EFFECTS OF 3 TRANS ISOMERS OF EICOSAPENTAENOIC ACID ON RAT PLATELET-AGGREGATION AND ARACHIDONIC-ACID METABOLISM

Three trans isomers of eicosapentaenoic acid (EPA) were added to rat p latelets stimulated with arachidonic acid (AA) in order to compare the ir effects on platelet aggregation and on AA oxygenation with those of EPA. The production of metabolites from radiolabelled 20:5 Delta 17tr ans was studied also. EPA induced an inhibition of platelet aggregatio n of 26.7 +/- 6,6 % for a 20:5/20:4 ratio equal to 1. The 20:5 Delta 1 1trans and the 20:5 Delta 11trans, 17trans were twice as antiaggregant . In contrast, the 20:5 Delta 17trans induced similar antiaggregant ef fect as its cis homologue. Each fatty acid showed a dose-dependent eff ect. In opposition to EPA, 20:51 Delta 17trans was also able to induce platelet aggregation (12 +/- 4.9% at 5 mu M). With regards to the met abolism of AA, 20:5 Delta 11trans, 20:5 Delta 17trans and 20:5 Delta 1 1trans, 17trans (20:5/20:4 = 1) reduced the formation of the cyclooxyg enase metabolites (-63%, -37% and -68%, respectively) and enhanced tha t of 12-HETE (+67%, +38% and +74%, respectively) as compared tb EPA. T he analysis showed that radiolabelled 20:5 Delta 17trans was metaboliz ed into five compounds which remained to be identified. The Rf of thre e of these compounds (X-1, X-2 and X-4) were those of the metabolites of EPA. Experiments using baicalein induced an inhibition of the produ ction of X-2. This suggested that this compound was formed through the 12-lipoxygenase pathway. In the same way, using indomethacin as inhib itor, we observed that X-1, and X-4 were produced by the cyclooxygenas e pathway. Our results suggest that the trans double bond in the Delta 11 position may be responsible of the different physiological effects of the trans polyunsaturated fatty acids as compared to their cis hom ologue (EPA). Furthermore, 20:5 Delta 17trans seems to be recognised b y the enzymatic system as 20:4 n-6.