Inhibition of pulmonary prostaglandin metabolism by exposure of animals to oxygen or nitrogen dioxide

Abstract

The effects of exposure of animals to 100% O2 and NO2 on the rate of prostaglandin metabolism by lung and kidney were studied in vitro. Exposure of guinea pigs to 100% O2 for 48 h inhibited the metabolism of prostaglandin F2 alpha by both NAD+- and NADP+-dependent prostaglandin dehydrogenase in lung, but had no effect on the metabolism in kidney. Succinate dehydrogenase, but not glucose 6-phosphate dehydrogenase, in guinea-pig lung was inhibited by exposure to 100% O2. Exposure to 46 p.p.m. but not 16 or 29 p.p.m. NO2 for 6 h inhibited guinea-pig lung prostaglandin dehydrogenase in vitro. The inhibition of pulmonary prostaglandin dehydrogenase by exposure to 100% O2 or to 49 p.p.m. NO2 was dependent on the duration of exposure, but returned to control values within 7 days after cessation of the exposure. The pulmonary transport system responsible for removing circulating prostaglandins from the blood was not affected by exposure to 100% O2 as measured by using the isolated perfused lung. Kinetic analysis of the inhibition of pulmonary prostaglandin dehydrogenase activity in guinea pig exposed to 100% O2 showed non-competitive inhibition with respect to both prostaglandin F2 alpha and NAD+, which suggests destruction or inactivation of the enzyme. Pulmonary prostaglandin dehydrogenase appears to be inhibited by exposure to oxidant gases, which may lead to elevated prostaglandin concentrations in the lungs or in the systemic circulation.