The n-3 fatty acids, eicosapentaenoic acid (20:5n3) and docosahexaenoic acid (22:6n3), are known to be lipoxygenase substrates. We have previously reported that mammalian platelets enzymatically produce 12S-hydroxy- eicosapentaenoate (12-HEPE) and 14(S)-hydroxydocosahexaenoate (14-HDHE) from an exogenous source of fatty acids. Our present studies have investigated (i) the effects of ethanol and dietary permutations on the production of eicosanoids and docosanoids and (ii) the biological activities of these metabolites in platelet-smooth muscle cell interactions as well as other cellular responses. Dietary supplementation with n-3 fatty acids leads to the replacement of 20:4n6 with 20:5n3 and 22:6n3 in rat platelet. The eicosanoid/docosanoid profile was shifted towards the n-3 products as reflected by an increase in platelet 12-lipoxygenase products of 20:5n3 (12-HEPE) and 22:6n3 (14-HDHE) and decreased 20:4n6 products compared to an n-6 supplemented group. Platelets obtained from ethanol-dependent rats produce markedly more HDHE following up to a 7 day exposure, however, no change in HDHE production was observed following a 14 day ethanol exposure. The hydroxylated fatty acids (HEPE and HDHE) have been biosynthesized and purified in order to examine their functions in smooth muscle. It was confirmed that they antagonize thromboxane-induced contractile responses. This effect was most significant in vascular smooth muscle in comparison.
