Effects of anaesthesia on the nitrergic pathway during the micturition reflex in rats

OBJECTIVE: To investigate the effects of anaesthesia on the nitrergic pathway during the micturition reflex in rats. MATERIALS AND METHODS: The effects of N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, on bladder and urethral activities were evaluated by infusion cystometrography (CMG) and urethral perfusion pressure under isovolumetric conditions in awake or urethane-anaesthetized rats. L-NAME was administered intravenously (i.v.), intrathecally (i.t.), intracerebroventriculary (i.c.v.) or intravesically in normal rats or rats pre-treated with resiniferatoxin, a potent C-fibre afferent neurotoxin. RESULTS: L-NAME injected i.v. decreased the intercontraction interval (ICI) in the awake but increased it in the anaesthetized rats. L-NAME injected i.t. increased the ICI in both states and these effects were not apparent after pre-treatment with resiniferatoxin. L-NAME injected i.c.v. decreased the ICI in the awake but increased i.t. in the anaesthetized rats. Intravesical L-NAME decreased the ICI in the awake but not in the anaesthetized rats. L-NAME administered i.v., but not i.t. or i.c.v., increased bladder contraction during CMG. Under isovolumetric conditions, L-NAME administered i.v., but not i.t. or i.c.v., reduced the urethral relaxation without changing bladder contraction. CONCLUSIONS: These results indicate that spinal NO release facilitates the mechanoceptive C-fibres, and this facilitatory effect is masked by supraspinal (possibly forebrain) and local inhibitory effects of NO during the micturition reflex in awake rats. Urethane seems to inhibit the supraspinal and local inhibitory effects of NO, resulting in unmasking the facilitatory effect of NO in the spinal cord and brain stem. During the voiding phase, urethral relaxation depends on the peripheral but not the central NO system.