Pre‐clinical evidence for the use of phosphodiesterase‐5 inhibitors for treating benign prostatic hyperplasia and lower urinary tract symptoms

OBJECTIVE To evaluate the potential of sildenafil, vardenafil and tadalafil, all phosphodiesterase‐5 (PDE‐5) inhibitors used for treating erectile dysfunction, for treating benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). MATERIALS AND METHODS The mRNA expression of the PDE‐5 was determined in rat LUT tissues. The PDE‐5 inhibitors were also tested in organ‐bath experiments and in a partial bladder outlet obstruction (BOO) rat model in vivo. RESULTS The highest PDE‐5 mRNA expression was in the bladder, followed by the urethra and prostate. PDE‐5 inhibitors dose‐dependently reduced the contraction of the isolated bladder, urethral and prostate strips. The rank order of potency was vardenafil > sildenafil > tadalafil. In human prostate stromal cells vardenafil inhibited cell proliferation and was more effective than tadalafil and sildenafil. In the BOO model, there was a reduction in the non‐voiding contractions after bolus intravenous administration of 3 mg/kg sildenafil and vardenafil. CONCLUSION These results show that PDE‐5 is expressed in LUT tissues. PDE‐5 inhibitors induced significant relaxation of these tissues, inhibited the proliferation of human prostate stromal cells and reduced the irritative symptoms of BPH/LUTS in vivo. Therefore, PDE‐5 inhibitors could be used as an effective treatment for BPH/LUTS.