PT - JOURNAL ARTICLE AU - Subrata Chakrabarti AU - Olga Vitseva AU - David Iyu AU - Sonia Varghese AU - Jane E. Freedman TI - The Effect of Dipyridamole on Vascular Cell-Derived Reactive Oxygen Species AID - 10.1124/jpet.105.089987 DP - 2005 Nov 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 494--500 VI - 315 IP - 2 4099 - http://jpet.aspetjournals.org/content/315/2/494.short 4100 - http://jpet.aspetjournals.org/content/315/2/494.full SO - J Pharmacol Exp Ther2005 Nov 01; 315 AB - Platelet and vascular stimulation leads to release of reactive oxygen species (ROS) that are known to influence vascular reactivity and thrombosis. Dipyridamole is a vasodilator and platelet inhibitor that has previously been shown to have direct antioxidant properties. The antioxidant effects of dipyridamole on vascular cell-derived ROS are not known; therefore, dipyridamole was incubated with endothelial cells and platelets and cellular redox status and release of endogenous ROS were assessed. Dipyridamole decreased intracellular basal ROS generation from endothelial cells as measured by DCFDA (2′,7′-dichlorodihydrofluorescein diacetate) oxidation. Incubation of endothelial cells with dipyridamole also attenuated t-butylhydroperoxide-induced oxidative stress. Using a redox-sensitive fluorescent dye, dipyridamole improved cellular activity after treatment with t-butylhydroperoxide. Incubation with dipyridamole did not alter platelet release of nitric oxide or hydrogen peroxide but significantly attenuated superoxide release. Using flow cytometry and confocal microscopy, dipyridamole decreased platelet ROS generation. Dipyridamole also suppressed platelet-soluble CD40 ligand release. In summary, at therapeutically relevant concentrations, dipyridamole suppresses the formation of ROS in platelets and endothelial cells and improves cellular redox status. These data suggest that the redox-dependent properties of dipyridamole have a direct effect on vascular cells. The American Society for Pharmacology and Experimental Therapeutics