Int J Angiol 2011; 20(4): 189-212
DOI: 10.1055/s-0031-1288941
REVIEW ARTICLE

© Thieme Medical Publishers

Role of the Immune System in Hypertension: Modulation by Dietary Antioxidants

Sudesh Vasdev1 , Jennifer Stuckless1 , Vernon Richardson2
  • 1Discipline of Medicine, Health Sciences Centre, Memorial University, St. John's, Newfoundland, Canada
  • 2Divisions of Surgery and BioMedical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University, St. John's, Newfoundland, Canada
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Publikationsverlauf

Publikationsdatum:
14. September 2011 (online)

ABSTRACT

Hypertension is a major health problem worldwide. Individuals with hypertension are at an increased risk for stroke, heart disease, and kidney failure. Although the etiology of essential hypertension has a genetic component, lifestyle factors such as diet play an important role. Insulin resistance is a common feature of hypertension in both humans and animal models affecting glucose and lipid metabolism producing excess aldehydes including methylglyoxal. These aldehydes react with proteins to form conjugates called advanced glycation end products (AGEs). This alters protein structure and function and can affect vascular and immune cells leading to their activation and secretion of inflammatory cytokines. AGEs also act via receptors for advanced glycation end products on these cells altering the function of antioxidant and metabolic enzymes, and ion channels. This results in an increase in cytosolic free calcium, decrease in nitric oxide, endothelial dysfunction, oxidative stress, peripheral vascular resistance, and infiltration of vascular and kidney tissue with inflammatory cells leading to hypertension. Supplementation with dietary antioxidants including vitamins C, E, or B6, thiols such as cysteine and lipoic acid, have been shown to lower blood pressure and plasma inflammatory cytokines in animal models and humans with essential hypertension. A well-balanced diet rich in antioxidants that includes vegetables, fruits, low fat dairy products, low salt, and includes whole grains, poultry, fish and nuts, lowers blood pressure and vascular inflammation. These antioxidants may achieve their antihypertensive and anti-inflammatory/immunomodulatory effects by reducing AGEs and improving insulin resistance and associated alterations. Dietary supplementation with antioxidants may be a beneficial, inexpensive, front-line alterative treatment modality for hypertension.

REFERENCES

  • 1 World Health Organization .Chronic Disease- key risk factors include high cholesterol, high blood pressure, low fruit and vegetable intake. Available at: http://www.who.int/dietphysicalactivity/publications/facts/riskfactors/en/ Accessed June 9, 2010
  • 2 World Health Organization .Quantifying selected major risks to health. In: World Health Organization. The World Health Report [chapter 4]. Geneva: World Health Organization; 2002: 1-13
  • 3 He J, Whelton P K. Epidemiology and prevention of hypertension.  Med Clin North Am. 1997;  81 (5) 1077-1097
  • 4 Klag M J, Whelton P K, Randall B L et al.. Blood pressure and end-stage renal disease in men.  N Engl J Med. 1996;  334 (1) 13-18
  • 5 Deshmukh R, Smith A, Lilly L S. Hypertension. In: Lilly L S, ed. Pathophysiology of Heart Disease. 2nd ed. Philadelphia: Lippincott Williams and Wilkins; 1998: 267-288
  • 6 Fu M LX. Do immune system changes have a role in hypertension?.  J Hypertens. 1995;  13 (11) 1259-1265
  • 7 Luft F C, Mervaala E, Müller D N et al.. Hypertension-induced end-organ damage: A new transgenic approach to an old problem.  Hypertension. 1999;  33 (1 Pt 2) 212-218
  • 8 Sesso H D, Buring J E, Rifai N, Blake G J, Gaziano J M, Ridker P M. C-reactive protein and the risk of developing hypertension.  JAMA. 2003;  290 (22) 2945-2951
  • 9 Stumpf C, John S, Jukie J et al.. Enhanced levels of platelet P-selectin and circulatory cytokines in young patients with mild arterial hypertension.  J Hypertens. 2005;  23 995-1000
  • 10 Schillaci G, Pirro M, Gemelli F et al.. Increased C-reactive protein concentrations in never-treated hypertension: the role of systolic and pulse pressures.  J Hypertens. 2003;  21 (10) 1841-1846
  • 11 Chae C U, Lee R T, Rifai N, Ridker P M. Blood pressure and inflammation in apparently healthy men.  Hypertension. 2001;  38 (3) 399-403
  • 12 Cheng Z J, Vapaatalo H, Mervaala E. Angiotensin II and vascular inflammation.  Med Sci Monit. 2005;  11 (6) RA194-RA205
  • 13 Ferrannini E, Buzzigoli G, Bonadonna R et al.. Insulin resistance in essential hypertension.  N Engl J Med. 1987;  317 (6) 350-357
  • 14 Reaven G M. Insulin resistance, hyperinsulinemia, and hypertriglyceridemia in the etiology and clinical course of hypertension.  Am J Med. 1991;  90 (2A) 7S-12S
  • 15 Sagar S, Kallo I J, Kaul N, Ganguly N K, Sharma B K. Oxygen free radicals in essential hypertension.  Mol Cell Biochem. 1992;  111 (1-2) 103-108
  • 16 Kumar K V, Das U N. Are free radicals involved in the pathobiology of human essential hypertension?.  Free Radic Res Commun. 1993;  19 (1) 59-66
  • 17 Panza J A, Casino P R, Badar D M, Quyyumi A A. Effect of increased availability of endothelium-derived nitric oxide precursor on endothelium-dependent vascular relaxation in normal subjects and in patients with essential hypertension.  Circulation. 1993;  87 (5) 1475-1481
  • 18 Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A. Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension.  Circulation. 1998;  97 (22) 2222-2229
  • 19 Vasdev S, Ford C A, Longerich L, Parai S, Gadag V, Wadhawan S. Aldehyde induced hypertension in rats: prevention by N-acetyl cysteine.  Artery. 1998;  23 (1) 10-36
  • 20 Vasdev S, Ford C A, Parai S, Longerich L, Gadag V. Dietary alpha-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats.  J Hypertens. 2000;  18 (5) 567-573
  • 21 Vasdev S, Ford C A, Parai S, Longerich L, Gadag V. Dietary lipoic acid supplementation prevents fructose-induced hypertension in rats.  Nutr Metab Cardiovasc Dis. 2000;  10 (6) 339-346
  • 22 Vasdev S, Gill V, Longerich L, Parai S, Gadag V. Salt-induced hypertension in WKY rats: prevention by alpha-lipoic acid supplementation.  Mol Cell Biochem. 2003;  254 (1-2) 319-326
