ANIMAL-MODELS OF BLADDER OUTLET OBSTRUCTION AND MOLECULAR INSIGHTS INTO THE BASIS FOR THE DEVELOPMENT OF BLADDER DYSFUNCTION

In humans, chronic bladder outlet obstruction resulting from benign pr ostatic hypertrophy (BPH) can induce severe and irreversible upper uri nary 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 eli cit a pathology and symptomology similar to human BPH. The rabbit blad der responds to partial outlet obstruction in three characteristic sta ges: hypertrophy, compensation and decompensation. Basic fibroblast gr owth factor, epidermal growth factor and transforming growth factor-be ta 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 blad der remodelling subsequent to partial outlet obstruction are essential ly driven by reduction in blood flow to the bladder (ischaemia). Initi ally this ischaemia might stimulate a compensatory response enabling t he bladder to deal with the stress of outlet obstruction. However, the long-term reduction in blood flow resulting from cyclical filling of the obstructed bladder, ultimately induces the degenerative changes th at impede bladder function. These findings have important implications for the development of novel therapies to prevent or reverse bladder dysfunction resulting from BPH.