Endothelial cells synthesize prostacyclin (PGI2), an unstable prostaglandin that inhibits platelet aggregation and serotonin release. Because cyclooxygenase, which is necessary for synthesis of PGI2, is inactivated by aspirin, we examined the effect of aspirin on PGI2 production by cultured human endothelial cells. Endothelial cells synthesize PGI2 (20.1±7.2 ng/106 cells, mean±SD) when stimulated with 20 μM sodium arachidonate for 2 min. PGI2 production is inhibited by low-dose aspirin (5 μM); the t½ of inactivation is 6.0±1.3 min (mean±SEM, n = 3). Thus, endothelial cell cyclooxygenase is as sensitive to aspirin as the enzyme in platelets. After 1 h incubation with aspirin, endothelial cell PGI2 production was inhibited 50% by 2.1±0.4 μM aspirin and was inhibited 90% by 6.2±0.9 μM aspirin (mean±SEM, n = 4). When endothelial cells were incubated with 100 μM aspirin, washed, and recultured, their ability to synthesize PGI2 returned to control levels in 35.6±1.0 h (mean±SEM, n = 4). Recovery of endothelial PGI2 production after aspirin depended on de novo protein synthesis because treatment with cycloheximide (3 μg/ml) inhibited recovery by 92%.
Eric A. Jaffe, Babette B. Weksler