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Ben-Jebria A, Marthan R, Rossetti M, Savineau JP, Ultman JS: Effect of in vitro exposure to acrolein on carbachol responses in rat trachealis muscle. Respir Physiol. 1993 Jul;93(1):111-23.
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 acrolein, and the resulting change of smooth muscle contractility was evaluated by measuring the cumulative carbachol concentration-response curve. Using the product of acrolein concentration and time as a surrogate for the acrolein dose delivered to the smooth muscle cells, contractility measured after a variety of exposure concentrations from 0.01 to 3.0 microM and times from 5 to 60 min could be correlated in a dose-dependent manner. In the range of doses from 0.1 to 6 microM-min, relative contractility continuously increased from 0 to 50% above unexposed control values. At doses greater than 6 microM-min, the enhancement in contractility declined. This decline may have been due to cell damage or cell death which was so severe at a dose of 60 microM-min that contractility fell below control values. Below a threshold dose of 0.1 microM-min, acrolein had no effect on contractility. The role arachidonic acid metabolism in the enhancement of smooth muscle reactivity to carbachol was studied using indometacin to block the cyclo-oxygenase pathway and NDGA to block the lipoxygenase pathway. At a concentration of 10 microM of either indometacin or NDGA, the acrolein-induced enhancement in airway reactivity was completely inhibited. At lower concentrations, inhibition by these two chemicals was partially additive, suggesting that both the lipoxygenase and cyclo-oxygenase pathways play a role in the hyperreactive response. |
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