An experimental set up is used whereby the serosal (out)side or mucosal (in)side of the guinea-pig isolated tracheal tube can be stimulated selectively with drugs and reactivity measured. 2. Potassium induces a concentration-dependent (5-70 mM) monophasic contraction of tracheal tubes when added on the outside. In contrast, on the inside, potassium induces a concentration-dependent relaxation at low concentrations (5-40 mM) which was reversed into a contraction up to approximately basal tone at higher concentrations (50-70 mM). 3. Epithelium denudation reversed the potassium-induced relaxation into a contraction. Interestingly, in the 'half' epithelium-denuded trachea the contractions were significantly (P < 0.01) reduced by 46% compared to complete epithelium-denuded tissues. 4. Incubation with the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 120 microM) for 30 min on the inside of the tracheal tube completely prevented the relaxation. However, L-NAME did not reverse the potassium-induced relaxation into a contraction. This indicates that potassium does not penetrate through the epithelial layer. 5. It is concluded that depolarization of smooth muscle cells leads to a monophasic contraction and that depolarization of the epithelium leads to a relaxation of tracheal smooth muscle. The epithelial layer has an important barrier function and can release relaxing factors like NO.
