A proposed method for exploring anti-aggregatory effects of eicosapentaenoic acid in the rat.

Eicosapentaenoic acid (EPA) has been reported to be anti-aggregatory in humans, but it is difficult to confirm that anti-aggregatory effect in rat. To induce an anti-aggregatory effect of EPA even in rats, an attempt was made to modify fatty acid composition of the diet, i.e., a diet low in linoleic acid, which is a precursor of arachidonic acid (AA) in vivo. A group of rats eating EPA with butter, which contained low linoleic acid, as a lipid source for 12 consecutive days revealed significant inhibition of platelet aggregation induced by collagen. The inhibition was complete at 3.0 micrograms of collagen, a dose which caused complete aggregation in rats which received EPA with corn oil. In these experiments, the ratio of EPA to AA in platelet phospholipids was 0.038 for corn oil, 0.306 for corn oil plus EPA, 0.050 for butter and 0.703 for butter plus EPA. These results indicated that if one blocks the in vivo supply of AA, it causes an increase in EPA to AA ratio in platelet phospholipids, and consequently leads to an inhibition of platelet aggregation even in the rat.