Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Clinical Investigation
Evaluation of the Antiplatelet Effects of Cilostazol, a Phosphodiesterase 3 Inhibitor, by VASP Phosphorylation and Platelet Aggregation
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2008 Volume 72 Issue 11 Pages 1844-1851


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Abstract

Background Cilostazol, a phosphodiesterase 3 inhibitor, is an antiplatelet drug that is widely used for preventing cardiovascular events, although, to date, there are few methods for evaluating its effects. Methods and Results Blood samples were taken at baseline and at 3 and 12 h in 10 healthy male subjects after 100 mg cilostazol intake. Each sample was examined by Western blot for phosphorylation levels of vasodilator-stimulated phosphoprotein (VASP), an abundant cAMP-dependent kinase substrate in platelets, and by the optical aggregometer for ADP- and collagen-induced aggregation, before and after 8 nmol/L prostaglandin E1 (PGE1) treatment. Cilostazol intake did not affect VASP phosphorylation levels or the maximal aggregation rates without PGE1 treatment. However, cilostazol intake apparently enhanced PGE1-induced VASP phosphorylation and PGE1-mediated reduction of ADP-and collagen-induced maximal aggregation rates. Levels of VASP phosphorylated at Ser157 were correlated and the maximal aggregation rates induced by ADP were inversely correlated with cilostazol concentrations in the plasma. Conclusion The antiplatelet effects of cilostazol intake could be evaluated by measuring VASP phosphorylation levels and maximal aggregation rates in platelets by ex vivo treatment with a low concentration of PGE1. (Circ J 2008; 72: 1844 - 1851)

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© 2008 THE JAPANESE CIRCULATION SOCIETY
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