Effects of eicosapentaenoic acid on arachidonic acid metabolism in cultured vascular cells and platelets: species difference.

The metabolism of eicosapentaenoic acid (EPA) in cultured vascular smooth muscle cells isolated from human, rat, rabbit and miniature pig and bovine endothelial cells were studied. EPA was not able to be converted to any prostaglandins (PGs) in murine and porcine smooth muscle cells. However, in human and rabbit smooth muscle cells and bovine endothelial cells EPA was easily converted to delta 17-6-ketoPGF1 alpha, which is a stable metabolite of PGI3. Cyclooxygenase and 12-lipoxygenase activities in platelets isolated from human citrated blood were almost completely inhibited by EPA at the dose over 4 micrograms. But in platelets isolated from rat the inhibitory effects of EPA on arachidonic acid (AA) metabolism were much smaller than that in human platelets. In rat, EPA was not only being converted to no PGI3, but also being a blocker to PGI2 synthesis in vascular cells. Moreover, the rat EPA has much less activity in inhibiting thromboxane A2 (TXA2) synthesis in platelets. On the contrary, in human EPA was not only easily converted to PGI3 in vascular cells, but also blocking TXA2 synthesis in platelets. Thus, anti-aggregatory effects of EPA was positive in human and negative in rat perhaps due to species difference in sensitivity to EPA.