The F 2 -Isoprostane 8-Epiprostaglandin F 2α Increases Platelet Adhesion and Reduces the Antiadhesive and Antiaggregatory Effects of NO

Abstract

—F ₂ -isoprostanes are prostaglandin (PG) isomers produced in vivo through free radical–catalyzed peroxidation of arachidonic acid, which may affect platelet function. The current study investigated the effects of 8-epiprostaglandin F _2α (8-epi-PGF _2α ) on critical events of platelet activation. A dose-dependent increase in platelet adhesion to fibrinogen- and plasma-coated microwells by 8-epi-PGF _2α (1 to 1000 nmol/L) was observed when resting platelets (plasma from 1.3±0.2% to 5.5±0.2%, EC ₅₀ of 48 nmol/L; fibrinogen from 3.3±0.3% to 6.4±0.2%, EC ₅₀ of 35 nmol/L; mean±SEM, n=8, P 2α in resting platelets (from 64.8±2.1% to 83.9±1.3%; n=5, P 2α (from 48.5±3.1% to 63.1±2.0%, P 2α , 30.8±6.9%; n=14, P 2α , 30.7±5.3%; n=15, P 2α . In conclusion, F ₂ -isoprostanes may participate in oxidative injury by inducing platelet activation and by reducing the antiplatelet activity of NO: increased platelet adhesiveness and expression of the fibrinogen receptor are induced by nanomolar amounts of 8-epi-PG-F _2α . Platelet secretion and aggregation can also be induced in the presence of platelet agonists.