BENEFICIAL-EFFECTS OF TADENAN THERAPY AFTER 2 WEEKS OF PARTIAL OBSTRUCTION IN THE RABBIT

Tadenan(R) (Debat Laboratories, France) is a plant extract used in Eur ope for the treatment of micturition disorders associated with benign prostatic hypertrophy (BPH). Prior studies demonstrated that pretreatm ent of rabbits with Tadenan significantly reduced the contractile dysf unction observed after 2 weeks of partial outlet obstruction. The spec ific aim of the present study was to determine the effect of Tadenan t herapy 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 ra bbits (3-5 kg) were separated into 3 groups of 5 rabbits each. Each ra bbit in groups 1 and 2 was obstructed using standard methodology. Rabb its in group 3 served as controls and did not receive any surgery. Aft er 2 weeks, each rabbit in group 1 received Tadenan orally at 100 mg/k g/day for 3 weeks; each rabbit in group 2 received vehicle (peanut oil ). After 3 weeks of treatment (5 weeks after partial outlet obstructio n), rabbits were anesthetized and cystometries were performed. Immedia tely after cystometry, the rabbits were euthanized, the bladder rapidl y removed, and 4 longitudinal strips prepared and mounted in individua l baths for contractile studies. The contractile responses to field st imulation, carbachol, adenosine-5'-triphosphate (ATP), and potassium c hloride (KCl) were determined, as follows: (1) Bladder mass approximat ely doubled in the mildly obstructed groups. Bladder mass increased si gnificantly (3-5-fold) in the severely obstructed groups. (2) Cystomet rograms from the mildly obstructed rabbits treated with peanut oil sho wed low-compliance, whereas those of the mildly obstructed rabbits tre ated with Tadenan showed normal compliance. The cystometrograms of all severely obstructed rabbits showed low compliance. (3) Mild obstructi on caused small but significant decreases in the contractile response to field stimulation that were reversed by Tadenan treatment. No chang es were noted in response to bethanechol, ATP, and KCl stimulation. (4 ) Severe obstruction caused significant decreases in the response of b ladder strips to field stimulation and bethanechol. Following Tadenan therapy, there was a significant improvement in the response to high-f requency field stimulation and a substantial improvement in the respon se to bethanechol (response equal to control). No changes were noted i n response to ATP and KCl stimulation. In conclusion, Tadenan treatmen t reversed the bladder dysfunctions induced by mild partial outlet obs truction, and resulted in improved bladder function in the severe mode l of outlet obstruction. These studies are consistent with previous st udies showing that Tadenan pretreatment protects the bladder against t he development of contractile dysfunctions. (C) 1997 Wiley-Liss, Inc.