HUMAN BRONCHIAL SMOOTH-MUSCLE RESPONSIVENESS AFTER IN-VITRO EXPOSURE TO ACROLEIN

Human isolated bronchi obtained at thoracotomy from 42 patients were e xposed to aqueous solutions of acrolein, and the resulting change in c ontractile responses was evaluated by measuring agonist cumulative con centration-response curves (CCRC). Contractile responses to carbachol were measured after a variety of exposure concentrations, from 0.01 to 3.0 mu M, and at times from 5 to 60 min. The optimal condition to ind uce airway smooth muscle hyperresponsiveness was an exposure duration of 20 min at a concentration of 0.3 mu M. The effect of acrolein expos ure on human bronchial smooth muscle was also assessed by examining th e contractile responses to potassium chloride (KCl), histamine, and ne urokinin A (NKA) in both the absence and the presence of phosphoramido n. Although in vitro exposure of the human bronchus to 0.3 mu M acrole in did not alter responses to KCl, it did increase the efficacy of car bachol and NKA without altering their potency. This concentration of a crolein also increased the contractile response to low concentrations of histamine and shifted the CCRC to the left. Pretreatment with phosp horamidon abolished the differential effect of acrolein on airway resp onse to NKA. These results suggest that the mechanism of action of acr olein includes inactivation of airway neutral endopeptidase as well as alterations in the pharmacomechanical, but not the electromechanical, coupling of human bronchial smooth muscle.