Inhibitory roles of peripheral nitrergic mechanisms in capsaicin-induced detrusor overactivity in the rat.

OBJECTIVES

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.

MATERIALS AND

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).

CONCLUSION

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.