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

The airway epithelium is responsible for the production of a number of arachidonic acid and non-prostanoid inhibitory factors. Epithelium synthesizes nitric oxide (NO) which may be important in regulating the function of airways smooth muscles. We studied in vitro the effect of histamine (100 nM-100 μM) which increases the NO release on rabbit airway smooth muscles induced by 80 mM KCl in the presence or not of 10-5 Methylene blue (MB) (inactivator of guanylate cyclase) or N(G)-monomethyl L- arginine (L-NMMA), a NOS inhibitor. All experiments were done in tracheal muscle strips from 28 rabbits with epithelium and after epithelium removal. The additional use of histamine (1 μM) on KCl contraction induced a relaxation of 10% of the initial contraction. The additional use of L-NMMA decreased 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 histamine (1 μM) 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