Abstract
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 onin vitro andin vivo production of prostacyclin. 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 then supplemented orally with either 90 mg/d of LA, AA or EPA, all as the ethyl esters, for a further two weeks while remaining on the high-fat diet. Forty-eight hour urine samples were collected at the end of the second and fourth weeks.In vivo prostacyclin production was determined by a stable isotope dilution, gas chromatography/mass spectrometry assay for the major urinary metabolite of prostacyclins (2,3-dinor-6-keto-PGF1α or PGI2-M and Δ17-2-3-dinor-6-keto-PGF1α or PGI3-M).In vitro prostacyclin production was determined by radioimmunoassay of the stable metabolite (6-keto-PGF1α) following incubation of arterial tissue. Oral supplementation with AA resulted in a rise in plasma and aorta 20∶4n−6, and increasedin vitro prostacyclin and urinary PGI2-M production. EPA supplementation resulted in a rise in plasma and aorta 20∶5n−3 and 22∶5n−3, and a decline in plasma 20∶4n−6, but not in the aorta. In the EPA-supplemented group, thein vitro prostacyclin and the urinary PGI3-M increased, but urinary PGI2-M decreased. The increase inin vitro prostacyclin production in the EPA-supplemented rats was unexpected and without obvious explanation. Supplementation with LA had minimal effect on fatty acid composition of plasma or aorta and caused no change in prostacyclin production with either method. Thein vivo measure of prostacyclin production was positively correlated with aorta AA levels, and negatively correlated with aorta levels of EPA. There was a significant positive correlation between thein vitro production of prostacyclin and thein vivo production (as measured by the urinary prostacyclin metabolite level), despite the differences observed in the EPA-fed group. There was a high inter-animal variability in prostacyclin production using either method. These results indicate that dietary AA stimulates and dietary EPA reducesin vivo PGI2 production in the rat. An equivalent amount of dietary LA was without effect.
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Abbreviations
- AA:
-
arachidonic acid (20∶4n−6)
- BSTFA:
-
N,N-bis(trimethylsilyl) trifluoroacetamide
- DHA:
-
docosahexaenoic acid (22∶6n−3)
- EPA:
-
eicosapentaenoic acid (20∶5n−3)
- GC/MS:
-
gas chromatography/mass spectrometry
- KRB:
-
Krebs Ringer bicarbonate buffer
- LA:
-
linoleic acid (18∶2n−6)
- NICI:
-
negative ion chemical ionization
- PGI:
-
prostaglandin I (prostacyclin)
- PGI2-M:
-
2,3-dinor-6-keto-PGF1α
- PGI3-M:
-
Δ17-2-3-dinor-6-keto-PGF1α
- PL:
-
phospholipid
- PUFA:
-
polyunsaturated fatty acid
- RIA:
-
radioimmunoassay
- SIM:
-
selected ion monitoring
- TLC:
-
thin-layer chromatography
References
O'Dea, K., Steel, M., Naughton, J., Sinclair, A.J., Hopkins, G. Augus, A., He, G.W., Niall, M., and Martin, T.J. (1988)Lipids 23, 234–241.
Steel, M.S., Naughton, J.M., Hopkins, G.W., Sinclair, A.J., and O'Dea, K. (1990)Prostaglandins, Leukotrienes and Essent. Fatty Acids 40, 249–253.
Steel, M.S., Naughton, J.M., Hopkins, G.W., Sinclair, A.J., and O'Dea, K. (1990)Lipids 25, 719–723.
Naughton, J.M., Sinclair, A.J., O'Dea, K., and Steel, M.S. (1988)Biochim. Biophys. Acta 962, 166–172.
Steel, M.S., Naughton, J.M., Hopkins, G.W., Sinclair, A.J., and O'Dea, K. (1993)Prostaglandins, Leukotrienes and Essent. Fatty Acids. 48, 247–251.
Needleman, P., Raz, A., Minkers, M.S., Ferrendelli, J.A., and Sprecher, H. (1979)Proc. Natl. Acad. Sci. USA 76, 944–948.
Cho, M.J., and Allen, M.A. (1978)Prostaglandins, 15, 943–954.
Falardeau, P., Oates, J.A., and Brash, A.R. (1981)Anal. Biochem. 115, 359–367.
