THE EFFECT OF LINOLEIC, ARACHIDONIC AND EICOSAPENTAENOIC ACID SUPPLEMENTATION ON PROSTACYCLIN PRODUCTION IN RATS

We examined the effect of dietary supplementation of linoleic acid (LA ), arachidonic acid (AA) or eicosapentaenoic acid (EPA) to rats fed a diet low in linoleic acid on in vitro and in vivo production of prosta cyclin. Male Sprague Dawley rats were fed a high-fat diet (50% energy as fat, 1.5% linoleic acid) for two weeks. Three of the groups were th en supplemented orally with either 90 mg/d of LA, AA or EPA, all as th e ethyl esters, for a further two weeks while remaining on the high-fa t diet. Forty-eight hour urine samples were collected at the end of th e second and fourth weeks. In vivo prostacyclin production was determi ned by a stable isotope dilution, gas chromatography/mass spectrometry assay for the major urinary metabolite of prostacyclins (2,3-dinor-6- keto-PGF(1) alpha or PGI(2)-M and Delta(17)-2,3-dinor-6-keto-PGF(1) al pha or PGI(3)-M). In vitro prostacyclin production was determined by r adioimmunoassay of the stable metabolite (6-keto-PGF(1) alpha) followi ng incubation of arterial tissue. Oral supplementation with AA resulte d in a rise in plasma and aorta 20:4n-6, and increased in vitro prosta cyclin and urinary PGI(2)-M production. EPA supplementation resulted i n a rise in plasma and aorta 20:5n-3 and 22:5n-3, and a decline in pla sma 20:4n-6, but not in the aorta. In the EPA-supplemented group, the in vitro prostacyclin and the urinary PGI(3)-M increased, but urinary PGI(2)-M decreased. The increase in in vitro prostacyclin production i n the EPA-supplemented rats was unexpected and without obvious explana tion. Supplementation with LA had minimal effect on fatty acid composi tion of plasma or aorta and caused no change in prostacyclin productio n with either method. The in vivo measure of prostacyclin production w as positively correlated with aorta AA levels, and negatively correlat ed with aorta levels of EPA. There was a significant positive correlat ion between the in vitro production of prostacyclin and the in vivo pr oduction (as measured by the urinary prostacyclin metabolite level), d espite the differences observed in the EPA-fed group. There was a high inter-animal variability in prostacyclin production using either meth od. These results indicate that dietary AA stimulates and dietary EPA reduces in vivo PGI(2) production in the rat. An equivalent amount of dietary LA was without effect.