title: Effects of hypoxia and hyperoxia on lung prostaglandin E1 metabolism.
abstract: Exposure to hypoxia (10% O2 for 5 to 7 days) results in increased survival and decreased pulmonary toxicity of adult rats subsequently exposed to hyperoxia (> 97% O2). These experiments tested whether hypoxia preexposure minimized the decrease in lung metabolism of prostaglandin E1 (PGE1), a vasoactive and antiinflammatory prostaglandin, caused by hyperoxia. Transpulmonary PGE1 clearance was measured as fractional metabolism of PGE1 (2 microM to 30 microM) infused during a 45-second period in an isolated, buffer-perfused rat lung preparation after exposure of rats to one of the following conditions: (1) hyperoxia (> 97% O2 for 48 hours), (2) hypoxia (10% O2 for 120 hours), or (3) hypoxia followed by hyperoxia. Hyperoxia exposure decreased both lung PGE1 metabolism and lung prostaglandin dehydrogenase activity (PGDH). Hypoxia also decreased lung PGE1 metabolism but, in contrast, increased lung PGDH activity. Hypoxia preexposure did not prevent the depression of PGE1 metabolism or PGDH activity caused by hyperoxia, which indicates that survival in hyperoxia did not depend on lung PGE1 metabolism. Hypoxia itself impaired transpulmonary metabolism of PGE1 despite increasing PGDH activity, which suggests possible interference with substrate delivery.
authors.affiliation: Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Pisarello
authors.forename: D
authors.initials: D
authors.lastname: Flores
authors.forename: R M
authors.initials: RM
authors.lastname: Jackson
mesh_terms: D000527:Alprostadil / Q000378:metabolism*; D000818:Animals; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D018496:Hyperoxia / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006911:Hydroxyprostaglandin Dehydrogenases; D000527:Alprostadil