  • 23 Vasdev S, Gill V, Singal P. Role of advanced glycation end products in hypertension and atherosclerosis: therapeutic implications.  Cell Biochem Biophys. 2007;  49 (1) 48-63
  • 24 Wu L. Is methylglyoxal a causative factor for hypertension development?.  Can J Physiol Pharmacol. 2006;  84 (1) 129-139
  • 25 Midaoui A E, Elimadi A, Wu L, Haddad P S, de Champlain J. Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production.  Am J Hypertens. 2003;  16 (3) 173-179
  • 26 Wang X, Desai K, Clausen J T, Wu L. Increased methylglyoxal and advanced glycation end products in kidney from spontaneously hypertensive rats.  Kidney Int. 2004;  66 (6) 2315-2321
  • 27 Wang X, Desai K, Chang T, Wu L. Vascular methylglyoxal metabolism and the development of hypertension.  J Hypertens. 2005;  23 (8) 1565-1573
  • 28 Folli F, Kahn C R, Hansen H, Bouchie J L, Feener E P. Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in insulin/angiotensin II crosstalk.  J Clin Invest. 1997;  100 (9) 2158-2169
  • 29 Schulman I H, Zhou M S, Raij L. Nitric oxide, angiotensin II, and reactive oxygen species in hypertension and atherogenesis.  Curr Hypertens Rep. 2005;  7 (1) 61-67
  • 30 Schmieder R E, Langenfeld M R, Friedrich A, Schobel H P, Gatzka C D, Weihprecht H. Angiotensin II related to sodium excretion modulates left ventricular structure in human essential hypertension.  Circulation. 1996;  94 (6) 1304-1309
  • 31 Ogihara T, Asano T, Ando K et al.. Angiotensin II-induced insulin resistance is associated with enhanced insulin signaling.  Hypertension. 2002;  40 (6) 872-879
  • 32 Crowley S D, Gurley S B, Herrera M J et al.. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney.  Proc Natl Acad Sci U S A. 2006;  103 (47) 17985-17990
  • 33 Scherrer U, Randin D, Vollenweider P, Vollenweider L, Nicod P. Nitric oxide release accounts for insulin's vascular effects in humans.  J Clin Invest. 1994;  94 (6) 2511-2515
  • 34 Kahn N N, Acharya K, Bhattacharya S et al.. Nitric oxide: the “second messenger” of insulin.  IUBMB Life. 2000;  49 (5) 441-450
  • 35 Montagnani M, Ravichandran L V, Chen H, Esposito D L, Quon M J. Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells.  Mol Endocrinol. 2002;  16 (8) 1931-1942
  • 36 Zeng G, Nystrom F H, Ravichandran L V et al.. Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells.  Circulation. 2000;  101 (13) 1539-1545
  • 37 Kamide K, Hori M T, Zhu J H, Barrett J D, Eggena P, Tuck M L. Insulin-mediated growth in aortic smooth muscle and the vascular renin-angiotensin system.  Hypertension. 1998;  32 (3) 482-487
  • 38 Kamide K, Rakugi H, Nagai M et al.. Insulin-mediated regulation of the endothelial renin-angiotensin system and vascular cell growth.  J Hypertens. 2004;  22 (1) 121-127
  • 39 Beisswenger P J, Howell S K, Smith K, Szwergold B S. Glyceraldehyde-3-phosphate dehydrogenase activity as an independent modifier of methylglyoxal levels in diabetes.  Biochim Biophys Acta. 2003;  1637 (1) 98-106
  • 40 Thornalley P J. Modification of the glyoxalase system in disease processes and prospects for therapeutic strategies.  Biochem Soc Trans. 1993;  21 (2) 531-534
  • 41 Alexander M C, Lomanto M, Nasrin N, Ramaika C. Insulin stimulates glyceraldehyde-3-phosphate dehydrogenase gene expression through cis-acting DNA sequences.  Proc Natl Acad Sci U S A. 1988;  85 (14) 5092-5096
  • 42 Morgan P E, Dean R T, Davies M J. Inactivation of cellular enzymes by carbonyls and protein-bound glycation/glycoxidation products.  Arch Biochem Biophys. 2002;  403 (2) 259-269
  • 43 Chang K C, Paek K S, Kim H J, Lee Y S, Yabe-Nishimura C, Seo H G. Substrate-induced up-regulation of aldose reductase by methylglyoxal, a reactive oxoaldehyde elevated in diabetes.  Mol Pharmacol. 2002;  61 (5) 1184-1191
  • 44 Vasdev S, Gill V D, Singal P K. Modulation of oxidative stress-induced changes in hypertension and atherosclerosis by antioxidants.  Exp Clin Cardiol. 2006;  11 (3) 206-216
  • 45 Zeng J, Davies M J. Evidence for the formation of adducts and S-(carboxymethyl)cysteine on reaction of alpha-dicarbonyl compounds with thiol groups on amino acids, peptides, and proteins.  Chem Res Toxicol. 2005;  18 (8) 1232-1241
  • 46 Collison K S, Parhar R S, Saleh S S et al.. RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs).  J Leukoc Biol. 2002;  71 (3) 433-444
  • 47 Horiuchi S, Sakamoto Y, Sakai M. Scavenger receptors for oxidized and glycated proteins.  Amino Acids. 2003;  25 (3-4) 283-292
  • 48 Nagaraj R H, Sarkar P, Mally A, Biemel K M, Lederer M O, Padayatti P S. Effect of pyridoxamine on chemical modification of proteins by carbonyls in diabetic rats: characterization of a major product from the reaction of pyridoxamine and methylglyoxal.  Arch Biochem Biophys. 2002;  402 (1) 110-119
  • 49 Karachalias N, Babaei-Jadidi R, Ahmed N, Thornalley P J. Accumulation of fructosyl-lysine and advanced glycation end products in the kidney, retina and peripheral nerve of streptozotocin-induced diabetic rats.  Biochem Soc Trans. 2003;  31 (Pt 6) 1423-1425
  • 50 Wautier M P, Chappey O, Corda S, Stern D M, Schmidt A M, Wautier J L. Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE.  Am J Physiol Endocrinol Metab. 2001;  280 (5) E685-E694
  • 51 Kaplan N. Kaplan's Clinical Hypertension. 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2006
  • 52 Vasdev S, Gill V. Antioxidants in the treatment of hypertension.  Int J Angiol. 2005;  14 60-73
  • 53 Wen Y, Killalea S, McGettigan P, Feely J. Lipid peroxidation and antioxidant vitamins C and E in hypertensive patients.  Ir J Med Sci. 1996;  165 (3) 210-212
  • 54 Nyyssönen K, Parviainen M T, Salonen R, Tuomilehto J, Salonen J T. Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland.  BMJ. 1997;  314 (7081) 634-638
  • 55 Ness A R, Khaw K T, Bingham S, Day N E. Vitamin C status and blood pressure.  J Hypertens. 1996;  14 (4) 503-508
  • 56 Kashyap M K, Yadav V, Sherawat B S et al.. Different antioxidants status, total antioxidant power and free radicals in essential hypertension.  Mol Cell Biochem. 2005;  277 (1-2) 89-99
