Effects of phosphodiesterase type 5 inhibitor on the contractility of prostate tissues and urethral pressure responses in a rat model of benign prostate hyperplasia

Abstract

This study was performed to investigate the effect of DA-8159, a selective phosphodiesterase 5 (PDE5) inhibitor, on benign prostatic hyperplasia (BPH) both in vitro and in vivo. We assessed the influence of DA-8159 on the contractility of rat prostate tissues in an organ-bath experiment. In addition, in order to investigate whether chronic administration of DA-8159 prevents the increase of electrostimulation-induced intraurethral pressure (IUP) responses associated with BPH, BPH was induced by steroid hormones (testosterone plus 17beta-estradiol) and DA-8159 (5, 20 mg/kg) was concomitantly administered once a day for 8 weeks. After that the electrostimulation-induced IUP responses were measured. Finally, we investigated the acute treatment effect of DA-8159 on IUP responses in an established BPH model after a single intravenous injection of DA-8159 (0.3, 1 mg/kg). DA-8159 concentration-dependently reduced the contraction of the isolated prostate strips with an IC50 value of 70 microM. In chronic treatment study, while the BPH control rats showed a significantly increased IUP both at the baseline and by electrostimulation, the chronic DA-8159 treatment significantly attenuated the increase in IUP responses in a dose- and frequency-dependent manner. In the acute treatment study, a single intravenous injection of DA-8159 also prevented the increase in urethral pressure in a dose-dependent manner. These results suggest that DA-8159 may be beneficial on lowering the urethral pressure associated with BPH via dilatation of the prostate, but a further evaluation of the efficacy on humans needs to be performed.