, Volume 38, Issue 4, pp 459–464 | Cite as

Increased blood pressure later in life may be associated with perinatal n−3 fatty acid deficiency

  • James A. Armitage
  • Adrian D. Pearce
  • Andrew J. Sinclair
  • Algis J. Vingrys
  • Richard S. Weisinger
  • Harrison S. Weisinger


Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Previous work in both animals and humans with high blood pressure has demonstrated the antihypertensive effects of n−3 polyunsaturated fatty acids (PUFA), although it is not known whether these nutrients are effective in preventing hypertension. The predominant n−3 PUFA in the mammalian nervous system, docosahexaenoic acid (DHA), is deposited into synaptic membranes at a high rate during the perinatal period, and recent observations indicate that the perinatal environment is important for the normal development of blood pressure control. This study investigated the importance of perinatal n−3 PUFA supply in the control of blood pressure in adult Sprague-Dawley rats. Pregnant rat dams were fed semisynthetic diets that were either deficient in (DEF) or supplemented with (CON) n−3 PUFA. Offspring were fed the same diets as their mothers until 9 wk; then, half of the rats from each group were crossed over to the opposite diet, creating four groups, i.e., CON-CON; CON-DEF; DEF-DEF, DEF-CON. Mean arterial blood pressures (MAP) were measured directly, at 33 wk of age, by cannulation of the femoral artery. The phospholipid fatty acid profile of the hypothalamic region was determined by capillary gas-liquid chromatography. The tissue phospholipid fatty acid profile reflected the diet that the rats were consuming at the time of testing. Both groups receiving DEF after 9 wk of age (i.e., DEF-DEF and CON-DEF) had similar profiles with a reduction in DHA levels of 30%, compared with rats receiving CON (i.e., CON-CON and DEF-CON). DEF-DEF rats had significantly raised MAP compared with all other groups, with differences as great as 17 mm Hg. DEF-CON rats had raised MAP compared with CON-CON rats, and DEF-DEF rats had higher MAP than CON-DEF rats, despite the fact that their respective fatty acid profiles were not different. These findings indicate that inadequate levels of DHA in the perinatal period are associated with altered blood pressure control in later life. The way in which these long-term effects are produced remains to be elucidated.



(18∶3n−3, α-linolenic acid)


n−3-sufficient diet


cardiovascular disease


circumventricular organ


n−3-deficient diet


(22∶6n−3, docosahexaenoic acid)


