The effect of ozone inhalation on metabolic functioning of vascular endothelium and on ventilatory function.
The primary purpose of this research was to determine the effect of ozone inhalation on pulmonary vascular endothelium. Male Fischer-344 rats were exposed to 0.5 or 0.7 ppm ozone, 20 hr/day for 7 days. Lungs were excised and perfused with Krebs medium containing [14C]serotonin or [14C]hippurylhistidylleucine (HHL). When compared to controls, the animals exposed to the lower ozone concentration showed no statistically significant changes in serotonin removal. In contrast, the higher ozone concentration resulted in a 32% decrease (p less than 0.0001) in serotonin removal, but had no effect on HHL. Rats similarly exposed to 0.7 ppm ozone but allowed to recover for 14 days in clean air showed no decrease in serotonin removal compared to their controls. Animals exposed sequentially to 0.5 ppm ozone for 7 days and then to 0.7 ppm for 7 days showed no alteration in serotonin metabolism, suggesting the development of tolerance initiated by the lower dose. After 7 days exposure to 0.7 ppm ozone, lung ventilatory function measurements revealed small though significant decreases in several parameters. Electron microscopic evaluation of lung capillary endothelium from animals exposed to the 0.7 ppm ozone showed no changes. Positive control animals exposed to greater than 95% oxygen, 20 hr/day for 2 days showed a 23% decrease in serotonin removal (p less than 0.03) and a 12% decrease in HHL removal (p less than 0.017). These studies indicate that inhalation of ozone can induce functional alterations in the lung endothelium, and that this effect occurs at a dosage of ozone that produces minimal ventilatory changes and no observable endothelial ultrastructural changes.
Gross
K B
KB
Biomedical Science Department, General Motors Research Laboratories, Warren, Michigan 48090.
White
H J
HJ
Sargent
N E
NE
D000280:Administration, Inhalation; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004361:Drug Tolerance; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D009842:Oligopeptides / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000648:ultrastructure; D051381:Rats; D011916:Rats, Inbred F344; D012701:Serotonin / Q000378:metabolism; D014797:Vital Capacity / Q000187:drug effects
D009842:Oligopeptides; C010980:hippuryl-histidyl-leucine; D012701:Serotonin; D010126:Ozone; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D010100:Oxygen