Diltiazem potentiates the inhibitory effect of aspirin on platelet aggregation.
Platelet aggregation in vivo occurs through the combined effects of many agonists. Aspirin inhibits platelet aggregation but its antiaggregate effects can be overcome by the synergistic action of sodium arachidonate (AA) plus platelet activating factor (PAF). We tested the effect of a calcium entry-blocking agent, diltiazem, on AA-PAF-induced platelet aggregation in platelet-rich plasma from seven healthy volunteers. The studies were done before and after aspirin (100 mg/day) administration for 7 to 10 days. Stimulation of platelet was done in vitro by AA, PAF, or both. Before aspirin treatment, diltiazem (2 micrograms/ml) added in vitro to the platelet-rich plasma inhibited platelet aggregation induced by AA (0.75 mmol/L) by 50%. When PAF was used the inhibition of aggregation was obtained at a lower concentration of diltiazem (0.4 to 1 microgram/ml). After aspirin treatment, AA-induced aggregation was inhibited, and PAF alone (30 nmol/L) produced a first-wave aggregation followed by complete disaggregation. When AA and PAF were added together a full aggregation of postaspirin treatment platelets was obtained. Diltiazem added in vitro at the clinically attainable concentration of 0.1 microgram/ml produced a complete inhibition of this AA-PAF synergism on platelet aggregation. These results suggest that administration of a combination of low-dose aspirin and diltiazem may be of greater benefit than aspirin alone for prophylaxis of cardiovascular diseases where platelets are involved in the pathogenesis.
Centro de Estudios Medicos y Bioquimicos, Buenos Aires, Argentina.
R
R
Altman
A
A
Scazziota
C
C
Dujovne
D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D013997:Time Factors
D001095:Arachidonic Acids; D010972:Platelet Activating Factor; D004110:Diltiazem; D001241:Aspirin