Airway-hyperreactivity and arachidonic acid metabolism induced by various stimulations.

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In order to elucidate a mechanism of induction of airway hyperreactivity, it is important to clarify the relationship between arachidonic acid (AA) metabolites and airway hyperreactivity. Therefore we investigated on an effect of AA metabolites on reactivity of tracheal smooth muscle to chemical mediators, how to induce the airway hyperreactivity and analysis of a mechanism of airway hyperreactivity. Comparison of the reactivity and sensitivity of the tracheal smooth muscle to histamine in the presence and absence of endogenously released AA metabolites revealed that endogenous AA metabolites do not affect on the reactivity and sensitivity. Exogenously added leukotriene C_4, ananalogue of thromboxane A_2 or pros taglandin E2, did not affect on the reactivity and sensitivity of the tracheal smooth muscle.Exposure of O_3, NO_2 or H_2SO_4 aerosol induce airway hyperreactivity in guinea pigs. The NO_2 induced airway hyperreactivity was abolished by administration of OKY 046, an inhibitor of thromboxane synthetase. NO_2 and O_3 exposure inhibitprostacyclin synthetase markedly. At the time of induction of airway hyperreactivity, however, prostacyclin synthetase was notinhibited. Anaphylactic reaction also induces airway hyperreactivity. Comparison of the reactivity and sensitivity of the tracheal smooth muscle to histamine pre and post anaphylactic reaction revealed that anaphylactic reaction in vivo do not affect the reactivity and sensitivity to histamine, LTC_<C4> and isoproterenol in tracheal smooth muscle in vitro. On the contrary, reactivity to U46619 increased significantly. In conclusion, endogenously and exogenously added AA metabolites did not affect on the reactivity and sensitivity of the trachealsmooth muscle. Thromboxane A_2 could be one of an important factor of airway hyperreactivity induced by NO_2 exposure in vivo and hyperreactivity of tracheal smooth muscle induced by anaphylactic reaction in vivo.