The protective role of epithelium-derived nitric oxide in isolated bovine trachea

Airway epithelial cells from bovine airways can release relaxant factors such as nitric oxide (NO) and prostaglandin E(2) and the removal of airway epithelium results in an increased responsiveness of smooth muscle to spasmogen stimuli. In this study, we assessed whether or not epithelial NO modulates the contractile response of bovine trachea in vitro.Cumulative concentration-response curves to acetylcholine (ACh), histamine (Hist) and 5-hydroxytryptamine (5-HT) were obtained in both intact and epithelium denuded tracheal strips in the presence of indomethacin (10 microM).In intact, but not in epithelium denuded strips, preincubation with the NO synthase inhibitor L-N((G))-Nitro-arginine methyl ester (L-NAME), but not with D-NAME, shifted to the left the concentration-response curve to ACh (pD(2) values in the absence and in the presence of L-NAME were 3.47+/-0.1 and 4.60+/-0.1, respectively; P<0.05) and to Hist (pD(2) in the absence and in the presence of L-NAME: 3.89+/-0.1 and 4.54+/-0.1, respectively; P<0.05). This effect was reversed by L-arginine (1mM), but not by D-arginine. The contractile response to 5-HT was not affected by L-NAME in either intact or epithelium denuded strips.These data suggest that NO is an epithelial relaxant factor modulating airway cholinergic and histaminergic contraction of bovine trachea and that the activation of the epithelial NO synthase is a mediator-specific process.