Nutritional improvement of the endothelial control of vascular tone by polyphenols: role of NO and EDHF

  • Valérie B. Schini-Kerth
  • Cyril Auger
  • Jong-Hun Kim
  • Nelly Étienne-Selloum
  • Thierry Chataigneau
Invited Review

Abstract

Numerous studies indicate that regular intake of polyphenol-rich beverages (red wine and tea) and foods (chocolate, fruit, and vegetables) is associated with a protective effect on the cardiovascular system in humans and animals. Beyond the well-known antioxidant properties of polyphenols, several other mechanisms have been shown to contribute to their beneficial cardiovascular effects. Indeed, both experimental and clinical studies indicate that polyphenols improve the ability of endothelial cells to control vascular tone. Experiments with isolated arteries have shown that polyphenols cause nitric oxide (NO)-mediated endothelium-dependent relaxations and increase the endothelial formation of NO. The polyphenol-induced NO formation is due to the redox-sensitive activation of the phosphatidylinositol3-kinase/Akt pathway leading to endothelial NO synthase (eNOS) activation subsequent to its phosphorylation on Ser 1177. Besides the phosphatidylinositol3-kinase/Akt pathway, polyphenols have also been shown to activate eNOS by increasing the intracellular free calcium concentration and by activating estrogen receptors in endothelial cells. In addition to causing a rapid and sustained activation of eNOS by phosphorylation, polyphenols can increase the expression level of eNOS in endothelial cells leading to an increased formation of NO. Moreover, the polyphenol-induced endothelium-dependent relaxation also involves endothelium-derived hyperpolarizing factor, besides NO, in several types of arteries. Altogether, polyphenols have the capacity to improve the endothelial control of vascular tone not only in several experimental models of cardiovascular diseases such as hypertension but also in healthy and diseased humans. Thus, these experimental and clinical studies highlight the potential of polyphenol-rich sources to provide vascular protection in health and disease.

Keywords

Polyphenols eNOS NO EDHF Hypertension 

References

  1. 1.
    Agewall S, Wright S, Doughty RN et al (2000) Does a glass of red wine improve endothelial function? Eur Heart J 21:74–78PubMedCrossRefGoogle Scholar
  2. 2.
    Al-Awwadi NA, Araiz C, Bornet A et al (2005) Extracts enriched in different polyphenolic families normalize increased cardiac NADPH oxidase expression while having differential effects on insulin resistance, hypertension, and cardiac hypertrophy in high-fructose-fed rats. J Agric Food Chem 53:151–157PubMedCrossRefGoogle Scholar
  3. 3.
    Al-Awwadi NA, Bornet A, Azay J et al (2004) Red wine polyphenols alone or in association with ethanol prevent hypertension, cardiac hypertrophy, and production of reactive oxygen species in the insulin-resistant fructose-fed rat. J Agric Food Chem 52:5593–5597PubMedCrossRefGoogle Scholar
  4. 4.
    Andriambeloson E, Kleschyov AL, Muller B et al (1997) Nitric oxide production and endothelium-dependent vasorelaxation induced by wine polyphenols in rat aorta. Br J Pharmacol 120:1053–1058PubMedCrossRefGoogle Scholar
  5. 5.
    Anselm E, Chataigneau M, Ndiaye M et al (2007) Grape juice causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of eNOS. Cardiovasc Res 73:404–413PubMedCrossRefGoogle Scholar
  6. 6.
    Anselm E, Socorro VF, Dal-Ros S et al (2009) Crataegus special extract WS 1442 causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of endothelial NO synthase but not via activation of estrogen receptors. J Cardiovasc Pharmacol 53:253–260PubMedCrossRefGoogle Scholar
  7. 7.
    Anter E, Chen K, Shapira OM et al (2005) p38 mitogen-activated protein kinase activates eNOS in endothelial cells by an estrogen receptor alpha-dependent pathway in response to black tea polyphenols. Circ Res 96:1072–1078PubMedCrossRefGoogle Scholar
  8. 8.
    Anter E, Thomas SR, Schulz E et al (2004) Activation of endothelial nitric-oxide synthase by the p38 MAPK in response to black tea polyphenols. J Biol Chem 279:46637–46643PubMedCrossRefGoogle Scholar
  9. 9.
