Effect of arachidonic acid metabolites on intact and epithelium-denuded tracheal spirals of endotoxin-treated guinea pigs

Recently, we showed that in control preparations arachidonic acid (AA) induces relaxation in intact and contraction in epithelium denuded tracheal spirals. In the present study the role of the tracheal epithelium in the endotoxin-induced hyperreactivity was investigated in relation to a possible disturbed (AA) metabolism. Tracheas from endotoxin pretreated guinea pigs with or without epithelium and control trecheal spirals without epithelium all show a similarly increased contraction to histamine and arecoline which points to a possible disturbed function of the airway epithelial layer in the endotoxin treated animals. Since agonists which contract guinea pig tracheas (e.g. histamine), simultaneously cause a release of PGE2-like substances which probably inhibits this contractile response, it may well be that loss or damage to the epithelium disturbs the formation of these latter products. After indomethacin all groups show a contraction to arachidonic acid and no differences in the maximal contraction induced by histamine could be observed. These results also suggest that endotoxin pretreatment induces a dysfunction of the cyclooxygenase enzymes and as a consequence may mediate bronchial hyperreactivity. However, intact endotoxin tracheal spirals responded with a similar relaxation and denuded endotoxin preparations responded with a similar contraction to arachidonic acid as compared with their respective control group.