Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-β to prevent human essential hypertension

Abstract

Patients with uncontrolled essential hypertension have elevated concentrations of superoxide anion (O2−•), hydrogen peroxide (H2O2), lipid peroxides, endothelin, and transforming growth factor-β (TGF-β) with a simultaneous decrease in endothelial nitric oxide (eNO), superoxide dismutase (SOD), vitamin E, and long-chain polyunsaturated fatty acids (LCPUFAs). Physiological concentrations of angiotensin II activate NAD(P)H oxidase and trigger free radical generation (especially that of O2−•). Normally, angiotensin II-induced oxidative stress is abrogated by adequate production and release of eNO, which quenches O2−• to restore normotension. Angiotensin II also stimulates the production of endothelin and TGF-β. TGF-β enhances NO generation, which in turn suppresses TGF-β production. Thus, NO has a regulatory role on TGF-β production and is also a physiological antagonist of endothelin. Antihypertensive drugs suppress the production of O2−• and TGF-β and enhance eNO synthesis to bring about their beneficial actions. LCPUFAs suppress angiotensin-converting enzyme (ACE) activity, reduce angiotensin II formation, enhance eNO generation, and suppress TGF-β expression. Perinatal supplementation of LCPUFAs decreases insulin resistance and prevents the development of hypertension in adult life, whereas deficiency of LCPUFAs in the perinatal period results in raised blood pressure later in life. Patients with essential hypertension have low concentrations of various LCPUFAs in their plasma phospholipid fraction. Based on this, it is proposed that LCPUFAs serve as endogenous regulators of ACE activity, O2−•, eNO generation, and TGF-β expression. Further, LCPUFAs have actions similar to statins, inhibit (especially ω-3 fatty acids) cyclooxygenase activity and suppress the synthesis of proinflammatory cytokines, and activate the parasympathetic nervous system, all actions that reduce the risk of major vascular events. Hence, it is proposed that availability of adequate amounts of LCPUFAs during the critical periods of growth prevents the development of hypertension in adulthood.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  • Agarwal R, Siva S, Dunn SR & Sharma K (2002): Add-on angiotensin receptor blockade lowers urinary transforming growth factor-beta levels. Am. J. Kidney Dis. 39, 486–492.

    CAS  PubMed  Google Scholar 

  • Bachmann S & Mundel P (1994): Nitric oxide in the kidney: synthesis, localization, and function. Am. J. Kidney Dis. 24, 112–129.

    CAS  PubMed  Google Scholar 

  • Baur LA, O'Connor J, Pan DA, Kriketos AD & Storlien LH (1998): The fatty acid composition of skeletal muscle membrane phospholipids: its relationship with the type of feeding and plasma glucose levels in young children. Metabolism 47, 106–112.

    CAS  PubMed  Google Scholar 

  • Bayorh MA, Williams E, Thierry-Palmer M, Sanford G, Emmett N, Harris-Hooker S, Socci RR & Chu TC (1999): Enhanced nitric oxide synthesis reverses salt-induced alterations in blood flow and cGMP levels. Clin. Exp. Hypertens 21, 333–352.

    CAS  PubMed  Google Scholar 

  • Beswick RA, Dorrance AM, Leite R & Webb RC (2001): NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat. Hypertension 38, 1107–1111.

    CAS  PubMed  Google Scholar 

  • Boger RH, Bode-Boger SM, Szuba A, Tsao PS, Chan JR, Tangphao O, Blaschke TF & Cooke JP (1998): Asymmetric dimethylarginine: a novel risk factor for endothelial dysfunction. Its role in hypercholesterolemia. Circulation 98, 1842–1847.

    CAS  PubMed  Google Scholar 

  • Camilletti A, Moretti N, Giacchetti G, Faloia E, Martarelli D, Mantero F & Mazzanti L (2001): Decreased nitric oxide levels and increased calcium content in platelets of hypertensive patients. Am. J. Hypertens. 14 (4 Part 1), 382–386.

    CAS  PubMed  Google Scholar 

  • Campese VM, Amar M, Anjali C, Medhat T & Wurgaft A (1997): Effect of L-arginine on systemic and renal haemodynamics in salt-sensitive patients with essential hypertension. J. Hum. Hypertens. 11, 527–532.

