HUMAN BRONCHIAL SMOOTH-MUSCLE RESPONSIVENESS AFTER IN-VITRO EXPOSURE TO OXIDIZING POLLUTANTS

The aims of this work were (1) to determine the dose-response relation ship between ex vivo exposure to oxidizing pollutants such as nitrogen dioxide (NO2), the aldehyde acrolein, and ozone (O-3), and the reacti vity to agonists in isolated human bronchial smooth muscle; and (2) to investigate the alterations in the cellular mechanisms of human airwa y smooth muscle contraction induced by such exposures. Experiments wer e performed in isolated human bronchi obtained at thoracotomy. Isometr ic contraction in response to a variety of agonists was compared betwe en pollutant-exposed preparations and paired controls. Short exposures to NO2, acrolein, or O-3 altered the subsequent airway smooth muscle responsiveness in a dose-dependent manner. The cellular mechanisms pro ducing the airway hyperresponsiveness observed in vitro are shared by the three pollutants and include alterations in airway smooth muscle e xcitation-contraction coupling as well as indirect effects on neutral endopeptidase activity.