CELLULAR AND MOLECULAR ASPECTS OF BLADDER HYPERTROPHY

Bladder dysfunction secondary to benign prostatic hyperplasia (BPH) is a major affliction associated with ageing. As the disease slowly progr esses, the bladder changes from a state of compensation to decompensat ion, in which there are severe, irreversible alterations in bladder fu nction. Using a rabbit model of partial outlet obstruction we have ide ntified three major cellular changes in the bladder which result from such obstruction These include progressive denervation, mitochondrial dysfunction and disturbances of calcium storage and release from the s arcoplasmic reticulum. Our hypothesis is that outlet obstruction resul ts in bladder hypertrophy which induces ischaemia. This leads to a rel ease of intracellular calcium, leading to activation of specific enzym es and generation of free radicals. These then attack the membranes of nerves, sarcoplasmic reticulum and mitochondria. We have demonstrated that pretreatment of rabbits with Pygeum africanum extract (Tadenan(R )) significantly reduced the severity of both the contractile and meta bolic dysfunctions induced by partial outlet obstruction. Our current hypothesis is that Tadenan(R) may either prevent the activation of deg radative enzymes (or generation of free radicals), or protect the intr acellular membranes against the destructive effects of free radicals o r degredative enzymes. In conclusion, identifying cellular mechanisms responsible for bladder dysfunction induced by partial outlet obstruct ion provides new possibilities for non-surgical treatment of BPH. Our studies on Tadenan(R) support this concept that the bladder provides a novel target for therapeutic intervention.