title: Effect of in vitro exposure to acrolein on carbachol responses in rat trachealis muscle.
abstract: 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.
authors.affiliation: Laboratoire de Physiologie, Faculté de Médecine Victor Pachon, Université de Bordeaux II, France.
authors.forename: A
authors.initials: A
authors.lastname: Ben-Jebria
authors.forename: R
authors.initials: R
authors.lastname: Marthan
authors.forename: M
authors.initials: M
authors.lastname: Rossetti
authors.forename: J P
authors.initials: JP
authors.lastname: Savineau
authors.forename: J S
authors.initials: JS
authors.lastname: Ultman
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012132:Respiratory Muscles / Q000187:drug effects* / Q000502:physiology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
chemical_list: D016718:Arachidonic Acid; D000171:Acrolein; D009637:Masoprocol; D002217:Carbachol; D007213:Indomethacin