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Effects of phosphodiesterase type 5 inhibitor on the contractility of prostate tissues and urethral pressure responses in a rat model of benign prostate hyperplasia
Author(s) -
Kang Kyung K,
Kim Ju M,
Yu Jae Y,
Ahn Byoung O,
Yoo Moohi,
Kim Young C
Publication year - 2007
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/j.1442-2042.2007.01874.x
Subject(s) - medicine , prostate , contractility , hyperplasia , urology , in vivo , cgmp specific phosphodiesterase type 5 , prostate cancer , phosphodiesterase inhibitor , erectile dysfunction , endocrinology , cancer , microbiology and biotechnology , biology
Aim: 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 . Methods: 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 17β‐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). Results: DA‐8159 concentration‐dependently reduced the contraction of the isolated prostate strips with an IC 50 value of 70 μM. 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. Conclusions: 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.