Inhibitory roles of peripheral nitrergic mechanisms in capsaicin-induced detrusor overactivity in the rat.
OBJECTIVE
To investigate the peripheral role of nitric oxide (NO) in capsaicin-induced detrusor overactivity (DO), as exogenously applied vanilloids can evoke NO release in urothelial cells but its functional role has not yet been reported.


METHODS
The effects of N(G)-nitro-l-arginine methyl ester (L-NAME), an inhibitor of NO synthase (NOS), on bladder activity during intravesical capsaicin (30 microm) instillation were examined by using continuous infusion cystometry in urethane-anaesthetized rats. L-NAME was administered intravenously (i.v., 20 mg/kg), intrathecally (i.t., 270 microg/rat), intracerebroventricularly (i.c.v., 270 microg/rat) or intravesically (10 mg/mL) before or during capsaicin instillation.


RESULTS
During cystometry with intravesical saline infusion, L-NAME injected i.v., i.t. and i.c.v., but not intravesically, significantly increased the intercontraction intervals (ICI) and L-NAME injected i.v., but not i.t., i.c.v. or intravesically, increased the maximum voiding pressure (MVP) without affecting the baseline pressure. Capsaicin instillation induced DO evidenced by a significant reduction in the ICI. L-NAME administered i.v. further decreased the ICI and increased the MVP and the baseline pressure during capsaicin instillation. Co-intravesical application of capsaicin and L-NAME also similarly enhanced capsaicin-induced DO. However, L-NAME injected i.t. or i.c.v. had no effect on capsaicin-induced DO. The excitatory effects of i.v and intravesical L-NAME on the ICI, MVP and baseline pressure during capsaicin infusion were significantly suppressed by desensitization of C-fibre afferent pathways by capsaicin pretreatment (125 mg/kg s.c., 4 days before cystometry).


CONCLUSIONS
These results indicate that locally released NO can suppress DO induced by capsaicin-mediated C-fibre activation and that central NO pathways are not involved in capsaicin-induced DO.
Masuda
Hitoshi
H
Department of Urology and Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. hi-masu.uro@tmd.ac.jp
Kim
Jang H
JH
Kihara
Kazunori
K
Chancellor
Michael B
MB
de Groat
William C
WC
Yoshimura
Naoki
N
D000283:Administration, Intravesical; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage; D005260:Female; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053201:Urinary Bladder, Overactive / Q000503:physiopathology*; D014563:Urodynamics / Q000502:physiology*; D019459:Urothelium / Q000503:physiopathology