BERKELEY, CA (UroToday.com) - The expression of variants of type 5 phosphodiesterase (PDE5) and PDE4 have been demonstrated in normal and PD human and rat TA. Experiments by the UCLA lab have demonstrated that long-term (45 days) continuous administration of high dose (10 mg/kg/day) of the PDE5-inhibitor sildenafil prevents the development of PD-like plaque in a rat model of PD.⁴ The authors hypothesized that increasing cGMP in target tissues prevents fibrosis. This same group now presented a similar rat PD model and explored the PDE5 inhibitor, vardenafil, administered at lower doses and different regimens. Vardenafil was given either continuously in drinking water or as an oral gavage at low (1 mg/kg/day) and intermediate (3 mg/kg/day) doses starting at the time of PD creation or after plaque formation for 42 days. Penile tissue cross-sections were used for histochemical and immunohistochemical staining followed by quantitative image analysis for varying parameters. As per the results, vardenafil at the intermediate dose in the preventative treatment arm significantly reduced the collagen/smooth muscle by 80%, collagen III/I ratios by 50%, and number of myofibroblasts and TGFβ¹ cells by 65 - 70% in the PD-like plaque as compared to similar groups without vardenafil. There was also a selective increase in the apoptotic index in the PD plaques in this rat model. These findings suggest that long-term vardenafil treatment slows down and reverses the early stages of PD-like plaque in the rat and may help diminish more advanced plaques. These early experimental observations may broaden the clinical indications for oral PDE5 inhibitors of the future.

References:

• Ferrini M, Lovanecz I, Nolazco G, Rajfer J, Gonazlez-Kadavid N. Long-term treatment with vardenafil reduces the development of the fibrotic plaque in a rat model of Peyronie's disease. J Sex Med 2005; 3 (Suppl 1):27 (Abstract #43).

Addtional References

Summary of SMSNA Meeting, New York, New York, November 17 - 20, 2005
Author: Wayne J. G. Hellstrom, M.D., F.A.C.S.
Reviewed and Edited: GA Broderick

Written by Gregory A. Broderick, MD, a Contributing Editor with UroToday.

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