Effect of oral Tadenan treatment on rabbit bladder structure and function after partial outlet obstruction.
OBJECTIVE
There is increasing evidence that the progressive dysfunction induced by partial outlet obstruction is mediated by ischemia-reperfusion, and bladder decompensation results from ischemia-reperfusion induced damage to the cellular and subcellular organelle membranes of nerve and smooth muscle, mitochondria and sarcoplasmic reticulum. Tadenan, an extract of Pygeum africanum, is a therapeutic prescribed in Europe to relieve symptoms of obstructive bladder dysfunction secondary to benign prostatic hyperplasia. There is excellent experimental evidence that Tadenan treatment of obstructed rabbits reduces and reverses the progression of bladder decompensation. We determined whether Tadenan therapy can reverse the morphological damage associated with obstructive dysfunction.


METHODS
A total of 36 male New Zealand White rabbits were separated into 6 groups of 6 each. Rabbits in groups 1 and 2 underwent sham operation. For 3 weeks beginning 2 weeks after sham operation group 1 was treated with vehicle and group 2 was treated with 30 mg./kg. Tadenan daily. Rabbits in groups 3 to 6 underwent partial outlet obstruction surgery. Two weeks after obstruction each rabbit was treated for 3 weeks with vehicle in group 3, and with 1, 10 and 30 mg./kg. Tadenan in groups 4, 5 and 6, respectively. After the completion of treatment cystometry was performed on each rabbit and isolated bladder strips were evaluated for contractile responses to field stimulation, adenosine triphosphate, carbachol and KCl. Separate strips were fixed for electron microscopy to determine the location and severity of cellular and subcellular membrane damage.


RESULTS
Partial outlet obstruction resulted in reduced compliance, decreased responses of bladder strips to all forms of stimulation tested, and significant and extensive damage to cellular and subcellular organelle membranes consistent with an ischemia-reperfusion etiology. Daily 1 and 10 mg./kg. Tadenan treatments had little effect on the obstruction induced increase in bladder weight or the deleterious changes in bladder function and structure. However, treating obstructed rabbits with 30 mg./kg. Tadenan daily resulted in reduced bladder hypertrophy, improved compliance, improved contractile responses to nearly normal levels of isolated bladder strips to all stimuli tested and reversal of obstruction induced structural damage to cellular and subcellular organelle membranes.


CONCLUSIONS
Tadenan treatment of obstructed rabbits resulted in a dose dependent improvement in bladder ultrastructure in parallel with improved bladder compliance and contractile responses of isolated strips to stimulation, providing support for the hypothesis that damage to cellular and subcellular organelle membranes mediates the contractile dysfunction induced by partial outlet obstruction.
Levin
Robert M
RM
Albany College of Pharmacy, Albany Medical College and Stratton Veterans Affairs Medical Center, Albany, New York, USA.
Hass
Martha A
MA
Bellamy
Francois
F
Horan
Pat
P
Whitbeck
Katherine
K
Chow
Pak Ham
PH
Kung
L S
LS
Gosling
John
J
D000818:Animals; D005233:Fatty Alcohols / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts; D011470:Prostatic Hyperplasia / Q000473:pathology / Q000503:physiopathology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D001743:Urinary Bladder / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000473:pathology / Q000503:physiopathology*; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology
D005233:Fatty Alcohols; D010936:Plant Extracts; C009375:Tadenan