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Kim, Hwang, and Kim: The Effect of Muscarinic Receptor Subtype Antagonists on Detrusor Overactivity Induced by Bladder Outlet Obstruction in Rats
Original Article
Korean Journal of Urology

Korean Journal of Urology 2007; 48(10): 1044-1049.

Published online: 31 October 2007

DOI: https://doi.org/10.4111/kju.2007.48.10.1044

The Effect of Muscarinic Receptor Subtype Antagonists on Detrusor Overactivity Induced by Bladder Outlet Obstruction in Rats

Su Jin Kim, Tae-Kon Hwang, Joon Chul Kim

Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Corresponding author (kjc@catholic.ac.kr)

Received 15 June 2007       Accepted 30 August 2007

Copyright © 2007 The Korean Urological Association

Abstract

Purpose

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

Materials and Methods

Forty Sprague-Dawley rats were used for this study. They were divided into 15 controls and 25 experimental rats. Partial BOO was induced for 3 weeks and a sham operation was performed on the control group animals. A cystometrogram (CMG) was performed in 20 BOO and 10 control rats. During the CMG, M2 selective muscarinic receptor antagonist (methoctramine) and nonselective muscarinic receptor antagonist (tolterodine) drugs were administrated intravesically. The contraction intervals and pressure were evaluated. Bladder muscle strips were prepared from five BOO and five control rats. The contractile responses were evaluated at 2-, 4-, 8-, 16-, and 32Hz field stimulation in the control and BOO groups and after administration of the methoctramine and tolterodine.

Results

The results of the CMG showed that the rats in the BOO group had a decreased contraction interval and increased contraction pressure compared to the control group (p<0.05). The contraction intervals were increased after intravesical administration of methoctramine and tolterodine compared to the BOO group (p<0.05). However, the contraction pressures were similar among the methoctramine, tolterodine and BOO groups. For the muscle strip study, the BOO group demonstrated increased contractile responses compared to the control group (p<0.05). However, the contractile responses were decreased after administration of methoctramine (only in 32Hz) and tolterodine (p<0.05).

Conclusions

The results of this study showed that detrusor overactivity induced by BOO in rats is primarily mediated by M3 muscarinic receptors in the detrusor muscle, and by M2 and M3 muscarinic receptors in the urothelium.

Keywords: Muscarinic receptor, Overactive detrusor, Urothelium, Bladder outlet obstruction

Figures and Tables

Fig. 1
The changes of bladder weight in the controls and bladder outlet obstruction. The bladder weight of the BOO group was significantly higher than that of control group. The data were expressed as mean±SEM. *: p<0.05 as compared with control, BOO: bladder outlet obstruction.
kju-48-1044-g001
Fig. 2
The changes of the contraction interval in the control, BOO, methoctramine, and tolterodine group. The contraction interval in the BOO group decreased significantly compared with the control group. However, the contraction interval of methoctramine and tolterodine treated group increased compared with the BOO group. The data were expressed as mean±SEM. *: p<0.05 as compared with control group, †: p<0.05 as compared with BOO group, ‡: p<0.05 as compared with methoctramine group, BOO: bladder outlet obstruction.
kju-48-1044-g002
Fig. 3
The changes of contraction pressure in the control, BOO, methoctramine, and tolterodine group. The contraction pressure of the BOO group increased significantly compared with the control group. The contraction pressure of the methoctramine and tolterodine treated group was similar to the BOO group. The data were expressed as mean±SEM. *: p<0.05 as compared with control group, BOO: bladder outlet obstruction.
kju-48-1044-g003
Fig. 4
The contractile response of the bladder muscle strip to 2-, 4-, 8-, 16-, and 32Hz field stimulation in the control, obstruction, methoctramine, and tolterodine group. The data were expressed as mean±SEM. *: p<0.05 as compared with control group, †: p< 0.05 as compared with BOO group, ‡: p<0.05 as compared with methoctramine group, BOO: bladder outlet obstruction.
kju-48-1044-g004

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