  • 57 Gey K F, Puska P, Jordan P, Moser U K. Inverse correlation between plasma vitamin E and mortality from ischemic heart disease in cross-cultural epidemiology.  Am J Clin Nutr. 1991;  53 (1, Suppl) 326S-334S
  • 58 Yochum L A, Folsom A R, Kushi L H. Intake of antioxidant vitamins and risk of death from stroke in postmenopausal women.  Am J Clin Nutr. 2000;  72 (2) 476-483
  • 59 Manning Jr R D, Meng S, Tian N. Renal and vascular oxidative stress and salt-sensitivity of arterial pressure.  Acta Physiol Scand. 2003;  179 (3) 243-250
  • 60 Ambrose J A, Barua R S. The pathophysiology of cigarette smoking and cardiovascular disease: an update.  J Am Coll Cardiol. 2004;  43 (10) 1731-1737
  • 61 Wu D, Cederbaum A I. Alcohol, oxidative stress, and free radical damage.  Alcohol Res Health. 2003;  27 (4) 277-284
  • 62 Kaul N, Siveski-Iliskovic N, Hill M, Slezak J, Singal P K. Free radicals and the heart.  J Pharmacol Toxicol Methods. 1993;  30 (2) 55-67
  • 63 Stadtman T C. Selenium biochemistry.  Annu Rev Biochem. 1990;  59 111-127
  • 64 Park Y S, Koh Y H, Takahashi M et al.. Identification of the binding site of methylglyoxal on glutathione peroxidase: methylglyoxal inhibits glutathione peroxidase activity via binding to glutathione binding sites Arg 184 and 185.  Free Radic Res. 2003;  37 (2) 205-211
  • 65 Wu L, Juurlink B H. Increased methylglyoxal and oxidative stress in hypertensive rat vascular smooth muscle cells.  Hypertension. 2002;  39 (3) 809-814
  • 66 Farahmand F, Lou H, Singal P K. Oxidative stress in cardiovascular complications in diabetes. In: Pierce G N, Nagano M, Zahradka P, Dhalla N S, eds. Atheroscleriosis, Hypertension and Diabetes. Boston: Kleuver Academic Publishers; 2003: 427-437
  • 67 Chang T, Wang R, Wu L. Methylglyoxal-induced nitric oxide and peroxynitrite production in vascular smooth muscle cells.  Free Radic Biol Med. 2005;  38 (2) 286-293
  • 68 Kaplan P, Babusikova E, Lehotsky J, Dobrota D. Free radical-induced protein modification and inhibition of Ca2+-ATPase of cardiac sarcoplasmic reticulum.  Mol Cell Biochem. 2003;  248 (1-2) 41-47
  • 69 Viner R I, Williams T D, Schöneich C. Peroxynitrite modification of protein thiols: oxidation, nitrosylation, and S-glutathiolation of functionally important cysteine residue(s) in the sarcoplasmic reticulum Ca-ATPase.  Biochemistry. 1999;  38 (38) 12408-12415
  • 70 Nakashima I, Takeda K, Kawamoto Y, Okuno Y, Kato M, Suzuki H. Redox control of catalytic activities of membrane-associated protein tyrosine kinases.  Arch Biochem Biophys. 2005;  434 (1) 3-10
  • 71 Rainwater R, Parks D, Anderson M E, Tegtmeyer P, Mann K. Role of cysteine residues in regulation of p53 function.  Mol Cell Biol. 1995;  15 (7) 3892-3903
  • 72 Liu H, Colavitti R, Rovira I I, Finkel T. Redox-dependent transcriptional regulation.  Circ Res. 2005;  97 (10) 967-974
  • 73 Suzuki Y J, Ford G D. Redox regulation of signal transduction in cardiac and smooth muscle.  J Mol Cell Cardiol. 1999;  31 (2) 345-353
  • 74 Dargel R. Lipid peroxidation—a common pathogenetic mechanism?.  Exp Toxicol Pathol. 1992;  44 (4) 169-181
  • 75 Chakravarti R N, Kirshenbaum L A, Singal P K. Atherosclerosis: its pathophysiology with special reference to lipid peroxidation.  J Appl Cardiol. 1991;  6 91-112
  • 76 Berliner J A, Watson A D. A role for oxidized phospholipids in atherosclerosis.  N Engl J Med. 2005;  353 (1) 9-11
  • 77 Touyz R M, Schiffrin E L. Reactive oxygen species in vascular biology: implications in hypertension.  Histochem Cell Biol. 2004;  122 (4) 339-352
  • 78 Chiarugi P, Cirri P. Redox regulation of protein tyrosine phosphatases during receptor tyrosine kinase signal transduction.  Trends Biochem Sci. 2003;  28 (9) 509-514
  • 79 Tabatabaie T, Floyd R A. Susceptibility of glutathione peroxidase and glutathione reductase to oxidative damage and the protective effect of spin trapping agents.  Arch Biochem Biophys. 1994;  314 (1) 112-119
  • 80 Túri S, Friedman A, Bereczki C et al.. Oxidative stress in juvenile essential hypertension.  J Hypertens. 2003;  21 (1) 145-152
  • 81 Kedziora-Kornatowska K, Czuczejko J, Pawluk H et al.. The markers of oxidative stress and activity of the antioxidant system in the blood of elderly patients with essential arterial hypertension.  Cell Mol Biol Lett. 2004;  9 (4A) 635-641
  • 82 Russo C, Olivieri O, Girelli D et al.. Anti-oxidant status and lipid peroxidation in patients with essential hypertension.  J Hypertens. 1998;  16 (9) 1267-1271
  • 83 Chen P F, Tsai A L, Wu K K. Cysteine 184 of endothelial nitric oxide synthase is involved in heme coordination and catalytic activity.  J Biol Chem. 1994;  269 (40) 25062-25066
  • 84 Xia Y, Tsai A L, Berka V, Zweier J L. Superoxide generation from endothelial nitric-oxide synthase. A Ca2+/calmodulin-dependent and tetrahydrobiopterin regulatory process.  J Biol Chem. 1998;  273 (40) 25804-25808
  • 85 Landmesser U, Dikalov S, Price S R et al.. Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension.  J Clin Invest. 2003;  111 (8) 1201-1209
  • 86 Shinozaki K, Kashiwagi A, Masada M, Okamura T. Molecular mechanisms of impaired endothelial function associated with insulin resistance.  Curr Drug Targets Cardiovasc Haematol Disord. 2004;  4 (1) 1-11
  • 87 Ma X L, Gao F, Nelson A H et al.. Oxidative inactivation of nitric oxide and endothelial dysfunction in stroke-prone spontaneous hypertensive rats.  J Pharmacol Exp Ther. 2001;  298 (3) 879-885
  • 88 Touyz R M. Recent advances in intracellular signalling in hypertension.  Curr Opin Nephrol Hypertens. 2003;  12 (2) 165-174
  • 89 Ikemoto F, Song G, Tominaga M, Yamamoto K. Oxidation-induced increase in activity of angiotensin converting enzyme in the rat kidney.  Biochem Biophys Res Commun. 1988;  153 (3) 1032-1037
  • 90 Griendling K K, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease.  Circ Res. 2000;  86 (5) 494-501
  • 91 Fortuño A, Oliván S, Beloqui O et al.. Association of increased phagocytic NADPH oxidase-dependent superoxide production with diminished nitric oxide generation in essential hypertension.  J Hypertens. 2004;  22 (11) 2169-2175
