Potentiation of anti-platelet aggregating activity of cilostazol with vascular endothelial cells.
We developed the new system in which the platelet aggregation was detected turbidimetrically using glass cuvettes which were coated cultured vascular endothelial cells. Using this system, we evaluated the effect of cilostazol, having a selective inhibitory effect on cAMP-PDE, on the ADP-induced platelet aggregation in the presence of endothelial cells. Cilostazol inhibited the platelet aggregation dose-dependently in the presence or absence of endothelial cells. The inhibitory effect of cilostazol on platelet aggregation was potentiated by the presence of endothelial cells, and the slope of the dose-response curves were identified to be as the same between both experiments in the presence and the absence of endothelial cells. The pretreatment of endothelial cells with aspirin reversed the potentiated inhibitory effect of cilostazol on the platelet aggregation with endothelial cells. The amount of 6-keto-prostaglandin F1 alpha accumulated in the cuvette was reduced in this condition. On the other hand, the inhibitory effect of prostaglandin E1 on the platelet aggregation was not potentiated by the presence of endothelial cells. These results suggest that the endothelium-derived prostacyclin plays a role on the potentiation of anti-platelet aggregatory effect of cilostazol.
Igawa
T
T
Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Japan.
Tani
T
T
Chijiwa
T
T
Shiragiku
T
T
Shimidzu
S
S
Kawamura
K
K
Kato
S
S
Unemi
F
F
Kimura
Y
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology*; D002478:Cells, Cultured; D000077407:Cilostazol; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009391:Nephelometry and Turbidimetry / Q000295:instrumentation / Q000379:methods*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism
D001393:Azoles; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D000244:Adenosine Diphosphate; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000527:Alprostadil; D000077407:Cilostazol