Ozone inhibits endothelial cell cyclooxygenase activity through formation of hydrogen peroxide.
We have previously demonstrated that a 2H exposure of cultured pulmonary endothelial cells to ozone (0.0-1.0 ppm) in-vitro resulted in a concentration-dependent reduction of endothelial prostacyclin production (90% decrease at the 1.0 ppm level). Ozone-exposed endothelial cells, incubated with 20 uM arachidonate, also demonstrated a significant inhibition of prostacyclin synthesis. To further examine the mechanisms of the inhibition of prostacyclin synthesis, bovine pulmonary endothelial cells were exposed to 1.0 ppm ozone for 2H. A significant decrease in prostacyclin synthesis was found within 5 min of exposure (77 +/- 36% of air-exposed control values, p less than 0.05). Endothelial prostacyclin synthesis returned to baseline levels by 12H after ozone exposure, a time point which was similar to the recovery time of unexposed endothelium treated with 0.5 uM acetylsalicylic acid. Incubation of endothelial cells, previously exposed to 1.0 ppm ozone for 2 hours, with 4 uM PGH2 resulted in restoration of essentially normal prostacyclin synthesis. When endothelial cells were co-incubated with catalase (5 U/ml) during ozone exposure, no inhibition of prostacyclin synthesis was observed. Co-incubation with either heat-inactivated catalase or superoxide dismutase (10 U/ml) did not affect the ozone-induced inhibition of prostacyclin synthesis. These data suggest that H2O2 is a major toxic species produced in endothelial cells during ozone exposure and responsible for the inhibition of endothelial cyclooxygenase activity.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors; D004730:Endothelium, Vascular / Q000201:enzymology*; D006861:Hydrogen Peroxide / Q000032:analysis; D008054:Lipid Peroxides / Q000032:analysis; D008297:Male; D010126:Ozone / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000201:enzymology; D011863:Radioimmunoassay; D012669:Seminal Vesicles / Q000201:enzymology; D012756:Sheep; D013053:Spectrophotometry
D016861:Cyclooxygenase Inhibitors; D008054:Lipid Peroxides; D010126:Ozone; D006861:Hydrogen Peroxide; D001241:Aspirin