ADDITIVE EFFECT OF DILTIAZEM (DIL) ON THE INHIBITION OF PLATELET AGGREGATION PRODUCED BY ASPIRIN (ASA).
Platelet activation in vivo occurs by the action of several stimuli. It is generally agreed that actives products of arachidonic acid derived via the cyclooxy-genase pathway can stimulate platelet aggregation. ASA decrease thromboxane A2 generation and thereby inhibit platelet aggregation produced by AA and, partially, by others agonists. Nevertheless, the antiaggregating effect of ASA can be overcome by the conjointly activity of arachidonic acid(AA) and platelet activating factor (PAF). The inhibition of this cooperative aggregating effect can be important in platelet function suppressive therapy. The effect of DIL was tested in this sys tern. DIL was added in vitro to platelet rich plasma oS talned from volunteers before and after ASA(100mg/dayT intake for 7 days. DIL (2ug/ml) inhibited 50% platelet aggregation induced by AA (0.75mM) in non aspiri-nated volunteers. At even lower concentrations of DIL (0.4-lug/ml) an inhibition of aggregation induced by 300nM of PAF was also observed. After ASA, no aggregation by AA, only a first wave followed by disaggregation when PAF (30nM) was used and a full response when this pair of agonists were added together was obtained. DIL (0.lug/ml) added in vitro, produced significant inhibition of the synergism.The effect in vivo of DIL plus low dose of ASA was also explored. In vivo administration of therapeutic dose of DIL (60mg T.I.D.) and low dose of ASA (75-100 mg/day), prevented the synergistic activity of AA plus PAF on platelet aggregation. In conclusion, DIL may enhance the effectiveness of low dose of ASA in the prevention of arterial thromboembolism.