Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Research
  • Published:

Topical application of a Rho-kinase inhibitor in rats causes penile erection

International Journal of Impotence Research volume 16, pages 294–298 (2004)Cite this article

Abstract

Studies from this laboratory have demonstrated that RhoA/Rho-kinase signaling mediates vasoconstriction in the penile circulation of the rat and that erection results from inhibition of this activity with Y-27632. In prior animal studies, Y-27632 was administered to the rats by intracavernous injection. To determine if topical application of the Rho-kinase inhibitor is an effective mode of delivery, Y-27632 was applied to the surface of the tunica albuginea or to the glans penis and surrounding skin in intact or castrated rats. Both sites of drug administration resulted in a marked increase in the erectile response both with and without stimulation of the autonomic innervation of the penile vasculature. Although high doses of the drug were found to reduce systemic blood pressure, topical administration of the Rho-kinase inhibitor, in appropriate doses, may have clinical value for the treatment erectile dysfunction.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Pryor JL, Redmon B . New therapies and delivery mechanisms for treatment of erectile dysfunction. Int J Impot Res 2000; 12: S158–S162.

    Article  PubMed  Google Scholar 

  2. Morales A . Developmental status of topical therapies for erectile and ejaculatory dysfunction. Int J Impot Res 2000; 12: S80–S85.

    Article  PubMed  Google Scholar 

  3. Bechara A et al. Comparative study of papaverine plus phentolamine versus prostaglandin E1 in erectile dysfunction. J Urol 1997; 157: 2132–2134.

    Article  CAS  PubMed  Google Scholar 

  4. Fulgham PF et al. Disappointing initial results with transurethral alprostadil for erectile dysfunction in a urology practice setting. J Urol 1998; 160: 2041–2046.

    Article  CAS  PubMed  Google Scholar 

  5. Carson CC, Burnett AL, Levine LA, Nehra A . The efficacy of sildenafil citrate (Viagra) in clinical populations: an update. Urology 2002; 60(Suppl 2): 12–27.

    Article  PubMed  Google Scholar 

  6. Steers W et al. Assessment of the efficacy and safety of Viagra (sildenafil citrate) in men with erectile dysfunction during long-term treatment. Int J Impot Res 2001; 13: 261–267.

    Article  CAS  PubMed  Google Scholar 

  7. Meuleman EJ . Prevalence of erectile dysfunction: need for treatment? Int J Impot Res 2002; 14: S22–S28.

    Article  PubMed  Google Scholar 

  8. Carson CC . Erectile dysfunction in the 21st century: whom we can treat, whom we cannot treat and patient education. Int J Impot Res 2002; 14: S29–S34.

    Article  PubMed  Google Scholar 

  9. Chitaley K, Webb RC, Mills TM . The ups and downs of Rho-kinase and penile erection: upstream regulators and downstream substrates of Rho-kinase and their potential role in the erectile response. Int J Impot Res 2003; 15: 105–109.

    Article  CAS  PubMed  Google Scholar 

  10. Chitaley K et al. Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway. Nat Med 2001; 7: 119–122.

    Article  CAS  PubMed  Google Scholar 

  11. Rees RW et al. Human and rabbit cavernosal smooth muscle cells express Rho-kinase. Int J Impot Res 2002; 14: 1–7.

    Article  CAS  PubMed  Google Scholar 

  12. Rees RW et al. Y-27632, an inhibitor of Rho-kinase, antagonizes noradrenergic contractions in the rabbit and human penile corpus cavernosum. Br J Pharmacol 2001; 133: 455–458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wang H et al. RhoA-mediated Ca2+ sensitization in erectile function. J Biol Chem 2003; 277: 30614–30621.

    Article  Google Scholar 

  14. Uehata M et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 1997; 389: 990–994.

    Article  CAS  PubMed  Google Scholar 

  15. Ishizaki T et al. Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases. Mol Pharmacol 2000; 57: 976–983.

    CAS  PubMed  Google Scholar 

  16. Mills TM et al. Effect of Rho-kinase inhibition on vasoconstriction in the penile circulation. J Appl Physiol 2001; 91: 1269–1273.

    Article  CAS  PubMed  Google Scholar 

  17. Mills TM, Chitaley K, Lewis R . Vasoconstrictors in erectile physiology. Int J Impot Res 2001; 13: S29–S34.

    Article  PubMed  Google Scholar 

  18. Mills T et al. Endothelin-1 induced vasoconstriction is inhibited during erection in rats. Am J Physiol 2001; 281: R476–R483.

    CAS  Google Scholar 

  19. Somlyo AP, Somlyo AV . Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J Physiol 2000; 522: 177–185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mills TM, Chitaley K, Lewis RW, Webb RC . Nitric oxide inhibits RhoA/Rho-kinase signaling to cause erection. Eur J Pharmacol 2002; 439: 173–174.

    Article  CAS  PubMed  Google Scholar 

  21. Chitaley K, Webb RC, Dorrance AM, Mills TM . Decreased penile erection in DOCA-salt and stroke prone-spontaneously hypertensive rats. Int J Impot Res 2001; 13: S16–S20.

    Article  PubMed  Google Scholar 

  22. Shabsigh R . The effects of testosterone on the cavernous tissue and erectile function. World J Urol 1997; 15: 21–26.

    Article  CAS  PubMed  Google Scholar 

  23. Marin R, Escrig A, Abreu P, Mas M . Androgen-dependent nitric oxide release in rat penis correlates with levels of constitutive nitric oxide synthase isoenzymes. Biol Reprod 1999; 61: 1012–1016.

    Article  CAS  PubMed  Google Scholar 

  24. Reilly CM, Zamorano P, Stopper VS, Mills TM . Androgenic regulation of NO availability in rat penile erection. J Androl 1997; 18: 110–115.

    CAS  PubMed  Google Scholar 

  25. Reilly CM, Stopper VS, Mills TM . Androgens modulate the alpha-adrenergic responsiveness of vascular smooth muscle in the corpus cavernosum. J Androl 1997; 18: 26–31.

    CAS  PubMed  Google Scholar 

  26. Wingard C, Johnson J, Holmes A, Prikosh A . Improved erectile function following Rho-kinase inhibition in a rat castrate model of erectile dysfunction. Am J Physiol 2003; 284: R1572–R1580.

    CAS  Google Scholar 

  27. Chitaley K et al. Adeno-associated viral gene transfer of dominant negative RhoA enhances erectile function in rats. Biochem Biophys Res Commun 2002; 298: 427–432.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA

    Y Dai, K Chitaley, R C Webb & T M Mills

  2. Department of Surgery (Urology), Medical College of Georgia, Augusta, Georgia, USA

    Y Dai, R W Lewis & T M Mills

  3. Department of Urology, Nanjing Drum Tower Hospital, Nanjing, China

    Y Dai

Authors
  1. Y Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Chitaley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R C Webb
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R W Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T M Mills
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T M Mills.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dai, Y., Chitaley, K., Webb, R. et al. Topical application of a Rho-kinase inhibitor in rats causes penile erection. Int J Impot Res 16, 294–298 (2004). https://doi.org/10.1038/sj.ijir.3901171

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijir.3901171

Keywords

This article is cited by

Search

Advanced search

Quick links