    Appeldoorn MM, Venema DP, Peters TH et al (2009) Some phenolic compounds increase the nitric oxide level in endothelial cells in vitro. J Agric Food Chem 57:7693–7699PubMedCrossRefGoogle Scholar
  10. 10.
    Arts IC, Hollman PC (2005) Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr 81:317S–325SPubMedGoogle Scholar
  11. 11.
    Auger C, Caporiccio B, Landrault N et al (2002) Red wine phenolic compounds reduce plasma lipids and apolipoprotein B and prevent early aortic atherosclerosis in hypercholesterolemic golden Syrian hamsters (Mesocricetus auratus). J Nutr 132:1207–1213PubMedGoogle Scholar
  12. 12.
    Auger C, Gerain P, Laurent-Bichon F et al (2004) Phenolics from commercialized grape extracts prevent early atherosclerotic lesions in hamsters by mechanisms other than antioxidant effect. J Agric Food Chem 52:5297–5302PubMedCrossRefGoogle Scholar
  13. 13.
    Balzer J, Rassaf T, Heiss C et al (2008) Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial. J Am Coll Cardiol 51:2141–2149PubMedCrossRefGoogle Scholar
  14. 14.
    Baraboi VA, Stoian OP (1968) Effect of natrium gallate and some other polyphenols on systemic arterial pressure and tonus of vessels of the skeletal muscles in cats. Fiziol Zh 14:782–790PubMedGoogle Scholar
  15. 15.
    Bell DR, Gochenaur K (2006) Direct vasoactive and vasoprotective properties of anthocyanin-rich extracts. J Appl Physiol 100:1164–1170PubMedCrossRefGoogle Scholar
  16. 16.
    Bernatova I, Pechanova O, Babal P et al (2002) Wine polyphenols improve cardiovascular remodeling and vascular function in NO-deficient hypertension. Am J Physiol Heart Circ Physiol 282:H942–H948PubMedGoogle Scholar
  17. 17.
    Burns J, Gardner PT, O’Neil J et al (2000) Relationship among antioxidant activity, vasodilation capacity, and phenolic content of red wines. J Agric Food Chem 48:220–230PubMedCrossRefGoogle Scholar
  18. 18.
    Caulin-Glaser T, Garcia-Cardena G, Sarrel P et al (1997) 17 beta-estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization. Circ Res 81:885–892PubMedGoogle Scholar
  19. 19.
    Chen G, Suzuki H, Weston AH (1988) Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels. Br J Pharmacol 95:1165–1174PubMedGoogle Scholar
  20. 20.
    Chen LG, Liu YC, Hsieh CW et al (2008) Tannin 1-alpha-O-galloylpunicalagin induces the calcium-dependent activation of endothelial nitric-oxide synthase via the phosphatidylinositol 3-kinase/Akt pathway in endothelial cells. Mol Nutr Food Res 52:1162–1171PubMedCrossRefGoogle Scholar
  21. 21.
    Chen ZY, Zhang ZS, Kwan KY et al (1998) Endothelium-dependent relaxation induced by hawthorn extract in rat mesenteric artery. Life Sci 63:1983–1991PubMedCrossRefGoogle Scholar
  22. 22.
    Chou EJ, Keevil JG, Aeschlimann S et al (2001) Effect of ingestion of purple grape juice on endothelial function in patients with coronary heart disease. Am J Cardiol 88:553–555PubMedCrossRefGoogle Scholar
  23. 23.
    Cienfuegos-Jovellanos E, Quinones MM, Muguerza B et al (2009) Antihypertensive effect of a polyphenol-rich cocoa powder industrially processed to preserve the original flavonoids of the cocoa beans. J Agric Food Chem 57:6156–6162PubMedCrossRefGoogle Scholar
  24. 24.
    Cishek MB, Galloway MT, Karim M et al (1997) Effect of red wine on endothelium-dependent relaxation in rabbits. Clin Sci (Lond) 93:507–511Google Scholar
  25. 25.
    Csiszar A, Labinskyy N, Pinto JT et al (2009) Resveratrol induces mitochondrial biogenesis in endothelial cells. Am J Physiol Heart Circ Physiol 297:H13–H20PubMedCrossRefGoogle Scholar
  26. 26.
