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:

The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats

A Corrigendum to this article was published on 01 November 2006

Abstract

The aim of this study was to assess the effect of phosphodiesterase 5 inhibitor, DA-8159, on erectile function throughout the quantitative analysis of vascular endothelial cell, smooth muscle (SM), TGF-β1 expression in rat corpus cavernosum and measurement of intracavernous pressure (ICP) in diabetic rats. DA-8159 (0, 5, 10, 20 mg/kg) was administered orally once a day to diabetic rats. After 8 weeks, immunohistochemistry and computerized image analysis were performed to quantify the percent area within the Corpora Cavernosa occupied by the endothelial cells, SM cells and fibrotic tissues. ICP/mean arterial pressure (MAP) was also measured by electrostimulation of the cavernous nerve. Diabetic rats showed a significant decrease in the SM and endothelial cell content, and an increase in the TGF-β1 expression level within the cavernosa areas compared to the normal rats. The mean cavernous SM, endothelial cell content and TGF-β1 expression level were 9.7±0.7, 4.5±0.7 and 17.9±2.1%, respectively. DA-8159 prevented reduction of SM (12.3±0.4% (5 mg/kg), 13.8±0.4% (20 mg/kg)) and endothelial cell content (5.6±0.5% (5 mg/kg), 6.3±0.6% (20 mg/kg)). Immunoreactivity of TGF-β1 and intracorporal fibrosis were also significantly lower in DA-8159-treated groups (11.8±1.2% (5 mg/kg), 9.5±1.1% (20 mg/kg)). Electrostimulation of the cavernous nerve induced significant increase in maximum ICP (62.2±13.6 mmHg in 10 mg/kg vs 37.5±17.5 mmHg in diabetic group) and area under the curve of the ratio of ICP/MAP (8891.09±1957 in 10 mg/kg vs 6315.87±2272 in diabetic group). These results suggest that subchronic treatment of DA-8159 can prevent the development of erectile dysfunction (ED), and provides a rationale for the use of DA-8159 as treatment of diabetic ED.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1
Figure 2
Figure 4
Figure 3
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Metro MJ, Broderick GA . Diabetes and vascular impotence: does insulin dependence increase the relative severity? Int J Impot Res 1999; 11: 87–89.

    Article  CAS  Google Scholar 

  2. Vinik A, Richardson D . Erectile dysfunction in diabetes. Diab Rev 1998; 6: 16–33.

    Google Scholar 

  3. Rendell MS, Rajfer J, Wicker PA, Smith MD . Sildenafil for treatment of erectile dysfunction in men with diabetes: a randomized controlled trial. Sildenafil Diabetes Study Group. JAMA 1999; 281: 421–426.

    Article  CAS  Google Scholar 

  4. Saenz De Tejada I, Anglin G, Knight JR, Emmick JT . Effects of tadalafil on erectile dysfunction in men with diabetes. Diab Care 2002; 25: 2159–2164.

    Article  Google Scholar 

  5. Goldstein I et al. Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study. Diab Care 2003; 26: 777–783.

    Article  CAS  Google Scholar 

  6. Kang KK et al. DA-8159, a new PDE5 inhibitor, induces penile erection in conscious and acute spinal cord injured rabbits. Eur Urol 2003; 43: 689–695.

    Article  CAS  Google Scholar 

  7. Kang KK et al. The effect of DA-8159 on corpus cavernosal smooth muscle relaxation and penile erection in diabetic rabbits. Urol Res 2004; 32: 107–111.

    Article  CAS  Google Scholar 

  8. Rotella DP . Phosphodiesterase 5 inhibitors: current status and potential applications. Nat Rev Drug Discov 2002; 1: 674–682.

    Article  CAS  Google Scholar 

  9. Jackson G . PDE5 inhibitors: looking beyond ED. Int J Clin Pract 2003; 57: 159–160.

    PubMed  Google Scholar 

  10. McPherson MA et al. A cyclic nucleotide PDE5 inhibitor corrects defective mucin secretion in submandibular cells containing antibody directed against the cystic fibrosis transmembrane conductance regulator protein. FEBS Lett 1999; 464: 48–52.

    Article  CAS  Google Scholar 

  11. Bortolotti M et al. Effect of sildenafil on hypertensive lower oesophageal sphincter. Eur J Clin Invest 2002; 32: 682–685.

    Article  CAS  Google Scholar 

  12. Prasad S, Wilkinson J, Gatzoulis MA . Sildenafil in primary pulmonary hypertension. N Engl J Med 2000; 343: 1342.

    Article  CAS  Google Scholar 

  13. Katz SD . Potential role of type 5 phosphodiesterase inhibition in the treatment of congestive heart failure. Congest Heart Fail 2003; 9: 9–15.

    Article  CAS  Google Scholar 

  14. Kimura M et al. PDE5 inhibitor sildenafil citrate augments endothelium-dependent vasodilation in smokers. Hypertension 2003; 41: 1106–1110.

