Human bronchial smooth muscle responsiveness after in vitro exposure to acrolein.
Human isolated bronchi obtained at thoracotomy from 42 patients were exposed to aqueous solutions of acrolein, and the resulting change in contractile responses was evaluated by measuring agonist cumulative concentration-response curves (CCRC). Contractile responses to carbachol were measured after a variety of exposure concentrations, from 0.01 to 3.0 microM, and at times from 5 to 60 min. The optimal condition to induce airway smooth muscle hyperresponsiveness was an exposure duration of 20 min at a concentration of 0.3 microM. The effect of acrolein exposure on human bronchial smooth muscle was also assessed by examining the contractile responses to potassium chloride (KCl), histamine, and neurokinin A (NKA) in both the absence and the presence of phosphoramidon. Although in vitro exposure of the human bronchus to 0.3 microM acrolein did not alter responses to KCl, it did increase the efficacy of carbachol and NKA without altering their potency. This concentration of acrolein also increased the contractile response to low concentrations of histamine and shifted the CCRC to the left. Pretreatment with phosphoramidon abolished the differential effect of acrolein on airway response to NKA. These results suggest that the mechanism of action of acrolein includes inactivation of airway neutral endopeptidase as well as alterations in the pharmacomechanical, but not the electromechanical, coupling of human bronchial smooth muscle.
Ben-Jebria
A
A
Laboratoire de Physiologie, Faculté de Médecine Victor Pachon, Université de Bordeaux II, France.
Marthan
R
R
Rossetti
M
M
Savineau
J P
JP
Ultman
J S
JS
D000171:Acrolein / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D016084:Bronchoconstriction / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology; D015260:Neprilysin / Q000378:metabolism; D015288:Neurokinin A / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology
D011189:Potassium Chloride; D000171:Acrolein; D006632:Histamine; D015288:Neurokinin A; D002217:Carbachol; D015260:Neprilysin