A study of ozone-induced edema in the isolated rat lung in relation to arachidonic acid metabolism, mixed-function oxidases and angiotensin converting enzyme activities.
In order to elucidate the role of arachidonic acid in the pathogenesis of ozone-induced pulmonary edema, isolated rat lungs were exposed to 14C-arachidonic acid in the presence or absence of ozone and the incorporation of radiolabelled arachidonate into pulmonary cell lipids was studied. The perfusates from these studies were also subjected to differential extraction and thin layer chromatography (t.l.c.) to determine synthesis of both cyclo-oxygenase and lipoxygenase products. In the presence of an edemagenic concentration of ozone, isolated lungs incorporated significantly less exogenous arachidonic acid into phosphatidyl choline and phosphatidyl ethanolamine, whereas incorporation into phosphatidyl inositol or serine was not affected. The edemagenic concentration of ozone also increased production of a variety of arachidonic acid metabolites via cyclo-oxygenase and lipoxygenase pathways. In separate studies, a similar ozone exposure did not affect 14CO2 production, resulting from the metabolism of 14C-antipyrine by mixed function oxidases (MFO). Similarly, an edemagenic concentration of ozone did not affect pulmonary angiotensin converting enzyme activity (ACE) as determined by the rate of formation of 14C-hippuric acid from 14C-hippuryl-histidyl-leucine (14C-HHL). Thus, acute ozone exposure is specifically associated with a reduced incorporation of arachidonate into phospholipids and with an increased conversion of arachidonate into bio-active metabolites.
Dutta
S
S
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Chatterjee
M
M
Teknos
T N
TN
Carlson
R W
RW
D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010126:Ozone / Q000633:toxicity*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010477:Perfusion; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D008563:Membrane Lipids; D002245:Carbon Dioxide; D016718:Arachidonic Acid; D010126:Ozone; D006899:Mixed Function Oxygenases; D007703:Peptidyl-Dipeptidase A; D000983:Antipyrine