Evaluation of anti-platelet aggregatory effects of aspirin, cilostazol and ramatroban on platelet-rich plasma and whole blood.
To compare property in anti-platelet effects of aspirin (a cyclooxygenase inhibitor), cilostazol (a phosphodiesterase III inhibitor) and ramatroban (a specific thromboxane A2 receptor antagonist), we measured human platelet-rich plasma (PRP) aggregation induced by adenosine diphosphate (ADP), collagen and arachidonic acid, and whole blood (WB) aggregation induced by ADP. The release of P-selectin, transforming growth factor-beta 1, and the formation of thromboxane A2 in response to agonists were also investigated. Inhibitory effects of 100 micromol/l aspirin, 10 micromol/l cilostazol and 1 micromol/l ramatroban on 5 micromol/l ADP-induced PRP aggregation were similar. However, aspirin strongly inhibited thromboxane A2 formation in response to 5 micromol/l ADP compared with other drugs. Inhibitory effects of 10 micromol/l cilostazol on PRP aggregation and the release of molecules were quite similar in responsiveness induced by the three agonists. Aspirin and cilostazol inhibited platelet aggregation in a concentration-dependent, non-linear fashion, while ramatroban inhibited linearly with increasing concentration. Anti-platelet effects of drugs having different pharmacological mechanisms were demonstrated clearly by measuring PRP aggregation induced by the three agonists, and by measuring WB aggregation that most probably reflects not only platelet-platelet interactions, but also platelet-leukocyte interactions, as well as the release of intraplatelet molecules.
Kariyazono
Hiroko
H
Department of Clinical Pharmacy and Pharmacology, Division of Maxillofacial Radiology and Department of Space Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Nakamura
Kazuo
K
Arima
Junko
J
Ayukawa
Osamu
O
Onimaru
Shunji
S
Masuda
Hiroshi
H
Iguro
Yoshifumi
Y
Majima
Hideyuki J
HJ
Sakata
Ryuzo
R
Yamada
Katsushi
K
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D000077407:Cilostazol; D003094:Collagen / Q000494:pharmacology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D018613:Microscopy, Confocal; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010949:Plasma; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors; D015203:Reproducibility of Results; D013449:Sulfonamides / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*
D002227:Carbazoles; D016861:Cyclooxygenase Inhibitors; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013449:Sulfonamides; D013777:Tetrazoles; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000077407:Cilostazol; C063119:ramatroban; D001241:Aspirin