mean arterial pressure


change in mean arterial pressure


polyunsaturated fatty acid


spontaneously hypertensive rat


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Minino, A.M., Arias, E., Kochanek, K.D., Murphy, S.L., and Smith, B.L. (2002) Deaths: Final Data for 2000, Natl. Vital Stat. Rep. 50, 1–119.PubMedGoogle Scholar
  2. 2.
    Minino, A.M., and Smith, B.L. (2001) Deaths: Preliminary Data for 2000, Natl. Vital Stat. Rep. 49, 1–40.Google Scholar
  3. 3.
    American Heart Association (2001) 2002 Heart and Stroke Statistical Update, American Heart Association, Dallas.Google Scholar
  4. 4.
    Guyton, A.C., and Hall, J.E. (2000) Nervous Regulation of the Circulation, and Rapid Control of Arterial Pressure, in Textbook of Medical Physiology, pp. 184–194, W.B. Saunders Company, Philadelphia.Google Scholar
  5. 5.
    McKinley, M.J., Pennington, G.L., and Oldfield, B.J. (1996) Anteroventral Wall of the Third Ventricle and Dorsal Lamina Terminalis: Headquarters for Control of Body Fluid Homeostasis? Clin. Exp. Pharmacol. Physiol. 23, 271–281.PubMedGoogle Scholar
  6. 6.
    Weisinger, H.S., Armitage, J.A., Sinclair, A.J., Vingrys, A.J., Burns, P.L., and Weisinger, R.S. (2001) Perinatal Omega-3 Fatty Acid Deficiency Affects Blood Pressure Later in Life, Nat. Med. 7, 258–259.CrossRefPubMedGoogle Scholar
  7. 7.
    Sinclair, A.J. (1975) Long-Chain Polyunsaturated Fatty Acids in the Mammalian Brain, Proc. Nutr. Soc. 34, 287–291.CrossRefPubMedGoogle Scholar
  8. 8.
    Arbuckle, L.D., and Innis, S.M. (1993) Docosahexaenoic Acid Is Transferred Through Maternal Diet to Milk and to Tissues of Natural Milk-Fed Piglets, J. Nutr. 123, 1668–1675.PubMedGoogle Scholar
  9. 9.
    Bazan, N.G., and Scott, B.L. (1990) Dietary Omega-3 Fatty Acids and Accumulation of Docosahexaenoic Acid in Rod Photoreceptor Cells of the Retina and at Synapses, Upsala J. Med. Sci. (Suppl. 48), 97–107.Google Scholar
  10. 10.
    Benolken, R.M., Anderson, R.E., and Wheeler, T.G. (1973) Membrane Fatty Acids Associated with the Electrical Response in Visual Excitation, Science 182, 1253–1254.CrossRefPubMedGoogle Scholar
  11. 11.
    Neuringer, M., Connor, W.E., Lin, D.S., Barstad, L., and Luck, S. (1986) Biochemical and Functional Effects of Prenatal and Postnatal Omega 3 Fatty Acid Deficiency on Retina and Brain in Rhesus Monkeys, Proc. Natl. Acad. Sci. USA 83, 4021–4025.CrossRefPubMedGoogle Scholar
  12. 12.
    Weisinger, H.S., Vingrys, A.J., Bui, B.V., and Sinclair, A.J. (1999) Effects of Dietary n−3 Fatty Acid Deficiency and Repletion in the Guinea Pig Retina, Investig. Ophthalmol. Vis. Sci. 40, 327–338.Google Scholar
  13. 13.
    Makrides, M., Neumann, M.A., Simmer, K., Pater, J., and Gibson, R.A. (1995) Are Long Chain Polyunsaturated Fatty Acids Essential Nutrients in Infancy? Lancet 345, 1463–1468.CrossRefPubMedGoogle Scholar
  14. 14.
    Uauy, R.D., Birch, D.G., Birch, E.E., Tyson, J.E., and Hoffman, D.R. (1990) Effect of Dietary Omega-3 Fatty Acids on Retinal Function of Very-Low-Birth-Weight Neonates, Pediatr. Res. 28, 485–492.PubMedGoogle Scholar
  15. 15.
    Greiner, R.S., Moriguchi, T., Hutton, A., Slotnick, B.M., and Salem, N. (1999) Rats with Low Levels of Brain Docosahexaenoic Acid Show Impaired Performance in Olfactory-Based and Spatial Learning Tasks, Lipids 34, S239-S243.PubMedGoogle Scholar
  16. 16.
    Reisbick, S., Neuringer, M., Connor, W.E., and Barstad, L. (1992) Postnatal Deficiency of Omega-3 Fatty Acids in Monkeys: Fluid Intake and Urine Concentration, Physiol. Behav. 51, 473–479.CrossRefPubMedGoogle Scholar
