Antimuscarinic Drug Inhibits Detrusor Overactivity Induced by Topical Application of Prostaglandin E2 to the Urethra With a Decrease in Urethral Pressure

Purpose: Antimuscarinic drugs increase bladder capacity without prominent side effects such as urinary retention even when administered to patients with mild to moderate BOO. Some mechanisms might exist in the urethra to compensate for the emptying function of the detrusor after administration of antimuscarinic drugs. We investigated the influences of an antimuscarinic drug, propiverine, on urethral function. Materials and Methods: Urethral pressure and rhythmic bladder pressure were simultaneously monitored in urethane-anesthetized female Sprague-Dawley rats. PGE2 was continuously administered intravesically or intraurethrally to induce detrusor overactivity. Next, to eliminate the influence of bladder activity and to monitor urethral baseline pressure, isovolumetric pressure of the urethra was recorded after cystectomy and ligation of the external urethral meatus. Furthermore, the in vitro contractile responses of the urethral circular smooth muscle to field stimulation were examined in the presence of propiverine, tamsulosin, verapamil, ω-conotoxin, and atropine. Results: The intravesical or intraurethral administration of PGE2 significantly decreased bladder contraction interval (BCI) by 10.7% and 36.0%, respectively. The intraarterial administration of 2x102 nM/kg propiverine significantly increased BCI in rats receiving intraurethral PGE2 by 81.8%, but had no marked effect on rats receiving intravesical PGE2. Significant decreases in urethral baseline pressure were found after propiverine administration. Field stimulation-induced contraction was inhibited by propiverine and verapamil, but not by tamsulosin, ω-conotoxin or atropine. Conclusions: These results suggest that inhibitory effects of propiverine are more prominent in rats with detrusor overactivity induced by intraurethral PGE2 than those by intravesical PGE2. Propiverine may compensate for detrusor function by decreasing urethral resistance in the voiding phase