Inherent tone of human bronchus: role of eicosanoids and the epithelium.

1. Airway preparations of different species possess varying degrees of inherent tone which is the result of different metabolites of arachidonic acid in different species. In human bronchial smooth muscle in vitro we have investigated the effects of 5-lipoxygenase inhibition (zileuton, 10 microM), cyclo-oxygenase inhibition (indomethacin, 1 microM) and mechanical epithelium removal on inherent tone. The shunting of arachidonic acid by inhibition of one or other of these enzymes, as a possible explanation for the effects observed, has also been investigated. 2. Zileuton caused a significant fall in tone either alone (-107 +/- 33 mg) or after cyclo-oxygenase inhibition (-203 +/- 48 mg) and this effect was not significantly altered by epithelial removal (-191 +/- 43 mg alone; -333 +/- 88 mg after indomethacin). Indomethacin increased tone when applied alone (160 +/- 94 mg), but this effect only reached statistical significance after 5-lipoxygenase inhibition, (210+/-81 mg; P<0.05). Epithelial removal did not alter the effect of indomethacin when applied alone (213+/-97 mg), but significantly reduced the effect of indomethacin after 5-lipoxygenase inhibition (34 +/- 23 mg; P<0.05). 3. These data suggest that inherent tone in human bronchus is largely the result of contractile 5-lipoxygenase products. However, the involvement of cyclo-oxygenase products cannot entirely be discounted, since in the presence of 5-lipoxygenase inhibition contractile and relaxant eicosanoids originating from the bronchial epithelium appear to influence significantly inherent tone.