  17. 17.
    Armitage, J.A., Burns, P.L., Sinclair, A.J., Weisinger, H.S., Vingrys, A.J., and Wisinger, R.S. (2001) Permatal Omega-3 Fatty Acid Deprivation Alters Thirst and Sodium Appetite in Adult Rats, Appetite 37, 258.Google Scholar
  18. 18.
    Kimura, S., Minami, M., Saito, H., Kobayashi, T., and Okuyama, H. (1995) Dietary Docosahexaenoic Acid (22∶6n−3) Prevents the Development of Hypertension in SHRSP, Clin. Exp. Pharmacol. Physiol. 22 (Suppl. 1), S308-S309.Google Scholar
  19. 19.
    Mori, T.A., Bao, D.Q., Burke, V., Puddey, I.B., and Beilin, L.J. (1999) Docosahexaenoic Acid but Not Eicosapentaenoic Acid Lowers Ambulatory Blood Pressure and Heart Rate in Humans, Hypertension 34, 253–260.PubMedGoogle Scholar
  20. 20.
    Singer, P., Wirth, M., Voigt, S., Richter-Heinrich, E., Godicke, W., Berger, I., Naumann, E., Listing, J., Hartrodt, W., and Taube, C. (1985) Blood Pressure- and Lipid-Lowering Effect of Mackerel and Herring Diet in Patients with Mild Essential Hypertension, Atherosclerosis 56, 223–235.CrossRefPubMedGoogle Scholar
  21. 21.
    Norris, P.G., Jones, C.J., and Weston, M.J. (1986) Effect of Dietary Supplementation with Fish Oil on Systolic Blood Pressure in Mild Essential Hypertension, Br. Med. J. 293, 104–105.Google Scholar
  22. 22.
    Knapp, H.R., and FitzGerald, G.A. (1989) The Antihypertensive Effects of Fish Oil. A Controlled Study of Polyunsaturated Fatty Acid Supplements in Essential Hypertension, N. Engl. J. Med. 320, 1037–1043.PubMedCrossRefGoogle Scholar
  23. 23.
    Connor, S.L., and Connor, W.E. (1997) Are Fish Oils Beneficial in the Prevention and Treatment of Coronary Artery Disease? Am. J. Clin. Nutr. 66, 1020S-1031S.PubMedGoogle Scholar
  24. 24.
    Pietinen, P. (1994) Dietary Fat and Blood Pressure, Ann. Med. 26, 465–468.PubMedGoogle Scholar
  25. 25.
    Marchioli, R., Schweiger, C., Tavazzi, L., and Valagussa, F. (2001) Efficacy of n−3 Polyunsaturated Fatty Acids After Myocardial Infarction: Results of GISSI-Prevenzione Trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico, Lipids 36, S119–126.CrossRefGoogle Scholar
  26. 26.
    Mizushima, S., Moriguchi, E.H., Ishikawa, P., Hekman, P., Nara, Y., Mimura, G., Moriguchi, Y., and Yamori, Y. (1997) Fish Intake and Cardiovascular Risk Among Middle-Aged Japanese in Japan and Brazil, J. Cardiovasc. Risk 4, 191–199.CrossRefPubMedGoogle Scholar
  27. 27.
    Kagan, A., Rhoads, G.G., Zeegen, P.D., and Nichaman, M.Z. (1971) Coronary Heart Disease Among Men of Japanese Ancestry in Hawaii. The Honolulu Heart Study, Isr. J. Med. Sci. 7, 1573–1577.PubMedGoogle Scholar
  28. 28.
    Barker, D.J., Bull, A.R., Osmond, C., and Simmonds, S.J. (1990) Fetal and Placental Size and Risk of Hypertension in Adult Life, Br. Med. J. 301, 259–262.CrossRefGoogle Scholar
  29. 29.
    Langley-Evans, S.C. (2000) Critical Differences Between Two Low Protein Diet Protocols in the Programming of Hypertension in the Rat, Int. J. Food Sci. Nutr. 51, 11–17.CrossRefPubMedGoogle Scholar
  30. 30.
    Godfrey, K.M., and Barker, D.J. (2000) Fetal Nutrition and Adult Disease, Am. J. Clin. Nutr. 71, 1344S-1352S.PubMedGoogle Scholar
  31. 31.
    Kwong, W.Y., Wild, A.E., Roberts, P., Willis, A.C., and Fleming, T.P. (2000) Maternal Undernutrition During the Preimplantation Period of Rat Development Causes Blastocyst Abnormalities and Programming of Postnatal Hypertension, Development 127, 4195–4202.PubMedGoogle Scholar
  32. 32.
    Langley-Evans, S.C. (1996) Intrauterine Programming of Hypertension in the Rat: Nutrient Interactions, Comp. Biochem. Physiol. A. Physiol. 114, 327–333.CrossRefPubMedGoogle Scholar