  • 92 Schulman I H, Zhou M S, Raij L. Interaction between nitric oxide and angiotensin II in the endothelium: role in atherosclerosis and hypertension.  J Hypertens Suppl. 2006;  24 (1) S45-S50
  • 93 Zaidi N F, Lagenaur C F, Abramson J J, Pessah I, Salama G. Reactive disulfides trigger Ca2+ release from sarcoplasmic reticulum via an oxidation reaction.  J Biol Chem. 1989;  264 (36) 21725-21736
  • 94 Tabet F, Savoia C, Schiffrin E L, Touyz R M. Differential calcium regulation by hydrogen peroxide and superoxide in vascular smooth muscle cells from spontaneously hypertensive rats.  J Cardiovasc Pharmacol. 2004;  44 (2) 200-208
  • 95 Suzuki Y J, Ford G D. Inhibition of Ca(2+)-ATPase of vascular smooth muscle sarcoplasmic reticulum by reactive oxygen intermediates.  Am J Physiol. 1991;  261 (2 Pt 2) H568-H574
  • 96 Gordeeva A V, Zvyagilskaya R A, Labas Y A. Cross-talk between reactive oxygen species and calcium in living cells.  Biochemistry (Mosc). 2003;  68 (10) 1077-1080
  • 97 Mehta P K, Griendling K K. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system.  Am J Physiol Cell Physiol. 2007;  292 (1) C82-C97
  • 98 Griendling K K, Minieri C A, Ollerenshaw J D, Alexander R W. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells.  Circ Res. 1994;  74 (6) 1141-1148
  • 99 Pueyo M E, Gonzalez W, Nicoletti A, Savoie F, Arnal J F, Michel J B. Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-kappaB activation induced by intracellular oxidative stress.  Arterioscler Thromb Vasc Biol. 2000;  20 (3) 645-651
  • 100 Hoch N E, Guzik T J, Chen W et al.. Regulation of T-cell function by endogenously produced angiotensin II.  Am J Physiol Regul Integr Comp Physiol. 2009;  296 (2) R208-R216
  • 101 Jurewicz M, McDermott D H, Sechler J M et al.. Human T and natural killer cells possess a functional renin-angiotensin system: further mechanisms of angiotensin II-induced inflammation.  J Am Soc Nephrol. 2007;  18 (4) 1093-1102
  • 102 Nataraj C, Oliverio M I, Mannon R B et al.. Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway.  J Clin Invest. 1999;  104 (12) 1693-1701
  • 103 Grassi G, Mancia G. Neurogenic hypertension: is the enigma of its origin near the solution?.  Hypertension. 2004;  43 (2) 154-155
  • 104 Daniels S R, Arnett D K, Eckel R H et al.. Overweight in children and adolescents: pathophysiology, consequences, prevention, and treatment.  Circulation. 2005;  111 (15) 1999-2012
  • 105 Michel M C, Brodde O E, Insel P A. Peripheral adrenergic receptors in hypertension.  Hypertension. 1990;  16 (2) 107-120
  • 106 Hirooka Y, Sagara Y, Kishi T, Sunagawa K. Oxidative stress and central cardiovascular regulation. Pathogenesis of hypertension and therapeutic aspects.  Circ J. 2010;  74 (5) 827-835
  • 107 Zhang Z H, Wei S G, Francis J, Felder R B. Cardiovascular and renal sympathetic activation by blood-borne TNF-α in rat: the role of central prostaglandins.  Am J Physiol Regul Integr Comp Physiol. 2003;  284 (4) R916-R927
  • 108 Fuchs B A, Albright J W, Albright J F. β-adrenergic receptors on murine lymphocytes: density varies with cell maturity and lymphocyte subtype and is decreased after antigen administration.  Cell Immunol. 1988;  114 (2) 231-245
  • 109 Petitto J M, Huang Z, McCarthy D B. Molecular cloning of NPY-Y1 receptor cDNA from rat splenic lymphocytes: evidence of low levels of mRNA expression and [125I]NPY binding sites.  J Neuroimmunol. 1994;  54 (1-2) 81-86
  • 110 Ricci A, Bronzetti E, Conterno A et al.. α1-adrenergic receptor subtypes in human peripheral blood lymphocytes.  Hypertension. 1999;  33 (2) 708-712
  • 111 Schmid-Schönbein G W, Seiffge D, DeLano F A, Shen K, Zweifach B W. Leukocyte counts and activation in spontaneously hypertensive and normotensive rats.  Hypertension. 1991;  17 (3) 323-330
  • 112 Arndt H, Smith C W, Granger D N. Leukocyte-endothelial cell adhesion in spontaneously hypertensive and normotensive rats.  Hypertension. 1993;  21 (5) 667-673
  • 113 Rodriguez-Iturbe B, Zhan C D, Quiroz Y, Sindhu R K, Vaziri N D. Antioxidant-rich diet relieves hypertension and reduces renal immune infiltration in spontaneously hypertensive rats.  Hypertension. 2003;  41 (2) 341-346
  • 114 Guzik T J, Hoch N E, Brown K A et al.. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction.  J Exp Med. 2007;  204 (10) 2449-2460
  • 115 Bataillard A, Blanc-Brunat N, Vivier G et al.. Antihypertensive effect of thymectomy in Lyon hypertensive rats. Vascular reactivity, renal histology, and sodium excretion.  Am J Hypertens. 1996;  9 (2) 171-177
  • 116 Hilgers K F. Monocytes/macrophages in hypertension.  J Hypertens. 2002;  20 (4) 593-596
  • 117 Capers IV Q, Alexander R W, Lou P P et al.. Monocyte chemoattractant protein-1 expression in aortic tissues of hypertensive rats.  Hypertension. 1997;  30 (6) 1397-1402
  • 118 Chen X L, Tummala P E, Olbrych M T, Alexander R W, Medford R M. Angiotensin II induces monocyte chemoattractant protein-1 gene expression in rat vascular smooth muscle cells.  Circ Res. 1998;  83 (9) 952-959
  • 119 Rodríguez-Iturbe B, Quiroz Y, Nava M et al.. Reduction of renal immune cell infiltration results in blood pressure control in genetically hypertensive rats.  Am J Physiol Renal Physiol. 2002;  282 (2) F191-F201
  • 120 Tian N, Gu J W, Jordan S, Rose R A, Hughson M D, Manning Jr R D. Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension.  Am J Physiol Heart Circ Physiol. 2007;  292 (2) H1018-H1025
  • 121 Rodríguez-Iturbe B, Quiroz Y, Shahkarami A, Li Z, Vaziri N D. Mycophenolate mofetil ameliorates nephropathy in the obese Zucker rat.  Kidney Int. 2005;  68 (3) 1041-1047
  • 122 Mattson D L, James L, Berdan E A, Meister C J. Immune suppression attenuates hypertension and renal disease in the Dahl salt-sensitive rat.  Hypertension. 2006;  48 (1) 149-156
  • 123 Quiroz Y, Pons H, Gordon K L et al.. Mycophenolate mofetil prevents salt-sensitive hypertension resulting from nitric oxide synthesis inhibition.  Am J Physiol Renal Physiol. 2001;  281 (1) F38-F47
  • 124 Rodríguez-Iturbe B, Pons H, Quiroz Y et al.. Mycophenolate mofetil prevents salt-sensitive hypertension resulting from angiotensin II exposure.  Kidney Int. 2001;  59 (6) 2222-2232
