GASTRIC MOTILITY IN NORMAL AND DYSTROPHIC MICE

Muscular dystrophies are a heterogeneous group of inherited diseases. Duchenne muscular dystrophy (DMD), the commonest form of dystrophy, other than skeletal and cardiac muscles, also affects gastrointestinal smooth muscle causing severe motor alterations. Experiments carried out on the mdx mouse, an animal model of DMD, indicate an impaired neural control of gastrointestinal smooth muscle even before functional alterations in the smooth muscle itself appear. A defective production/release of the inhibitory neurotransmitter nitric oxide (NO), from non-adrenergic, non-cholinergic nervous fibres supplying smooth muscle of the gut, might be involved in gastric dismotility observed in mdx mice. An impaired production/release of NO may be related to a reduced expression and/or activity of NO synthase, that synthesises NO from the aminoacid L-arginine. Recently, NO synthase deficiency has been also revealed in the gastrointestinal smooth muscle. Aim of the present study is to investigate the development of the dystrophic process and its related morpho-functional aspects in the stomach of ageing mdx mice. The role of NO and NO synthase in gastric motor dysfunctions will be examined at both nervous and muscular levels. Furthermore, NO production will be stimulated by means of hormonal substances to increase NO levels, thereby relieving or delaying the onset of gastrointestinal dismotility that occurs in Duchenne muscular dystrophy.