ABSTRACT
We investigated the effects of the phosphodiesterase type 5 inhibitor, tadalafil on prostatic hyperplasia in a hypertensive rat model. Twelve-week-old male spontaneously hypertensive rats (SHRs) were orally treated with tadalafil (2 or 10 mg/kg/day) or vehicle for six weeks. Wistar Kyoto (WKY) rats treated with vehicle were used as controls. The effect of tadalafil was evaluated by measuring prostate weight, blood pressure, and prostatic blood flow. The presence of malondialdehyde (MDA), interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-ß1), and basic fibroblast growth factor (bFGF) in the ventral prostate were examined. Hematoxylin and eosin staining was performed to assess the morphological change. The prostatic contractility was evaluated by an organ bath experiment. The vehicle-treated SHRs demonstrated a significantly higher prostate weight, prostate weight/body weight ratio (PBR), blood pressure, and tissue levels of MDA, IL-6, TGF-ß1, and bFGF, and lower prostatic blood flow compared to the vehicle-treated WKY rats. Moreover, the SHRs showed glandular morphological abnormalities in the ventral prostate compared to the WKY rats. There was no significant difference in potassium chloride or noradrenaline-induced prostatic contractility between the WKY rats and the SHRs. Treatment with tadalafil decreased prostate weight and PBR in a dose-dependent manner, and improved prostatic blood flow and tissue levels of MDA, IL-6, TGF-ß1, and bFGF in SHRs, without affecting the blood pressure. Furthermore, tadalafil ameliorated the glandular morphological abnormalities in the SHR ventral prostate. In conclusion, tadalafil could suppress the prostatic hyperplasia via recovery of reduction in prostatic blood flow in SHRs.
