title: 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 SRawNaCl (SRaw after inhalation of 0.9% NaCl), 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.
authors.affiliation: Department of Basic Medical Sciences, National Institute for Environmental Studies, Ibaraki, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Shinozaki
mesh_terms: D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001249:Asthma / Q000139:chemically induced; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D004342:Drug Hypersensitivity / Q000209:etiology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects; D008689:Methacrylates / Q000494:pharmacology; D009585:Nitrogen Dioxide / Q000633:toxicity*; D013928:Thromboxane A2 / Q000502:physiology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013997:Time Factors
chemical_list: D000393:Air Pollutants; D008689:Methacrylates; D013928:Thromboxane A2; D006632:Histamine; D013930:Thromboxane-A Synthase; C034364:ozagrel; D009585:Nitrogen Dioxide