title: Inhibition of prostacyclin by treatment of endothelium with aspirin. Correlation with platelet adherence.
abstract: Aspirin treatment of cultured endothelial cells from the umbilical vein increased the adherence of 51Cr-platelets when thrombin was present. If the cyclooxygenase activity of endothelium was inhibited by aspirin, as it is in the platelet, reduction of endogenous prostacyclin (PGI2) production could have been responsible. By correlating thrombin-induced adherence of platelets to endothelial monolayers with PGI2 release (as measured by radioimmunoassay for 6-keto-prostaglandin FI1 alpha [6-keto-PGF1 alpha]), we have demonstrated an inverse relationship between platelet adherence and PGI2 levels. Untreated endothelial monolayers exposed to thrombin and platelets resulted in 4% platelet adherence and 107 nM 6-keto-PGF1 alpha. With 0.1 mM aspirin treatment, which is known to block platelet cyclooxygenase, adherence was 5% and 6-keto-PGF1 alpha decreased to 45 nM. Increasing the aspirin concentration to 1 mM resulted in 44% adherence and less than 3 nM 6-keto-PGF1 alpha. When 25 nM exogenous PGI2 was added to 1 mM aspirin-treated endothelium, adherence returned to 5%. The increase in thrombin-induced platelet adherence to 1 mM aspirin-treated monolayers was reversed 2 h after removal of the aspirin solution. 6-Keto-PGF1 alpha returned to 37% of the untreated monolayer value. Recovery from the aspirin effect did not occur when cycloheximide, an inhibitor of protein synthesis, was present during the 2-h period.
mesh_terms: D001241:Aspirin / Q000494:pharmacology*; D004727:Endothelium / Q000378:metabolism / Q000502:physiology*; D011464:Epoprostenol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011453:Prostaglandins / Q000494:pharmacology*; D011460:Prostaglandins F / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
chemical_list: D011453:Prostaglandins; D011460:Prostaglandins F; D011464:Epoprostenol; D013917:Thrombin; D001241:Aspirin