Effects of polyunsaturated fatty acids and some of their metabolites on mitotic activity of vascular smooth muscle explants from the coronary artery of rainbow trout (Oncorhynchus mykiss)

Abstract

This study is the first to examine the effects of polyunsaturated fatty acids and some of their metabolites on [3H]thymidine incorporation into vascular smooth muscle explants from the coronary artery of rainbow trout (Oncorhynchus mykiss). At a concentration of 120 μM, eicosapentaenoic acid (EPA; 20:5ω3), arachidonic acid (AA; 20:4ω6), and eicosatrienoic acid (ETA; 20:3ω6) all approximately doubled [3H]thymidine incorporation relative to controls. At a concentration of 20 μM, EPA had no significant effect, while ETA inhibited and AA caused an almost 5-fold increase in [3H]thymidine incorporation. The large mitogenic effect of 20 μM AA was completely inhibited by simultaneous addition of EPA to the culture medium. ETA only partially inhibited the mitogenic effect of 20 μM AA. Four AA-derived eicosanoids (or their stable analogues) were also tested. [3H]Thymidine incorporation was at least doubled with 1000 ng/mL carbacyclin (a prostacyclin analogue), 120 ng/mL prostaglandin F2α, and U-46619 (a thromboxane A2 analogue), but did not reach the level of stimulation produced by 20 μM AA. Leukotriene C4 had no significant effect. We conclude that dietary modulation of polyunsaturated fatty acids (PUFAs) in salmonids could have significant effects on coronary vascular smooth muscle mitosis through the incorporation of PUFAs into cell membranes and the production of eicosanoids.