Effects of tolterodine on an overactive bladder depend on suppression of C-fiber bladder afferent activity in rats.
OBJECTIVE
We determined whether the effects of antimuscarinics depend on the suppression of C-fiber bladder afferent nerves. We administered tolterodine intravenously or intravesically.


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.
Yokoyama
Osamu
O
Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan. oyoko@fmsrsa.fukui-med.ac.jp
Yusup
Anwar
A
Miwa
Yoshiji
Y
Oyama
Nobuyuki
N
Aoki
Yoshitaka
Y
Akino
Hironobu
H
D000283:Administration, Intravesical; D000344:Afferent Pathways / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D003408:Cresols / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007262:Infusions, Intravenous; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000502:physiology; D010665:Phenylpropanolamine / Q000494:pharmacology*; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D018709:Statistics, Nonparametric; D000068737:Tolterodine Tartrate; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation*; D014549:Urinary Incontinence / Q000188:drug therapy* / Q000503:physiopathology
D001559:Benzhydryl Compounds; D003408:Cresols; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate