Chronic administration of udenafil, a selective phosphodiesterase type 5 inhibitor, promotes erectile function recovery in an animal model of bilateral cavernous nerve crush injury

Journal of Sexual Medicine

Volumn 8, Issue 5, 2011, Pages 1330-1340

  Lee, Chan Ho ^a   Kim, Hae Sun ^a   Goo, Moon Jung ^a   Kang, Kyung Koo ^a   Ahn, Byoung Ok ^a   Kim, Soon Hoe ^a   Yang, Dae Yul ^b  

^a Dong A Pharmaceutical Company   (South Korea)

^b Hallym University   (South Korea)

Author keywords

Apoptosis; Cavernous Nerve Crush Injury; Erectile Dysfunction; Sonic Hedgehog; Udenafil

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; COLLAGEN; DNA NUCLEOTIDYLEXOTRANSFERASE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ENDOTHELIN B RECEPTOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; NERVE GROWTH FACTOR; NEURONAL NITRIC OXIDE SYNTHASE; SONIC HEDGEHOG PROTEIN; TRANSFORMING GROWTH FACTOR BETA1; UDENAFIL;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CHRONIC DRUG ADMINISTRATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CRUSH TRAUMA; DOSE RESPONSE; ELECTROSTIMULATION; ERECTILE DYSFUNCTION; GENE EXPRESSION; HISTOPATHOLOGY; IMMUNOHISTOCHEMISTRY; MALE; NERVE INJURY; NERVE STIMULATION; NICK END LABELING; NONHUMAN; PENIS ERECTION; PENIS INJURY; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; SHAM PROCEDURE;

EID: 79955129522     PISSN: 17436095     EISSN: 17436109     Source Type: Journal    
DOI: 10.1111/j.1743-6109.2011.02228.x     Document Type: Article

References (37)