  • 125 Boesen E I, Williams D L, Pollock J S, Pollock D M. Immunosuppression with mycophenolate mofetil attenuates the development of hypertension and albuminuria in deoxycorticosterone acetate-salt hypertensive rats.  Clin Exp Pharmacol Physiol. 2010;  37 (10) 1016-1022
  • 126 Franco M, Martínez F, Rodríguez-Iturbe B et al.. Angiotensin II, interstitial inflammation, and the pathogenesis of salt-sensitive hypertension.  Am J Physiol Renal Physiol. 2006;  291 (6) F1281-F1287
  • 127 Cirillo P, Sautin Y Y, Kanellis J et al.. Systemic inflammation, metabolic syndrome and progressive renal disease.  Nephrol Dial Transplant. 2009;  24 (5) 1384-1387
  • 128 Glushakova O, Kosugi T, Roncal C et al.. Fructose induces the inflammatory molecule ICAM-1 in endothelial cells.  J Am Soc Nephrol. 2008;  19 (9) 1712-1720
  • 129 Gersch M S, Mu W, Cirillo P et al.. Fructose, but not dextrose, accelerates the progression of chronic kidney disease.  Am J Physiol Renal Physiol. 2007;  293 (4) F1256-F1261
  • 130 Mattioli L F, Holloway N B, Thomas J H, Wood J G. Fructose, but not dextrose, induces leukocyte adherence to the mesenteric venule of the rat by oxidative stress.  Pediatr Res. 2010;  67 (4) 352-356
  • 131 Tan H W, Xing S S, Bi X P et al.. Felodipine attenuates vascular inflammation in a fructose-induced rat model of metabolic syndrome via the inhibition of NF-kappaB activation.  Acta Pharmacol Sin. 2008;  29 (9) 1051-1059
  • 132 Nyby M D, Abedi K, Smutko V, Eslami P, Tuck M L. Vascular Angiotensin type 1 receptor expression is associated with vascular dysfunction, oxidative stress and inflammation in fructose-fed rats.  Hypertens Res. 2007;  30 (5) 451-457
  • 133 Kokkola R, Andersson A, Mullins G et al.. RAGE is the major receptor for the proinflammatory activity of HMGB1 in rodent macrophages.  Scand J Immunol. 2005;  61 (1) 1-9
  • 134 Nagai N, Oike Y, Izumi-Nagai K et al.. Angiotensin II type 1 receptor-mediated inflammation is required for choroidal neovascularization.  Arterioscler Thromb Vasc Biol. 2006;  26 (10) 2252-2259
  • 135 Oliveira L, Costa-Neto C M, Nakaie C R, Schreier S, Shimuta S I, Paiva A C. The angiotensin II AT1 receptor structure-activity correlations in the light of rhodopsin structure.  Physiol Rev. 2007;  87 (2) 565-592
  • 136 Ramasamy R, Yan S F, Schmidt A M. RAGE: therapeutic target and biomarker of the inflammatory response—the evidence mounts.  J Leukoc Biol. 2009;  86 (3) 505-512
  • 137 Niskanen L, Laaksonen D E, Nyyssönen K et al.. Inflammation, abdominal obesity, and smoking as predictors of hypertension.  Hypertension. 2004;  44 (6) 859-865
  • 138 Sesso H D, Wang L, Buring J E, Ridker P M, Gaziano J M. Comparison of interleukin-6 and C-reactive protein for the risk of developing hypertension in women.  Hypertension. 2007;  49 (2) 304-310
  • 139 Zhang Y, Thompson A M, Tong W et al.. Biomarkers of inflammation and endothelial dysfunction and risk of hypertension among Inner Mongolians in China.  J Hypertens. 2010;  28 (1) 35-40
  • 140 Dörffel Y, Lätsch C, Stuhlmüller B et al.. Preactivated peripheral blood monocytes in patients with essential hypertension.  Hypertension. 1999;  34 (1) 113-117
  • 141 Wirtz P H, von Känel R, Frey K, Ehlert U, Fischer J E. Glucocorticoid sensitivity of circulating monocytes in essential hypertension.  Am J Hypertens. 2004;  17 (6) 489-494
  • 142 Fliser D, Buchholz K, Haller H. EUropean Trial on Olmesartan and Pravastatin in Inflammation and Atherosclerosis (EUTOPIA) Investigators . Antiinflammatory effects of angiotensin II subtype 1 receptor blockade in hypertensive patients with microinflammation.  Circulation. 2004;  110 (9) 1103-1107
  • 143 Dohi Y, Ohashi M, Sugiyama M, Takase H, Sato K, Ueda R. Candesartan reduces oxidative stress and inflammation in patients with essential hypertension.  Hypertens Res. 2003;  26 (9) 691-697
  • 144 Koh K K, Quon M J, Han S H, Chung W J, Lee Y, Shin E K. Anti-inflammatory and metabolic effects of candesartan in hypertensive patients.  Int J Cardiol. 2006;  108 (1) 96-100
  • 145 Manabe S, Okura T, Watanabe S, Fukuoka T, Higaki J. Effects of angiotensin II receptor blockade with valsartan on pro-inflammatory cytokines in patients with essential hypertension.  J Cardiovasc Pharmacol. 2005;  46 (6) 735-739
  • 146 Ishimitsu T, Numabe A, Masuda T et al.. Angiotensin-II receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension.  Hypertens Res. 2009;  32 (11) 962-968
  • 147 Vanhala M, Kautiainen H, Kumpusalo E. Proinflammation and hypertension: a population-based study.  Mediators Inflamm. 2008;  2008 619704
  • 148 Larrousse M, Bragulat E, Segarra M, Sierra C, Coca A, de La Sierra A. Increased levels of atherosclerosis markers in salt-sensitive hypertension.  Am J Hypertens. 2006;  19 (1) 87-93
  • 149 Tappy L, Lê K A. Metabolic effects of fructose and the worldwide increase in obesity.  Physiol Rev. 2010;  90 (1) 23-46
  • 150 Choi M E. The not-so-sweet side of fructose.  J Am Soc Nephrol. 2009;  20 (3) 457-459
  • 151 Cirillo P, Gersch M S, Mu W et al.. Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators in proximal tubular cells.  J Am Soc Nephrol. 2009;  20 (3) 545-553
  • 152 O'Brien P J, Siraki A G, Shangari N. Aldehyde sources, metabolism, molecular toxicity mechanisms, and possible effects on human health.  Crit Rev Toxicol. 2005;  35 (7) 609-662
  • 153 Madhur M S, Lob H E, McCann L A et al.. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction.  Hypertension. 2010;  55 (2) 500-507
  • 154 de Ferranti S, Mozaffarian D. The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences.  Clin Chem. 2008;  54 (6) 945-955
  • 155 Suganami T, Tanimoto-Koyama K, Nishida J et al.. Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages.  Arterioscler Thromb Vasc Biol. 2007;  27 (1) 84-91
  • 156 Shi H, Kokoeva M V, Inouye K, Tzameli I, Yin H, Flier J S. TLR4 links innate immunity and fatty acid-induced insulin resistance.  J Clin Invest. 2006;  116 (11) 3015-3025
  • 157 Itani S I, Ruderman N B, Schmieder F, Boden G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-α.  Diabetes. 2002;  51 (7) 2005-2011
  • 158 Ellis B A, Poynten A, Lowy A J et al.. Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscle.  Am J Physiol Endocrinol Metab. 2000;  279 (3) E554-E560
