Skip to main content

Thank you for visiting 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.

The effect of DA-8159, a novel PDE5 inhibitor, on erectile function in the rat model of hypercholesterolemic erectile dysfunction


This study examined the effects of a new phosphodiesterase type 5 inhibitor, DA-8159, on erectile function associated with hypercholesterolemia. First of all, in order to investigate whether chronic administration of DA-8159 prevents the development of erectile dysfunction associated with hypercholesterolemia, male SD rats were divided into four groups (normal control, hypercholesterolemic control, DA-8159 5 or 20 mg/kg/day). Over a 5-month period, the animals were fed a 2% cholesterol diet and administered DA-8159 orally once a day. After 5 months, the electrostimulation-induced penile erection and the vascular function using acetylcholine-induced vasodilation with endothelium-intact aortic rings were examined. Furthermore, the plasma lipid profiles, endothelin and NG,NG-dimethylarginine (asymmetrical dimethylarginine, ADMA) concentrations were measured. In order to investigate the acute treatment effect of DA-8159 on the erectile function in an established hypercholesterolemic model, additional animals were given a 2% cholesterol diet for 5 months without DA-8159. At the end of 5 months, the rats were divided into three groups (hypercholesterolemic control, DA-8159 0.3 or 1 mg/kg). DA-8159 was administered intravenously 1 min prior to the intracavernous pressure (ICP) measurement. In a chronic treatment study, while the hypercholesterolemic control showed a significantly lower erectile function, vascular reactivity, and increased plasma cholesterol, endothelin and ADMA concentration, the chronic DA-8159 treatment clearly restored the erectile responses by electric stimulation, preserved the potential of thoracic aortic relaxation in a dose-dependent manner, and significantly decreased the plasma endothelin and ADMA concentrations. In an acute treatment study, DA-8159 induced a dose- and frequency-dependent increase in ICP. The ICP/BP ratio and the corresponding AUC values, and the detumescence time were also significantly increased compared to the hypercholesterolemic control. These results suggest that DA-8159 is beneficial for erectile dysfunction in a rat hypercholesterolemic model and provided a rationale for the potential use of DA-8159 for treating erectile dysfunction secondary to hypercholesterolemia.

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

Access options

Rent or buy this article

Prices vary by article type



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

Figure 1
Figure 2
Figure 3
Figure 4


  1. DeWire DM . Evaluation and treatment of erectile dysfunction. Am Fam Physician 1996; 53: 2101–2107.

    CAS  PubMed  Google Scholar 

  2. Wei M et al. Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction. Am J Epidemiol 1994; 140: 930–937.

    Article  CAS  Google Scholar 

  3. Kim JH et al. Experimental hypercholesterolemia in rabbits induces cavernosal atherosclerosis with endothelial and smooth muscle cell dysfunction. J Urol 1994; 151: 198–205.

    Article  CAS  Google Scholar 

  4. Azadzoi KM, Saenz de Tejada I . Hypercholesterolemia impairs endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle. J Urol 1991; 146: 238–240.

    Article  CAS  Google Scholar 

  5. 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 

  6. Wespes E et al. Corporeal veno-occlusive dysfunction: predominantly intracavernous muscular pathology. J Urol 1997; 157: 1678–1680.

    Article  CAS  Google Scholar 

  7. Sattar AA, Merckx LA, Wespes E . Penile electromyography and its smooth muscle content: interpretation of 25 impotent patients. J Urol 1996; 155: 909–912.

    Article  CAS  Google Scholar 

  8. Azadzoi KM, Goldstein I . Erectile dysfunction due to atherosclerotic vascular disease: the development of an animal model. J Urol 1992; 147: 1675–1681.

    Article  CAS  Google Scholar 

  9. Bakircioglu ME et al. Effect of a Chinese herbal medicine mixture on a rat model of hypercholesterolemic erectile dysfunction. J Urol 2000; 164: 1798–1801.

    Article  CAS  Google Scholar 

  10. Gholami SS et al. The effect of vascular endothelial growth factor and adeno-associated virus mediated brain derived neurotrophic factor on neurogenic and vasculogenic erectile dysfunction induced by hyperlipidemia. J Urol 2003; 169: 1577–1581.

    Article  CAS  Google Scholar 

  11. Behr-Roussel D et al. Distinct mechanisms implicated in atherosclerosis-induced erectile dysfunction in rabbits. Atherosclerosis 2002; 162: 355–362.

    Article  CAS  Google Scholar 

  12. Bahng MY et al. Tolerance and pharmacokinetics of single-dose DA-8159, in healthy male. Int J Impot Res 2002; 14: S101.

    Article  Google Scholar 

  13. Amakye D, Ward J, Bryson S, Han K . DA-8159-phase I studies to investigate the safety and pharmacokinetics in healthy male caucasian subjects. Clin Pharmacol Ther 2004; 75: 86.

    Article  Google Scholar 

  14. Padma-Nathan H et al. Phase 1, double-blind, placebo-controlled study in healthy male subjects to investigate the safety, tolerability, and pharmacokinetics of DA-8159. J Urol 2004; 171: S234.

    Article  Google Scholar 

  15. Oh TY et al. Erectogenic effect of the selective phosphodiesterase type 5 inhibitor, DA-8159. Arch Pharm Res 2000; 23: 471–476.

    Article  CAS  Google Scholar 

  16. 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 

  17. 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 

  18. Doh H et al. Mechanism of erectogenic effect of the selective phosphodiesterase type 5 inhibitor, DA-8159. Arch Pharm Res 2002; 25: 873–878.

    Article  CAS  Google Scholar 

  19. Vallance P et al. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992; 339: 572–575.

    Article  CAS  Google Scholar 

  20. Dai Q et al. Systemic basic fibroblast growth factor induces favorable histological changes in the corpus cavernosum of hypercholesterolemic rabbits. J Urol 2003; 170: 664–668.

    Article  CAS  Google Scholar 

  21. Best PJ et al. Chronic endothelin receptor antagonism preserves coronary endothelial function in experimental hypercholesterolemia. Circulation 1999; 99: 1747–1752.

    Article  CAS  Google Scholar 

  22. Yu XJ, Li YJ, Xiong Y . Increase of an endogenous inhibitor of nitric oxide synthesis in serum of high cholesterol fed rabbits. Life Sci 1994; 54: 753–758.

    Article  CAS  Google Scholar 

  23. Tsao PS, Cooke JP . Endothelial alterations in hypercholesterolemia: more than simply vasodilator dysfunction. J Cardiovasc Pharmacol 1998; 32: S48–S53.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  26. 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 

  27. Sommer F, Engelmann UH . What are the long term effects on erectile function of taking sildenafil on a daily basis?. 99th AUA, San Francisco, Abstract No. 903, 2004.

  28. Ahn GJ et al. The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats. Int J Impot Res 2005; 17: 134–141.

    Article  CAS  Google Scholar 

  29. Kuan J, Brock G . Selective phosphodiesterase type 5 inhibition using tadalafil for the treatment of erectile dysfunction. Expert Opin Invest Drugs 2002; 11: 1605–1613.

    Article  CAS  Google Scholar 

Download references


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


Corresponding author

Correspondence to K K Kang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kang, K., Yu, J., Yoo, M. et al. The effect of DA-8159, a novel PDE5 inhibitor, on erectile function in the rat model of hypercholesterolemic erectile dysfunction. Int J Impot Res 17, 409–416 (2005).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


This article is cited by


Quick links