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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on July 26, 2005; DOI: 10.1124/jpet.105.089987

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Received for publication May 24, 2005.
Revised July 19, 2005.
Accepted for publication July 19, 2005.

The Effect of Dipyridamole on Vascular Cell-Derived Reactive Oxygen Species

Subrata Chakrabarti 1, Olga Vitseva 1, David Iyu 2, Sonia Varghese 1, Jane E Freedman 1*

1 Boston University School of Medicine 2 University of Murcia Medical School

* Address correspondence to: E-mail: freedmaj{at}bu.edu

Abstract

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 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) 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 (sCD40L) release. In summary, at therapeutically relevant concentrations, dipyridamole suppresses 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.


Key words: Antioxidant, Nitric oxide, Platelet, Reactive oxygen species, Superoxide, Thrombosis


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