Salutary effects of prostaglandin E1 in perfused rat lungs injured with hydrogen peroxide.
Studies were conducted in isolated, buffer-perfused rat lungs to determine if prostaglandin (PG) E1 attenuated pulmonary edema provoked by hydrogen peroxide (H2O2). When lungs were challenged by 60 min of perfusion with H2O2 (generated by the reaction between glucose and glucose oxidase) the wet weight-to-dry weight ratio increased from control by 54%, indicating development of pulmonary edema. In contrast, lungs treated simultaneously with H2O2 plus PGE1 (1 microgram/min) failed to exhibit an elevated wet-to-dry weight ratio. H2O2-injured lungs demonstrated a modest 2 torr increase in pulmonary arterial perfusion pressure that was not influenced by simultaneous treatment with PGE1. Both radioimmunoassay (RIA) and high-performance liquid chromatographic (HPLC) analysis detected increased amounts of (5S)-5-hydroxy-6,8,11,14 eicosatetraenoic acid in the perfusion medium of H2O2-injured lungs (RIA, 48.0 +/- 14.7; HPLC, 54.8 +/- 13.5) relative to controls (RIA, 6.6 +/- 1.6; HPLC, 6.8 +/- 1.9), and simultaneous treatment with PGE1 tended to blunt this increase (RIA, 29.2 +/- 8.3; HPLC, 29.8 +/- 7.6). PGE1 abolished the increase in wet weight-to-dry weight ratio induced by exogenous leukotriene C4. Production of H2O2 by the glucose-glucose oxidase reaction was not influenced by PGE1. Taken together, these observations indicate that PGE1 attenuates H2O2-induced pulmonary edema formation in buffer-perfused rat lungs by mechanisms that may relate to inhibition of lung 5'-lipoxygenase activation and/or to inhibition of the injurious effects of endogenously produced lipoxygenase products.
D000527:Alprostadil / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D005949:Glucose Oxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000096:biosynthesis; D008168:Lung / Q000187:drug effects*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010477:Perfusion; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000188:drug therapy
D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D000527:Alprostadil