Molecular and Cellular Biochemistry

, Volume 225, Issue 1–2, pp 109–119 | Cite as

Dietary n‐3 polyunsaturated fatty acids affect the development of renovascular hypertension in rats

  • D. Rousseau
  • C. Héliès‐Toussaint
  • D. Raederstorff
  • D. Moreau
  • A. Grynberg


The consequences of a dietary n‐3 PUFA supply was investigated on the blood pressure (BP) increase elicited by left renal artery stenosis in rats distributed in 3 groups (n = 8) fed for 8 weeks a semi‐purified diet either as control diet or enriched diets (docosahexaenoic acid, DHA, or eicosapentaenoic acid, EPA). The PUFA intake induced large alterations in heart and kidney phospholipid fatty acid profile, but did not influence body weight, cardiac hypertrophy, renal left atrophy and right hypertrophy. Within 4 weeks, BP raised from 120–180 ± 2 mm Hg in the control group, but only to 165 ± 3 mm Hg in the n‐3 PUFA groups. After stabilization of BP in the 3 groups, the rats received a short administration of increasing dose of perindopril. The lower dose (0.5 mg/kg) moderately decreased BP only in the control group. With higher doses (1, 5 and 10 mg/kg) BP was normalized in the 3 groups, with a higher amplitude of the BP lowering effect in the control group. A moderate n‐3 PUFA intake can contribute to prevent the development of peripheral hypertension in rats by a mechanism that may involve angiotensin converting enzyme.

