The role of nitric oxide in the micturation reflex and modulation of smooth muscle tone of the lower urinary tract

We have tested the hypothesis that a local release of NO, possibly through an axon reflex mechanism is involved in detrusor relaxation. The effects of NO donors on isolated rat detrusor and the effects of NOS inhibition on the response to increases in passive tension have been investigated. SNP and SIN-1 (10-3M) were found to cause 29.9% and 26.4% relaxation respectively in isolated rat detrusor. When the tissue was precontracted with 10-6M carbachol, the inhibitory effects of 10-3M SNP and SIN-1 were increased to 39.3% and 63.5% respectively. Although rat detrusor responds to exogenous NO with relaxation, L-NAME was found to have no effect on the length tension relationship in vitro in both non-precontracted tissue and that which had been precontracted with carbachol. The tissue that had not been pre-treated with carbachol was examined for NADPH-diaphorase activity and positive fibres were found to be present. L-NAME also had no effect on the pressure volume relationship recorded during a continuous infusion of saline into the bladder in vivo.Chemical irritation of the bladder mucosa leads to the development of a bladder hyperactivity and induces the expression of c-Fos in the L6 and S1 segments of the spinal cord. A continuous infusion of 2% acetic acid led to a marked bladder hyperactivity followed by a desensitisation. Significant increases (p<0.05) in c-Fos expression were observed in L6, S1 and S2 following bladder irritation with a clear peak occurring in S1.Although we have demonstrated that rat detrusor responds to exogenous NO donors with relaxation and that NADPH-diaphorase positive fibres are present in this tissue, we have been unable to find any evidence of a role for peripheral NO in bladder compliance. However, these studies do suggest that NO may play a pro-nociceptive role in conditions of bladder inflammation at both peripheral and central levels.