Acrolein-induced smooth muscle hyperresponsiveness and eicosanoid release in excised ferret tracheae.
Acrolein is a ubiquitous toxic air pollutant that can have adverse lung effects. To understand the mechanism governing airway reactivity in relation to acrolein uptake, in vitro experiments were conducted in which excised tracheae from ferrets were exposed for 1 hr to a unidirectional constant flow (100 ml/min) of an acrolein-in-air mixture at several concentrations (0-12.5 ppm). During exposure, acrolein uptake into the trachea was determined by a chromatographic analysis of gas samples 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 eicosanoids released in the perfusate baths were assayed. The results indicate that the fractional uptake into an excised ferret trachea was strongly dependent on inlet concentration, implying that diffusion and reaction processes of acrolein in airway tissue are not linear. Only the low concentration of acrolein caused an increase of eicosanoid release from the exposed tracheae in the perfusate bath; it is possible that, at higher exposure concentration, the epithelium was sloughed off and most of the eicosanoids were lost. Although acrolein did not alter smooth muscle response to KCl, it did increase the contractile responses to CCh and ACh, suggesting an alteration in the pharmacomechanical but not the electromechanical coupling of ferret tracheal smooth muscle; therefore, it is more likely that this hyperresponsiveness occurs primarily by a mobilization of intracellular Ca2+ stores rather than by an increased influx of extracellular Ca2+ through voltage-dependent channels.
D000171:Acrolein / Q000493:pharmacokinetics / Q000633:toxicity*; D000393:Air Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D015777:Eicosanoids / Q000096:biosynthesis / Q000378:metabolism*; D005289:Ferrets; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism*; D014132:Trachea
D000393:Air Pollutants; D015777:Eicosanoids; D000171:Acrolein