Obstructive Bladder Dysfunction: Morphological, Biochemical and Molecular Changes

Abstract

Obstruction can cause changes in bladder structure and function, which may at a certain point in time become irreversible. Both the rabbit and the rat have proven to be excellent models to study the morphological, biochemical and molecular changes that occur in the bladder following obstruction. Similarities between partial outflow obstruction in animals and obstructive dysfunction in man include increased bladder mass, increased fibrosis, reduced compliance, increased incidence of detrusor instability and decreased contractile ability. Obstructed bladder function can remain relatively normal for prolonged periods of time, even though bladder mass is increased (compensated stage). If the obstruction is not relieved, bladder function destabilizes and then decompensates, with subsequent risk of serious complications. It is hypothesized that the shift from the compensated to the decompensated stage is related to cyclical periods of ischaemia followed by reperfusion (I/R). This initiates degenerative membrane effects, which supports the process of bladder decompensation. It seems that relief of obstruction during the compensated stage, at least in animals, can induce a rapid and full restoration of the bladder function. However, if the obstruction is relieved during the decompensated phase, bladder function only partially recovers. Irreversible bladder decompensation may be prevented by reducing increased bladder mass and/or by reducing ischaemia/increasing blood supply to the bladder. The antioxidant Vitamin E seems to reduce the progression of decompensation in rabbits. Treatment of rats with the α 1-adrenoceptor antagonist doxazosin prior to partial outlet obstruction increases blood flow to the bladder, significantly decreases the effect of obstruction on bladder weight, and significantly protects the contractile function of the obstructed bladder. Pre-treatment of rabbits with the α 1-adrenoceptor antagonist tamsulosin partly prevents the development of bladder wall hypertrophy due to obstruction. In conclusion, there is evidence that I/R plays an important role in the pathogenesis of obstructive bladder dysfunction. Therefore, I/R should be prevented or relieved. As I/R is the consequence of increased bladder mass following obstruction, therapies that prevent or reduce increased bladder mass (such as the α 1-adrenoceptor antagonist tamsulosin) are likely to protect the bladder from (further) dysfunction. Therapies based on both the relief of I/R (increasing blood flow to the bladder, e.g. α 1-adrenoceptor antagonists) and preventing I/R induced cellular damage (e.g. antioxidant activity) have been shown experimentally to significantly reduce the severity of bladder dysfunction secondary to partial outflow obstruction. Of course, these potentially useful and novel mechanisms of action of therapy should also be investigated in humans.