heart transplant recipients: Possible role of proinflammatory cytokines. Clin Transplant 2000;14:218-25.
116. Bhagat K, Vallance P. Inflammatory cytokines impair endothelium-dependent dilatation in human veins in vivo. Circulation 1997;96:3042-7.
117. Karadag F, Ozcan H, Karul AB, Ceylan E, Cildag O. Correlates of erectile dysfunction in moderate-to-severe chronic obstructive pulmonary disease patients. Respirology 2007;12:248-53.
118. Carneiro FS, Sturgis LC, Giachini FR, Carneiro ZN, Lima VV, Wynne BM, San Martin S, Brands MW, Tostes RC, Webb RC. TNF-alpha knockout mice have increased corpora cavernosa relaxation. J Sex Med 2009;6:115-25.
119. Alexander BT, Cockrell KL, Massey MB, Bennett WA, Granger JP. Tumor necrosis factor-alpha-induced hypertension in pregnant rats results in decreased renal neuronal nitric oxide synthase expression. Am J Hypertens 2002;15:170-5.
120. Hayward MD, Jones BK, Saparov A, Hain HS, Trillat AC, Bunzel MM, Corona A, Li-Wang B, Strenkowski B, Giordano C, Shen H, Arcamone E, Weidlick J, Vilensky M, Tugusheva M, Felkner RH, Campbell W, Rao Y, Grass DS, Buiakova O. An extensive phenotypic characterization of the hTNFalpha transgenic mice. BMC Physiol 2007;7:13.
121. Kifor I, Williams GH, Vickers MA, Sullivan MP, Jodbert P, Dluhy RG. Tissue angiotensin II as a modulator of erectile function. I. Angiotensin peptide content, secretion and effects in the corpus cavernosum. J Urol 1997;157:1920-5.
122. Schiffrin EL, Touyz RM. From bedside to bench to bedside: Role of renin-angiotensin-aldosterone system in remodeling of resistance arteries in hypertension. Am J Physiol Heart Circ Physiol 2004;287:H435-46.
123. Granchi S, Vannelli GB, Vignozzi L, Crescioli C, Ferruzzi P, Mancina R, Vinci MC, Forti G, Filippi S, Luconi M, Ledda F, Maggi M. Expression and regulation of endothelin-1 and its receptors in human penile smooth muscle cells. Mol Hum Reprod 2002;8:1053-64.
124. Schiffrin EL. Vascular endothelin in hypertension. Vascul Pharmacol 2005;43:19-29.
125. Tostes RC, Muscara MN. Endothelin receptor antagonists: Another potential alternative for cardiovascular diseases. Curr Drug Targets Cardiovasc Haematol Disord 2005;5:287-301.
126. Marsden PA, Brenner BM. Transcriptional regulation of the endothelin-1 gene by TNF-alpha. Am J Physiol 1992;262:C854-61.
127. Ferreri NR, Zhao Y, Takizawa H, McGiff JC. Tumor necrosis factor-alpha-angiotensin interactions and regulation of blood pressure. J Hypertens 1997;15:1481-4.
128. Luo B, Liu L, Tang L, Zhang J, Ling Y, Fallon MB. ET-1 and TNF-alpha in HPS: Analysis in prehepatic portal hypertension and biliary and nonbiliary cirrhosis in rats. Am J Physiol Gastrointest Liver Physiol 2004;286:G294-303.
129. Kagawa T, Takao T, Horino T, Matsumoto R, Inoue K, Morita T, Hashimoto K. Angiotensin II receptor blocker inhibits tumour necrosis factor-alpha-induced cell damage in human renal proximal tubular epithelial cells. Nephrology (Carlton) 2008;13:309-15.
130. Elmarakby AA, Quigley JE, Pollock DM, Imig JD. Tumor necrosis factor alpha blockade increases renal Cyp2c23 expression and slows the progression of renal damage in salt-sensitive hypertension. Hypertension 2006;47:557-62.
131. Elmarakby AA, Quigley JE, Imig JD, Pollock JS, Pollock DM. TNF-alpha inhibition reduces renal injury in DOCA-salt hypertensive rats. Am J Physiol Regul Integr Comp Physiol 2008;294:R76-83.
132. Carneiro FS, Giachini FR, Lima VV, Carneiro ZN, Nunes KP, Ergul A, Leite R, Tostes RC, Webb RC. DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosum. Can J Physiol Pharmacol 2008;86:320-8.
133. Carneiro FS, Nunes KP, Giachini FR, Lima VV, Carneiro ZN, Nogueira EF, Leite R, Ergul A, Rainey WE, Clinton Webb R, Tostes RC. Activation of the ET-1/ETA pathway contributes to erectile dysfunction associated with mineralocorticoid hypertension. J Sex Med 2008;5:2793-807.
134. Ermertcan AT. Sexual dysfunction in dermatological diseases. J Eur Acad Dermatol Venereol 2009;9:985-1117.
135. Blake DJ, Maisiak R, Koplan A, Alarcon GS, Brown S. Sexual dysfunction among patients with arthritis. Clin Rheumatol 1988;7:50-60.
136. Dincer U, Cakar E, Kiralp MZ, Dursun H. Assessment of sexual dysfunction in male patients with Ankylosing Spondylitis. Rheumatol Int 2007;27:561-6.
137. Cakar E, Dincer U, Kiralp MZ, Taskaynatan MA, Yasar E, Bayman EO, Ozgul A, Dursun H. Sexual problems in male ankylosing spondylitis patients: Relationship with functionality, disease activity, quality of life, and emotional status. Clin Rheumatol 2007;26:1607-13.
138. Pirildar T, Muezzinoglu T, Pirildar S. Sexual function in ankylosing spondylitis: A study of 65 men. J Urol 2004;171:1598-600.