Effect of alpha1 adrenoceptor antagonist on the urodynamics of the upper and lower urinary tract of the male rat.

In this investigation, we examined the impact of the alpha1 adrenoceptor (alpha1-ADR) antagonist prazosin on the urodynamic characteristics of upper urinary tract function and associated micturition characteristics of the adult male rat. The focus of the study was to evaluate the extent to which prazosin affects urine production and ureteral transport relative to its effect on micturition. Control micturition studies were first performed using 28 awake Sprague-Dawley rats that were placed in metabolic cages for characterization of the frequency and mean and total volume voided over a 4-hr period. Following the control studies, the effect of intraperitoneal prazosin, 30 microg/kg, was evaluated under identical conditions. Urodynamic studies were done to identify the bladder filling and voiding characteristics of anesthetized rats that were infused with saline at a rate of 0.22 ml/min. From the urodynamic studies the parameters of bladder pressure (Pves) and volume (V) during filling, urethral opening (Puo) measured at the moment of micturition, and maximum detrusor pressure during voiding (Pdetmax) were evaluated. External sphincter electromyography was also monitored and recorded together with bladder pressure during voiding. Renal pelvic pressure was measured via a nephrostomy catheter and recordings were made simultaneously with bladder filling and voiding. The upper urinary tract was visualized using microscopic video imaging of the ureter, contrasted by perfusing the renal pelvis with indigo carmine. Characterization of upper tract transport was made in terms of renal pelvic pressure, ureteral peristaltic rate, and bolus length and velocity. The results show that in the awake rat, 30 microg/kg of prazosin decreased the urine production rate from 4.8 +/- 0.074 to 1.6 +/- 0.23 ml (P < 0.001) and micturition frequency by a similar proportion from 1.99 +/- 0.44 to 0.53 +/- 0.08/hr. In the lower urinary tract, prazosin did not change the baseline pressure of the bladder but produced significant dose-dependent decreases in Pdetmax, Puo, and frequency of micturition. In the upper urinary tract, ureteral and pelvic frequencies decreased, whereas the length of bolus increased significantly corresponding to increased doses of prazosin. These results suggest that, although prazosin facilitates micturition by reducing urethral opening pressure, it also reduces the rate of urine production and modulates the function of urine transport in the upper urinary tract.