Reduced prostacyclin formation after reoxygenation of anoxic endothelium.
Human umbilical vein endothelial cells subjected to 24 h of anoxia followed by reoxygenation released less prostacyclin (PGI2) in response to thrombin, calcium ionophore A23187, or arachidonic acid. This was associated with a substantial increase in stimulated platelet adherence. Increased lactate dehydrogenase and 51Cr release occurred after 1 h of reoxygenation, but the high rate of release did not persist during the subsequent 23 h of reoxygenation. The changes in platelet adherence and PGI2 release partially resolved over 24 h. PGI2 formation from prostaglandin H2 was not reduced, suggesting that cyclooxygenase activity, but not prostacyclin synthase, is affected by reoxygenation. A decrease in arachidonic acid release from cellular lipids also occurred. The reduction in cyclooxygenase activity, but not arachidonic acid release, was prevented by the presence of ibuprofen during reoxygenation. Addition of catalase or superoxide dismutase during reoxygenation increased PGI2 release but did not completely overcome the reduction relative to control cultures. These findings suggest that the increase in platelet adherence during reoxygenation may be mediated in part by a change in cyclooxygenase activity. This is only partly overcome by extracellular oxygen species scavengers but is prevented by the presence of a reversible cyclooxygenase inhibitor during reoxygenation.
Hempel
S L
SL
Department of Internal Medicine, University of Iowa, Iowa City.
Haycraft
D L
DL
Hoak
J C
JC
Spector
A A
AA
D000332:Aerobiosis; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia; D007700:Kinetics; D010973:Platelet Adhesiveness; D013482:Superoxide Dismutase / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D000001:Calcimycin; D011464:Epoprostenol; D013482:Superoxide Dismutase; D013917:Thrombin