hypertension heart PUFA nutrition prevention perindopril rat 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Grynberg A, Ziegler D, Rupp H: Sympathoadrenergic overactivity and lipid metabolism. Cardiovasc Drugs Ther 10(suppl 1): 223–230, 1996Google Scholar
  2. 2.
    AHA, Nutrition Committee: Circulation 88: 3008–3029, 1993Google Scholar
  3. 3.
    Dyerberg J: n-3 polyunsaturated fatty acids and their possible role in the prevention of diseases. Nord Med 103: 161–165, 188, 1988Google Scholar
  4. 4.
    Dyerberg J, Bang HO, Hjorne N: Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr 28: 958–966, 1975Google Scholar
  5. 5.
    Kenny D, Egan BM: Is there a role for dietary fish oil in the treatment of hypertension? J Hum Hypertens 8: 895–905, 1994Google Scholar
  6. 6.
    Bjerregaard P, Dyerberg J: Fish oil and ischaemic heart disease in Greenland (letter). Lancet 2: 514, 1988Google Scholar
  7. 7.
    Salem N Jr, Hullin F, Yoffe AM, Karanian JW, Kim HY: Fatty acid and phospholipid species composition of rat tissues after a fish oil diet. Adv Prostagland Thromboxane Leukot Res 19: 618–622, 1989Google Scholar
  8. 8.
    Charnock JS, Abeywardena MY, McLennan PL: Comparative changes in the fatty-acid composition of rat cardiac phospholipids after longterm feeding of sunflower seed oil-or tuna fish oil-supplemented diets. Ann Nutr Metab 30: 393–406, 1986Google Scholar
  9. 9.
    Abeywardena MY, McLennan PL, Charnock JS: Changes in myocardial eicosanoid production following long-term dietary lipid supplementation in rats. Am J Clin Nutr 53: 1039S–1041S, 1991Google Scholar
  10. 10.
    Raederstorff D, Moser U: Influence of an increased intake of linoleic acid on the incorporation of dietary (n-3) fatty acids in phospholipids and on prostanoid synthesis in rat tissues. Biochim Biophys Acta 1165: 194–200, 1992Google Scholar
  11. 11.
    Nakada T, Kubota Y, Suzuki H, Sasagawa I, Watanabe M, Ishigooka M: Suppression of sympathetic nervous system attenuates the development of two-kidney, one-clip Goldblatt hypertension. J Urol 156: 1480–1484, 1996Google Scholar
  12. 12.
    Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: Results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico (see comments). Lancet 354: 447–455, 1999Google Scholar
  13. 13.
    Horrobin DF: Abnormal membrane concentrations of 20 and 22-carbon essential fatty acids: a common link between risk factors and coronary and peripheral vascular disease? Prostagland Leukot Essent Fatty Acids 53: 385–396, 1995Google Scholar
  14. 14.
    Horrocks LA, Yeo YK: Docosahexaenoic acid-enriched foods: Production and effects on blood lipids. Lipids 34(suppl): S313, 1999Google Scholar
  15. 15.
    Howe PR, Rogers PF, Lungershausen Y: Blood pressure reduction by fish oil in adult rats with established hypertension - dependence on sodium intake. Prostagland Leukot Essent Fatty Acids 44: 113–117, 1991Google Scholar
  16. 16.
    Morris MC, Sacks F, Rosner B: Does fish oil lower blood pressure? A meta-analysis of controlled trials (see comments). Circulation 88: 523–533, 1993Google Scholar
  17. 17.
    Singer P, Melzer S, Goschel M, Augustin S: Fish oil amplifies the effect of propranolol in mild essential hypertension. Hypertension 16: 682–691, 1990Google Scholar
  18. 18.
    Mills DE: Dietary omega 3 and omega 6 fatty acids and cardiovascular responses to pressor and depressor stimuli. World Rev Nutr Diet 66: 349–357, 1991Google Scholar
  19. 19.
    Rousseau D, Moreau D, Raederstorff D, Sergiel JP, Rupp H, Muggli R, Grynberg A: Is a dietary n-3 fatty acid supplement able to influence the cardiac effect of the psychological stress? Mol Cell Biochem 178: 353–366, 1998Google Scholar
  20. 20.
    Goldblatt H, Lynch J, Hanzal RF, Summerville WW: Studies on experimental hypertension. I. Production of persistent elevation of systolic blood pressure by means of renal ischemia. J Exp Med 59: 347–379, 1934Google Scholar
  21. 21.
    Rayner TE, Howe PR: Purified omega-3 fatty acids retard the development of proteinuria in salt-loaded hypertensive rats. J Hypertens 13: 771–780, 1995Google Scholar
  22. 22.
    Eriksson BM, Persson BA: Determination of catecholamines in rat heart tissue and plasma samples by liquid chromatography with electrochemical detection. J Chromatogr 228: 143–154, 1982Google Scholar
  23. 23.
    Folch J, Lees M, Sloane-Stanley GH: A simple method for isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497–509, 1957Google Scholar
  24. 24.
    Dagnelie P: Théories et Méthodes Statistiques, vol. 2. Presses Agronomiques de Gembloux, Gembloux, Belgium, 1975Google Scholar
  25. 25.
    Michel JB, Dussaule JC, Choudat L, Auzan C, Nochy D, Corvol P, Menard J: Effects of antihypertensive treatment in one-clip, two kidney hypertension in rats. Kidney Int 29: 1011–1020, 1986Google Scholar
  26. 26.
    Benediktsdottir VE, Gudbjarnason S: Reversible alterations in fatty acid composition of heart muscle membrane phospholipids induced by epinephrine in rats fed different fats. J Lipid Res 29: 765–772, 1988Google Scholar
  27. 27.
    De Simone G, Devereux RB, Camargo MJ, Volpe M, Wallerson DC, Atlas SA, Laragh JH: In vivo left ventricular anatomy in rats with twokidney, one clip and one-kidney, one clip renovascular hypertension. J Hypertens 10: 725–732, 1992Google Scholar
  28. 28.
