The effect of dipyridamole on vascular cell-derived reactive oxygen species.
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.
Chakrabarti
Subrata
S
Whitaker Cardiovascular Institute and Evans Department of Medicine, Boston University School of Medicine, MA 02118, USA.
Vitseva
Olga
O
Iyu
David
D
Varghese
Sonia
S
Freedman
Jane E
JE
D000975:Antioxidants; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D019013:CD40 Antigens; D002478:Cells, Cultured; D004396:Coloring Agents; D004176:Dipyridamole / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood; D010078:Oxazines; D010084:Oxidation-Reduction; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013927:Thrombosis / Q000139:chemically induced / Q000473:pathology; D014966:Xanthenes; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D000975:Antioxidants; D019013:CD40 Antigens; D004396:Coloring Agents; D010078:Oxazines; D010975:Platelet Aggregation Inhibitors; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014966:Xanthenes; D013481:Superoxides; C005843:resazurin; D009569:Nitric Oxide; D004176:Dipyridamole; D020122:tert-Butylhydroperoxide