    Dal-Ros S, Bronner C, Schott C et al (2009) Angiotensin II-induced hypertension is associated with a selective inhibition of endothelium-derived hyperpolarizing factor-mediated responses in the rat mesenteric artery. J Pharmacol Exp Ther 328:478–486PubMedCrossRefGoogle Scholar
  27. 27.
    David-Dufilho M, Privat C, Brunet A et al (2001) Transition metals and nitric oxide production in human endothelial cells. C R Acad Sci III 324:13–21PubMedGoogle Scholar
  28. 28.
    de Moura RS, Miranda DZ, Pinto AC et al (2004) Mechanism of the endothelium-dependent vasodilation and the antihypertensive effect of Brazilian red wine. J Cardiovasc Pharmacol 44:302–309PubMedCrossRefGoogle Scholar
  29. 29.
    Di CA, Rotondo S, Iacoviello L et al (2002) Meta-analysis of wine and beer consumption in relation to vascular risk. Circulation 105:2836–2844CrossRefGoogle Scholar
  30. 30.
    Dimmeler S, Fleming I, Fisslthaler B et al (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399:601–605PubMedCrossRefGoogle Scholar
  31. 31.
    Djousse L, Ellison RC, McLennan CE et al (1999) Acute effects of a high-fat meal with and without red wine on endothelial function in healthy subjects. Am J Cardiol 84:660–664PubMedCrossRefGoogle Scholar
  32. 32.
    Dresse A, Lecomte J (1960) Action of polyphenols and of metanephrine on the myocardial effects of adrenalin. C R Seances Soc Biol Fil 154:851–854PubMedGoogle Scholar
  33. 33.
    Duarte J, Jimenez R, Villar IC et al (2001) Vasorelaxant effects of the bioflavonoid chrysin in isolated rat aorta. Planta Med 67:567–569PubMedCrossRefGoogle Scholar
  34. 34.
    Duffy SJ, Vita JA, Holbrook M et al (2001) Effect of acute and chronic tea consumption on platelet aggregation in patients with coronary artery disease. Arterioscler Thromb Vasc Biol 21:1084–1089PubMedGoogle Scholar
  35. 35.
    Edirisinghe I, Burton-Freeman B, Tissa KC (2008) Mechanism of the endothelium-dependent relaxation evoked by a grape seed extract. Clin Sci (Lond) 114:331–337CrossRefGoogle Scholar
  36. 36.
    Edirisinghe I, Burton-Freeman B, Varelis P et al (2008) Strawberry extract caused endothelium-dependent relaxation through the activation of PI3 kinase/Akt. J Agric Food Chem 56:9383–9390PubMedCrossRefGoogle Scholar
  37. 37.
    Engler MB, Engler MM, Chen CY et al (2004) Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults. J Am Coll Nutr 23:197–204PubMedGoogle Scholar
  38. 38.
    Feletou M, Vanhoutte PM (1988) Endothelium-dependent hyperpolarization of canine coronary smooth muscle. Br J Pharmacol 93:515–524PubMedGoogle Scholar
  39. 39.
    Fitzpatrick DF, Bing B, Rohdewald P (1998) Endothelium-dependent vascular effects of Pycnogenol. J Cardiovasc Pharmacol 32:509–515PubMedCrossRefGoogle Scholar
  40. 40.
    Fitzpatrick DF, Fleming RC, Bing B et al (2000) Isolation and characterization of endothelium-dependent vasorelaxing compounds from grape seeds. J Agric Food Chem 48:6384–6390PubMedCrossRefGoogle Scholar
  41. 41.
    Fitzpatrick DF, Hirschfield SL, Coffey RG (1993) Endothelium-dependent vasorelaxing activity of wine and other grape products. Am J Physiol Heart Circ Physiol 265:H774–H778Google Scholar
  42. 42.
    Fitzpatrick DF, Hirschfield SL, Ricci T et al (1995) Endothelium-dependent vasorelaxation caused by various plant extracts. J Cardiovasc Pharmacol 26:90–95PubMedCrossRefGoogle Scholar
  43. 43.
    Flesch M, Schwarz A, Bohm M (1998) Effects of red and white wine on endothelium-dependent vasorelaxation of rat aorta and human coronary arteries. Am J Physiol 275:H1183–H1190PubMedGoogle Scholar
  44. 44.
