Alterations in Contractility and Regulatory Enzymes in Partial Bladder Outlet Obstruction- Induced Compensation and Decompensation of Rat Bladder

초록

Introduction and Objectives: Bladder contractility is known to be dependent on ATP as the main source of metabolic energy. The aim of this study was to investigate the effects of bladder outlet obstruction during the initial 2 weeks on detrusor contractility and the activity of signaling enzymes of energy control or mechanotransduction, such as AMPactivated kinase (AMPK), extracellular signal-regulated kinase (ERK) 1/2, and protein kinase C, in compensated and decompensated bladders of awake rats. Materials and Methods: Twenty-seven rats were randomly subjected to sham operations (n=7) or partial bladder outlet obstruction (n=20). Cystometric investigations were performed to measure intra-abdominal pressure to discriminate detrusor contractility. Decompensated bladder was defined as a bladder with a residual urine volume percentage compared with bladder capacity of more than 25%. The expression and phosphorylation of AMPKα, ERK1/2 and PKCα were assessed by Western blotting. Results: In compensated rat bladder (n=10), contractility during the filling phase was significantly correlated with that during the voiding phase. This correlation disappeared in decompensated bladder (n=6). The phosphorylation levels of AMPK and ERK1/2 in compensated bladders decreased significantly compared with those in sham and decompensated bladders, whereas the levels in decompensated bladders were restored to the level of sham-operated bladders. Conclusion: The decompensated bladder as defined by our criteria appears to lose control over the correlations among the reactions of the three different contractilities to obstruction during the filling and voiding phases, whereas this control is maintained in compensated bladder. The signaling pathways of AMPK and ERK1/2 may play a role in mediating the transition from a compensated to a decompensated stage.