Effects of long-term vardenafil treatment on the development of fibrotic plaques in a rat model of Peyronie's disease.
OBJECTIVE
To determine whether the phosphodiesterase-5 (PDE5) inhibitor, vardenafil, given orally and in different regimens, has a similar effect to that of the PDE5 inhibitor sildenafil, which prevented the development of a Peyronie's disease (PD)-like plaque formation induced by injecting transforming growth factor beta1 (TGF-beta1) into the tunica albuginea of the rat.


METHODS
Vardenafil was given to male rats (eight per group) either in the drinking water or as an oral instillation once daily, at approximately 1 and approximately 3 mg/kg/day for 45 days after one injection with TGF-beta1 into the tunica albuginea, as an 'early preventive' treatment for TGF-beta1-induced formation of a PD-like plaque. Other groups received the two doses of vardenafil only in the drinking water, starting with a well-formed plaque, for 42 days ('late, therapeutic' administration). Sections of penile tissue were stained histochemically or immunohistochemically, followed by quantitative image analysis for collagen/smooth muscle and collagen III/I ratios, myofibroblast content (alpha-smooth muscle actin), TGF-beta1 expression, and apoptotic index.


RESULTS
Preventative treatment with vardenafil at the higher dose (both continuous and once-daily treatments) reduced the collagen/smooth muscle and collagen III/I ratios, and the numbers of myofibroblasts and TGF-beta1-positive cells, and selectively increased the apoptotic index in the PD-like plaque. The lower dose was less effective, When vardenafil was given continuously in the drinking water for 41 days after the PD-like plaque was formed, there was only a partial reduction of the plaque.


CONCLUSIONS
Long-term oral treatment with vardenafil slows and reverses the early stages of an experimental PD-like plaque in the rat, and might ameliorate a more advanced plaque.
Ferrini
Monica G
MG
Division of Urology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Kovanecz
Istvan
I
Nolazco
Gaby
G
Rajfer
Jacob
J
Gonzalez-Cadavid
Nestor F
NF
D000284:Administration, Oral; D000818:Animals; D007093:Imidazoles / Q000008:administration & dosage*; D007150:Immunohistochemistry; D008297:Male; D010411:Penile Induration / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D013450:Sulfones / Q000008:administration & dosage; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014227:Triazines / Q000008:administration & dosage; D000069058:Vardenafil Dihydrochloride
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014227:Triazines; D000069058:Vardenafil Dihydrochloride