    CAS  PubMed  Google Scholar 

  • Cardillo C, Kilcoyne CM, Quyyumi AA, Cannon III RO & Panza JA (1998): Selective defect in nitric oxide synthesis may explain the impaired endothelium-dependent vasodilation in patients with essential hypertension. Circulation 97, 851–856.

    CAS  PubMed  Google Scholar 

  • Carneado J, Alvarez de Sotomayor M, Perez-Guerrero C, Jimmenez L, Herrera MD, Pamies E, Martin-Sanz MD, Stiefel P, Miranda M, Bravo L & Marhuenda E (2002): Simvastatin improves endothelial function in spontaneously hypertensive rats through a superoxide dismutase mediated antioxidant effect. J. Hypertens. 20, 429–437.

    CAS  PubMed  Google Scholar 

  • Chabrashvili T, Tojo A, Onozato ML, Kitiyakara C, Quinn MT, Fujita T, Welch WJ & Wilcox CS (2002): Expression and cellular localization of classic NADPH oxidase subunits in the spontaneously hypertensive rat kidney. Hypertension 39, 269–274.

    CAS  PubMed  Google Scholar 

  • Craven PA, Studer RK, Felder J, Phillips S & DeRubertis FR (1997): Nitric oxide inhibition of transforming growth factor-beta and collagen synthesis in mesangial cells. Diabetes 46, 671–681.

    CAS  PubMed  Google Scholar 

  • Das UN (1985): Minerals, trace elements, and vitamins interact with essential fatty acids and prostaglandins to prevent hypertension, thrombosis, hypercholesterolemia, and atherosclerosis and their attendant complications. IRCS Med. Sci. 13, 684–688.

    CAS  Google Scholar 

  • Das UN (1987): Biological significance of arachidonic acid. Med. Sci. Res. 24, 1485–1489.

    Google Scholar 

  • Das UN (1991): Essential fatty acids: biology and their clinical implications. Asia Pacific J. Pharmacol. 6, 317–330.

    Google Scholar 

  • Das UN (1995): Essential fatty acid metabolism in patients with essential hypertension, diabetes mellitus, and coronary heart disease. Prostaglandins Leukot. Essent. Fatty Acids 52, 387–391.

    CAS  PubMed  Google Scholar 

  • Das UN (1999): Essential fatty acids in health and disease. J. Assoc. Physicians India 47, 906–911.

    CAS  PubMed  Google Scholar 

  • Das UN (2000a): Hypertension and ascorbic acid. Lancet 355, 1273.

    CAS  PubMed  Google Scholar 

  • Das UN (2000b): Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? Prostaglandins Leukot. Essent. Fatty Acids 63, 351–362.

    CAS  PubMed  Google Scholar 

  • Das UN (2001): Nutritional factors in the pathobiology of human essential hypertension. Nutrition 17, 337–346.

    CAS  PubMed  Google Scholar 

  • Das UN (2001b): Exploring the actions of vitamin C. Can. Med. Assoc. J. 165, 13–14.

    CAS  Google Scholar 

  • Das UN (2001c): Can perinatal supplementation of long-chain polyunsaturated fatty acids prevent hypertension in adult life? Hypertension 38: e6–e8.

    CAS  PubMed  Google Scholar 

  • Das UN (2001d): Essential fatty acids as possible mediators of the actions of statins. Prostaglandins Leukot. Essent. Fatty Acids 65, 37–40.

    CAS  PubMed  Google Scholar 

  • Das UN (2001e): The brain–lipid–heart connection. Nutrition 17, 260–263.

    CAS  PubMed  Google Scholar 

  • Das UN (2001f): Is obesity an inflammatory condition? Nutrition 17, 953–966.

    CAS  PubMed  Google Scholar 

  • Das UN (2002a): Obesity, metabolic syndrome X, and inflammation. Nutrition 18, 430–432.

    CAS  PubMed  Google Scholar 

  • Das UN (2002b): Metabolic syndrome X is common in South Asians, but why and how? Nutrition 18, 774–776.

    PubMed  Google Scholar 

  • Das UN (2002c): A Perinatal Strategy for Preventing Adult Disease: The Role of Long-Chain Polyunsaturated Fatty Acids. Boston: Kluwer Academic Publisher, 2002.

    Google Scholar 

  • Das UN, Kumar KV & Ramesh G (1994): Essential fatty acid metabolism in South Indians. Prostaglandins Leukot. Essent. Fatty Acids 50, 253–256.

