Effects of Rho Kinase Inhibitor on Detrusor Overactivity after Bladder Outlet Obstruction in Rats / 대한비뇨기과학회지

ABSTRACT

PURPOSE: A partial bladder outlet obstruction(PBOO) related detrusor hypertrophy is associated with up-regulation of the Rho kinase activity in an experimental animal model, and has been implicated in PBOO induced bladder dysfunction. The effect of a Rho kinase inhibitor on the voiding function in anesthetized rats with PBOO was investigated. MATERIALS AND METHODS: Eighteen Sprague-Dawley rats were divided into control(9 rats) and experimental(9 rats) groups. The experimental group was partially obstructed for 6 weeks, with cystometrograms(CMG) then were performed. The number of voids, and the intercontraction interval (ICI) and peak pressure(PP) were recorded. Rho kinase inhibitors were administered to the experimental group. An additional CMG was performed to observe the effects of Rho kinase inhibition. Bladder tissues were immunohistochemically(IHC) evaluated for the expression of RhoA protein. RESULTS: The bladder weights of the PBOO group were significantly increased compared with the control group(p<0.05). Significant increases in the voiding frequency and PP, but a significant decrease in the ICI was observed in the PBOO group compared to the control group on the CMG (p<0.05). The voiding frequency of the PBOO group was significantly decreased after Rho kinase inhibitor treatment(p<0.05). The Rho kinase inhibitor treated group showed a decrease in the PP and an increase in the ICI compared to the PBOO group. The IHC showed a higher RhoA protein expression in the bladder tissues of the PBOO group. CONCLUSIONS: H-1152, a specific inhibitor of Rho kinase, attenuates the PBOO-related detrusor overactivity in a rat model. The Rho kinase inhibitor appears to be a novel strategy for the management of bladder overactivity.