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 di...

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Bibliographic Details
Published in:The Journal of pharmacology and experimental therapeutics 2005-11, Vol.315 (2), p.494-500
Main Authors: Chakrabarti, Subrata, Vitseva, Olga, Iyu, David, Varghese, Sonia, Freedman, Jane E
Format: Article
Language:English
Subjects:
Antioxidants
Blood Platelets - drug effects
Blood Platelets - metabolism
CD40 Antigens
Cells, Cultured
Coloring Agents
Dipyridamole - pharmacology
Endothelial Cells - drug effects
Endothelial Cells - metabolism
Flow Cytometry
Humans
In Vitro Techniques
Microscopy, Confocal
Muscle Contraction - drug effects
Nitric Oxide - biosynthesis
Nitric Oxide - blood
Oxazines
Oxidation-Reduction
Platelet Aggregation Inhibitors - pharmacology
Reactive Nitrogen Species - metabolism
Reactive Oxygen Species - metabolism
Superoxides - metabolism
tert-Butylhydroperoxide - pharmacology
Thrombosis - chemically induced
Thrombosis - pathology
Xanthenes
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Summary: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.
ISSN:0022-3565
1521-0103
DOI:10.1124/jpet.105.089987