    CAS  PubMed  Google Scholar 

  • Das UN, Horrobin DF, Begin ME, Huang YS, Cunnane SC & Manku MS (1988): Clinical significance of essential fatty acids. Nutrition 4, 337–342.

    CAS  Google Scholar 

  • Delles C, Jacobi J, John S, Fleischmann I & Schieder RE (2002): Effects of enalapril and eprosartan on the renal vascular nitric oxide system in human essential hypertension. Kidney Int. 61, 1462–1468.

    CAS  PubMed  Google Scholar 

  • Derhaschnig U, Shehata M, Herkner H, Bur A, Woisetschlager C, Laggner AN & Hirschl MM (2002): Increased levels of transforming growth factor-beta 1 in essential hypertension. Am. J. Hypertens. 15, 207–211.

    CAS  PubMed  Google Scholar 

  • Dhaly AJ, Hoagland KM, Flasch AK, Jha S, Ledbetter SR & Roman RJ (2002): Antihypertensive effects of chronic anti-TGF-beta antibody therapy in Dahl S rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283, R757–R767.

    Google Scholar 

  • Diederich D, Skopec J, Diederich A & Dai FX (1994): Cyclosporine produces endothelial dysfunction by increased production of superoxide. Hypertension 23(3 Part 2), 957–961.

    CAS  PubMed  Google Scholar 

  • El Midaoui A, Wu R & De Champlain J (2002): Prevention of hypertension, hyperglycemia and vascular oxidative stress by aspirin treatment in chronically glucose-fed rats. J. Hypertens. 20, 1407–1412.

    CAS  PubMed  Google Scholar 

  • Esmatjes E, Flores L, Inigo P, Lario S, Ruilope LM & Campistol JM (2001): Effect of losartan on TGF-beta1 and urinary albumin excretion in patients with type 2 diabetes mellitus and microalbuminuria. Nephrol. Dialysis Transplant. 16(Suppl 1), 90–93.

    CAS  Google Scholar 

  • Fakhouri F, Placier S, Ardaillou R, Dussaule JC & Chatziantoniou C (2001): Angiotensin II activates collagen type 1 gene in the renal cortex and aorta of transgenic mice through interaction with endothelin and TGF-beta. J. Am. Soc. Nephrol. 12, 2701–2710.

    CAS  PubMed  Google Scholar 

  • Fujiwara N, Osanai T, Kamada T, Katoh T, Takahashi K & Okumura K (2000): Study on the relationship between plasma nitrite and nitrate level and salt sensitivity in human hypertension: modulation of nitric oxide synthesis by salt intake. Circulation 101, 856–861.

    CAS  PubMed  Google Scholar 

  • Gonzalez-Santiago L, Lopez-Ongil S, Lamas S, Quereda C, Rodriguez-Puyol M & Rodriguez-Puyol D (2000): Imbalance in endothelial vasoactive factors as a possible cause of cyclosporine toxicity: a role for endothelin-converting enzyme. J. Lab. Clin. Med. 136, 395–401.

    CAS  PubMed  Google Scholar 

  • Guzik TJ, West NE, Pillai R, Taggart DP & Channon KM (2002): Nitric oxide modulates superoxide release and peroxynitrite formation in human blood vessels. Hypertension 39, 1088–1094.

    CAS  PubMed  Google Scholar 

  • Hamilton CA, Brosnan MJ, McIntyre M, Graham D & Dominiczak AF (2001): Superoxide excess in hypertension and aging: a common cause of endothelial dysfunction. Hypertension 37(2 Part 2), 529–534.

    CAS  PubMed  Google Scholar 

  • Haynes WG, Noon JP, Walker BR & Webb DJ (1993): Inhibition of nitric oxide synthesis increases blood pressure in healthy humans. J. Hypertens. 11, 1375–1380.

    CAS  PubMed  Google Scholar 

  • Houlihan CA, Akdeniz A, Tsalamandris C, Cooper ME, Jerums G & Gilbert RE (2002): Urinary transforming growth factor-beta excretion in patients with hypertension, type 2 diabetes, and elevated albumin excretion rate: effects of angiotensin receptor blockade and sodium restriction. Diabetes Care 25, 1072–1077.

