Exogenously administered opioids contract the female rat intrinsic urethral sphincter in vivo

Abstract

Previous studies have reported immunoreactive opioid nerve fibers in the detrusor and lower urinary tract sphincters. However, there is a paucity of in vivo studies demonstrating the direct effect of endogenous opioids in these structures. In the present study, we investigated the contractile actions of intra-arterially administered exogenous Dynorphin-A, Met-enkephalin, Leu-enkephalin, morphine, and the opioid antagonist naltrexone on the female rat intrinsic urethral sphincter in vivo. Intraurethral pressure was recorded by a catheter placed at the maximum pressure zone of the intrinsic urethral sphincter in anesthetized female Sprague-Dawley rats. The effects of different opioids were studied and expressed as means and as percentages of pressure change (cmH(2)O) of the baseline intraurethral pressure. Dynorphin-A, Met-enkephalin, and Leu-enkephalin evoked rapid, long-lasting contractile effects on the female rat urethra. The greatest intraurethral pressure increase was evoked by Dynorphin-A (89.2 +/- 15.3%). For Met-enkephalin, intraurethral pressure increased by 70.2 +/- 21.8% and for Leu-enkephalin, the pressure increase was 60.6 +/- 20%. Morphine, however, evoked inconsistent intraurethral pressure changes, increasing the urethral pressure in three subjects and lowering the pressure in the remaining six subjects. The opioid antagonist naltrexone reduced the intraurethral pressure by a mean of -19.0 +/- 5.8%. Results of the present study suggest that endogenous opioids by their contractile action on the intrinsic urethral sphincter may play a role in the control of continence in rats, additional to cholinergic and noradrenergic pathways.