Long term partial bladder outlet obstruction induced contractile dysfunction in male rabbits: a role for Rho-kinase.

摘要

AIMS: In this study we examined the expression of Rho-kinase (ROK) isoforms in rabbit detrusor smooth muscle during the progression of partial bladder outlet obstruction and correlated them with the time course of obstruction. METHODS: Detrusor samples were obtained from bladders after 1, 2, 4, and 8 weeks of obstruction and also sham operated control rabbits. Contractile responses to field stimulation (FS) and also the smooth muscle (SM) to collagen ratio were determined in isolated bladder strips. Reverse transcriptase-polymerase chain reaction, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting were used to determine the relative levels of ROK isoform expression at the mRNA and protein levels. RESULTS: Bladder weight increased gradually and contractile responses were reduced significantly over the course of obstruction. The smooth muscle/collagen ratio increased significantly during the course of obstruction. The expression of ROKalpha increased significantly to approximately the same extent in 1-4-week obstructed groups and increased further in the 8-week obstructed group, both at the mRNA and protein levels. In contrast, there was a significant decrease in the expression of ROKbeta in the obstructed groups, which gradually decrease during the course of 1-4-week obstruction period and are slightly upregulated at the decompensated stage at 8-week obstruction. CONCLUSIONS: The change in the isoforms of ROK may be part of the molecular mechanism for bladder compensation following partial bladder outlet obstruction.