Study On The Relationship Between Rho Kinase And Detrusor Instability

Background: Detrusor instability (DI) is one of the most common bladder dyfunction diseases in clinic. The etiology remains unknown, and the therapeutic effect is poor. The further studies on the regulation of detrusor muscle function and pathogenesis of DI are necessary and significant. Recently, it was widly attention that the Rho/Rho kinase signal transduction pathway regulates Ca²⁺ sensitization and play the significant role in abnormal vascular smooth contractility.In this investigation, the effections of Rho kinase inhibitor on the contraction of detrusor muscle were observed through tensile force experiments of smooth muscle strips in vitro. And RT-PCR was performed to detect the mRNA expressions of ROCKI and ROCKII, two subtypes of Rho kinase in both the normal and DI detrusor muscle tissues of rats. The role of Rho kinase on the regulation of detrusor muscle function and the relationship between Rho kinase and DI were discussed.Materials and methods: Bladder outlet obstruction (BOO) was created in female SD rats by ligating the proximal urethra in DI group. In the normal group, pseudooperations were performed. DI was identified by cystometries in anaesthetic rats after suprapubic bladder catheter implantation. In the tensile force experiments of detrusor smooth muscle strips in vitro, spontaneous contraction frequency and force were recorded before and after Y-27632, a Rho specific inhibitor was applied in the two groups. And the mRNA expression of ROCKI and ROCKII were detected by semiquantitative RT-PCR.Results: (1) 74.19% of the rats which underwent BOO operation developed DI. Bladder pressure and capacity remained normal in control rats, while significantly increased with high compliance in DI rats. (2) Detrusor muscle strips of all groups contracted at definite tension. DI strips contracted at lower tension and had a higher contraction frequency than that of the normal (P<0.01). Both the contraction frequency and force of the bladder strips were obviously decreased by Y-27632 in DI groups (P<0.01), andthe influence of Y-27632 on normal group is not significant. (3) Both ROCKI and ROCKII were detected in the detrusor tissues of the two groups. The quantity of ROCKI is much higher in DI group than in control group. However, the difference of ROCKII expression between the two groups is not statistically significant.Conclusion: 1. DI model of rats was successfully established by proximal urethra ligating. Bladder pressure and capacity were significantly increased in DI rats. 2. The spontaneous contraction frequency was elevated in DI detrusor, indicated the enhanced excitability of DI. 3. Y-27632 can decrease the myogenic excitability and contraction force of detrusor in DI, and have no effection on normal bladders. 4. The expression of ROCKI is much higher in DI than normal group. It may play an important role in the occurence of DI.