    Freedman JE, Parker C III, Li L et al (2001) Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation 103:2792–2798PubMedGoogle Scholar
  45. 45.
    Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376PubMedCrossRefGoogle Scholar
  46. 46.
    Grassi D, Necozione S, Lippi C et al (2005) Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension 46:398–405PubMedCrossRefGoogle Scholar
  47. 47.
    Hashimoto M, Kim S, Eto M et al (2001) Effect of acute intake of red wine on flow-mediated vasodilatation of the brachial artery. Am J Cardiol 88:1457–1460PubMedCrossRefGoogle Scholar
  48. 48.
    Hertog MG, Kromhout D, Aravanis C et al (1995) Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 155:381–386PubMedCrossRefGoogle Scholar
  49. 49.
    Hsieh TC, Juan G, Darzynkiewicz Z et al (1999) Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21(WAF1/CIP1), and suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G2. Cancer Res 59:2596–2601PubMedGoogle Scholar
  50. 50.
    Hu JP, Calomme M, Lasure A et al (1995) Structure-activity relationship of flavonoids with superoxide scavenging activity. Biol Trace Elem Res 47:327–331PubMedCrossRefGoogle Scholar
  51. 51.
    Ignarro LJ, Buga GM, Wood KS et al (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A 84:9265–9269PubMedCrossRefGoogle Scholar
  52. 52.
    Ihm SH, Lee JO, Kim SJ et al (2009) Catechin prevents endothelial dysfunction in the prediabetic stage of OLETF rats by reducing vascular NADPH oxidase activity and expression. Atherosclerosis 206:47–53PubMedCrossRefGoogle Scholar
  53. 53.
    Jimenez R, Lopez-Sepulveda R, Kadmiri M et al (2007) Polyphenols restore endothelial function in DOCA-salt hypertension: role of endothelin-1 and NADPH oxidase. Free Radic Biol Med 43:462–473PubMedCrossRefGoogle Scholar
  54. 54.
    Jin BH, Qian LB, Chen S et al (2009) Apigenin protects endothelium-dependent relaxation of rat aorta against oxidative stress. Eur J Pharmacol 616:200–205PubMedCrossRefGoogle Scholar
  55. 55.
    Kane MO, Anselm E, Rattmann YD et al (2009) Role of gender and estrogen receptors in the rat aorta endothelium-dependent relaxation to red wine polyphenols. Vascul Pharmacol 51:140–146PubMedCrossRefGoogle Scholar
  56. 56.
    Kane M, Etienne-Selloum N, Madeira S et al (2010) Endothelium-derived contracting factors mediate the Ang II-induced endothelial dysfunction in the rat aorta: preventive effect of red wine polyphenols. Pflügers Arch, in press. doi:10.1007/s00424-009-0759-7
  57. 57.
    Karim M, McCormick K, Kappagoda CT (2000) Effects of cocoa extracts on endothelium-dependent relaxation. J Nutr 130:2105S–2108SPubMedGoogle Scholar
  58. 58.
    Keevil JG, Osman HE, Reed JD et al (2000) Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation. J Nutr 130:53–56PubMedGoogle Scholar
  59. 59.
    Kim JA, Formoso G, Li Y et al (2007) Epigallocatechin gallate, a green tea polyphenol, mediates NO-dependent vasodilation using signaling pathways in vascular endothelium requiring reactive oxygen species and Fyn. J Biol Chem 282:13736–13745PubMedCrossRefGoogle Scholar
  60. 60.
    Kim SH, Kang KW, Kim KW et al (2000) Procyanidins in crataegus extract evoke endothelium-dependent vasorelaxation in rat aorta. Life Sci 67:121–131PubMedCrossRefGoogle Scholar
  61. 61.
    Klinge CM, Blankenship KA, Risinger KE et al (2005) Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells. J Biol Chem 280:7460–7468PubMedCrossRefGoogle Scholar
  62. 62.
    Kwan CY, Zhang WB, Deyama T et al (2004) Endothelium-dependent vascular relaxation induced by Eucommia ulmoides Oliv. bark extract is mediated by NO and EDHF in small vessels. Naunyn Schmiedebergs Arch Pharmacol 369:206–211PubMedCrossRefGoogle Scholar
  63. 63.
