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Epithelium-dependent regulation of airways smooth muscle function. A histamine-nitric oxide pathway

摘要


THE airway epithelium is responsible for the production of a number of arachidonic acid and non-prostanoid inhibitory factors . Epithelium synthesises nitric oxide (NO) which may be important in regulating the function of airways smooth muscles . We studied in vitro the effect of his tamine (100 nM- 100μM) which increases the NO release on rabbit airway smooth muscles induced by 80 mM KCl in the pr esence or not of 10^(-5) Methylene blue (MB) (inactivato r of guanylate cyclase ) or N(G)-monomethyl L-arginine (L-NMMA), a NOS inhibitor. All experiments we redone in tracheal muscle s trips from 28 rabbits with epithelium and after epithelium removal. The additional use of his tamine (1μM) on KCl contraction induced a relaxation of 10% of the initial contraction. The additional us e of L-NMMA de creased the relaxation to 5% of initial contraction. MB rather than L-NMMA increased the contraction significantly (p <0.01). Epithelium removal increased the contraction induced by KCl (80 mM) and his tamine (1 μ M) by about 30% (p <0.001). NO release especially from epithelium regulates the airways smooth muscle functions. Damage to the epithelium may contribute to an increase in airways sensitivity, observed in asthma.

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