Sildenafil Promotes Smooth Muscle Preservation and Ameliorates Fibrosis Through Modulation of Extracellular Matrix and Tissue Growth Factor Gene Expression After Bilateral Cavernosal Nerve Resection in the Rat

Journal of Sexual Medicine

Volumn 8, Issue 4, 2011, Pages 1048-1060

  Sirad, Fara ^a   Hlaing, Su ^a   Kovanecz, Istvan ^b,c   Artaza, Jorge N ^a,c   Garcia, Leah A ^a   Rajfer, Jacob ^b,c   Ferrini, Monica G ^a,c  

^a CHARLES R DREW UNIVERSITY OF MEDICINE AND SCIENCE   (United States)

^b HARBOR UCLA MEDICAL CENTER   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Angiogenesis; Bilateral Cavernosal Nerve Resection; Epiregulin, Smooth Muscle; Fibrosis; Sildenafil

Indexed keywords

CONNECTIVE TISSUE GROWTH FACTOR; EPIDERMAL GROWTH FACTOR; EPIREGULIN; GELATINASE B; SILDENAFIL; STROMELYSIN; TRANSFORMING GROWTH FACTOR BETA2;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; CORPUS CAVERNOSUM; DOWN REGULATION; DRUG EFFECT; DRUG MECHANISM; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; MALE; NERVE FIBER TRANSECTION; NONHUMAN; PENILE FIBROSIS; PRIORITY JOURNAL; PROSTATECTOMY; RAT; SMOOTH MUSCLE; TREATMENT OUTCOME; UPREGULATION;

EID: 79953320193     PISSN: 17436095     EISSN: 17436109     Source Type: Journal    
DOI: 10.1111/j.1743-6109.2010.02195.x     Document Type: Article

References (50)