  • 159 Cai D, Yuan M, Frantz D F et al.. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-kappaB.  Nat Med. 2005;  11 (2) 183-190
  • 160 Poggi M, Bastelica D, Gual P et al.. C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet.  Diabetologia. 2007;  50 (6) 1267-1276
  • 161 Kim F, Pham M, Luttrell I et al.. Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity.  Circ Res. 2007;  100 (11) 1589-1596
  • 162 Geiger H, Fierlbeck W, Mai M et al.. Effects of early and late antihypertensive treatment on extracellular matrix proteins and mononuclear cells in uninephrectomized SHR.  Kidney Int. 1997;  51 (3) 750-761
  • 163 Harrison D G, Guzik T J, Lob H E et al.. Inflammation, immunity, and hypertension.  Hypertension. 2011;  57 (2) 132-140
  • 164 Brasier A R, Recinos III A, Eledrisi M S. Vascular inflammation and the renin-angiotensin system.  Arterioscler Thromb Vasc Biol. 2002;  22 (8) 1257-1266
  • 165 Sekiguchi K, Li X, Coker M et al.. Cross-regulation between the renin-angiotensin system and inflammatory mediators in cardiac hypertrophy and failure.  Cardiovasc Res. 2004;  63 (3) 433-442
  • 166 Beg M, Gupta A, Khanna V N. Oxidative stress in essential hypertension and role of antioxidants.  JIACM. 2010;  11 287-293
  • 167 Volpe E, Servant N, Zollinger R et al.. A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses.  Nat Immunol. 2008;  9 (6) 650-657
  • 168 Platten M, Youssef S, Hur E M et al.. Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity.  Proc Natl Acad Sci U S A. 2009;  106 (35) 14948-14953
  • 169 Schmitz D, Wilsenack K, Lendemanns S, Schedlowski M, Oberbeck R. β-Adrenergic blockade during systemic inflammation: impact on cellular immune functions and survival in a murine model of sepsis.  Resuscitation. 2007;  72 (2) 286-294
  • 170 Wang J, Li J, Sheng X et al.. β-adrenoceptor mediated surgery-induced production of pro-inflammatory cytokines in rat microglia cells.  J Neuroimmunol. 2010;  223 (1-2) 77-83
  • 171 Agarwal D, Haque M, Sriramula S, Mariappan N, Pariaut R, Francis J. Role of proinflammatory cytokines and redox homeostasis in exercise-induced delayed progression of hypertension in spontaneously hypertensive rats.  Hypertension. 2009;  54 (6) 1393-1400
  • 172 Tian N, Moore R S, Braddy S et al.. Interactions between oxidative stress and inflammation in salt-sensitive hypertension.  Am J Physiol Heart Circ Physiol. 2007;  293 (6) H3388-H3395
  • 173 Loppnow H, Libby P. Proliferating or interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6.  J Clin Invest. 1990;  85 (3) 731-738
  • 174 Ikeda U, Ikeda M, Oohara T et al.. Interleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner.  Am J Physiol. 1991;  260 (5 Pt 2) H1713-H1717
  • 175 Amrani Y, Bronner C. Tumor necrosis factor alpha potentiates the increase in cytosolic free calcium induced by bradykinin in guinea-pig tracheal smooth muscle cells.  C R Acad Sci III. 1993;  316 (12) 1489-1494
  • 176 Lazaar A L, Amrani Y, Hsu J et al.. CD40-mediated signal transduction in human airway smooth muscle.  J Immunol. 1998;  161 (6) 3120-3127
  • 177 Ducreux S, Zorzato F, Müller C et al.. Effect of ryanodine receptor mutations on interleukin-6 release and intracellular calcium homeostasis in human myotubes from malignant hyperthermia-susceptible individuals and patients affected by central core disease.  J Biol Chem. 2004;  279 (42) 43838-43846
  • 178 Rask-Madsen C, Domínguez H, Ihlemann N, Hermann T, Køber L, Torp-Pedersen C. Tumor necrosis factor-α inhibits insulin's stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans.  Circulation. 2003;  108 (15) 1815-1821
  • 179 Valerio A, Cardile A, Cozzi V et al.. TNF-α downregulates eNOS expression and mitochondrial biogenesis in fat and muscle of obese rodents.  J Clin Invest. 2006;  116 (10) 2791-2798
  • 180 Moller D E. Potential role of TNF-α in the pathogenesis of insulin resistance and type 2 diabetes.  Trends Endocrinol Metab. 2000;  11 (6) 212-217
  • 181 Hotamisligil G S. Inflammatory pathways and insulin action.  Int J Obes Relat Metab Disord. 2003;  27 (Suppl 3) S53-S55
  • 182 Sabio G, Das M, Mora A et al.. A stress signaling pathway in adipose tissue regulates hepatic insulin resistance.  Science. 2008;  322 (5907) 1539-1543
  • 183 Senn J J, Klover P J, Nowak I A et al.. Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes.  J Biol Chem. 2003;  278 (16) 13740-13746
  • 184 Torisu T, Sato N, Yoshiga D et al.. The dual function of hepatic SOCS3 in insulin resistance in vivo.  Genes Cells. 2007;  12 (2) 143-154
  • 185 Emanuelli B, Peraldi P, Filloux C et al.. SOCS-3 inhibits insulin signaling and is up-regulated in response to tumor necrosis factor-α in the adipose tissue of obese mice.  J Biol Chem. 2001;  276 (51) 47944-47949
  • 186 Emanuelli B, Peraldi P, Filloux C, Sawka-Verhelle D, Hilton D, Van Obberghen E. SOCS-3 is an insulin-induced negative regulator of insulin signaling.  J Biol Chem. 2000;  275 (21) 15985-15991
  • 187 Klover P J, Zimmers T A, Koniaris L G, Mooney R A. Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice.  Diabetes. 2003;  52 (11) 2784-2789
  • 188 Saura M, Zaragoza C, Bao C, Herranz B, Rodriguez-Puyol M, Lowenstein C J. Stat3 mediates interleukin-6 inhibition of human endothelial nitric-oxide synthase expression.  J Biol Chem. 2006;  281 (40) 30057-30062
  • 189 Andreozzi F, Laratta E, Procopio C et al.. Interleukin-6 impairs the insulin signaling pathway, promoting production of nitric oxide in human umbilical vein endothelial cells.  Mol Cell Biol. 2007;  27 (6) 2372-2383
  • 190 Hung M J, Cherng W J, Hung M Y, Wu H T, Pang J HS. Interleukin-6 inhibits endothelial nitric oxide synthase activation and increases endothelial nitric oxide synthase binding to stabilized caveolin-1 in human vascular endothelial cells.  J Hypertens. 2010;  28 (5) 940-951
  • 191 Jager J, Grémeaux T, Cormont M, Le Marchand-Brustel Y, Tanti J F. Interleukin-1β-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression.  Endocrinology. 2007;  148 (1) 241-251
  • 192 Brasier A R, Li J, Wimbish K A. Tumor necrosis factor activates angiotensinogen gene expression by the Rel A transactivator.  Hypertension. 1996;  27 (4) 1009-1017
