The Role of Muscarinic Receptor Subtype on Detrusor Overactivity induced by Bladder Outlet Obstruction in Rats

Introduction and Objectives

We studied the role of muscarinic receptor subtype on urothelium and detrusor in rats with detrusor overactivity induced by bladder outlet obstruction (BOO).

Materials

Fourty Sprague-Dawley rats were used for this study and divided into 15 control and 25 experimental groups. Partial BOO was induced for 3 weeks and sham operation was done in control group. The cystometrogram (CMG) was done in 20 BOO and 10 control rats. During CMG, M2 selective muscarinic receptor antagonist (methoctramine) and nonselective muscarinic receptor antagonist (tolterodine) were administrated intravesically. Contraction interval and contraction pressure were checked. The bladder muscle strips were made in the 5 BOO and 5 control rats. Contractile responses were checked to 2-, 4-, 8-, 16-, and 32 Hz field stimulation in control, BOO groups and after administration of methoctramine and tolterodine.

Results

On CMG, BOO group showed decreased contraction interval and increased contraction pressure compared to control group (p<0.05). Contraction intervals increased after intravesical instillation of methoctramine and tolterodine as compared with BOO group (p<0.05). Moreover, contraction interval of tolterodine group increased much more than that of methoctramine group (p<0.05). Contraction pressures were similar among BOO, methoctramine, and tolterodine groups. On muscle strip study, BOO group showed increased contractile response compared to control group (p<0.05). After administration of methoctramine, the contractile responses decreased only in 32Hz field stimulation, but administration of tolterodine decreased contractile responses in all Hz field stimulation except 2 Hz. In addition, contractile responses of tolterodine group decreased much more than that of methoctramine group (Fig. 1) (p<0.05).

Conclusions

Detrusor overactivity induced by BOO in rat is mainly mediated by M3 muscarinic receptor in detrusor, and by M2 and M3 muscarinic receptors in urothelium. It seems to need to ascertain the existence of M2 and M3 muscarinic receptors in the detrusor overactivity induced by BOO in rat.

Key words

Muscarinic receptor, Overactive detrusor, Urothelium, Bladder outlet obstruction

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