Lung edema due to hydrogen peroxide is independent of cyclooxygenase products.
Active oxygen species can cause lung injury. Although a direct action on endothelial cells is proposed, the possibility exists that they might cause injury via mediators. We considered that active oxygen species would stimulate the generation of cyclooxygenase metabolites, which then alter pulmonary vasoreactivity and cause edema. We chemically produced hydrogen peroxide by adding glucose oxidase to a plasma- and cell-free, but beta-D-glucose-containing, solution, which perfused isolated rat lungs. Addition of glucose oxidase to the perfusate caused a marked decrease in pulmonary vasoreactivity, accompanied by an increase in the concentrations of prostacyclin, thromboxane A2, and prostaglandin F2 alpha. Pretreatment with catalase, a specific scavenger of hydrogen peroxide, preserved pulmonary vasoreactivity, inhibited the increase of the concentration of the measured prostaglandins, and prevented edema formation. Indomethacin effectively blocked lung prostaglandin production but neither prevented the decrease in vasoreactivity nor inhibited edema formation. From these data we conclude that hydrogen peroxide impaired pulmonary vasoreactivity and subsequently caused edema. Despite the fact that hydrogen peroxide stimulated lung prostaglandin production, cyclooxygenase-derived products neither caused the decrease in vasoreactivity nor the development of edema.
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D005949:Glucose Oxidase / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011460:Prostaglandins F / Q000032:analysis; D011654:Pulmonary Edema / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000032:analysis
D011460:Prostaglandins F; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D011451:Prostaglandin-Endoperoxide Synthases