PLATELET AND AORTA ARACHIDONIC AND EICOSAPENTAENOIC ACID LEVELS AND IN-VITRO EICOSANOID PRODUCTION IN RATS FED HIGH-FAT DIETS

There is a significant interest in the interrelationship between long- chain n-3 and n-6 fatty acids due to their ability to modulate eicosan oid production. In general, the intake of arachidonic acid (AA) result s in enhanced eicosanoid production, whereas n-3 polyunsaturated fatty acids (PUFA) decrease the production of eicosanoids from AA. The purp ose of this study was to investigate whether the effects of dietary AA on eicosanoid production in the rat were correlated with the AA and E PA levels in platelets and aorta (eicosanoid-producing tissues). Four groups of male Sprague-Dawley rats were fed a high-fat diet enriched w ith eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (approx imately 100 mg/day of EPA + DHA) for 24 d. During the last 10 d, the f our groups were orally supplemented with 0, 30, 60, and 90 mg/day of e thyl arachidonate. A further group of rats was fed a control diet (wit hout long-chain n-3 PUFA) for 24 d. In vitro aorta prostacyclin (PGI(2 )) production, serum thromboxane A(2) (TxA(2)) production and plasma, and platelet and aorta phospholipid (PL) fatty acids were measured. En riching the diet with n-3 PUFA resulted in significant reductions in t issue AA levels and an increase in the n-3 PUFA, particularly EPA. On this diet, the AA to EPA ratio was 1:1 in platelet PL, and it was 2:1 in the aorta PL. There were significant decreases in the in vitro PGI( 2) and TxA(2) production compared with the control animals. The inclus ion of AA in the diet resulted in marked increases in AA levels in the platelet and aorta PL with corresponding decreases in EPA. The lowest dose of AA (30 mg/rat) reversed the effects of 100 mg/day of n-3 PUFA on AA levels in platelet and aortic PL and on in vitro aorta PGI(2) a nd serum TxA(2) production. The dietary AA caused a differential (twof old) increase in TxA(2) relative to PGI(2) for all three levels of AA supplementation. There were greater changes in the levels of AA and/or EPA in platelet PL compared with the aorta PL, which might have accou nted for the differential effects of these PUFA on thromboxane product ion compared with PGI(2) production in this study.