Rosenkranz, B., Kitajima, W., and Frolich, J. (1981)Kidney Int. 19, 755–759.
Rosenkranz, B., Fischer, C., Weimer, K.E., and Frolich, J. (1980)J. Biol. Chem. 255, 10194–10198.
Sun, F.F., and Taylor, B.T. (1978)Biochemistry 17, 4096–4101.
Seyberth, H.W., Tulassay, T., Kuhl, P.G., Soeding, K., Rascher, W., and Schweer, H. (1988)Prostaglandins 35, 221–232.
Bieri, J.G., Stoews, G.S., and Briggs, G.M. (1977)J. Nutr. 107, 1340–1348.
Folch, J., Lees, M., and Sloane-Stanley, G.H. (1957)J. Biol. Chem. 226, 497–509.
Sinclair, A.J., O'Dea, K., Dunstan, G., Ireland, P.D., and Niall, M. (1987)Lipids 22, 523–529.
Fitzgerald, G.A., Lawson, J., Blair, I.A., and Brash, A.R. (1985).Adv. Prostaglandin, Thromboxane Leukotriene Res. 15, 87–90.
Fischer, S., Weber, P.C., and Dyerberg, J. (1986)Prostaglandins 32, 235–241.
Knapp, H.R., and Fitzgerald, G.A. (1989)New Engl. J. Med. 320, 1037–1043.
Knapp, H.R., Reilly, I.A.G., Alessandrini, P., and Fitzgerald, G.A. (1986)New Engl. J. Med. 314, 937–942.
Falardeau, P., and Martineau, A. (1989)J. Hyperten, 7, 625–632.
Galli, C., Agradi, E., Petrone, A., and Tremoli, E. (1981)Lipids 16, 165–172.
Wey, H.E., Ziller, S., and Subbiah, M.T.R. (1983)Prostaglandins, Leukotrienes, Med. 12, 169–174.
Spector, A., Kaduce, T.L., Hoak, J.C., and Czervionke, R.L. (1983)Arteriosclerosis 3, 323–331.
Ramesha, C.S., Gronke, R.S., Sivarajan, M., and Lands, W.E.M. (1985)Prostaglandins 29, 991–1009.
Fischer, S., Vischer, A., Preac-Mursic, V., and Weber, P.C. (1987)Prostaglandins 34, 367–375.
Charnock, J.S., Sundram, K., Tan, D., and Abeywardena, M.Y. (1993) inEssential Fatty Acids and Eicosanoids (Sinclair, A.J., and Gibson, R.A. eds) pp. 239–244, AOCS Press, Champaign.
Mohrhauer, H., and Holman, R.T. (1963)J. Lipid Res. 4, 151–159.
Leyton, J., Drury, P.J., and Crawford, M.A. (1987)Br. J. Nutr. 57, 383–393.
Knapp, H.R., and Salem, Jr., N. (1989)Prostaglandins 38, 509–521.
Morita, I., Saito, Y., Chang, W.C., and Murota, S. (1983)Lipids 18, 42–49.
Whitaker, M.O., Wyche, A., Fitzpatrick, F., Sprecher, H., and Needleman, P., (1979)Proc. Natl. Acad. Sci. USA 76, 5919–5923.
Fischer, S., and Weber, P.C. (1984)Nature 307, 165–168.
Scherhag, R., Kramer, H.J., and Dusing, R. (1982)Prostaglandins 23, 369–382.
Hamazaki, T., Hirai, A., Terano, T., Sajiki, S., Kondo, S., Fujita, T., Tamura, Y., and Kumagai, A. (1982)Prostaglandins 23, 557–567.
DeCaterina, R., Giannessi, D., Mazzone, A., Berini, W., Lazzerini, G., Maffei, S., Cerri, M., Salvatore, L., and Weksler, B. (1990)Circulation 82, 428–437.
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Mann, N.J., Warrick, G.E., O'Dea, K. et al. The effect of linoleic, arachidonic and eicosapentaenoic acid supplementation on prostacyclin production in rats. Lipids 29, 157–162 (1994). https://doi.org/10.1007/BF02536723
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DOI: https://doi.org/10.1007/BF02536723