  • 193 Cowling R T, Zhang X, Reese V C et al.. Effects of cytokine treatment on angiotensin II type 1A receptor transcription and splicing in rat cardiac fibroblasts.  Am J Physiol Heart Circ Physiol. 2005;  289 (3) H1176-H1183
  • 194 Takeshita Y, Takamura T, Ando H et al.. Cross talk of tumor necrosis factor-α and the renin-angiotensin system in tumor necrosis factor-α-induced plasminogen activator inhibitor-1 production from hepatocytes.  Eur J Pharmacol. 2008;  579 (1-3) 426-432
  • 195 Wassmann S, Stumpf M, Strehlow K et al.. Interleukin-6 induces oxidative stress and endothelial dysfunction by overexpression of the angiotensin II type 1 receptor.  Circ Res. 2004;  94 (4) 534-541
  • 196 Lee D L, Sturgis L C, Labazi H et al.. Angiotensin II hypertension is attenuated in interleukin-6 knockout mice.  Am J Physiol Heart Circ Physiol. 2006;  290 (3) H935-H940
  • 197 Madhur M S, Lob H E, McCann L A et al.. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction.  Hypertension. 2010;  55 (2) 500-507
  • 198 Basuroy S, Bhattacharya S, Tcheranova D et al.. HO-2 provides endogenous protection against oxidative stress and apoptosis caused by TNF-α in cerebral vascular endothelial cells.  Am J Physiol Cell Physiol. 2006;  291 (5) C897-C908
  • 199 Eringa E C, Stehouwer C DA, Walburg K et al.. Physiological concentrations of insulin induce endothelin-dependent vasoconstriction of skeletal muscle resistance arteries in the presence of tumor necrosis factor-α dependence on c-Jun N-terminal kinase.  Arterioscler Thromb Vasc Biol. 2006;  26 (2) 274-280
  • 200 Zhang H, Zhang J, Ungvari Z, Zhang C. Resveratrol improves endothelial function: role of TNFα and vascular oxidative stress.  Arterioscler Thromb Vasc Biol. 2009;  29 (8) 1164-1171
  • 201 Heo S K, Yun H J, Park W H, Park S D. Emodin inhibits TNF-α-induced human aortic smooth-muscle cell proliferation via caspase- and mitochondrial-dependent apoptosis.  J Cell Biochem. 2008;  105 (1) 70-80
  • 202 Chamberlain J, Francis S, Brookes Z et al.. Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding.  PLoS ONE. 2009;  4 (4) e5073
  • 203 Papanicolaou D A, Petrides J S, Tsigos C et al.. Exercise stimulates interleukin-6 secretion: inhibition by glucocorticoids and correlation with catecholamines.  Am J Physiol. 1996;  271 (3 Pt 1) E601-E605
  • 204 Torpy D J, Papanicolaou D A, Lotsikas A J, Wilder R L, Chrousos G P, Pillemer S R. Responses of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis to interleukin-6: a pilot study in fibromyalgia.  Arthritis Rheum. 2000;  43 (4) 872-880
  • 205 Gwosdow A R. Mechanisms of interleukin-1-induced hormone secretion from the rat adrenal gland.  Endocr Res. 1995;  21 (1-2) 25-37
  • 206 Zhang Z H, Wei S G, Francis J, Felder R B. Cardiovascular and renal sympathetic activation by blood-borne TNF-α in rat: the role of central prostaglandins.  Am J Physiol Regul Integr Comp Physiol. 2003;  284 (4) R916-R927
  • 207 Lopez-Garcia E, Schulze M B, Fung T T et al.. Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction.  Am J Clin Nutr. 2004;  80 (4) 1029-1035
  • 208 Holt E M, Steffen L M, Moran A et al.. Fruit and vegetable consumption and its relation to markers of inflammation and oxidative stress in adolescents.  J Am Diet Assoc. 2009;  109 (3) 414-421
  • 209 Genkinger J M, Platz E A, Hoffman S C, Comstock G W, Helzlsouer K J. Fruit, vegetable, and antioxidant intake and all-cause, cancer, and cardiovascular disease mortality in a community-dwelling population in Washington County, Maryland.  Am J Epidemiol. 2004;  160 (12) 1223-1233
  • 210 Guadagni M, Biolo G. Effects of inflammation and/or inactivity on the need for dietary protein.  Curr Opin Clin Nutr Metab Care. 2009;  12 (6) 617-622
  • 211 Casas-Agustench P, Bulló M, Salas-Salvadó J. Nuts, inflammation and insulin resistance.  Asia Pac J Clin Nutr. 2010;  19 (1) 124-130
  • 212 Ros E. Nuts and novel biomarkers of cardiovascular disease.  Am J Clin Nutr. 2009;  89 (5) 1649S-1656S
  • 213 King D E, Egan B M, Woolson R F, Mainous III A G, Al-Solaiman Y, Jesri A. Effect of a high-fiber diet vs a fiber-supplemented diet on C-reactive protein level.  Arch Intern Med. 2007;  167 (5) 502-506
  • 214 Shen J, Lai C Q, Mattei J, Ordovas J M, Tucker K L. Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study.  Am J Clin Nutr. 2010;  91 (2) 337-342
  • 215 Morris M S, Sakakeeny L, Jacques P F, Picciano M F, Selhub J. Vitamin B-6 intake is inversely related to, and the requirement is affected by, inflammation status.  J Nutr. 2010;  140 (1) 103-110
  • 216 Scheurig A C, Thorand B, Fischer B, Heier M, Koenig W. Association between the intake of vitamins and trace elements from supplements and C-reactive protein: results of the MONICA/KORA Augsburg study.  Eur J Clin Nutr. 2008;  62 (1) 127-137
  • 217 Singh U, Devaraj S, Jialal I. Vitamin E, oxidative stress, and inflammation.  Annu Rev Nutr. 2005;  25 151-174
  • 218 Devaraj S, Leonard S, Traber M G, Jialal I. Gamma-tocopherol supplementation alone and in combination with alpha-tocopherol alters biomarkers of oxidative stress and inflammation in subjects with metabolic syndrome.  Free Radic Biol Med. 2008;  44 (6) 1203-1208
  • 219 Wu S J, Liu P L, Ng L T. Tocotrienol-rich fraction of palm oil exhibits anti-inflammatory property by suppressing the expression of inflammatory mediators in human monocytic cells.  Mol Nutr Food Res. 2008;  52 (8) 921-929
  • 220 Wannamethee S G, Lowe G DO, Rumley A, Bruckdorfer K R, Whincup P H. Associations of vitamin C status, fruit and vegetable intakes, and markers of inflammation and hemostasis.  Am J Clin Nutr. 2006;  83 (3) 567-574 quiz 726-727
  • 221 Helmersson J, Arnlöv J, Larsson A, Basu S. Low dietary intake of β-carotene, α-tocopherol and ascorbic acid is associated with increased inflammatory and oxidative stress status in a Swedish cohort.  Br J Nutr. 2009;  101 (12) 1775-1782
  • 222 Aguirre R, May J M. Inflammation in the vascular bed: importance of vitamin C.  Pharmacol Ther. 2008;  119 (1) 96-103
