Beyond hemostasis: The antiflammatory and antioxidant effects of dipyridamole

Background Platelet stimulation leads to release of reactive oxygen species (ROS) that are known to influence platelet function and thrombosis. Dipyridamole is a vasodilator and platelet inhibitor that decreases adenosine uptake and may be a highly efficient chain breaking antioxidant. The antioxidant effects of dipyridamole on platelet-derived ROS and the potential (anti)inflammatory effects are not known. Methods Human platelets were incubated with dipyridamole (0–100 μM) and specific antioxidant and antiflammatory mediators were measured. Results Incubation with dipyridamole did not alter platelet release of nitric oxide but significantly attenuated superoxide release (17±3.7 a.u. for control vs. 7.4±1.1 a.u. for 20μM; n=5, P<0.001). Using flow cytometry, dipyridamole decreased intracellular levels of ROS, as measured by 2',7'-dichlorodihydrofluorescein diacetate fluorescence dye (1±0.34% control vs. 0.66±0.2% for 20μM, n=4, P=0.03). There was also a dose-dependent (0–100μM) suppression of soluble CD40 ligand release (P<0.05). Conclusions In summary, at a clinically relevant concentration, dipyridamole suppresses stimulation-dependent release of superoxide as well as the formation of ROS and leads to the attenuated release of sCD40L from platelets. These data suggest that dipyridamole, beyond inhibition of platelet aggregation, suppresses the platelet inflammatory reactions recently shown to be relevant in the development of atherothrombotic disease. Clinical Pharmacology & Therapeutics (2005) 77, P11–P11; doi: 10.1016/j.clpt.2004.11.044