Synergistic effect of cilostazol and dipyridamole mediated by adenosine on shear-induced platelet aggregation.

Abstract:

INTRODUCTION:The Cilostazol Stroke Prevention Study found that cilostazol, a phosphodiesterase 3 inhibitor, can reduce the risk of subsequent stroke in Japanese patients with cerebral infarction. Here, we measured the effects of cilostazol in vitro on shear-induced platelet aggregation, an important mechanism of thrombosis at arterial bifurcations or stenotic lesions. We also evaluated the influences of intrinsic adenosine on the ability of cilostazol to inhibit shear-induced platelet aggregation by investigating the effect of dipyridamole, an inhibitor of cellular adenosine reuptake, in combination with cilostazol in vitro. MATERIALS AND METHODS:We measured platelet aggregation induced by a shear rate of 10,800 s(-1) in whole blood and in platelet-rich plasma from healthy volunteers using a cone-plate streaming chamber. RESULTS:Both cilostazol and adenosine dose-dependently inhibited shear-induced platelet aggregation in platelet-rich plasma samples. Adding a low concentration of adenosine (0.3 microM) did not inhibit shear-induced platelet aggregation, but significantly enhanced the inhibitory effect of cilostazol in platelet-rich plasma. Dipyridamole dose-dependently inhibited shear-induced platelet aggregation in whole blood and significantly enhanced the inhibitory effect of cilostazol on shear-induced platelet aggregation, but did not affect shear-induced platelet aggregation in platelet-rich plasma. The inhibitory effects of cilostazol combined with dipyridamole in whole blood were almost completely reversed by adenosine deaminase. CONCLUSIONS:Dipyridamole appears to synergistically enhance the inhibitory effect of cilostazol on shear-induced platelet aggregation by maintaining high plasma levels of adenosine.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Nakamura T,Uchiyama S,Yamazaki M,Iwata M

doi

10.1016/j.thromres.2006.05.005

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

511-6

issue

4

eissn

0049-3848

issn

1879-2472

pii

S0049-3848(06)00181-2

journal_volume

119

pub_type

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