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J Urol. 2005 Nov;174(5):2032-6.

Effects of tolterodine on an overactive bladder depend on suppression of C-fiber bladder afferent activity in rats.

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  • 1Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan. oyoko@fmsrsa.fukui-med.ac.jp

Abstract

PURPOSE:

We determined whether the effects of antimuscarinics depend on the suppression of C-fiber bladder afferent nerves. We administered tolterodine intravenously or intravesically.

MATERIALS AND METHODS:

To induce C-fiber bladder afferent nerve desensitization resiniferatoxin (RTX) (0.3 mg/kg) was injected subcutaneously in female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO). As controls, we used rats treated with ethanol and saline vehicle (VEH). Insertion of a polyethylene catheter through the bladder dome and MCAO were performed using halothane anesthesia. The effects of intravenous (0.2 to 2000 nM/kg) or intravesical (0.2 or 2 nM) tolterodine, an antimuscarinic agent, on cystometrography were investigated in conscious rats with a cerebral infarct (CI). Tolterodine was instilled intravesically for 30 minutes and cystometry was repeated.

RESULTS:

Bladder capacity (BC) was markedly decreased after MCAO in RTX treated (RTX-CI) and VEH treated (VEH-CI) rats. Low tolterodine doses (0.2 or 2 nM/kg) significantly increased BC in VEH-CI rats without increasing residual volume but it had no effects on BC in RTX-CI rats. At the highest dose (2,000 nM/kg) the drug significantly decreased bladder contraction pressure and increased residual volume in RTX-CI and VEH-CI rats. Intravesical administration of tolterodine (0.2 or 2 nM) significantly increased BC in VEH-CI rats. However, tolterodine had no effect on BC in RTX-CI rats.

CONCLUSIONS:

These results suggest that at low doses tolterodine exerts an inhibitory effect on C-fiber bladder afferent nerves, thereby, improving BC during the storage phase.

[PubMed - indexed for MEDLINE]
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