ACROLEIN-INDUCED SMOOTH-MUSCLE HYPERRESPONSIVENESS AND EICOSANOID RELEASE IN EXCISED FERRET TRACHEAS

Acrolein is a ubiquitous toxic air pollutant that can have adverse lun g effects. To understand the mechanism governing airway reactivity in relation to acrolein uptake, in vitro experiments were conducted in wh ich excised tracheae from ferrets were exposed for 1 hr to a unidirect ional constant how (100 ml/min) of an acrolein-in-air mixture at sever al concentrations (0-12.5 ppm). During exposure, acrolein uptake into the trachea was determined by a chromatographic analysis of gas sample s taken at the entrance and at the exit of the trachea, Smooth muscle contractility in response to carbachol (CCh), acetylcholine (ACh), and potassium chloride (KCl) was measured following exposure, and eicosan oids released in the perfusate baths were assayed. The results indicat e that the fractional uptake into an excised ferret trachea was strong ly dependent on inlet concentration, implying that diffusion and react ion processes of acrolein in airway tissue are not linear. Only the lo w concentration of acrolein caused an increase of eicosanoid release f rom the exposed tracheae in the perfusate bath; it is possible that, a t higher exposure concentration, the epithelium was sloughed off and m ost of the eicosanoids were lost. Although acrolein did not alter smoo th muscle response to KCl, it did increase the contractile responses t o CCh and ACh, suggesting an alteration in the pharmacomechanical but not the electromechanical coupling of ferret tracheal smooth muscle; t herefore, it is more likely that this hyperresponsiveness occurs prima rily by a mobilization of intracellular Ca2+ stores rather than by an increased influx of extracellular Ca2+ through voltage-dependent chann els. (C) 1995 Academic Press, Inc.