Duodenal contractile activity in dystrophic (mdx) mice: Reduction of nitric oxide influence

The present study was undertaken to analyse duodenal contractility in adult dystrophic (mdx) mice. The spontaneous changes of the isometric tension and the responses of longitudinal duodenal muscle to nonadrenergic, noncholinergic (NANC) nerve stimulation and to exogenous drugs were compared between normal and mdx mice. Duodenal segments from mdx mice displayed spontaneous contractions with higher frequency than normals. N\u3c9-nitro-L-arginine methyl ester (L-NAME) increased the frequency of contractions in normals without affecting that in mdx mice. In normals, NANC nerve stimulation elicited a transient relaxation abolished by L-NAME. In mdx mice a frank relaxation was not observed, the inhibitory response consisted just in the suppression of the phasic activity. This response was reduced by L-NAME and abolished by the subsequent addition of \u3b1-chymotrypsin. In normals, \u3b1-chymo-trypsin hardly affected NANC relaxation, whilst it significantly antagonised that in mdx mice. Mdx duodenal muscle also showed a reduced responsiveness to sodium nitroprusside, and to 8-bromoguanosine 3\u2032, 5\u2032-cyclic monophosphate in comparison with normal preparations. The results indicate that mdx mice experience duodenal contractile disturbances due to an impairment of NO function with defective responsiveness of the muscle to NO. The reduction in NO influence is functionally compensated by the peptidergic system