Hydroperoxide and cigarette smoke induced effects on lung mechanics and glutathione status in rat isolated perfused and ventilated lungs.

The effects of t-butylhydroperoxide (TBH) and cigarette smoke on lung mechanics (CDYN and RL) and glutathione status (GSH) were studied using an isolated perfused and ventilated rat lung preparation. TBH (200, 400, 1000 microM) infused via the pulmonary circulation caused a dose-related bronchoconstriction. The lung GSH-levels were also significantly reduced. Pretreatment of rats with diethylmaleate (DEM) potentiated the TBH elicited bronchoconstriction. DEM (1 mM) infused into the pulmonary circulation caused an almost complete depletion of GSH-content but no effects on lung mechanics were seen. Indomethacin (2.8 and 28 microM) infusion attenuated TBH (400 microM) induced bronchoconstriction. These findings suggest that the TBH induced bronchoconstriction is at least partly mediated via arachidonic acid metabolites. When TBH was administered intratracheally, weak and not dose-related bronchoconstriction was observed even though doses higher than those given intravascularly were used. However, the GSH-content of the lungs was markedly decreased. Cigarette smoke caused weak if any effects on lung mechanics but significantly decreased lung GSH-content.