Effects of Long-Term Exposure to Low Levels of Ozone in Guinea Pigs

Airway hyperresponsiveness to infused methacholine and hyporesponsiveness to inhaled methacholine

Abstract

This study was performed to determine the effects of long-term exposure to low levels of ozone (O₃) on airway responsiveness in guinea pigs. The animals were exposed either to filtered air or 0.2ppm O₃ for 9-10 weeks. Airway responsiveness to intravenously indused (iv) or inhaled aerosolized methacholine (Mch) was then determined. When Mch was administered iv, the O₃-exposed guinea pigs showed airway hyperresponsivcness. Infusion of 1 and 2μg/kg Mch for 5minutes resulted in a decrease of Grs (resp; ratory conductance) to 82 and 62% of that seen after the infusion of saline, respectively. In contrast, in the air-exposed animals, these doses of Mch reduced Grs only to 94 and 84% of that seen after saline infusion. The opposite was seen when Mch was administered by aerosol: the O₃-exposed guinea pigs were hyporesponsive. Specifically, the aerosol administration of 100, 200 and 400mg/ml of Mch to O₃-exposed guinea pigs resulted in a decrease of Grs to 96, 85, and 71% of that seen after saline administration, whereas these doses of Mch reduced the Grs of air-exposed animals to 75, 53, and 42% of that seen after saline. These results suggest that long-term exposure to low levels of O₃ induces changes that tend both to increase and decrease airway responsiveness. These data support the hypothesis that changes in the muco-epithelial barrier of ozone-exposed guinea pigs attenuates the effects of enhanced sensitivity of airway smooth muscle to Mch after ozone exposure.