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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 omega-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 alpha-chymotrypsin. In normals, alpha-chymotrypsin 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', 5'-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.

Aim: This study investigates whether a local renin-angiotensin system (RAS) exists in mouse colon and whether angiotensin II (Ang II) may play a role in the regulation of the contractile activity. Methods: Isometric recordings were performed in vitro on the longitudinal muscle of mouse proximal and distal colon. Transcripts encoding for RAS components were investigated by RT-PCR. Results: Ang II caused, in both preparations, a concentration-dependent contractile effect, antagonized by losartan, AT 1 receptor antagonist, but not by PD123319, AT 2 receptor antagonist. The combination of losartan plus PD123319 caused no change on the Ang II-induced contraction than losartan alone. Tetrodotoxin, neural blocker, reduced the contractile response to Ang II in the proximal colon, whilst the response was abolished in the distal colon. In both preparations, atropine, muscarinic receptor antagonist, or SR140333, NK 1 receptor antagonist, reduced the Ang II responses. Ondansetron, 5-HT 3 receptor antagonist, SR48968, NK 2 receptor antagonist, or hexamethonium, nicotinic receptor antagonist, were ineffective. The joint application of atropine and SR140333 produced no additive effect. Atropine reduced NK 1 -induced contraction. Transcripts encoding RAS components were detected in the colon samples. However, just AT 1A mRNA was expressed in both preparations, and AT 2 mRNA was expressed only in the distal colon. Conclusion: In the murine colon, local RAS may play a significant role in the control of contractile activity. Ang II positively modulates the spontaneous contractile activity via activation of post-junctional and pre-junctional AT 1A receptors, the latter located on the enteric neurones, modulating the release of tachykinins and acetylcholine.