  33. 33.
    Weisinger, H.S., Vingrys, A.J., and Sinclair, A.J. (1995) Dietary Manipulation of Long-Chain Polyunsaturated Fatty Acids in the Retina and Brain of Guinea Pigs, Lipids 30, 471–473.CrossRefPubMedGoogle Scholar
  34. 34.
    Weisinger, H.S., Vingrys, A.J., and Sinclair, A.J. (1998) Effect of Diet on the Rate of Depletion of n−3 Fatty Acids in the Retina of the Guinea Pig, J. Lipid Res. 39, 1274–1279.PubMedGoogle Scholar
  35. 35.
    Bonaa, K.H., Bjerve, K.S., Straume, B., Gram, I.T., and Thelle, D. (1990) Effect of Eicosapentaenoic and Docosahexaenoic Acids on Blood Pressure in Hypertension. A Population-Based Intervention Trial from the Tromsø Study, N. Engl. J. Med. 322, 795–801.PubMedCrossRefGoogle Scholar
  36. 36.
    Morris, M.C., Sacks, F., and Rosner, B. (1993) Does Fish Oil Lower Blood Pressure? A Meta-analysis of Controlled Trials, Circulation 88, 523–533.PubMedGoogle Scholar
  37. 37.
    Appel, L.J., Miller, E.R., 3rd, Seidler, A.J., and Whelton, P.K. (1993) Does Supplementation of Diet with “Fish Oil” Reduce Blood Pressure? A Meta-analysis of Controlled Clinical Trials, Arch. Intern. Med. 153, 1429–1438.CrossRefPubMedGoogle Scholar
  38. 38.
    Geleijnse, J.M., Giltay, E.J., Grobbee, D.E., Donders, A.R., and Kok, F.J. (2002) Blood Pressure Response to Fish Oil Supplementation: Metaregression Analysis of Randomized Trials, J. Hypertens. 20, 1493–1499.CrossRefPubMedGoogle Scholar
  39. 39.
    Liu, D., Diorio, J., Day, J.C., Francis, D.D., and Meaney, M.J. (2000) Maternal Care, Hippocampal Synaptogenesis and Cognitive Development in Rats, Nat. Neurosci. 3, 799–806.CrossRefPubMedGoogle Scholar
  40. 40.
    Contreras, R.J. (1989) Differences in Perinatal NaCl Exposure Alters Blood Pressure Levels of Adult Rats, Am. J. Physiol. 256, R70-R77.PubMedGoogle Scholar
  41. 41.
    Denton, D.A., Weisinger, R.S., Mundy, N.I., Wickings, E.J., Dixson, A., Moisson, P., Pingrad, A.M., Shade, R., Carey, D., Ardaillou, R., et al. (1995) The Effect of Increased Salt Intake on Blood Pressure of Chimpanzees, Nat. Med. 1, 1009–1016.CrossRefPubMedGoogle Scholar
  42. 42.
    Campese, V.M. (1994) Salt Sensitivity in Hypertension. Renal and Cardiovascular Implications, Hypertension 23, 531–550.PubMedGoogle Scholar
  43. 43.
    Weinberger, M.H. (1996) Salt Sensitivity of Blood Pressure in Humans, Hypertension 27, 481–490.PubMedGoogle Scholar
  44. 44.
    Granger, J.P., and Schnackenberg, C.G. (2000) Renal Mechanisms of Angiotensin II-Induced Hypertension, Semin. Nephrol. 20, 417–425.PubMedGoogle Scholar
  45. 45.
    Kitajka, K., Puskas, L.G., Zvara, A., Hackler, L., Jr., Barcelo-Coblijn, G., Yeo, Y.K., and Farkas, T. (2002) The Role of n−3 Polyunsaturated Fatty Acids in Brain: Modulation of Rat Brain Gene Expression by Dietary n−3 Fatty Acids, Proc. Natl. Acad. Sci. USA 99, 2619–2624.CrossRefPubMedGoogle Scholar

Copyright information

© AOCS Press 2003

Authors and Affiliations

  • James A. Armitage
    • 3
    • 1
  • Adrian D. Pearce
    • 3
  • Andrew J. Sinclair
    • 2
  • Algis J. Vingrys
    • 1
  • Richard S. Weisinger
    • 3
  • Harrison S. Weisinger
    • 3
  1. 1.Department of Optometry and Vision SciencesUniversity of MelbourneVictoriaAustralia
  2. 2.Department of Food ScienceRoyal Melbourne Institute of Technology UniversityMelbournneVictoriaAustralia
  3. 3.Section of Neurobiology, Howard Florey Institute of Experimental Physiology and MedicineUniversity of MelbourneVictoriaAustralia

Personalised recommendations