(1) Department Of Urology, Shinshu University School Of Medicine, Matsumoto/Asahi/, Japan
Cold stress such as rapid change to a low temperature environment or prolonged exposure to low temperature is one of the factors in exacerbation of lower urinary tract symptoms. It has reported that high dose α1 blocker, 0.3 mg/kg naftopidil could inhibit the detrusor overactivity induced cold stress (1). This study determined if low dose combination of α1 blocker and PDE5 inhibitor could mediate the cold stress-induced detrusor overactivity in rats with lower urinary tract obstruction.
The urethras of 10-weeks female Sprague-Dawley rats were ligated. After 4 weeks, cystometric investigations were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were intraperitoneally administrated with 0.15 mg/kg naftopidil and 0.5 mg/kg tadalafil (n=11) or vehicle (n=11). Twenty minutes later, they were smoothly and quickly transferred to low temperature (LT, 4 ± 2°C) for 40 min. Finally, they were transferred to at room temperature (RT, 27 ± 2°C).
At room temperature, there was no differences in micturition parameters between both groups. During LT exposure, detrusor overactivity, which were shorter voiding interval and lower micturition volume and bladder capacity compared to the RT values was observed in the both groups. After transferring to LT exposure, micturition volume and bladder capacity in the naftopidil and tadalafil-treated rats were decreased. However, the decreases in the combination-treated rats were significantly inhibited compared to the vehicle-treated ones.
In this study, we showed that the low dose combination of α1 blocker and PDE5 inhibitor could partially inhibited the cold stress-induced detrusor overactivity in rats with bladder outlet obstruction.