1. Garcia FJ, Brock G. Current state of penile rehabilitation after radical prostatectomy. Curr Opin Urol 2010;20:234-40.
2. Tal R, Valenzuela R, Aviv N, Parker M, Waters WB, Flanigan RC, Mulhall JP. Persistent erectile dysfunction following radical prostatectomy: The association between nerve-sparing status and the prevalence and chronology of venous leak. J Sex Med 2009;6:2813-9.
3. Walsh PC, Mostwin JL. Radical prostatectomy and cystoprostatectomy with preservation of potency. Results using a new nerve-sparing technique. Br J Urol 1984;56:694-7.
4. Magheli A, Burnett AL. Erectile dysfunction following prostatectomy: Prevention and treatment. Nat Rev Urol 2009;6:415-27.
5. Leungwattanakij S, Bivalacqua TJ, Usta MF, Yang DY, Hyun JS, Champion HC, Abdel-Mageed AB, Hellstrom WJ. Cavernous neurotomy causes hypoxia and fibrosis in rat corpus cavernosum. J Androl 2003;24:239-45.
6. Ferrini MG, Davila HH, Kovanecz I, Sanchez SP, Gonzalez-Cadavid NF, Rajfer J. Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat. Urology 2006;68:429-35.
7. Ferrini MG, Kovanecz I, Sanchez S, Umeh C, Rajfer J, Gonzalez-Cadavid NF. Fibrosis and loss of smooth muscle in the corpora cavernosa precede corporal veno-occlusive dysfunction (CVOD) induced by experimental cavernosal nerve damage in the rat. J Sex Med 2009;6:415-28.
8. Kovanecz I, Rambhatla A, Ferrini M, Vernet D, Sanchez S, Rajfer J, Gonzalez-Cadavid N. Long-term continuous sildenafil treatment ameliorates corporal veno-occlusive dysfunction (CVOD) induced by cavernosal nerve resection in rats. Int J Impot Res 2008;20:202-12.
9. Kovanecz I, Rambhatla A, Ferrini MG, Vernet D, Sanchez S, Rajfer J, Gonzalez-Cadavid N. Chronic daily tadalafil prevents the corporal fibrosis and veno-occlusive dysfunction that occurs after cavernosal nerve resection. BJU Int 2008;101:203-10.
10. Vignozzi L, Morelli A, Filippi S, Vannelli GB, Mungai S, Marini M, Boddi V, Forti G, Maggi M. Effect of sildenafil administration on penile hypoxia induced by cavernous neurotomy in the rat. Int J Impot Res 2008;20:60-7.
11. El-Sakka AI, Yassin AA. Amelioration of penile fibrosis: Myth or reality. J Androl 2010;31:324-35.
12. Vignozzi L, Filippi S, Morelli A, Marini M, Chavalmane A, Fibbi B, Silvestrini E, Mancina R, Carini M, Vannelli GB, Forti G, Maggi M. Cavernous neurotomy in the rat is associated with the onset of an overt condition of hypogonadism. J Sex Med 2009;6:1270-83.
13. Hatzimouratidis K, Burnett AL, Hatzichristou D, McCullough AR, Montorsi F, Mulhall JP. Phosphodiesterase type 5 inhibitors in postprostatectomy erectile dysfunction: A critical analysis of the basic science rationale and clinical application. Eur Urol 2009;55:334-47.
14. Vignozzi L, Filippi S, Morelli A, Ambrosini S, Luconi M, Vannelli GB, Donati S, Crescioli C, Zhang XH, Mirone V, Forti G, Maggi M. Effect of chronic tadalafil administration on penile hypoxia induced by cavernous neurotomy in the rat. J Sex Med 2006;3:419-31.
15. Magheli A, Burnett AL. Medscape. Erectile dysfunction following prostatectomy: Prevention and treatment. Nat Rev Urol 2009;6:415-27.
16. Gonzalez-Cadavid NF, Rajfer J. Experimental models of Peyronie's disease. Implications for new therapies. J Sex Med 2009;6:303-13.
17. Mostafa T. Oral phosphodiesterase type 5 inhibitors: Nonerectogenic beneficial uses. J Sex Med 2008;5:2502-18.
18. Burnett AL. Molecular pharmacotherapeutic targeting of PDE5 for preservation of penile health. J Androl 2008;29:3-14.
19. Schwartz EJ, Wong P, Graydon RJ. Sildenafil preserves intracorporeal smooth muscle after radical prostatectomy. J Urol 2004;171:771-4.
20. Padma-Nathan H, McCullough AR, Levine LA, Lipshultz LI, Siegel R, Montorsi F, Giuliano F, Brock G, Andrianne R, Bell D, Broderick G, Carrier S, Cuzin B, Deeths HJ, Hellstrom W, Herschorn S, Lewis RW, Rosen RC, Shabsigh R, Stricker P. Randomized, double-blind, placebo-controlled study of postoperative nightly sildenafil citrate for the prevention of erectile dysfunction after bilateral nerve-sparing radical prostatectomy. Int J Impot Res 2008;20:479-86.
21. Montorsi F, Brock G, Lee J, Shapiro J, Van Poppel H, Graefen M, Stief C. Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy. Eur Urol 2008;54:924-31.
22. Briganti A, Gallina A, Salonia A, Zanni G, Cestari A, Guazzoni G, Rigatti P, Montorsi F. The case for postoperative PDE-5 inhibitor drug treatment after radical prostatectomy. J Endourol 2008;22:2025-7; discussion 2035.
23. Deho F, Gallina A, Salonia A, Briganti A, Suardi N, Zanni G, Guazzoni G, Rigatti P, Montorsi F. Prophylaxis of erectile function after radical prostatectomy with phosphodiesterase type 5 inhibitors. Curr Pharm Des 2009;15:3496-501.
24. Karamysheva AF. Mechanism of angiogenesis. Biochemistry 2008;73:751-62.
25. de Visser YP, Walther FJ, Laghmani el H, Boersma H, van der Laarse A, Wagenaar GT. Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury. Respir Res 2009;29:10-30.
26. Bednar MM. The role of sildenafil in the treatment of stroke. Curr Opin Investig Drugs 2008;9:754-9.
