Improvement in Bladder Storage Function by Tamsulosin Depends on Suppression of C-Fiber Urethral Afferent Activity in Rats

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Abstract

Purpose

α1-Blockers improve voiding symptoms by decreasing prostatic and urethral smooth muscle tone. However, to our knowledge the mechanism underlying improvements in storage symptoms is not known. Topical application of prostaglandin E2 to the rat lower urinary tract stimulates the micturition reflex. Using an animal model we investigated whether the α1-blocker tamsulosin (Astellas Pharma, Tokyo, Japan) acts on C-fiber afferent activity and, if so, the location of this effect.

Materials and Methods

To induce desensitization of C-fiber afferent activity resiniferatoxin (0.3 mg/kg) was subcutaneously injected in female Sprague-Dawley rats 2 days before experiments. Simultaneous recordings of urethral pressure and rhythmic bladder pressure were made with the rats under urethane anesthesia. Prostaglandin E2 (0.4 mg/ml) was continuously administered intravesically or intraurethrally to rats pretreated with resiniferatoxin (resiniferatoxin rats) or rats without pretreatment (nonresiniferatoxin rats). We investigated the effects on the micturition reflex of intravenous (2.2 × 10−1 to 2.2 × 103 nM/kg) or intrathecal (0.001 to 0.1 nmol) administration of tamsulosin.

Results

The bladder contraction interval was markedly decreased after intravesical or intraurethral administration of prostaglandin E2 in nonresiniferatoxin rats but it was unchanged in resiniferatoxin rats. This effect was antagonized by the EP1 receptor antagonist ONO-8711 (6-[(2S,3S)-3-(4-chloro-2-methylphenylsulfonylaminomethyl)-bicyclo[2.2.2]octan-2-yl]-5Z-hexenoic acid). Intravenous administration of tamsulosin significantly increased the bladder contraction interval in nonresiniferatoxin rats receiving intraurethral prostaglandin E2 but it had no effect on nonresiniferatoxin rats receiving intravesical prostaglandin E2. Intrathecal administration of tamsulosin produced a slight and insignificant increase in the bladder contraction interval in nonresiniferatoxin rats receiving intraurethral prostaglandin E2.

Conclusions

These results suggest that prostaglandin E2 enhances the micturition reflex through C-fiber afferents and tamsulosin had an inhibitory effect on the C-fiber urethral afferent nerves, thereby improving bladder storage function.

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