    CAS  PubMed  Google Scholar 

  • Inoue N, Venema RC, Sayegh HS, Ohara Y, Murphy TJ & Harrison DG (1995): Molecular regulation of the bovine endothelial cell nitric oxide synthase by transforming growth factor-beta 1. Arterioscler. Thromb. Vasc. Biol. 15, 1255–1261.

    CAS  PubMed  Google Scholar 

  • Jain S, Rajeshwari J, Khullar M & Kumari S (2001): Enalapril acts through release of nitric oxide in patients with essential hypertension. Renal Failure 23, 651–657.

    CAS  PubMed  Google Scholar 

  • Jun T, Ke-yan F & Catalano M (1996): Increased superoxide anion production in humans: a possible mechanism for the pathogenesis of hypertension. J. Hum. Hypertens. 10, 305–309.

    CAS  PubMed  Google Scholar 

  • Kaehler J, Sill B, Koester R, Mittmann C, Orzechowski HD, Muenzel T & Meinertz T (2002): Endothelin-1 mRNA and protein in vascular wall cells is increased by reactive oxygen species. Clin. Sci. (London) 103(Suppl 1), 176S–178S.

    CAS  Google Scholar 

  • Katusic ZS & Vanhoutte PM (1989): Superoxide anion is an endothelium derived contracting factor. Am. J. Physiol. 257, 433–437.

    Google Scholar 

  • Kitamoto S, Egashira K, Kataoka C, Usui M, Koyanagi M, Takemoto M & Takeshita A (2000): Chronic inhibition of nitric oxide synthesis in rats increases aortic superoxide anion production via the action of angiotensin II. J. Hypertens. 18, 1795–1800.

    CAS  PubMed  Google Scholar 

  • Kohno M, Yokokawa K, Minami M, Yasunari K, Maeda K, Kano H, Hanehira T & Yaoshikawa J (1999): Plasma levels of nitric oxide and related vasoactive factors following long-term treatment with angiotensin-converting enzyme inhibitor in patients with essential hypertension. Metabolism 48, 1256–1259.

    CAS  PubMed  Google Scholar 

  • Koide M, Kawahara Y, Tsuda T, Nakayama I & Yokoyama M (1994): Expression of nitric oxide synthase by cytokines in vascular smooth muscle cells. Hypertension 23(1 Suppl), 145–148.

    Google Scholar 

  • Kumar KV & Das UN (1993): Are free radicals involved in the pathobiology of human essential hypertension? Free Radical Res. Commun. 19, 59–66.

    CAS  Google Scholar 

  • Kumar GS & Das UN (1994): Effect of prostaglandins and their precursors on the proliferation of human lymphocytes and their secretion of tumor necrosis factor and various interleukins. Prostaglandins Leukot. Essent. Fatty Acids 50, 331–336.

    CAS  PubMed  Google Scholar 

  • Kumar KV & Das UN (1997): Effect of cis-unsaturated fatty acids, prostaglandins, and free radicals on angiotensin converting enzyme activity in vitro. Proc. Exp. Biol. Med. 214, 374–379.

    CAS  Google Scholar 

  • Lagadec P, Raynal S, Lieubeau B, Onier N, Arnould L, Saint-Giorgio V, Lawrence DA & Jeannin JF (1999): Evidence for control of nitric oxide synthesis by intracellular transforming growth factor-beta 1 in tumor cells. Implications for tumor development. Am. J. Pathol. 154, 1867–1876.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mohan IK & Das UN (2000): Effect of L-arginine-nitric oxide system on the metabolism of essential fatty acids in chemical-induced diabetes mellitus. Prostaglandins Leukot. Essent. Fatty Acids 62, 35–46.

    CAS  PubMed  Google Scholar 

  • Mohan IK & Das UN (2001): Prevention of chemically induced diabetes mellitus in experimental animals by polyunsaturated fatty acids. Nutrition 17, 126–151.

    Google Scholar 

  • McAllister AS, Atkinson AB, Johnston GD, Hadden DR, Bell PM & McCance DR (1999): Basal nitric oxide production is impaired in offspring of patients with essential hypertension. Clin. Sci. (London) 97, 141–147.

    CAS  Google Scholar 

  • McCarron DA, Morris CD, Henry HJ & Santon JL (1984): Blood pressure and nutrient intake in the United States. Science 224, 1392–1398.

