Effect of ozone on respiratory response of guinea pigs to histamine

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.