Induction of transient airway hyperresponsiveness by exposure to 4 ppm nitrogen dioxide in guinea pigs

Abstract

In the present study, we investigated (1) whether airway responsiveness to inhaled histamine‐aerosol could be induced during 7‐d exposure of guinea pigs to 4 ppm NO₂ and, if so, (2) whether thromboxane A₂ may be involved in such increase. Female Hartley guinea pigs were divided into 6 groups (n ‐ 15/group). Three groups were exposed to filtered air and the other 3 groups were exposed to NO₂ for 1, 3, or 7 d (24 h/d). Baseline specific airway resistance (SRaw₀) did not change significantly after exposure to 4 ppm NO₂ or air. Airway responsiveness was determined 1 wk before the beginning of exposure and on the day of termination of the exposure. Prior to exposure to NO₂ the EC₂₀₀His, the concentrations of inhaled histamine necessary to double SRaw_NaCl (SRaw after inhalation of 0.9% NaCI), were 1.07 ± 0.20, 1.30 ± 0.20, and 1.01 ± 0.18 mM for the 3 groups later given NO₂ for 1, 3, and 7 d, respectively. Following exposure to NO₂ for 1, 3, or 7 d, EC₂₀₀His values were 1.42 ± 0.25, 0.66 ± 0.10 (p < .05), and 1.05 ± 0.22 mM, respectively. These results show that 7‐d exposure to 4 ppm NO₂ induced a significant increase in airway responsiveness on d 3. Exposure to air had no significant effect on the airway responsiveness. This transient hyperresponsiveness was inhibited by a specific inhibitor of thromboxane synthetase, OKY 046. These results indicated that (1) a lower concentration (4 ppm) of NO₂ than that previously reported can induce transient hyperresponsiveness in guinea pigs during appropriate long‐term exposure, and (2) thromboxane A₂ may play an important role in this transient airway hyperresponsiveness.