    CAS  PubMed  Google Scholar 

  • McVeigh GE, Brennan GM, Johnson GD, McDermott BJ, McGrath LT, Henry WR, Andrews JW & Hayes JR (1993): Dietary fish oil augments nitric oxide production or release in patients with type 2 (non-insulin dependent) diabetes mellitus. Diabetologia 36, 33–38.

    CAS  PubMed  Google Scholar 

  • Miyazaki M, Takemura N, Watanabe S, Hata N, Misawa Y & Okuyama H (2000): Dietary docosahexaenoic acid ameliorates, but rapeseed oil and safflower oil accelerate renal injury in stroke-prone spontaneously hypertensive rats as compared with soybean oil, which is associated with expression for renal transforming growth factor-beta, fibronectin and renin. Biochim. Biophys. Acta. 1483, 101–110.

    CAS  PubMed  Google Scholar 

  • Morawietz H, Weber M, Rueckschloss U, Lauer N, Hacker A & Kojda G (2001): Upregulation of vascular NAD(P)H oxidase subunit gp91phox and impairment of the nitric oxide signal transduction pathway in hypertension. Biochem. Biophys. Res. Commun. 285, 1130–1135.

    CAS  PubMed  Google Scholar 

  • Nakanishi K, Hara N, Nagai Y (2002): Salt-sensitive hypertension in conscious rats induced by chronic nitric oxide blockade. Am. J. Hypertens. 15(2 Part 1), 150–156.

    CAS  PubMed  Google Scholar 

  • Nakazono L, Watanabe N, Matsuno K, Sasaki J, Sato T & Inoue M (1991): Does superoxide underlie the pathogenesis of hypertension? Proc. Natl. Acad. Sci. USA 88, 10045–10048.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nakayama M, Fukuda N, Watanabe Y, Soma M, Hu WY, Kishipka H, Satoh C, Kubo A & Kannatsuse K (1999): Low dose of eicosapentaenoic acid inhibits the exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats through suppression of transforming growth factor-beta. J. Hypertens. 17, 1421–1430.

    CAS  PubMed  Google Scholar 

  • On YK, Kim CH, Oh BH, Lee MM & Park YB (2002): Effects of angiotensin converting enzyme inhibitor and calcium antagonist on endothelial function in patients with essential hypertension. Hypertens. Res. 25, 365–371.

    CAS  PubMed  Google Scholar 

  • Passmore JC, Hatton DC & McCarron DA (1997): Dietary calcium decreases blood pressure without decreasing renal vascular resistance or altering the response to NO blockade. J. Lab. Clin. Med. 130, 627–634.

    CAS  PubMed  Google Scholar 

  • Rey FE, Cifuentes ME, Kiarash A, Quinn MT & Pagano PJ (2001): Novel competitive inhibitor of NAD(P)H oxidase assembly attenuates vascular O(2)(−) and systolic blood pressure in mice. Circ. Res. 89, 408–414.

    CAS  PubMed  Google Scholar 

  • Riser BL, Cortes P, Yee J, Sharba AK, Asano K, Rodriguez-Barbero A & Narins RG (1998): Mechanical strain- and high-glucose induced alterations in mesangial cell collagen metabolism: role of TGF-beta. J. Am. Soc. Nephrol. 9, 827–836.

    CAS  PubMed  Google Scholar 

  • Russo LM, Osicka TM, Bonnet F, Jerums G & Comper WD (2002): Albuminuria in hypertension is linked to altered lysosomal activity and TGF-beta 1 expression. Hypertension 39, 281–286.

    CAS  PubMed  Google Scholar 

  • Schmidt RJ, Beierwaltes WH & Baylis C (2001): Effects of aging and alterations in dietary sodium intake on total nitric oxide production. Am. J. Kidney Dis. 37, 900–908.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shin GT, Khanna A, Ding R, Sharma VK, Lagman M, Li B & Suthanthiran M (1998): In vivo expression of transforming growth factor-beta1 in humans: stimulation by cyclosporine. Transplantation 65, 313–318.

    CAS  PubMed  Google Scholar 

  • Singhal A, Cole TJ & Lucas A (2001): Early nutrition in preterm infants and later blood pressure: two cohorts after randomized trials. Lancet 357, 413–419.

