The effects of ovariectomy and estrogen replacement on acetylcholine release from nerve fibres and passive stretch-induced acetylcholine release in female rat bladder.
OBJECTIVE
The present study investigated the effects of ovariectomy and estrogen replacement on the release of acetylcholine (Ach) from cholinergic neurons as well as on the tetrodotoxin (TTX)-insensitive stretch-induced Ach release in isolated rat detrusor. In addition, the above effects on rat micturition characteristics were also studied.


METHODS
Thirty female rats randomly received a sham operation, ovariectomy, or ovariectomy plus estrogen replacement. Using metabolic cages, micturition parameters were recorded. Then, in vitro functional experiments that included the measurements of nerve-mediated detrusor muscle contraction, Ach release from nerve fibres, and stretch-induced TTX-insensitive Ach release were performed. Ach release was measured using microdialysis and high-performance liquid chromatography.


RESULTS
Ovariectomized rats showed a significant decrease in voided volume and significant increase in 24-hr frequency of voiding. Ovariectomy caused the significant increase in both TTX-insensitive basal Ach release and TTX-insensitive stretch-induced Ach release. On the other hand, ovariectomy caused a significant decrease in Ach release from nerve fibres, resulting in the decrease in the contractile responses of detrusor muscle to electrical nerve stimulation. Estrogen replacement restored these alterations induced by ovariectomy.


CONCLUSIONS
Our findings showed that as a results of estrogen deficiency, Ach release from nerve fibres decreased, suggesting that this reduction of Ach released from cholinergic nerves may cause the decrease in detrusor contractility. Furthermore, this study also demonstrated that stretch-induced TTX-insensitive Ach release was increased by ovariectomy. This may be a contributing factor to the development of overactive bladder in elderly women.
Yoshida
Junya
J
Department of Urology, Fukushima Medical University, Fukushima, Japan. junyoshi@fmu.ac.jp
Aikawa
Ken
K
Yoshimura
Yasukuni
Y
Shishido
Keiichi
K
Yanagida
Tomohiko
T
Yamaguchi
Osamu
O
D000109:Acetylcholine / Q000378:metabolism*; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D017551:Microdialysis; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D014554:Urination / Q000187:drug effects
D000777:Anesthetics; D013779:Tetrodotoxin; D004958:Estradiol; D000109:Acetylcholine