Effects of Local Anesthetics on the Intrinsic Nerve and Smooth Muscle in Rat Bladder

Lim, Daejung; Oh, Seung June; Choi, Hwang

Abstract

PURPOSE: Local anesthetic effect is thought to be a part of mechanisms of musculotropic agents, and the clinical trials of local anesthetics in the treatment of hyperreflexic neurogenic bladder or in the cystoscopic biopsies have been made, but not much has been uncovered about their exact mechanism of the action on bladder. We attempted to uncover the effects of several local anesthetics on the intrinsic nerve and the smooth muscle of the bladder, and compare the potencies of them.
MATERIALS AND METHODS
Male 12 week-old Sprague-Dawley rats(384+/-31gm, n=36) were killed by cervical dislocation and the urinary bladder was immediately obtained. The urinary bladder was dissected free from surrounding tissues and the bladder muscle strips(0.7x1.1x5.6mm) were prepared. The contractile responses were monitored via an FT03 force transducer(Grass) and recorded on a Grass Polyview in 95%O2/5%CO2-bicarbonate solutions. Utilizing electrical field stimulation and carbachol(5.0microM), the inhibitory effect of local anesthetics(lidocaine, bupivacaine, tetracaine) in intrinsic nerves and smooth muscle of the bladder were studied.
RESULTS
The contractile response elicited by electrical field stimulation(70V/cm2, 0.8msec duration, 50Hz, trains of 2.5sec every 3 min) in local anesthetics treated Tyrode`s solution were diminished in a dose dependent manner. And their potency was in following order(bupivacaine, tetracaine, lidocaine, IC50=1-10microM) In order to study the effects on the smooth muscle itself, tetrodotoxin(0.3microM) were given to block the intrinsic nerve. After doing this, the contractile response elicited by electrical field stimulation(800msec duration pulse) in local anesthetics treated Tyrode`s solution were diminished in a dose dependent manner. And local anesthetics reduced the maximum contractile response of isolated rat detrusor muscle to carbachol(5microM) in a dose dependent, noncompetitive manner with potency in following order(tetracaine, bupivacaine, lidocaine, IC50=50-500microM).
CONCLUSIONS
From these studies, local anesthetics is shown to exert direct inhibitory effect on bladder muscle as well as the intrinsic nerve, and further studies on the exact mechanism of the action on bladder smooth muscle will be needed.