Beneficial effects of Tadenan therapy after two weeks of partial obstruction in the rabbit.
Tadenan (Debat Laboratories, France) is a plant extract used in Europe for the treatment of micturition disorders associated with benign prostatic hypertrophy (BPH). Prior studies demonstrated that pretreatment of rabbits with Tadenan significantly reduced the contractile dysfunction observed after 2 weeks of partial outlet obstruction. The specific aim of the present study was to determine the effect of Tadenan therapy following the creation of partial outlet obstruction. Two sets of experiments were performed: one with mild and the other with severe outlet obstruction. For both sets of experiments, male New Zealand rabbits (3-5 kg) were separated into 3 groups of 5 rabbits each. Each rabbit in groups 1 and 2 was obstructed using standard methodology. Rabbits in group 3 served as controls and did not receive any surgery. After 2 weeks, each rabbit in group 1 received Tadenan orally at 100 mg/kg/day for 3 weeks; each rabbit in group 2 received vehicle (peanut oil). After 3 weeks of treatment (5 weeks after partial outlet obstruction), rabbits were anesthetized and cystometries were performed. Immediately after cystometry, the rabbits were euthanized, the bladder rapidly removed, and 4 longitudinal strips prepared and mounted in individual baths for contractile studies. The contractile responses to field stimulation, carbachol, adenosine-5'-triphosphate (ATP), and potassium chloride (KCl) were determined, as follows: (1) Bladder mass approximately doubled in the mildly obstructed groups. Bladder mass increased significantly (3-5-fold) in the severely obstructed groups. (2) Cystometrograms from the mildly obstructed rabbits treated with peanut oil showed low compliance, whereas those of the mildly obstructed rabbits treated with Tadenan showed normal compliance. The cystometrograms of all severely obstructed rabbits showed low compliance. (3) Mild obstruction caused small but significant decreases in the contractile response to field stimulation that were reversed by Tadenan treatment. No changes were noted in response to bethanechol, ATP, and KCl stimulation. (4) Severe obstruction caused significant decreases in the response of bladder strips to field stimulation and bethanechol. Following Tadenan therapy, there was a significant improvement in the response to high-frequency field stimulation and a substantial improvement in the response to bethanechol (response equal to control). No changes were noted in response to ATP and KCl stimulation. In conclusion, Tadenan treatment reversed the bladder dysfunctions induced by mild partial outlet obstruction, and resulted in improved bladder function in the severe model of outlet obstruction. These studies are consistent with previous studies showing that Tadenan pretreatment protects the bladder against the development of contractile dysfunctions.
Levin
R M
RM
Albany College of Pharmacy, New York 12208-3492, USA.
Das
A K
AK
Haugaard
N
N
Novitsky
Y
Y
Horan
P
P
Leggett
R E
RE
Riffaud
J P
JP
Longhurst
P A
PA
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003187:Compliance; D005233:Fatty Alcohols / Q000627:therapeutic use*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D000074241:Peanut Oil; D010936:Plant Extracts; D010938:Plant Oils / Q000627:therapeutic use; D011817:Rabbits; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D014563:Urodynamics / Q000502:physiology
D005233:Fatty Alcohols; D000074241:Peanut Oil; D010936:Plant Extracts; D010938:Plant Oils; C009375:Tadenan; D002217:Carbachol