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 progresses, the bladder changes from a state of compensation to decompensation, in which there are severe, irreversible alterations in bladder function. Using a rabbit model of partial outlet obstruction we have identified 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 sarcoplasmic reticulum. Our hypothesis is that outlet obstruction results in bladder hypertrophy which induces ischaemia. This leads to a release of intracellular calcium, leading to activation of specific enzymes 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) significantly reduced the severity of both the contractile and metabolic dysfunctions induced by partial outlet obstruction. Our current hypothesis is that Tadenan may either prevent the activation of degradative enzymes (or generation of free radicals), or protect the intracellular membranes against the destructive effects of free radicals or degredative enzymes. In conclusion, identifying cellular mechanisms responsible for bladder dysfunction induced by partial outlet obstruction provides new possibilities for non-surgical treatment of BPH. Our studies on Tadenan support this concept that the bladder provides a novel target for therapeutic intervention.
Levin
R M
RM
Albany College of Pharmacy, N.Y., USA.
Levin
S S
SS
Zhao
Y
Y
Buttyan
R
R
D000375:Aging / Q000473:pathology; D000818:Animals; D005233:Fatty Alcohols / Q000494:pharmacology; D006801:Humans; D006984:Hypertrophy; D007511:Ischemia / Q000209:etiology; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D011292:Premedication; D011470:Prostatic Hyperplasia / Q000150:complications* / Q000473:pathology; D011817:Rabbits; D001743:Urinary Bladder / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control
D005233:Fatty Alcohols; D010936:Plant Extracts; C009375:Tadenan