EFFECTS OF TADENAN PRETREATMENT ON BLADDER PHYSIOLOGY AND BIOCHEMISTRY FOLLOWING PARTIAL OUTLET OBSTRUCTION

Purpose: Tadenan is a pharmaceutical agent used in the treatment of BP H. Prior studies demonstrated that pretreatment of rabbits with Tadena n significantly reduced the contractile dysfunction following two week s of partial outlet obstruction, The specific aim of the present study was to determine the effect of Tadenan pretreatment on the time cours e of the response to partial outlet obstruction and correlate the effe ct of Tadenan on the contractile responses to field stimulation, betha nechol, and KCl with both mitochondrial enzyme activity (citrate synth ase) and sarcoplasmic reticular function (calcium-ATP'ase activity). M aterials and Methods: Sixty male New Zealands white rabbit (3 to 5 kg. ) were separated into 12 groups of 5 rabbits each. Each rabbit in grou ps 1-6 received Tadenan orally at 100 mg./kg./day for three weeks; eac h rabbit in groups 7-12 received vehicle (peanut oil). Each rabbit in groups 2-6 and 8-12 received a partial outlet obstruction as described below. One group of Tadenan treated and one group of vehicle-treated rabbits were euthanized at 1, 3, 5, 7, and 14 days following partial o utlet obstruction. The non-obstructed groups were studied after 4 week s of drug or vehicle treatment. Each bladder was rapidly removed and w eighed, and 3 longitudinal strips prepared and mounted in individual b aths for contractile studies. The remainder of the bladder was frozen for biochemical analysis. The contractile responses to field stimulati on, bethanechol, and KCl were determined; and the enzyme activities of citrate synthase (marker for mitochondrial function) and calcium-ATP' ase (marker for sarcoplasmic reticulum) were determined, Results: 1) T adenan did not reduce the effect of partial outlet obstruction on blad der mass. 2) Although the contractile responses to all forms of stimul ation were reduced at 1 day following partial outlet obstruction, Tade nan pretreatment resulted in a significant protective effect on the co ntractile responses to field stimulation, bethanechol, and KCl at 3, 5 , 7, and 14 days of obstruction. 3) The activities of both citrate syn thase and calcium ATP'ase were reduced significantly at 1 day followin g obstruction for both Tadenan treated and vehicle treated groups. The activities of both enzymes returned to near normal levels at 7 and 14 days for the Tadenan groups whereas the activities of both enzymes re mained significantly reduced in the vehicle treated groups. Conclusion s: These results clearly demonstrate that Tadenan pretreatment protect ed the bladder from both the contractile and metabolic dysfunctions in duced by partial outlet obstruction.