    CAS  PubMed  Google Scholar 

  • Smith AP, Demoncheaux EA & Higenbottam TW (2002): Nitric oxide gas decreases endothelin-1 mRNA in cultured pulmonary artery endothelial cells. Nitric Oxide 6, 153–159.

    CAS  PubMed  Google Scholar 

  • Somers MJ & Harrison DG (1999): Reactive oxygen species and the control of vasomotor tone. Curr. Hypertens. Rep. 1, 102–108.

    CAS  PubMed  Google Scholar 

  • Studer RK, Georgescu HI, Miller LA & Evans CH (1999): Inhibition of transforming growth factor beta production by nitric oxide-treated chondrocytes: implications for matrix synthesis. Arthritis Rheum. 42, 248–257.

    CAS  PubMed  Google Scholar 

  • Stys T, Stys A, Paczwa P, Szczepanska-Sadowska E & Lipkowski AW (1998): Decreased hypotensive responsiveness to nitric oxide donor S-nitroso N-acetyl-DL-penicillamine (SNAP) in spontaneously hypertensive (SHR) rats. J. Physiol. Pharmacol. 49, 37–49.

    CAS  PubMed  Google Scholar 

  • Surdacki A, Nowicki M, Sandmann J, Tsikas D, Boeger RH, Bode-Boeger SM, Kruszelnicka-Kwiatkowska O, Kokot F, Dubiel JS & Froelich JC (1999): Reduced urinary excretion of nitric oxide metabolites and increased plasma levels of asymmetric dimethylarginine in men with essential hypertension. J. Cardiovasc. Pharmacol. 33, 652–658.

    CAS  PubMed  Google Scholar 

  • Suryaprabha P, Das UN, Koratkar R, Sangeetha P & Ramesh G (1990): Free radical generation, lipid peroxidation and essential fatty acids in uncontrolled hypertension. Prostaglandins Leukot. Essent. Fatty Acids 41, 27–33.

    Google Scholar 

  • Suthanthiran M, Li B, Song JO, Ding R, Sharma VK, Schwartz JE & August P (2000): Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage. Proc. Natl. Acad. Sci. USA 97, 3479–3484.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Taddei S, Virdis A, Ghiadoni L, Salvetti G, Bernini G, Magagna A & Salvetti A (2001): Age-related reduction of NO availability and oxidative stress in humans. Hypertension 38, 274–279.

    CAS  PubMed  Google Scholar 

  • Taddei S, Mattei P, Virdis A, Sudano L, Ghiadoni L & Salvetti A (1994): Effect of potassium on vasodilation to acetylcholine in essential hypertension. Hypertension 23, 485–490.

    CAS  PubMed  Google Scholar 

  • Taddei S, Virdis A, Mattei P, Ghiadoni L, Sudano I & Salvetti A (1996): Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation 94, 1298–1303.

    CAS  PubMed  Google Scholar 

  • Taddei S, Virdis A, Ghiadoni L, Magagna A & Salvetti A (1998): Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation 97, 2222–2229.

    CAS  PubMed  Google Scholar 

  • Taddei S, Virdis A, Ghiadoni L, Magagna A, Favilla S, Pompella A & Salvetti A (2001): Restoration of nitric oxide availability after calcium antagonist treatment in essential hypertension. Hypertension 37, 943–948.

    CAS  PubMed  Google Scholar 

  • Taittonen L, Nuutinen M, Turtinen J & Uhari M (1996): Perinatal factors in predicting later blood pressure among children: cardiovascular risk in young Finns. Pediatr. Res. 40, 627–632.

    CAS  PubMed  Google Scholar 

  • Takahashi H, Hara K, Komiyama Y, Masuda M, Murakami T, Nishimura M, Nambu A & Yoshimura M (1995): Mechanism of hypertension induced by chronic inhibition of nitric oxide in rats. Hypertens. Res. 18, 319–324.

    CAS  PubMed  Google Scholar 

  • Takase H, Sugiyama M, Nakazawa A, Sato K, Ueda R & Dohi Y (2000): Long-term effect of antihypertensive therapy with calcium antagonist or angiotensin converting enzyme inhibitor on serum nitrite/nitrate levels in human essential hypertension. Arzneimittelforschung 50, 530–534.

