Animal models of bladder outlet obstruction and molecular insights into the basis for the development of bladder...

In humans, chronic bladder outlet obstruction resulting from benign prostatic hypertrophy (BPH) can induce severe and irreversible upper urinary tract changes, especially in the bladder. BPH can be mimicked in rabbits by artificially creating a partial obstruction of the bladder outlet. The structural and functional changes initiated eventually elicit a pathology and symptomology similar to human BPH. The rabbit bladder responds to partial outlet obstruction in three characteristic stages: hypertrophy, compensation and decompensation Basic fibroblast growth factor, epidermal growth factor and transforming growth factor-beta appear to be involved in the hypertrophy phase. During this initial phase normal bladder function is maintained but in the later phases, it is drastically impaired. We propose that the various stages of bladder remodelling subsequent to partial outlet obstruction are essentially driven by reduction in blood flow to the bladder (ischaemia). Initially this ischaemia might stimulate a compensatory response enabling the bladder to deal with the stress outlet obstruction. However, the long-term reduction in blood flow resulting from cyclical filling of the obstructed bladder, ultimately induces the degenerative changes that impede bladder function. These findings have important implications for the development of novel therapies to prevent or reverse bladder dysfunction resulting from BPH.