Concentration- and time-dependent increase in specific airway resistance after induction of airway hyperresponsiveness by subchronic exposure of guinea pigs to nitrogen dioxide.

In the present study utilizing male Hartley guinea pigs, we investigated (1) the concentration and time dependency of the effects of subchronic exposure to nitrogen dioxide (NO2) on airway responsiveness and (2) the concentration and time dependency of the effects on specific airway resistance under room air (SRaw0). Animals were exposed to filtered air, 0.06, 0.5, 1.0, 2.0, or 4.0 ppm NO2 for 6 and 12 weeks (24 hr/day). Airway responsiveness and SRaw0 were determined 1 week before the beginning of exposure at 10 weeks of age and on the day of termination of the exposure. Our results revealed that (1) subchronic exposure to NO2 induces airway hyperresponsiveness, both concentration and time dependently, (2) such exposure also induces an increase in SRaw0, both concentration and time dependently, and (3) subsequent to the airway hyperresponsiveness induced by NO2 is an increase in the SRaw0. Therefore, NO2 could be a potent risk factor for alteration of pulmonary function and airway responsiveness.