27. Bremer YA, Salloum F, Ockaili R, Chou E, Moskowitz WB, Kukreja RC. Sildenafil citrate (viagra) induces cardioprotective effects after ischemia/reperfusion injury in infant rabbits. Pediatr Res 2005;57:22-7.
28. Musicki B, Champion HC, Becker RE, Kramer MF, Liu T, Sezen SF, Burnett AL. In vivo analysis of chronic phosphodiesterase-5 inhibition with sildenafil in penile erectile tissues: No tachyphylaxis effect. J Urol 2005;174:1493-6.
29. Musicki B, Champion HC, Becker RE, Liu T, Kramer MF, Burnett AL. Erection capability is potentiated by long-term sildenafil treatment: Role of blood flow-induced endothelial nitric-oxide synthase phosphorylation. Mol Pharmacol 2005;68:226-32.
30. Lin G, Shindel AW, Fandel TM, Bella AJ, Lin CS, Lue TF. Neurotrophic effects of brain-derived neurotrophic factor and vascular endothelial growth factor in major pelvic ganglia of young and aged rats. BJU Int 2010;105:114-20.
31. Liu G, Sun X, Dai Y, Zheng F, Wang D, Huang Y, Bian J, Deng C. Chronic administration of sildenafil modified the impaired VEGF system and improved the erectile function in rats with diabetic erectile dysfunction. J Sex Med 2010;7:3868-78.
32. Artaza JN, Sirad F, Ferrini MG, Norris KC. 1, 25(OH)2vitamin D3 inhibits cell proliferation by promoting cell cycle arrest without inducing apoptosis and modifies cell morphology of mesenchymal multipotent cells. J Steroid Biochem Mol Biol 2010;119:73-83.
33. Artaza JN, Norris KC. Vitamin D reduces the expression of collagen and key profibrotic factors by inducing an antifibrotic phenotype in mesenchymal multipotent cells. J Endocrinol 2009;200:207-21.
34. Artaza JN, Singh R, Ferrini MG, Braga M, Tsao J, Gonzalez-Cadavid NF. Myostatin promotes a fibrotic phenotypic switch in multipotent C3H 10T1/2 cells without affecting their differentiation into myofibroblasts. J Endocrinol 2008;196:235-49.
35. Ferrini MG, Kovanecz I, Sanchez S, Vernet D, Davila HH, Rajfer J, Gonzalez-Cadavid NF. Long-term continuous treatment with sildenafil ameliorates aging-related erectile dysfunction and the underlying corporal fibrosis in the rat. Biol Reprod 2007;76:915-23.
36. Abraham D. Connective tissue growth factor: Growth factor, matricellular organizer, fibrotic biomarker or molecular target for anti-fibrotic therapy in SSc. Rheumatology (Oxford) 2008;47(5 suppl):8-9.
37. Cicha I, Goppelt-Struebe M. Connective tissue growth factor: Context-dependent functions and mechanism of regulation. Biofactors 2009;35:200-8.
38. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases structure, function, and biochemistry. Circ Res 2003;92:827-39.
39. Keil A, Blom IE, Goldschmeding R, Rupprecht HD. Nitric oxide down-regulates connective tissue growth factor in rat mesangial cells. Kidney Int 2002;62:401-11.
40. Ferrini MG, Vernet D, Magee TR, Shahed A, Qian A, Rajfer J, Gonzalez-Cadavid NF. Antifibrotic role of inducible nitric oxide synthase. Nitric Oxide 2002;6:283-94.
41. Ferrini MG, Rivera S, Moon J, Vernet D, Rajfer J, Gonzalez-Cadavid NF. The genetic inactivation of inducible nitric oxide synthase (iNOS) intensifies fibrosis and oxidative stress in the penile corpora cavernosa in type 1 diabetes. J Sex Med 2010;7:3033-44.
42. Taylor DS, Cheng X, Pawlowski JE, Wallace AR, Ferrer P, Molloy CJ. Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. Proc Natl Acad Sci U S A 1999;96:1633-8.
43. Zhuang S, Yan Y, Daubert RA, Schnellmann RG. Epiregulin promotes proliferation and migration of renal proximal tubular cells. Am J Physiol Renal Physiol 2007;293:F219-26.
44. Komurasaki T, Toyoda H, Uchida D, Nemoto N. Mechanism of growth promoting activity of epiregulin in primary cultures of rat hepatocytes. Growth Factors 2002;20:61-9.
45. Berasain C, García-Trevijano ER, Castillo J, Erroba E, Santamaría M, Lee DC, Prieto J, Avila MA. Novel role for amphiregulin in protection from liver injury. J Biol Chem 2005;280:19012-20.
46. Takahashi M, Hayashi K, Yoshida K, Ohkawa Y, Komurasaki T, Kitabatake A, Ogawa A, Nishida W, Yano M, Monden M, Sobue K. Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK-activated vascular smooth muscle cells. Circulation 2003;108:2524-9.
47. Draper BK, Komurasaki T, Davidson MK, Nanney LB. Epiregulin is more potent than EGF or TGFalpha in promoting in vitro wound closure due to enhanced ERK/MAPK activation. J Cell Biochem 2003;89:1126-37.
48. Yamanaka Y, Hayashi K, Komurasaki T, Morimoto S, Ogihara T, Sobue K. EGF family ligand-dependent phenotypic modulation of smooth muscle cells through EGF receptor. Biochem Biophys Res Commun 2001;281:373-7.
49. Pyriochou A, Zhou Z, Koika V, Petrou C, Cordopatis P, Sessa WC, Papapetropoulos A. The phosphodiesterase 5 inhibitor sildenafil stimulates angiogenesis through a protein kinase G/MAPK pathway. J Cell Physiol 2007;211:197-204.
50. Das A, Xi L, Kukreja RC. Protein kinase G-dependent cardioprotective mechanism of phosphodiesterase-5 inhibition involves phosphorylation of ERK and GSK3beta. J Biol Chem 2008;283:29572-85.