Analysis of pressure/flow characteristics in the female rat and their pharmacologic modulation

A new in vivo urodynamic animal model was developed to analyze the micturition characteristics of the rat. This model was used to study the modulating effect of pharmacological agents on vesicourethral function, using cystometry and uroflowmetry. Pressure-flow studies were done in 25 female rats anesthetized with urethane. Filling cystometry was recorded using a physiological rate of bladder filling through transvesical infusion. Micturition characterization was done by identifying the time course and amount of voided volume. Voided volume was measured by a novel application of a mechanotransducer, which provided the data to measure flow rate and compute the voided volume-time curve. Flow rate was calculated by differentiating the curve produced by the mechanotransducer. Using this system, comparative tests of pharmacological stimulus were done using anticholinergic stimulation, alpha 1, and a new N-methyl-D aspartate (NMDA) receptor antagonist. The effects of the intravenous use of these drugs in the lower urinary tract were evaluated at various dose levels. The results showed that anticholinergic stimulation produced an increase of bladder capacity and decreases of detrusor pressure and maximum flow rate. Although the alpha 1 blocker decreased detrusor pressure, flow rate did not change significantly. By contrast, NMDA receptor antagonism produced a depressant effect on bladder reflex contraction, and increased bladder capacity in a dose-dependent way. However, maximum flow rate increased at a dose of 10 mg/kg and decreased at 30 mg/kg significantly. These results suggest that a decrease in flow resistance through the outlet region was due to the effects of NMDA receptor inhibition at lower doses. In conclusion, this model enables the evaluation of drugs regarding lower urinary tract function and provides in small animals the possibility of evaluating the relationships between pressure and flow in various experimental models.