    Leikert JF, Rathel TR, Wohlfart P et al (2002) Red wine polyphenols enhance endothelial nitric oxide synthase expression and subsequent nitric oxide release from endothelial cells. Circulation 106:1614–1617PubMedCrossRefGoogle Scholar
  64. 64.
    Li HF, Chen SA, Wu SN (2000) Evidence for the stimulatory effect of resveratrol on Ca(2+)-activated K+ current in vascular endothelial cells. Cardiovasc Res 45:1035–1045PubMedCrossRefGoogle Scholar
  65. 65.
    Li HF, Tian ZF, Qiu XQ et al (2006) A study of mechanisms involved in vasodilatation induced by resveratrol in isolated porcine coronary artery. Physiol Res 55:365–372PubMedGoogle Scholar
  66. 66.
    Li Y, Ying C, Zuo X et al (2009) Green tea polyphenols down-regulate caveolin-1 expression via ERK1/2 and p38MAPK in endothelial cells. J Nutr Biochem 20:1021–1027PubMedCrossRefGoogle Scholar
  67. 67.
    Lorenz M, Wessler S, Follmann E et al (2004) A constituent of green tea, epigallocatechin-3-gallate, activates endothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation. J Biol Chem 279:6190–6195PubMedCrossRefGoogle Scholar
  68. 68.
    Madeira SV, Auger C, Anselm E et al (2009) eNOS activation induced by a polyphenol-rich grape skin extract in porcine coronary arteries. J Vasc Res 46:406–416PubMedCrossRefGoogle Scholar
  69. 69.
    Martin S, Andriambeloson E, Takeda K et al (2002) Red wine polyphenols increase calcium in bovine aortic endothelial cells: a basis to elucidate signalling pathways leading to nitric oxide production. Br J Pharmacol 135:1579–1587PubMedCrossRefGoogle Scholar
  70. 70.
    Matsui T, Korematsu S, Byun EB et al (2009) Apple procyanidins induced vascular relaxation in isolated rat aorta through NO/cGMP pathway in combination with hyperpolarization by multiple K+ channel activations. Biosci Biotechnol Biochem 73:2246–2251PubMedCrossRefGoogle Scholar
  71. 71.
    Mattagajasingh I, Kim CS, Naqvi A et al (2007) SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci U S A 104:14855–14860PubMedCrossRefGoogle Scholar
  72. 72.
    Michell BJ, Griffiths JE, Mitchelhill KI et al (1999) The Akt kinase signals directly to endothelial nitric oxide synthase. Curr Biol 9:845–848PubMedCrossRefGoogle Scholar
  73. 73.
    Miyazaki R, Ichiki T, Hashimoto T et al (2008) SIRT1, a longevity gene, downregulates angiotensin II type 1 receptor expression in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 28:1263–1269PubMedCrossRefGoogle Scholar
  74. 74.
    Mombouli JV, Vanhoutte PM (1999) Endothelial dysfunction: from physiology to therapy. J Mol Cell Cardiol 31:61–74PubMedCrossRefGoogle Scholar
  75. 75.
    Mukamal KJ, Maclure M, Muller JE et al (2002) Tea consumption and mortality after acute myocardial infarction. Circulation 105:2476–2481PubMedCrossRefGoogle Scholar
  76. 76.
    Mullen W, McGinn J, Lean ME et al (2002) Ellagitannins, flavonoids, and other phenolics in red raspberries and their contribution to antioxidant capacity and vasorelaxant properties. J Agric Food Chem 50:5191–5196PubMedCrossRefGoogle Scholar
  77. 77.
    Ndiaye M, Chataigneau M, Lobysheva I et al (2005) Red wine polyphenol-induced, endothelium-dependent NO-mediated relaxation is due to the redox-sensitive PI3-kinase/Akt-dependent phosphorylation of endothelial NO-synthase in the isolated porcine coronary artery. FASEB J 19:455–457PubMedGoogle Scholar
  78. 78.
    Ndiaye M, Chataigneau T, Andriantsitohaina R et al (2003) Red wine polyphenols cause endothelium-dependent EDHF-mediated relaxations in porcine coronary arteries via a redox-sensitive mechanism. Biochem Biophys Res Commun 310:371–377PubMedCrossRefGoogle Scholar
  79. 79.
