ENDOGENOUS NITRIC-OXIDE MODULATION OF POTASSIUM-INDUCED CHANGES IN GUINEA-PIG AIRWAY TONE

1 An experimental set up is used whereby the serosal (out)side or muco sal (in)side of the guinea-pig isolated tracheal tube can be stimulate d 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, potassiu m induces a concentration-dependent relaxation at low concentrations ( 5-40 mM) which was reversed into a contraction up to approximately bas al tone at higher concentrations (50-70 mM). 3 Epithelium denudation r eversed the potassium-induced relaxation into a contraction. Interesti ngly, in the 'half' epithelium-denuded trachea the contractions were s ignificantly (P<0.01) reduced by 46% compared to complete epithelium-d enuded tissues. 4 Incubation with the nitric oxide (NO) synthase inhib itor N-omega-nitro-L-arginine methyl ester (L-NAME, 120 mu M) for 30 m in on the inside of the tracheal tube completely prevented the relaxat ion. However, L-NAME did not reverse the potassium-induced relaxation into a contraction. This indicates that potassium does not penetrate t hrough the epithelial layer. 5 It is concluded that depolarization of smooth muscle cells leads to a monophasic contraction and that depolar ization of the epithelium leads to a relaxation of tracheal smooth mus cle. The epithelial layer has an important barrier function and can re lease relaxing factors like NO.