title: Epithelium-linked smooth muscle hyperresponsiveness in ferret tracheae exposed to acrolein.
abstract: The effects of acrolein exposure on tissue uptake and airway responses to substance P (SP) and nitroprusside (NIP) were determined in excised ferret tracheae exposed for 60 min to a constant flow of air or 0.3 and 3.5 ppm acrolein-air mixtures. Histological examination indicated that whereas the epithelium of an air-exposed trachea was intact with no apparent injury, acrolein-induced epithelium damage was more pronounced at 3.5 than at 0.3 ppm vapor concentration. The fractional uptake of acrolein into the tracheal tissue continually decreased during the 1 h of exposure and was found to be significantly concentration dependent at the 60 min measurement point. This suggests that the uptake process of acrolein in the mucosal layer is not linear and is dominated by irreversible reaction. In the absence of the neutral endopeptidase inhibitor, phosphoramidon, acrolein significantly increased the maximal response to SP. Pretreatment with phosphoramidon abolished the differential effect of acrolein on airway smooth muscle response to SP. Nitroprusside relaxed acrolein-exposed tracheal rings precontracted with carbachol to their baseline tone, but it induced relaxation of air-exposed tracheal rings below their initial resting tension, indicating the presence of endogenous as well as induced tone. Pretreatment with NIP also abolished the differential effect of acrolein on airway response to carbachol and modified the potency of this agonist. We conclude that acrolein-induced hyperresponsiveness of the underlying airway smooth muscle is linked to inactivation of neutral endopeptidase synthesis as well as to loss of epithelium-derived relaxation factor.
authors.affiliation: Department of Chemical Engineering and Environmental Resources Research Institute, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ben-Jebria
authors.forename: Y
authors.initials: Y
authors.lastname: Crozet
authors.forename: M L
authors.initials: ML
authors.lastname: Eskew
authors.forename: J S
authors.initials: JS
authors.lastname: Ultman