    Ndiaye M, Chataigneau T, Chataigneau M et al (2004) Red wine polyphenols induce EDHF-mediated relaxations in porcine coronary arteries through the redox-sensitive activation of the PI3-kinase/Akt pathway. Br J Pharmacol 142:1131–1136PubMedCrossRefGoogle Scholar
  80. 80.
    Nicholson SK, Tucker GA, Brameld JM (2008) Effects of dietary polyphenols on gene expression in human vascular endothelial cells. Proc Nutr Soc 67:42–47PubMedCrossRefGoogle Scholar
  81. 81.
    Nijveldt RJ, van Noods E, van Hoorn DE et al (2001) Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 74:418–425PubMedGoogle Scholar
  82. 82.
    Orallo F, Alvarez E, Camina M et al (2002) The possible implication of trans-Resveratrol in the cardioprotective effects of long-term moderate wine consumption. Mol Pharmacol 61:294–302PubMedCrossRefGoogle Scholar
  83. 83.
    Palmer RM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526PubMedCrossRefGoogle Scholar
  84. 84.
    Park YK, Kim JS, Kang MH (2004) Concord grape juice supplementation reduces blood pressure in Korean hypertensive men: double-blind, placebo controlled intervention trial. Biofactors 22:145–147PubMedCrossRefGoogle Scholar
  85. 85.
    Peng N, Clark JT, Prasain J et al (2005) Antihypertensive and cognitive effects of grape polyphenols in estrogen-depleted, female, spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 289:R771–R775PubMedGoogle Scholar
  86. 86.
    Perez-Vizcaino F, Duarte J, Jimenez R et al (2009) Antihypertensive effects of the flavonoid quercetin. Pharmacol Rep 61:67–75PubMedGoogle Scholar
  87. 87.
    Rakici O, Kiziltepe U, Coskun B et al (2005) Effects of resveratrol on vascular tone and endothelial function of human saphenous vein and internal mammary artery. Int J Cardiol 105:209–215PubMedCrossRefGoogle Scholar
  88. 88.
    Robak J, Gryglewski RJ (1988) Flavonoids are scavengers of superoxide anions. Biochem Pharmacol 37:837–841PubMedCrossRefGoogle Scholar
  89. 89.
    Rocha AP, Carvalho LC, Sousa MA et al (2007) Endothelium-dependent vasodilator effect of Euterpe oleracea Mart. (Acai) extracts in mesenteric vascular bed of the rat. Vascul Pharmacol 46:97–104PubMedCrossRefGoogle Scholar
  90. 90.
    Sarr M, Chataigneau M, Martins S et al (2006) Red wine polyphenols prevent angiotensin II-induced hypertension and endothelial dysfunction in rats: role of NADPH oxidase. Cardiovasc Res 71:794–802PubMedCrossRefGoogle Scholar
  91. 91.
    Schini VB, Boulanger C, Regoli D et al (1990) Bradykinin stimulates the production of cyclic GMP via activation of B2 kinin receptors in cultured porcine aortic endothelial cells. J Pharmacol Exp Ther 252:581–585PubMedGoogle Scholar
  92. 92.
    Schroeter H, Heiss C, Balzer J et al (2006) (–)–Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci U S A 103:1024–1029PubMedCrossRefGoogle Scholar
  93. 93.
    Shimokawa H, Yasutake H, Fujii K et al (1996) The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation. J Cardiovasc Pharmacol 28:703–711PubMedCrossRefGoogle Scholar
  94. 94.
    De Soares MR, Costa Viana FS, Souza MA et al (2002) Antihypertensive, vasodilator and antioxidant effects of a vinifera grape skin extract. J Pharm Pharmacol 54:1515–1520CrossRefGoogle Scholar
  95. 95.
    Sofi F, Cesari F, Abbate R et al (2008) Adherence to Mediterranean diet and health status: meta-analysis. BMJ 337:a1344PubMedCrossRefGoogle Scholar
  96. 96.
    St Leger AS, Cochrane AL, Moore F (1979) Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine. Lancet 1:1017–1020PubMedCrossRefGoogle Scholar
  97. 97.
    Stein JH, Keevil JG, Wiebe DA et al (1999) Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Circulation 100:1050–1055PubMedGoogle Scholar
  98. 98.
