Mammalian platelets are high in 12-lipoxygenase activity and capable of enzymatically producing 13-OH-18:2n6 (13-HODE), 12-OH-20:4n6 (12-HETE), 12-OH-20:5n3 (12-HEPE), 11-OH-22:6n3 (11-HDHE) and 14-OH-22:6n3 (14-HDHE). In addition, we have reported the production of a 15-lipoxygenase product, 17-OH-22:6n3 (17-HDHE). The biological activities of these metabolites have been examined with emphasis on their possible mechanisms of action. HDHE's dose-dependently stimulate lipoxygenase products from lung parenchymal tissue, neutrophils and monocytes. A direct correlation exists between endogenous leukotriene production and the contractile properties of HDHE in airway smooth muscle. In addition, HDHE's may specifically interact with thromboxane receptors as suggested by their relatively specific inhibition of U46619-induced contractions in smooth muscle. Preliminary data demonstrate a direct relationship between inhibition of U46619-induced platelet aggregation and 3H-U46619 specific binding by relatively high concentrations of HDHE. Moreover, vasculature obtained from ethanol-dependent or fish oil-fed rats are less contractile to the thromboxane analog, U46619. Ionophore-stimulated 13-HODE and 12-HEPE production was depressed in platelets obtained from ethanol-dependent rats. The production of these hydroxy fatty acids from platelets was markedly greater when the platelet membrane was enriched with the appropriate n-6 or n-3 precursor fatty acid. Moreover, supplementation with corn oil (n-6) countered the ethanol- induced decline in platelet n-6 hydroxy fatty acid. Similarly, supplemention with fish oil (n-3) effectively countered the observed decline in the production of the n-3 hydroxy fatty acid indicating that increasing substrate availability through dietary means is an effective way of countering the effects of ethanol in this regard.