    CAS  PubMed  Google Scholar 

  • Touyz RM & Schiffrin EL (2001): Increased generation of superoxide by angiotensin II in smooth muscle cells from resistance arteries of hypertensive patients: role of phospholipase D-dependent NAD(P)H oxidase-sensitive pathways. J. Hypertens. 19, 1245–1254.

    CAS  PubMed  Google Scholar 

  • Trachtman H, Koss I, Bogart M, Abramowitz J, Futterweit S, Franki N & Singhal PC (1998): High glucose enhances growth factor-stimulated nitric oxide production by cultured rats mesangial cells. Res. Commun. Mol. Pathol. Pharmacol. 100, 213–225.

    CAS  PubMed  Google Scholar 

  • Valkonen V-P, Paiva H, Salonen JT, Lakka TA, Lehtimaki T, Laakso J & Laaksonen R (2001): Risk of acute coronary events and serum concentrations of asymmetrical dimethylarginine. Lancet 358, 2127–2128.

    CAS  PubMed  Google Scholar 

  • Vallance P (2001): Importance of asymmetrical dimethylarginine in cardiovascular risk. Lancet 358, 2096–2097.

    CAS  PubMed  Google Scholar 

  • Weisinger HS, Armitage JA, Sinclair AJ, Vingrys AJ, Burns PL & Wesinger RS (2001): Perinatal omega-3 deficiency affects blood pressure in later in life. Nat. Med. 7, 258–259.

    CAS  PubMed  Google Scholar 

  • Williams G, Becker L, Bryant D, Willis S & Giroir BP (1996): Effects of transforming growth factor-beta 1 on nitric oxide synthesis by C2C12 skeletal myocytes. Am. J. Physiol. 270(1 Part 2), R145–R152.

    CAS  PubMed  Google Scholar 

  • Wilson AC, Forsyth JS, Greene SA, Irvine L, Hau C & Howie PW (1998): Relation of infant diet to childhood health: seven year follow up of cohort in Dundee infant feeding study. BMJ 316, 21–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wolf G (1998): Link between angiotensin II and TGF-beta in the kidney. Miner. Electrolyte Metab. 24, 174–180.

    CAS  PubMed  Google Scholar 

  • Wolf G (2000): Free radical production and angiotensin. Curr. Hypertens. Rep. 2, 167–173.

    CAS  PubMed  Google Scholar 

  • Wong VY, Laping NJ, Nelson AH, Contino LC, Olson BA, Gygielko E, Cambell Jr WG, Barone F & Brooks DP (2001): Renoprotective effects of carvedilol in hypertensive-stroke prone rats may involve inhibition of TGF beta expression. Br. J. Pharmacol. 134, 977–984.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yamada Y, Fujisawa M, Ando F, Niino N, Tanaka M & Shimokata H (2002): Association of a polymorphism of the transforming growth factor-beta 1 gene with blood pressure in Japanese individuals. J. Hum. Genet. 47, 243–248.

    CAS  PubMed  Google Scholar 

  • Ying WZ, Sanders PW (1999): Dietary salt increases endothelial nitric oxide synthase and TGF-beta in rat aortic endothelium. Am. J. Physiol. 277(4 Part 2), H1293–H1298.

    CAS  PubMed  Google Scholar 

  • Zalba G, San Jose G, Moreno MU, Fortuno MA, Fortuno A, Beaumont FJ & Diez J (2001): Oxidative stress in arterial hypertension: role of NAD(P)H oxidase. Hypertension 38, 1395–1399.

    CAS  PubMed  Google Scholar 

  • Zhang H, Schmeisser A, Garlichs CD, Plotze K, Damme U, Mugge A & Daniel WG (1999): Angiotensin II-induced superoxide anion generation in human vascular endothelial cells: role of membrane-bound NADH–NAD(P)H-oxidases. Cardiovasc. Res. 44, 215–222.

    CAS  PubMed  Google Scholar 

  • Zoccali C, Bode-Boger SM, Mallamaci F, Benedetto FA, Tripepi G, Malatino LS, Cataliotti A, Bellanuova I, Fermo I, Frolich JC & Boger RH (2001): Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet 358, 2113–2117.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to U N Das.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Das, U. Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-β to prevent human essential hypertension. Eur J Clin Nutr 58, 195–203 (2004). https://doi.org/10.1038/sj.ejcn.1601766

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1601766

Keywords

This article is cited by

Search

Quick links