EFFECT OF IN-VITRO EXPOSURE TO ACROLEIN ON CARBACHOL RESPONSES IN RATTRACHEALIS MUSCLE

Isolated tracheal rings obtained from male Wistar rats 10 to 15 weeks old and weighing 300 to 400 g were exposed to aqueous solutions of acr olein, and the resulting change of smooth muscle contractility was eva luated by measuring the cumulative carbachol concentration-response cu rve. Using the product of acrolein concentration and time as a surroga te for the acrolein dose delivered to the smooth muscle cells, contrac tility measured after a variety of exposure concentrations from 0.01 t o 3.0 muM and times from 5 to 60 min could be correlated in a dose-dep endent manner. In the range of doses from 0.1 to 6 muM-min, relative c ontractility continuously increased from 0 to 50%. above unexposed con trol values. At doses greater than 6 muM-min, the enhancement in contr actility declined. This decline may have been due to cell damage or ce ll death which was so severe at a dose of 60 muM-min that contractilit y fell below control values. Below a threshold dose of 0.1 muM-min, ac rolein had no effect on contractility. The role arachidonic acid metab olism in the enhancement of smooth muscle reactivity to carbachol was studied using indometacin to block the cyclo-oxygenase pathway and NDG A to block the lipoxygenase pathway. At a concentration of 10 muM of e ither indometacin or NDGA, the acrolein-induced enhancement in airway reactivity was completely inhibited. At lower concentrations, inhibiti on by these two chemicals was partially additive, suggesting that both the lipoxygenase and cyclo-oxygenase pathways play a role in the hype rreactive response.