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A conscious-rabbit model to study vardenafil hydrochloride and other agents that influence penile erection

International Journal of Impotence Research volume 13, pages 230–235 (2001)Cite this article

Abstract

Experimental models to study the effect of agents on penile erection usually include electrical stimulation of peripheral nerves in anesthetized animals combined with systemic or intracavernous injection of drugs. The objective of this study was to demonstrate that conscious rabbits can be used as a simple and quantitative model for the assessment of compounds that show potential for the treatment of erectile dysfunction. Erection was assessed by measuring the length of uncovered penile mucosa before and after the intravenous (i.v.) administration of agents. Animals did not require anesthesia during the course of the study. The phosphodiesterase 5 (PDE5) inhibitors vardenafil×HCl (hereafter called vardenafil) and sildenafil were given intravenously, and measurements were taken for 0–5 h. The effects of phentolamine and milrinone were also evaluated. Vardenafil (0.1–3 mg/kg) induced dose-dependent penile erections in conscious rabbits following i.v. administration. The efficacy of vardenafil was potentiated, and the minimal effective dose was reduced significantly to 0.01 mg/kg by simultaneous administration of the nitric oxide (NO) donor sodium nitroprusside (SNP). Administration of the NO-synthase inhibitor L-NAME abolished the effect. Sildenafil was effective in this model after i.v. administration. The α-adrenergic receptor antagonist phentolamine (0.1, 0.3 and 1 mg/kg i.v.) induced erections with a slower tmax compared with vardenafil and sildenafil. Intravenous administration of the PDE3 inhibitor milrinone (1 mg/kg i.v.) was less effective than the PDE5 inhibitor vardenafil. The conscious rabbit is a suitable and reliable model for the evaluation of compounds with potential for the treatment of erectile dysfunction. This was demonstrated using compounds that target different signaling pathways that induce smooth muscle relaxation in the penis.

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References

  1. Lue TF et al. Animal model for penile erection studies. Neurourol Urodyn 1983 2, 225–231

    Article  Google Scholar 

  2. Sjöstrand NO, Klinge EK . Principal mechanisms controlling penile retraction and protrusion in rabbit. Acta Physiol Scand 1979 106, 199–214

    Article  Google Scholar 

  3. Naganuma H, Egashira T, Fujii J . Neuroleptics induce penile erection in the rabbit. Clin Exper Pharmacol Physiol 1993 20, 177–183

    Article  CAS  Google Scholar 

  4. Anderson K-E, Wagner G . Physiology of penile erection. Physiol Rev 1995 75, 191–236

    Article  Google Scholar 

  5. Meinhardt W et al. The influence of medication on erectile dysfunction. Int J Impot Res 1997 9, 17–26

    Article  CAS  Google Scholar 

  6. Nehra A, Barrett DM, Moreland RB . Pharmacotherapeutic advances in the treatment of erectile dysfunction. Mayo Clin Proc 1999 74, 709–721

    Article  CAS  Google Scholar 

  7. Holmquist F, Stief CG, Jonas U, Anderson KE . Effects of the nitric oxide synthase inhibitor NG nitro-L-arginine on the erectile response to cavernous nerve stimulation in the rabbit. Acta Physiol Scand 1991 143, 299–304

    Article  CAS  Google Scholar 

  8. Ignarro LJ et al. Nitric oxide and cyclic GMP formation upon electric field stimulation cause relaxation of corpus caver-nosum smooth muscle. Biochem Biophys Res Commun 1990 170, 843–850

    Article  CAS  Google Scholar 

  9. Burnett AL . Nitric oxide in the penis. Physiology and pathology. J Urol 1997 157, 320–324

    Article  CAS  Google Scholar 

  10. Boolell M et al. Sildenafil—an orally active type 5 cyclic GMP-specific phosphoesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 1996 8, 47–52

    CAS  Google Scholar 

  11. Moreland RB, Goldstein I, Traish A . Sildenafil, a novel inhibitor of phosphodiesterase type 5 in human corpus cavernosum smooth muscle cells. Life Sci 1998 62: PL, 309–318

    Google Scholar 

  12. Kuthe A, Eckel H, Stief CG, Ückert S, Forssmann WG, Jonas U, Magert HJ . Molecular biological characterisation of phosphodiesterase 3A from human corpus cavernosum. Chem Biol Interact 1999 119–120, 593–598

    Article  Google Scholar 

  13. Stief CG, Ückert S, Becker AJ, Truss MC, Jonas U . The effect of the specific phosphodiesterase (PDE) inhibitors on human and rabbit corpus cavernous tissue in vitro and in vivo J Urol 1998 159, 1390–1393

    Article  CAS  Google Scholar 

  14. Traish AM, Kim NN, Goldstein I, Moreland RB . Alpha adrenergic receptors in the penis: identification, characterisation, and physiological function. J Androl 1999 20, 671–682

    CAS  PubMed  Google Scholar 

  15. Becker AJ et al. Oral phentolamine as treatment for erectile dysfunction. J Urol 1998 159, 1214–1216

    Article  CAS  Google Scholar 

  16. Taub HC, Lerner, SE . Relationship between contraction and relaxation in human and rabbit corpus cavernosum. Urology 1994 2, 698–671

    Google Scholar 

  17. Meyer MF et al. Intracavernous application of SIN-1 in rabbit and man: functional and toxicological results. Ann Urol (Paris) 1993 27, 179–182

    CAS  Google Scholar 

  18. Lin YM, Lin JSN . The rabbit as an intracavernous injection study model. Urol Res 1996 27, 27–32

    Article  Google Scholar 

  19. Boolell M, Gepi Attee S, Gingell JC, Allen MJ . Sildenafil, a novel oral therapy for male erectile dysfunction. Br J Urol 1996 78, 257–261

    Article  CAS  Google Scholar 

  20. Bischoff E et al. Vardenafil a potent and selective inhibitor of phosphodieterase type 5 increases cGMP in rabbit corpus cavernosum Int J Impot 2001 13(Suppl 1), S25

    Google Scholar 

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Acknowledgements

We thank E Perzborn and K Dembowsky for many helpful and encouraging discussions and also U Niewoehner and H Haning (Bayer, Pharma Chem-ical Research) for the synthesis of sildenafil and vardenafil.

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  1. BAYER AG Pharmaceutical Business Group, Institute of Cardiovascular Research II, Wuppertal, Germany

    E Bischoff & K Schneider

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  1. E Bischoff
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  2. K Schneider
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Correspondence to E Bischoff.

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Bischoff, E., Schneider, K. A conscious-rabbit model to study vardenafil hydrochloride and other agents that influence penile erection. Int J Impot Res 13, 230–235 (2001). https://doi.org/10.1038/sj.ijir.3900703

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