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

Abstract

The metabolism of eicosapentaenoic acid (EPA) in cultured vascular smooth muscle cells isolated from human, rat, rabbit and miniture 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 Δ 176-ketoPGF 1α, which is a stable metabolite of PGI 3. Cyclooxygenase and 12-lipoxygenase activities in platelets isolated from human citrated blood were almost completely inhibited by EPA at the dose over 4 μg. 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 PGI 3, but also being a blocker to PGI 2 synthesis in vascular cells. Moreover, in rat EPA has much less activity in inhibiting thromboxane A 2 (TXA 2) synthesis in platelets. On the contrary, in human EPA was not only easily converted to PGI 3 in vascular cells, but also blocking TXA 2 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.