EFFECTS OF HYPOXIA AND HYPEROXIA ON LUNG PROSTAGLANDIN E(1) METABOLISM

Exposure to hypoxia (10% O-2 for 5 to 7 days) results in increased sur vival and decreased pulmonary toxicity of adult rats subsequently expo sed to hyperoxia (>97% O-2), These experiments tested whether hypoxia preexposure minimized the decrease in lung metabolism of prostaglandin E(1) (PGE(1)), a vasoactive and antiinflammatory prostaglandin, cause d by hyperoxia, Transpulmonary PGE(1) clearance was measured as fracti onal metabolism of PGE(1) (2 mu M to 30 mu M) infused during a 45-seco nd period in an isolated, buffer-perfused rat lung preparation after e xposure of rats to one of the following conditions: (1) hyperoxia (>97 % O-2 for 48 hours), (2) hypoxia (10% O-2 for 120 hours), or (3) hypox ia followed by hyperoxia, Hyperoxia exposure decreased both lung PGE(1 ) metabolism and lung prostaglandin dehydrogenase activity (PGDH), Hyp oxia also decreased lung PGE(1) metabolism but, in contrast, increased lung PGDH activity, Hypoxia preexposure did not prevent the depressio n of PGE(1) metabolism or PGDH activity caused by hyperoxia, which ind icates that survival in hyperoxia did not depend on lung PGE(1) metabo lism, Hypoxia itself impaired transpulmonary metabolism of PGE(1) desp ite increasing PGDH activity, which suggests possible interference wit h substrate delivery.