Effects of long‐term vardenafil treatment on the development of fibrotic plaques in a rat model of Peyronie's disease

• Published in: BJU international Vol. 97; no. 3; pp. 625 - 633
• Main Authors: FERRINI, MONICA G., KOVANECZ, ISTVAN, NOLAZCO, GABY, RAJFER, JACOB, GONZALEZ‐CADAVID, NESTOR. F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2006; Blackwell
• Subjects: Administration, Oral; Animals; apoptosis; Biological and medical sciences; collagen; fibrosis; Genital system. Reproduction; Imidazoles - administration & dosage; Immunohistochemistry; inducible nitric oxide synthase; Male; Medical sciences; myofibroblast; Nephrology. Urinary tract diseases; nitric oxide; PDE5; Penile Induration - chemically induced; Penile Induration - drug therapy; Penile Induration - pathology; penis; Pharmacology. Drug treatments; Phosphodiesterase Inhibitors - administration & dosage; Piperazines - administration & dosage; Rats; Rats, Inbred F344; sildenafil; Sulfones - administration & dosage; tadalafil; TGF‐β; Transforming Growth Factor beta; Transforming Growth Factor beta1; Triazines - administration & dosage; tunica albuginea; Vardenafil Dihydrochloride; Nephrology; Vasodilator agent; Rat; 3',5'-Cyclic-GMP phosphodiesterase; Peyronie disease; Myofibroblast; Esterases; Vardenafil; Phosphoric diester hydrolases; Urology; Albuginea; inducible nitric oxide synthase; TGF-β; penis; Male genital diseases; PDE5; tunica albuginea; tadalafil; Enzyme; Glycoprotein; Rodentia; Enzyme inhibitor; Long term; sildenafil; Nitric-oxide synthase; Penile diseases; Vertebrata; Chemotherapy; Carboline derivatives; Mammalia; Treatment; Cell death; Animal; Nitric oxide; Collagen; Fibrosis; Hydrolases; Oxidoreductases; Apoptosis
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2006.05955.x

OBJECTIVES 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 β1 (TGF‐β1) into the tunica albuginea of the rat. MATERIALS AND METHODS Vardenafil was given to male rats (eight per group) either in the drinking water or as an oral instillation once daily, at ≈ 1 and ≈ 3 mg/kg/day for 45 days after one injection with TGF‐β1 into the tunica albuginea, as an ‘early preventive’ treatment for TGF‐β1‐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 (α‐smooth muscle actin), TGF‐β1 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‐β1‐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.