    Melaragno MG, Fink GD: Slow pressor effect of angiotensin II in normotensive rats with renal artery stenosis. Clin Exp Pharmacol Physiol 23: 140–144, 1996Google Scholar
  29. 29.
    Bennett MA, Thurston H: Effect of angiotensin-converting enzyme inhibitors on resistance artery structure and endothelium-dependent relaxation in two-kidney, one-clip Goldblatt hypertensive and shamoperated rats. Clin Sci (Colch) 90: 21–29, 1996Google Scholar
  30. 30.
    Norton GR, Woodiwiss AJ, Trifunovic B: Renal effects of a high unsaturated fat diet in renal artery stenosis in rats. Experientia 52: 34–41, 1996Google Scholar
  31. 31.
    McLennan P, Howe P, Abeywardena M, Muggli R, Raederstorff D, Mano M, Rayner T, Head R: The cardiovascular protective role of docosahexaenoic acid. Eur J Pharmacol 300: 83–89, 1996Google Scholar
  32. 32.
    Iacono JM, Dougherty RM: Effects of polyunsaturated fats on blood pressure. Annu Rev Nutr 13: 243–260, 1993Google Scholar
  33. 33.
    Howe PR: Can we recommend fish oil for hypertension? Clin Exp Pharmacol Physiol 22: 199–203, 1995Google Scholar
  34. 34.
    Mori TA, Bao DQ, Burke Veal: Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension 34: 253–260, 1999Google Scholar
  35. 35.
    Bonaa KH, Bjerve KS, Straume B, Gram IT, Thelle D: Effect of eicosapentaenoic and docosahexaenoic acids on blood pressure in hypertension. A population-based intervention trial from the Tromso study. N Engl J Med 322: 795–801, 1990Google Scholar
  36. 36.
    Gosse P, Grellet J, Bonoron S, Tariosse L, Besse P, Dallocchio M: Effects of perindopril on left ventricular hypertrophy, coronary reserve and mechanical properties of the papillary muscle of the rat with renovascular arterial hypertension. Arch Mal Coeur Vaiss 80: 905–910, 1987Google Scholar
  37. 37.
    Levy BI, Michel JB, Salzmann JL, Devissaguet M, Camilleri JP, Safar ME: Effects of chronic converting enzyme inhibition on the structure and function of large arteries in the rat. Clin Exper Theory Practice A11: 487–498, 1989Google Scholar
  38. 38.
    Singer P: Blood pressure-lowering effect of omega 3 polyunsaturated fatty acids in clinical studies. World Rev Nutr Diet 66: 329–348, 1991Google Scholar
  39. 39.
    Grynberg A, Fournier A, Sergiel JP, Athias P: Effect of docosahexaenoic acid and eicosapentaenoic acid in the phospholipids of rat heart muscle cells on adrenoceptor responsiveness and mechanism. J Mol Cell Cardiol 27: 2507–2520, 1995Google Scholar
  40. 40.
    Wing LM, Nestel PJ, Chalmers JP, Rouse I, West MJ, Bune AJ, Tonkin AL, Russell AE: Lack of effect of fish oil supplementation on blood pressure in treated hypertensives. J Hypertens 8: 339–343, 1990Google Scholar
  41. 41.
    Gray DR, Gozzip CG, Eastham JH, Kashyap ML: Fish oil as an adjuvant in the treatment of hypertension. Pharmacotherapy 16: 295–300, 1996Google Scholar
  42. 42.
    Oudot F, Cordelet C, Sergiel JP, Grynberg A: Polyunsaturated fatty acids influence prostanoid synthesis in vascular endothelial cells under hypoxia and reoxygenation. Int J Vit Nutr Res 68: 263–271, 1998Google Scholar
  43. 43.
    Sergiel JP, Martine L, Raederstorff D, Grynberg A, Demaison L: Individual effects of dietary EPA and DHA on the functioning of the isolated working rat heart. Can J Physiol Pharmacol 76: 728–736, 1998Google Scholar
  44. 44.
    Liautaud S, Grynberg A, Mourot J, Athias P: Fatty acids of hearts from rats fed linseed or sunflower oil and of cultured cardiomyocytes grown on their sera. Cardioscience 2: 55–61, 1991Google Scholar
  45. 45.
    Emilsson A, Gudbjarnason S: Reversible alterations of fatty acid profile of glycerophospholipids in rat heart muscle induced by repeated norepinephrine administration. Biochem Biophys Acta 750: 1–6, 1983Google Scholar
  46. 46.
    Martinez-Maldonado M: Pathophysiology of renovascular hypertension. Hypertension 17: 707–719, 1991Google Scholar
  47. 47.
    Lakatta EG: Diminished beta adrenergic modulation of cardiovascular function in advanced age. Cardiol Clin 4: 185–189, 1986Google Scholar
  48. 48.
    Gudmundsdottir E, Benediktsdottir VE, Gudbjarnason S: Combined effects of age and dietary fat on beta 1-receptors and Ca2+ channels in rat hearts. Am J Physiol 260: H66–H72, 1991Google Scholar
  49. 49.
    Webb RC, Johnson JC, Bohr DF: Adrenergic neurotransmission in tail arteries from two-kidney, one-clip, renal hypertensive rats. Hypertension 5: 298–306, 1983Google Scholar
  50. 50.
    Hoffmann P, Taube C, Heinroth-Hoffmann I, Fahr A, Beitz J, Forster W, Poleshuk WS, Markov CM: Antihypertensive action of dietary polyunsaturated fatty acids in spontaneously hypertensive rats. Arch Int Pharmacodyn Ther 276: 222–235, 1985Google Scholar
  51. 51.
    Knapp HR: Cardiovascular III: Circulation - Blood Pressure. Hypotensive effects of w3 fatty acids: Mechanistic aspects. Health effects of w3 polyunsaturated fatty acids in seafoods, 1991, pp 313–328Google Scholar
  52. 52.
    Engler MM, Engler MB, Goodfriend TL, Ball DL, Yu Z, Su P, Kroetz DL: Docosahexaenoic acid is an antihypertensive nutrient that affects aldosterone production in SHR. Proc Soc Exp Biol Med 221: 32–38, 1999Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • D. Rousseau
    • 1
  • C. Héliès‐Toussaint
    • 1
  • D. Raederstorff
    • 2
  • D. Moreau
    • 3
  • A. Grynberg
    • 3
  1. 1.Faculté de PharmacieINRA NASAParisFrance
  2. 2.F. Hoffmann‐La RocheBaselSwitzerland
  3. 3.Faculté de MédecineLPPCEDijonFrance

Personalised recommendations