  • 223 Chang H H, Chen C S, Lin J Y. High dose vitamin C supplementation increases the Th1/Th2 cytokine secretion ratio, but decreases eosinophilic infiltration in bronchoalveolar lavage fluid of ovalbumin-sensitized and challenged mice.  J Agric Food Chem. 2009;  57 (21) 10471-10476
  • 224 Jain S K, Velusamy T, Croad J L, Rains J L, Bull R. L-cysteine supplementation lowers blood glucose, glycated hemoglobin, CRP, MCP-1, and oxidative stress and inhibits NF-kappaB activation in the livers of Zucker diabetic rats.  Free Radic Biol Med. 2009;  46 (12) 1633-1638
  • 225 Tsai G Y, Cui J Z, Syed H et al.. Effect of N-acetylcysteine on the early expression of inflammatory markers in the retina and plasma of diabetic rats.  Clin Experiment Ophthalmol. 2009;  37 (2) 223-231
  • 226 Kim C J, Kovacs-Nolan J, Yang C, Archbold T, Fan M Z, Mine Y. L-cysteine supplementation attenuates local inflammation and restores gut homeostasis in a porcine model of colitis.  Biochim Biophys Acta. 2009;  1790 (10) 1161-1169
  • 227 Csontos C, Rezman B, Foldi V et al.. Effect of N-acetylcysteine treatment on the expression of leukocyte surface markers after burn injury.  Burns. 2011;  37 (3) 453-464
  • 228 Marracci G H, Jones R E, McKeon G P, Bourdette D N. Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis.  J Neuroimmunol. 2002;  131 (1-2) 104-114
  • 229 Morini M, Roccatagliata L, Dell'Eva R et al.. α-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis.  J Neuroimmunol. 2004;  148 (1-2) 146-153
  • 230 Schreibelt G, Musters R JP, Reijerkerk A et al.. Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity.  J Immunol. 2006;  177 (4) 2630-2637
  • 231 Chaudhary P, Marracci G H, Bourdette D N. Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis.  J Neuroimmunol. 2006;  175 (1-2) 87-96
  • 232 Yadav V, Marracci G, Lovera J et al.. Lipoic acid in multiple sclerosis: a pilot study.  Mult Scler. 2005;  11 (2) 159-165
  • 233 Salinthone S, Yadav V, Schillace R V, Bourdette D N, Carr D W. Lipoic acid attenuates inflammation via cAMP and protein kinase A signaling.  PLoS ONE. 2010;  5 (9) 1-10
  • 234 Şehirli AÖ, Tatlidede E, Yüksel M et al.. Protective effects of alpha-lipoic acid against oxidative injury in TNBS-induced colitis.  Erciyes Tip Dergisi. 2009;  31 15-26
  • 235 Appel L J, Moore T J, Obarzanek E DASH Collaborative Research Group et al. A clinical trial of the effects of dietary patterns on blood pressure.  N Engl J Med. 1997;  336 (16) 1117-1124
  • 236 Sacks F M, Svetkey L P, Vollmer W M DASH-Sodium Collaborative Research Group et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet.  N Engl J Med. 2001;  344 (1) 3-10
  • 237 Martin D W, Mayes P A, Rodwell V W. Harper's Review of Biochemistry. 19th ed. Los Altos, CA: Lange Medical Publications; 1983. 22 101-105 120 183-184 187-188 597-599
  • 238 Tsuchiya Y, Yamaguchi M, Chikuma T, Hojo H. Degradation of glyceraldehyde-3-phosphate dehydrogenase triggered by 4-hydroxy-2-nonenal and 4-hydroxy-2-hexenal.  Arch Biochem Biophys. 2005;  438 (2) 217-222
  • 239 Taddei S, Ghiadoni L, Virdis A, Versari D, Salvetti A. Mechanisms of endothelial dysfunction: clinical significance and preventive non-pharmacological therapeutic strategies.  Curr Pharm Des. 2003;  9 (29) 2385-2402
  • 240 Stocker R, Keaney Jr J F. Role of oxidative modifications in atherosclerosis.  Physiol Rev. 2004;  84 (4) 1381-1478
  • 241 Dickhout J G, Hossain G S, Pozza L M, Zhou J, Lhoták S, Austin R C. Peroxynitrite causes endoplasmic reticulum stress and apoptosis in human vascular endothelium: implications in atherogenesis.  Arterioscler Thromb Vasc Biol. 2005;  25 (12) 2623-2629
  • 242 Guzik T J, Sadowski J, Guzik B et al.. Coronary artery superoxide production and NOX isoform expression in human coronary artery disease.  Arterioscler Thromb Vasc Biol. 2006;  26 (2) 333-339
  • 243 Li W G, Miller Jr F J, Zhang H J, Spitz D R, Oberley L W, Weintraub N L. H(2)O(2)-induced O(2) production by a non-phagocytic NAD(P)H oxidase causes oxidant injury.  J Biol Chem. 2001;  276 (31) 29251-29256
  • 244 Jiang F, Drummond G R, Dusting G J. Suppression of oxidative stress in the endothelium and vascular wall.  Endothelium. 2004;  11 (2) 79-88
  • 245 Dixon L J, Hughes S M, Rooney K et al.. Increased superoxide production in hypertensive patients with diabetes mellitus: role of nitric oxide synthase.  Am J Hypertens. 2005;  18 (6) 839-843
  • 246 Bartlett R K, Bieber Urbauer R J, Anbanandam A, Smallwood H S, Urbauer J L, Squier T C. Oxidation of Met144 and Met145 in calmodulin blocks calmodulin dependent activation of the plasma membrane Ca-ATPase.  Biochemistry. 2003;  42 (11) 3231-3238
  • 247 Biswas S K, de Faria J B. Which comes first: renal inflammation or oxidative stress in spontaneously hypertensive rats?.  Free Radic Res. 2007;  41 (2) 216-224
  • 248 Franco M, Martínez F, Quiroz Y et al.. Renal angiotensin II concentration and interstitial infiltration of immune cells are correlated with blood pressure levels in salt-sensitive hypertension.  Am J Physiol Regul Integr Comp Physiol. 2007;  293 (1) R251-R256
  • 249 Crowley S D, Frey C W, Gould S K et al.. Stimulation of lymphocyte responses by angiotensin II promotes kidney injury in hypertension.  Am J Physiol Renal Physiol. 2008;  295 (2) F515-F524
  • 250 Peeters ACTM, Netea M G, Janssen M C, Kullberg B J, Van der Meer J W, Thien T. Pro-inflammatory cytokines in patients with essential hypertension.  Eur J Clin Invest. 2001;  31 (1) 31-36
  • 251 Sela S, Shurtz-Swirski R, Farah R et al.. A link between polymorphonuclear leukocyte intracellular calcium, plasma insulin, and essential hypertension.  Am J Hypertens. 2002;  15 (4 Pt 1) 291-295
  • 252 Lakoski S G, Herrington D M, Siscovick D M, Hulley S B. C-reactive protein concentration and incident hypertension in young adults: the CARDIA study.  Arch Intern Med. 2006;  166 (3) 345-349
  • 253 Antonelli A, Fallahi P, Rotondi M et al.. High serum levels of CXC chemokine ligand 10 in untreated essential hypertension.  J Hum Hypertens. 2008;  22 (8) 579-581

Sudesh VasdevD.V.M. Ph.D. F.A.C.B. 

Professor, Faculty of Medicine, Director, Renal Laboratory, Room H-4310, Health Sciences Centre

Memorial University, St. John's, Newfoundland, Canada A1B 3V6

eMail: svasdev@mun.ca