Chronology and urodynamic characterization of micturition in neurohormonally induced experimental prostate growth in the rat.

ABSTRACT

The purpose of this study was to evaluate the impact of chronic urinary tract obstruction which was produced in the rat using neurohormonally induced experimental prostate growth. In this model, we considered the chronology of changes in the micturition characteristics of awake rats relative to prostate weight and stiffness. The corresponding urodynamic characteristics of both the upper and lower tracts were evaluated in anesthetized animals relative to the development and extent of the obstruction produced. Prostate growth was produced by capitalizing on the synergistic properties afforded by the combined administration of dihydrotestosterone propionate (DHT) and the alpha1 adrenoreceptor antagonist prazosin (PRZ). DHT (1.25 mg/kg/day) was dissolved in 0.1 ml sesame oil (SO) and coadministered with PRZ 30 microg/kg/day subcutaneously for 14 days to 12 experimental rats. SO alone was given to 8 control rats. Micturition studies were first performed using all 20 awake rats, which were placed unrestrained in metabolic cages. Urodynamics of the upper and lower urinary tracts were repeated following anesthesia at the 5th, 10th, and 15th weeks after initiation of hormonal or SO treatment. Following the urodynamic studies, the rats were killed and prostates were removed and weighed, and stiffness was measured. Studies with awake rats show that hormonal treatment produces a significant and progressive increase in mean frequency of micturition, ranging from 0.63+/-0.16 in controls and reaching the maximum of 2.15+/-0.40/hr by the 10th wk. Results from urodynamic studies with anesthetized rats also show typical and progressive obstructive characteristics maximum detrusor voiding pressure (Pdetmax) increased from 52.7+/-2.03 in controls to a maximum of 77.5+/-2.2 cm H2O by the 10th week; urethral opening pressure Puo likewise increased from 52.6+/-2.7 in controls to 73.3+/-2.1 cm H2O in experimental rats. The duration of time during which the detrusor sustains contraction during voiding also rose, from 16.8+/-1.8 sec in controls to 32.0+/-3.2 sec by the 10th week. There were no significant changes in bladder capacity, baseline filling pressures, or arterial pressures. Prostate weight increased significantly from 0.76+/-0.05 g in controls to 1.17+/-0.1 g by the 15th week. Similarly, stiffness increased from control values of 1.33+/-0.18 g/cm to a maximum of 3.59+/-0.14 g/cm by the 10th week. It is concluded that neurohormonally stimulated prostate growth in the rat is a suitable animal model for the study of the development of urinary tract obstruction. Obstructive characteristics were validated in both awake rats by the increase in the frequency of micturition and urodynamically under anesthesia in terms of elevations in maximum detrusor pressures, urethral opening pressure, detrusor contraction time, and prostatic stiffness. The effect of obstruction was further shown to be associated with vesicoureteral reflux during micturition and elevated upper tract pressures.