Faculty Bibliography

The predominant airway site and mechanism underlying ozone (O3)-induced respiratory hyperresponsiveness was examined in anesthetized guinea pigs and in vitro tissue preparations. Animals exposed to 1.0 or 1.2 ppm O3 (1 h) demonstrated an enhanced airway response to subcutaneous histamine compared with air-exposed animals. The anatomic site of hyperresponsiveness most likely did not involve the parenchyma, since quasi-static deflationary pulmonary compliance was decreased to a similar extent by histamine in air- and O3-preexposed animals. In contrast, the conducting airways were probably involved as changes in pulmonary resistance elicited by subcutaneous histamine were greater in O3- than in air-exposed animals. Neither atropine nor vagotomy abolished this enhanced responsiveness induced by O3. Although vagal interruption did not alter responsiveness, O3-exposed animals demonstrated greater respiratory responses to efferent electrical stimulation of the vagi than air-exposed animals. This suggests the site of hyperresponsiveness may be located distal to the site of efferent stimulation, possibly in the smooth muscle itself or in its microenvironment.

This study sought to determine if ozone at levels known to induce bronchial hyperreactivity in guinea pigs would inhibit tissue cholinesterase activity. Male, Hartley guinea pigs were exposed to filtered air, 0.1 ppm ozone, or 0.8 ppm ozone for 1 hr. Two hours after exposure, brain, lung, and diaphragm tissue samples were frozen for assay of cholinesterase activity. Brain cholinesterase activity was only minimally inhibited in either ozone exposure group. Both levels of ozone significantly inhibited lung cholinesterase activity compared to control animals' activity: a 17% decrease in activity in the 0.1 ppm ozone group (P less than .05) and a 16% decrease in the 0.8 ppm ozone group (P less than .05). Ozone at 0.8 ppm also inhibited activity in the diaphragm by 14% (P less than .02). To determine the degree of involvement of cholinesterase inhibition in bronchial hyperreactivity, parathion pretreated animals were challenged with histamine and the pulmonary function changes monitored. Parathion-treated animals had a peak resistance increase of 330 +/- 104% (mean +/- SE), while the control vehicle animals' increase was 165 +/- 48%. The differences were not statistically significant, but show that cholinesterase inhibition may contribute to ozone-induced bronchial hyperreactivity.

The effect of preexposure to ozone on the respiratory response to histamine was studied. The Amdur-Mead technique was used to measure respiratory mechanics in Charles River Hartley guinea pigs. Groups of animals were exposed for 1 h to filtered control air or ozone. Control measurements were made 1 1/2 h after exposure, followed by sc injection of 0.125 mg/kg histamine dihydrochloride. Respiratory measurements were continued at 2-min intervals for 16 min, at which time resistance and compliance had returned to control values. The 2-h interval between exposure and injection and the 0.125 mg/kg histamine were the optimum time interval and dose, respectively, as determined by appropriate time-response and dose-response studies. Although control values did not differ between air-exposed and ozone-exposed animals, animals preexposed to 0.1, 0.2, 0.4, and 0.8 ppm ozone had increases in resistance of 111, 110, 93, and 97% after histamine administration, compared to the air-exposed animals, which had increases of 86, 86, 67, and 46%, respectively. Whereas the only significant difference in resistance between air and ozone animals was at the 0.8-ppm level (p less than 0.05), significant differences in compliance changes were found at all levels of ozone exposure. Ozone animals had compliance decreases of 40, 45, 46, and 46% after histamine injection, while their respective air controls decreased 24, 24, 27, and 31%. Exposures to ozone of 0.2 ppm for 4 h and 0.4 ppm for 2 h provided doses equal to that of 0.8 ppm for 1 h, yet no significant dose-time relationship was found. Lingering sensitivity to pharmacologically active agents is a subtle but important manifestation of ozone toxicity.