Low levels of hydrogen peroxide enhance platelet aggregation by cyclooxygenase activation

Platelet aggregation can be triggered by addition of exogenous arachidonate owing to its conversion to endoperoxides and thromboxane A2. The dose-response curve of arachidonate-induced platelet aggregation exhibited a very steep slope. Simultaneous addition of H2O2 (1-200 microM) significantly shifted this curve to the left. H2O2 alone did not induce aggregation up to a concentration of 1 mM; however, a reversible increase of cytoplasmic Ca2+ and a small increase of the thromboxane levels could be observed. In the presence of exogenous arachidonate H2O2 led to an increased formation of arachidonate metabolites. Our data demonstrate that at threshold levels of 20:4 H2O2 is able to promote conversion of 20:4 to proaggregatory prostaglandin endoperoxides, and subsequently platelet activation is facilitated. Thus we support the evidence for a role of H2O2 in the activation of cyclooxygenase possibly by providing an adequate peroxide tone.