Effects of Tadenan Pretreatment on Bladder Physiology and Biochemistry Following Partial Outlet Obstruction

Abstract

Tadenan is a pharmaceutical agent used in the treatment of BPH. Prior studies demonstrated that pretreatment of rabbits with Tadenan significantly reduced the contractile dysfunction following two weeks of partial outlet obstruction. The specific aim of the present study was to determine the effect of Tadenan pretreatment on the time course of the response to partial outlet obstruction and correlate the effect of Tadenan on the contractile responses to field stimulation, bethanechol, and KCl with both mitochondrial enzyme activity (citrate synthase) and sarcoplasmic reticular function (calcium-ATP'ase activity). Sixty male New Zealands white rabbit (3 to 5 kg.) were separated into 12 groups of 5 rabbits each. Each rabbit in groups 1-6 received Tadenan orally at 100 mg./kg./day for three weeks; each 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 outlet obstruction. The non-obstructed groups were studied after 4 weeks of drug or vehicle treatment. Each bladder was rapidly removed and weighed, and 3 longitudinal strips prepared and mounted in individual baths for contractile studies. The remainder of the bladder was frozen for biochemical analysis. The contractile response to field stimulation, 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. 1) Tadenan did not reduce the effect of partial outlet obstruction on bladder mass. 2) Although the contractile responses to all forms of stimulation were reduced at 1 day following partial outlet obstruction, Tadenan pretreatment resulted in a significant protective effect on the contractile responses to field stimulation, bethanechol, and KCl at 3, 5, 7, and 14 days of obstruction. 3) The activities of both citrate synthase and calcium ATP'ase were reduced significantly at 1 day following 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 enzyme remained significantly reduced in the vehicle treated groups. These results clearly demonstrate that Tadenan pretreatment protected the bladder from both the contractile and metabolic dysfunctions induced by partial outlet obstruction.