It has been clinically reported that cilostazol has a potent inhibitory effect on
platelet aggregation without changing the prostacyclin level. This study was undertaken
to elucidate this clinical effect by a technique developed by us in which platelet
aggregation could be evaluated in the presence of cultured endothelial cells. Human
umbililical cord vein endothelial cells (HUVEC) were coated (cultured for a few days
supplemented with 10% fetal claf serum) on the inner surface of glass cuvette, and
platelet aggregation was traced by the stimulation of citrated-PRP with 7.5 μM ADP
in this cuvette. The 6-keto-prostaglandin F1α (6-k-PGF) and thromboxane B2 (TXB) produced in the supernatant of the stimulated PRP were measured by radioimmunoassay
(Amersham). The cyclic adenosine monophosphate (cAMP) level in platelets and HUVEC
was measured by radioimmunoassay (YAMASA). Cilostazol showed a potent inhibitory effect
on platelet aggregation in the presence of HUVEC by the suppresion of TXB production,
but not by the suppression of 6-k-PGF production. Cilostazol stimulated cAMP production
in both platelets and HUVEC. On the other hand, aspirin also showed an inhibitory
effect on platelet aggregation in the presence of HUVEC, but suppressed production
of both TXB and 6-k-PGF.
As a result, the clinical effect of cilostazol was confirmed by the fact that TXA2 production in a platelet/HUVEC coexisting system was specifically suppressed.