    Stoclet JC, Kleschyov A, Andriambeloson E et al (1999) Endothelial no release caused by red wine polyphenols. J Physiol Pharmacol 50:535–540PubMedGoogle Scholar
  99. 99.
    Taubert D, Berkels R, Klaus W et al (2002) Nitric oxide formation and corresponding relaxation of porcine coronary arteries induced by plant phenols: essential structural features. J Cardiovasc Pharmacol 40:701–713PubMedCrossRefGoogle Scholar
  100. 100.
    Taubert D, Berkels R, Roesen R et al (2003) Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA 290:1029–1030PubMedCrossRefGoogle Scholar
  101. 101.
    Taylor SG, Weston AH (1988) Endothelium-derived hyperpolarizing factor: a new endogenous inhibitor from the vascular endothelium. Trends Pharmacol Sci 9:272–274PubMedCrossRefGoogle Scholar
  102. 102.
    Torel J, Cillard J, Cillard P (1986) Antioxidant activity of flavonoids and reactivity with peroxy radical. Phytochemistry 25:383–385CrossRefGoogle Scholar
  103. 103.
    Vera R, Galisteo M, Villar IC et al (2005) Soy isoflavones improve endothelial function in spontaneously hypertensive rats in an estrogen-independent manner: role of nitric-oxide synthase, superoxide, and cyclooxygenase metabolites. J Pharmacol Exp Ther 314:1300–1309PubMedCrossRefGoogle Scholar
  104. 104.
    Vera R, Sanchez M, Galisteo M et al (2007) Chronic administration of genistein improves endothelial dysfunction in spontaneously hypertensive rats: involvement of eNOS, caveolin and calmodulin expression and NADPH oxidase activity. Clin Sci (Lond) 112:183–191CrossRefGoogle Scholar
  105. 105.
    Wallerath T, Deckert G, Ternes T et al (2002) Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 106:1652–1658PubMedCrossRefGoogle Scholar
  106. 106.
    Wallerath T, Li H, Godtel-Ambrust U et al (2005) A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase. Nitric Oxide 12:97–104PubMedCrossRefGoogle Scholar
  107. 107.
    Wallerath T, Poleo D, Li H et al (2003) Red wine increases the expression of human endothelial nitric oxide synthase: a mechanism that may contribute to its beneficial cardiovascular effects. J Am Coll Cardiol 41:471–478PubMedCrossRefGoogle Scholar
  108. 108.
    Wang-Polagruto JF, Villablanca AC, Polagruto JA et al (2006) Chronic consumption of flavanol-rich cocoa improves endothelial function and decreases vascular cell adhesion molecule in hypercholesterolemic postmenopausal women. J Cardiovasc Pharmacol 47(Suppl 2):S177–S186PubMedCrossRefGoogle Scholar
  109. 109.
    Whelan AP, Sutherland WH, McCormick MP et al (2004) Effects of white and red wine on endothelial function in subjects with coronary artery disease. Intern Med J 34:224–228PubMedCrossRefGoogle Scholar
  110. 110.
    Widlansky ME, Hamburg NM, Anter E et al (2007) Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease. J Am Coll Nutr 26:95–102PubMedGoogle Scholar
  111. 111.
    Xu PH, Long Y, Dai F et al (2007) The relaxant effect of curcumin on porcine coronary arterial ring segments. Vascul Pharmacol 47:25–30PubMedCrossRefGoogle Scholar
  112. 112.
    Yamamoto M, Suzuki A, Hase T (2008) Short-term effects of glucosyl hesperidin and hesperetin on blood pressure and vascular endothelial function in spontaneously hypertensive rats. J Nutr Sci Vitaminol (Tokyo) 54:95–98CrossRefGoogle Scholar
  113. 113.
    Yamamoto M, Suzuki A, Jokura H et al (2008) Glucosyl hesperidin prevents endothelial dysfunction and oxidative stress in spontaneously hypertensive rats. Nutrition 24:470–476PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Valérie B. Schini-Kerth
    • 1
  • Cyril Auger
    • 1
  • Jong-Hun Kim
    • 1
  • Nelly Étienne-Selloum
    • 1
  • Thierry Chataigneau
    • 1
  1. 1.UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de PharmacieUniversité de StrasbourgIllkirchFrance

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