Improvement in bladder storage function by tamsulosin depends on suppression of C-fiber urethral afferent activity in rats.
OBJECTIVE
Alpha(1)-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 E(2) to the rat lower urinary tract stimulates the micturition reflex. Using an animal model we investigated whether the alpha(1)-blocker tamsulosin (Astellas Pharma, Tokyo, Japan) acts on C-fiber afferent activity and, if so, the location of this effect.


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 E(2) (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 x 10(-1) to 2.2 x 10(3) 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 E(2) 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 E(2) but it had no effect on nonresiniferatoxin rats receiving intravesical prostaglandin E(2). Intrathecal administration of tamsulosin produced a slight and insignificant increase in the bladder contraction interval in nonresiniferatoxin rats receiving intraurethral prostaglandin E(2).


CONCLUSIONS
These results suggest that prostaglandin E(2) 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.
Yokoyama
Osamu
O
Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan. oyoko@fmsrsa.fukumi-med.ac.jp
Yusup
Anwar
A
Oyama
Nobuyuki
N
Aoki
Yoshitaka
Y
Miwa
Yoshiji
Y
Akino
Hironobu
H
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D005260:Female; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*; D000077409:Tamsulosin; D014521:Urethra / Q000187:drug effects* / Q000294:innervation*; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D013449:Sulfonamides; D000077409:Tamsulosin