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To evaluate the effect of age on toxicant-induced pulmonary and extrapulmonary changes, we examined the effect of inhalation exposure to oxone (O3) on the ventilatory and heart rate (HR) responses in 4-6 and 20-22-month-old male rats. The rats, chronically implanted with an electrocardiographic (ECG) electrodes, were placed in a head-out plethysmograph for continuous ventilatory measurements of tidal volume and breathing frequency. Simultaneous measurements of HR were also obtained. A 6-hr exposure of each rat to filtered air was followed 2 days later by a 5-hr exposure to 0.1 ppm O3, 5 days later by a 5-hr exposure to 0.3 ppm O3 and 10 days later by a 5-hr exposure to 0.5 ppm O3. Each of the O3 exposures was preceded by a 1-hr exposure to filtered air. Transient rapid shallow breathing with slightly increased HR appeared 1-2 min after the start of O3 exposure. It was suggested on the basis of the electroencephalographic (EEG) activity of the olfactory bulb that this transient response was mediated through olfactory sensation. Persistent rapid shallow breathing with a progressive decrease in HR occurred with a latent period of 1-2 hr. The last 90-min averaged values for relative minute ventilation tended to decrease with the increase in the level of exposure to O3 and these values for young rats were significantly lower than those for old rats. An exposure of young rats to 0.1 ppm O3 for shorter than 5 hr significantly decreased the tidal volume and HR and increased breathing frequency, but no significant changes were observed in old rats. There were no differences between young and old rats in non-observable-adverse-effect-levels (NOAELs) for the O3-induced persistent ventilatory and HR responses, when the NOAELs were determined by exposure to 0.3 and 0.5 ppm O3. The present results, as well as the reported decrease in body temperature and blood pressure, suggested that the age-related changes in patterns and magnitude of the persistent rapid shallow breathing with a progressive decrease in HR are mediated through some age-related defense mechanism acting against O3 inhalation. The validity of the occupational exposure limit for O3 in workplaces was discussed in the light of the present findings.

Age-Related Changes in Ventilatory and Heart Rate Responses to Acute Ozone Exposure in the Conscious Rat.