1. Fall PA, Izikki M, Tu L, Swieb S, Giuliano F, Bernabe J, Souktani R, Abbou C, Adnot S, Eddahibi S, Yiou R. Apoptosis and effects of intracavernous bone marrow cell injection in a rat model of postprostatectomy erectile dysfunction. Eur Urol 2009;56:716-25.
2. Mulhall JP, Muller A, Donohue JF, Golijanin D, Tal R, Akin-Olugbade Y, Kobylarz K, Cohen-Gould L, Bennett NE, Scardino P. FK506 and erectile function preservation in the cavernous nerve injury model: Optimal dosing and timing. J Sex Med 2008;5:1334-44.
3. User HM, Hairston JH, Zelner DJ, McKenna KE, McVary KT. Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction. J Urol 2003;169:1175-9.
4. Mullerad M, Donohue JF, Li PS, Scardino PT, Mulhall JP. Functional sequelae of cavernous nerve injury in the rat: Is there model dependency. J Sex Med 2006;3:77-83.
5. Mulhall JP, Muller A, Donohue JF, Mullerad M, Kobylarz K, Paduch DA, Tal R, Li PS, Cohen-Gould L, Scardino PT. The functional and structural consequences of cavernous nerve injury are ameliorated by sildenafil citrate. J Sex Med 2008;5:1126-36.
6. Zippe C, Nandipati K, Agarwal A, Raina R. Sexual dysfunction after pelvic surgery. Int J Impot Res 2006;18:1-18.
7. Montorsi F, Brock G, Lee J, Shapiro J, Van Poppel H, Graefen M, Stief C. Effect of nightly vs. on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy. Eur Urol 2008;54:924-31.
8. Salem EA, Kendirci M, Hellstrom WJ. Udenafil, a long-acting PDE5 inhibitor for erectile dysfunction. Curr Opin Investig Drugs 2006;7:661-9.
9. Paick JS, Kim SW, Park YK, Hyun JS, Park NC, Lee SW, Park K, Moon KH, Chung WS. The efficacy and safety of udenafil (Zydena) for the treatment of erectile dysfunction in hypertensive men taking concomitant antihypertensive agents. J Sex Med 2009;6:3166-76.
10. Paick JS, Kim SW, Yang DY, Kim JJ, Lee SW, Ahn TY, Choi HK, Suh JK, Kim SC. The efficacy and safety of udenafil, a new selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction. J Sex Med 2008;5:946-53.
11. Kang KK, Ahn GJ, Ahn BO, Yoo M, Kim WB. DA-8159, a new PDE5 Iihibitor, induces penile erection in conscious and acute spinal cord injured rabbits. Eur Urol 2003;43:689-95.
12. Kang KK, Choi SM, Ahn GJ, Kwon JW, Kim WB. The effect of DA-8159 on corpus cavernosal smooth muscle relaxation and penile erection in diabetic rabbits. Urol Res 2004;32:107-11.
13. Doh H, Shin CY, Son M, Ko JI, Yoo M, Kim SH, Kim WB. Mechanism of erectogenic effect of the selective phosphodiesterase type 5 inhibitor, DA-8159. Arch Pharm Res 2002;25:873-8.
14. Ahn GJ, Chung HK, Lee CH, Kang KK, Ahn BO. Increased expression of the nitric oxide synthase gene and protein in corpus cavernosum by repeated dosing of udenafil in a rat model of chemical diabetogenesis. Asian J Androl 2009;11:435-42.
15. Angeloni NL, Bond CW, Monsivais D, Tang Y, Podlasek CA. The role of hedgehog-interacting protein in maintaining cavernous nerve integrity and adult penile morphology. J Sex Med 2009;6:2480-93.
16. Bond C, Tang Y, Podlasek CA. Neural influences on sonic hedgehog and apoptosis in the rat penis. Biol Reprod 2008;78:947-56.
17. Mulhall JP, Bella AJ, Briganti A, McCullough A, Brock G. Erectile function rehabilitation in the radical prostatectomy patient. J Sex Med 2010;7:1687-98.
18. Fraiman MC, Lepor H, McCullough AR. Changes in penile morphometrics in men with erectile dysfunction after nerve-sparing radical retropubic prostatectomy. Mol Urol 1999;3:109-15.
19. Podlasek CA, Gonzalez CM, Zelner DJ, Jiang HB, McKenna KE, McVary KT. Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction. Int J Impot Res 2001;13(5 suppl):S1-15.
20. Quinlan DM, Nelson RJ, Partin AW, Mostwin JL, Walsh PC. The rat as a model for the study of penile erection. J Urol 1989;141:656-61.
21. Canguven O, Burnett A. Cavernous nerve injury using rodent animal models. J Sex Med 2008;5:1776-85.
22. Tal R, Mueller A, Mulhall JP. The correlation between intracavernosal pressure and cavernosal blood oxygenation. J Sex Med 2009;6:2722-7.
23. Klein LT, Miller MI, Buttyan R, Raffo AJ, Burchard M, Devris G, Cao YC, Olsson C, Shabsigh R. Apoptosis in the rat penis after penile denervation. J Urol 1997;158:626-30.
24. Kim N, Vardi Y, Padma-Nathan H, Daley J, Goldstein I, Saenz de Tejada I. Oxygen tension regulates the nitric oxide pathway. Physiological role in penile erection. J Clin Invest 1993;91:437-42.
25. Moreland RB, Traish A, McMillin MA, Smith B, Goldstein I, Saenz de Tejada I. PGE1 suppresses the induction of collagen synthesis by transforming growth factor-beta 1 in human corpus cavernosum smooth muscle. J Urol 1995;153:826-34.
26. 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.
27. Ghofrani HA, Voswinckel R, Reichenberger F, Olschewski H, Haredza P, Karadas B, Schermuly RT, Weissmann N, Seeger W, Grimminger F. 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 2004;44:1488-96.
28. Choi SM, Kim JE, Kang KK. Chronic treatment of DA-8159, a new phosphodiesterase type V inhibitor, attenuates endothelial dysfunction in stroke-prone spontaneously hypertensive rat. Life Sci 2006;78:1211-6.
29. Chiappe-Gutierrez M, Kitzmueller E, Labudova O, Fuerst G, Hoeger H, Hardmeier R, Nohl H, Gille L, Lubec B. mRNA levels of the hypoxia inducible factor (HIF-1) and DNA repair genes in perinatal asphyxia of the rat. Life Sci 1998;63:1157-67.
30. Grainger DJ, Kemp PR, Witchell CM, Weissberg PL, Metcalfe JC. Transforming growth factor beta decreases the rate of proliferation of rat vascular smooth muscle cells by extending the G2 phase of the cell cycle and delays the rise in cyclic AMP before entry into M phase. Biochem J 1994;299(Pt 1):227-35.
31. 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.
32. Baveja R, Keller S, Yokoyama Y, Sonin N, Clemens MG, Zhang JX. LPS-induced imbalanced expression of hepatic vascular stress genes in cirrhosis: Possible mechanism of increased susceptibility to endotoxemia. Shock 2002;17:316-21.
33. 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.
34. Hayashi N, Minor TX, Carrion R, Price R, Nunes L, Lue TF. The effect of FK1706 on erectile function following bilateral cavernous nerve crush injury in a rat model. J Urol 2006;176:824-9.
35. Podlasek CA. Sonic hedgehog, apoptosis, and the penis. J Sex Med 2009;6(3 suppl):334-9.
36. Podlasek CA, Meroz CL, Tang Y, McKenna KE, McVary KT. Regulation of cavernous nerve injury-induced apoptosis by sonic hedgehog. Biol Reprod 2007;76:19-28.
37. Podlasek CA, Zelner DJ, Jiang HB, Tang Y, Houston J, McKenna KE, McVary KT. Sonic hedgehog cascade is required for penile postnatal morphogenesis, differentiation, and adult homeostasis. Biol Reprod 2003;68:423-38.