    Article  CAS  Google Scholar 

  15. Schwartz EJ, Wong P, Graydon RJ . Sildenafil preserves intracorporal smooth muscle after radical retropubic prostatectomy. J Urol 2004; 171: 771–774.

    Article  Google Scholar 

  16. De Young L, Yu D, Freeman D, Brock GB . The effect of PDE-5 inhibition combined with free oxygen radical scavenger therapy on erectile function in a diabetic animal model. Int J Impot Res 2003; 15: 347–354.

    Article  CAS  Google Scholar 

  17. Leungwattanakij S et al. Cavernous neurotomy causes hypoxia and fibrosis in rat corpus cavernosum. J Androl 2003; 24: 239–245.

    Article  Google Scholar 

  18. Mersdorf A et al. Ultrastructural changes in impotent penile tissue: a comparison of 65 patients. J Urol 1991; 145: 749–758.

    Article  CAS  Google Scholar 

  19. Nehra A et al. Cavernosal expandability is an erectile tissue mechanical property which predicts trabecular histology in an animal model of vasculogenic erectile dysfunction. J Urol 1998; 159: 2229–2236.

    Article  CAS  Google Scholar 

  20. Burchardt T et al. Reduction of endothelial and smooth muscle density in the corpora cavernosa of the streptozotocin induced diabetic rat. J Urol 2000; 164: 1807–1811.

    Article  CAS  Google Scholar 

  21. Sheenan DC, Hrapchak BB . Trichrome staining. In: Sheenan DC, Hrapchak BB (eds). Theory and Practice of Histotechnology 2nd edn. Battell Press: Richland, 1980, pp 190–191.

    Google Scholar 

  22. Richard E et al. Expression of transforming growth factor-beta1 and type IV collagen in the renal tubulointerstitium in experimental diabetes. Diabetes 1998; 47: 414–422.

    Article  Google Scholar 

  23. Park KS et al. Diabetes mellitus induces vaginal tissue fibrosis by TGF-beta1, expression in the rat model. J Sex Marital Ther 2001; 27: 577–587.

    Article  CAS  Google Scholar 

  24. Sattar AA, Haot J, Schulman CC, Wespes E . Comparison of anti-desmin and anti-actin staining for the computerized analysis of cavernous smooth muscle density. Br J Urol 1996; 77: 266–270.

    Article  CAS  Google Scholar 

  25. Wespes E et al. Computerized analysis of smooth muscle fibers in potent and impotent patients. J Urol 1991; 146: 1015–1017.

    Article  CAS  Google Scholar 

  26. Jevtich MJ, Kass M, Khawand N . Changes in the corpora cavernosa of impotent diabetics: comparing histological with clinical findings. J Urol 1985; 91: 281–285.

    CAS  Google Scholar 

  27. Rehman J et al. Diminished neurogenic but not pharmacological erections in the 2- to 3-month experimentally diabetic F-344 rat. Am J Physiol 1997; 272: 1960–1971.

    Article  Google Scholar 

  28. Vernet D et al. Reduction of penile nitric oxide synthase in diabetic BB/WORdp (type 1) and BBZ/WORdp (type II) rats with erectile dysfunction. Endocrinol 1995; 136: 5709–5717.

    Article  CAS  Google Scholar 

  29. Lin JS et al. Novel image analysis of corpus cavernous tissue in impotent men. Urol 2000; 55: 252–256.

    Article  CAS  Google Scholar 

  30. Persson C et al. Correlation of altered penile ultrastructure with clinical arterial evaluation. J Urol 1989; 142: 1462–1468.

    Article  CAS  Google Scholar 

  31. Jevtich M, Khawand NY, Vidic B . Clinical significance of ultrastructural findings in the corpus cavernosa of normal and impotent men. J Urol 1990; 143: 289–293.

    Article  CAS  Google Scholar 

  32. Luangkhot R et al. Collagen alterations in the corpus cavernosum of men with sexual dysfunction. J Urol 1992; 148: 467–471.

    Article  CAS  Google Scholar 

  33. Border WA, Noble NA . Transforming growth factor beta in tissue fibrosis. New Engl J Med 1994; 331: 1286–1292.

    Article  CAS  Google Scholar 

  34. Nehra A et al. Transforming growth factor-beta1 (TGF-beta1) is sufficient to induce fibrosis of rabbit corpus cavernosum in vivo. J Urol 1999; 162: 910–915.

    Article  CAS  Google Scholar 

  35. Quinlan DM et al. The rat as a model for the study of penile erection. J Urol 1989; 141: 656–661.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported in part by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (02-PJ2-PG4-PT01-0024).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K K Kang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ahn, G., Sohn, Y., Kang, K. et al. The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats. Int J Impot Res 17, 134–141 (2005). https://doi.org/10.1038/sj.ijir.3901295

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijir.3901295

Keywords

This article is cited by

Search

Quick links