Skip to main content

Advertisement

SpringerLink
Log in

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

  • Invited Review
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Agewall S, Wright S, Doughty RN et al (2000) Does a glass of red wine improve endothelial function? Eur Heart J 21:74–78

    Article  CAS  PubMed  Google Scholar 

  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 53:151–157

    Article  CAS  PubMed  Google Scholar 

  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 52:5593–5597

    Article  CAS  PubMed  Google Scholar 

  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 120:1053–1058

    Article  CAS  PubMed  Google Scholar 

  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 73:404–413

    Article  CAS  PubMed  Google Scholar 

  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 53:253–260

    Article  CAS  PubMed  Google Scholar 

  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 96:1072–1078

    Article  CAS  PubMed  Google Scholar 

  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 279:46637–46643

    Article  CAS  PubMed  Google Scholar 

  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 57:7693–7699

    Article  CAS  PubMed  Google Scholar 

  10. Arts IC, Hollman PC (2005) Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr 81:317S–325S

    CAS  PubMed  Google Scholar 

  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 132:1207–1213

    CAS  PubMed  Google Scholar 

  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 52:5297–5302

    Article  CAS  PubMed  Google Scholar 

  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 51:2141–2149

    Article  CAS  PubMed  Google Scholar 

  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 14:782–790

    CAS  PubMed  Google Scholar 

  15. Bell DR, Gochenaur K (2006) Direct vasoactive and vasoprotective properties of anthocyanin-rich extracts. J Appl Physiol 100:1164–1170

    Article  CAS  PubMed  Google Scholar 

  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–H948

    CAS  PubMed  Google Scholar 

  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 48:220–230

    Article  CAS  PubMed  Google Scholar 

  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 81:885–892

    CAS  PubMed  Google Scholar 

  19. Chen G, Suzuki H, Weston AH (1988) Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels. Br J Pharmacol 95:1165–1174

    CAS  PubMed  Google Scholar 

  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 52:1162–1171

    Article  CAS  PubMed  Google Scholar 

  21. Chen ZY, Zhang ZS, Kwan KY et al (1998) Endothelium-dependent relaxation induced by hawthorn extract in rat mesenteric artery. Life Sci 63:1983–1991

    Article  CAS  PubMed  Google Scholar 

  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 88:553–555

    Article  CAS  PubMed  Google Scholar 

  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 57:6156–6162

    Article  CAS  PubMed  Google Scholar 

  24. Cishek MB, Galloway MT, Karim M et al (1997) Effect of red wine on endothelium-dependent relaxation in rabbits. Clin Sci (Lond) 93:507–511

    CAS  Google Scholar 

  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–H20

    Article  CAS  PubMed  Google Scholar 

  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 328:478–486

    Article  CAS  PubMed  Google Scholar 

  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 324:13–21

    CAS  PubMed  Google Scholar 

  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 44:302–309

    Article  PubMed  Google Scholar 

  29. Di CA, Rotondo S, Iacoviello L et al (2002) Meta-analysis of wine and beer consumption in relation to vascular risk. Circulation 105:2836–2844

    Article  Google Scholar 

  30. Dimmeler S, Fleming I, Fisslthaler B et al (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399:601–605

    Article  CAS  PubMed  Google Scholar 

  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 84:660–664

    Article  CAS  PubMed  Google Scholar 

  32. Dresse A, Lecomte J (1960) Action of polyphenols and of metanephrine on the myocardial effects of adrenalin. C R Seances Soc Biol Fil 154:851–854

    CAS  PubMed  Google Scholar 

  33. Duarte J, Jimenez R, Villar IC et al (2001) Vasorelaxant effects of the bioflavonoid chrysin in isolated rat aorta. Planta Med 67:567–569

    Article  CAS  PubMed  Google Scholar 

  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 21:1084–1089

    CAS  PubMed  Google Scholar 

  35. Edirisinghe I, Burton-Freeman B, Tissa KC (2008) Mechanism of the endothelium-dependent relaxation evoked by a grape seed extract. Clin Sci (Lond) 114:331–337

    Article  CAS  Google Scholar 

  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 56:9383–9390

    Article  CAS  PubMed  Google Scholar 

  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 23:197–204

    CAS  PubMed  Google Scholar 

  38. Feletou M, Vanhoutte PM (1988) Endothelium-dependent hyperpolarization of canine coronary smooth muscle. Br J Pharmacol 93:515–524

    CAS  PubMed  Google Scholar 

  39. Fitzpatrick DF, Bing B, Rohdewald P (1998) Endothelium-dependent vascular effects of Pycnogenol. J Cardiovasc Pharmacol 32:509–515

    Article  CAS  PubMed  Google Scholar 

  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 48:6384–6390

    Article  CAS  PubMed  Google Scholar 

  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–H778

    CAS  Google Scholar 

  42. Fitzpatrick DF, Hirschfield SL, Ricci T et al (1995) Endothelium-dependent vasorelaxation caused by various plant extracts. J Cardiovasc Pharmacol 26:90–95

    Article  CAS  PubMed  Google Scholar 

  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–H1190

    CAS  PubMed  Google Scholar 

  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 103:2792–2798

    CAS  PubMed  Google Scholar 

  45. Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    Article  CAS  PubMed  Google Scholar 

  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 46:398–405

    Article  CAS  PubMed  Google Scholar 

  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 88:1457–1460

    Article  CAS  PubMed  Google Scholar 

  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 155:381–386

    Article  CAS  PubMed  Google Scholar 

  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 59:2596–2601

    CAS  PubMed  Google Scholar 

  50. Hu JP, Calomme M, Lasure A et al (1995) Structure-activity relationship of flavonoids with superoxide scavenging activity. Biol Trace Elem Res 47:327–331

    Article  CAS  PubMed  Google Scholar 

  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 84:9265–9269

    Article  CAS  PubMed  Google Scholar 

  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 206:47–53

    Article  CAS  PubMed  Google Scholar 

  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 43:462–473

    Article  CAS  PubMed  Google Scholar 

  54. Jin BH, Qian LB, Chen S et al (2009) Apigenin protects endothelium-dependent relaxation of rat aorta against oxidative stress. Eur J Pharmacol 616:200–205

    Article  CAS  PubMed  Google Scholar 

  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 51:140–146

    Article  CAS  PubMed  Google Scholar 

  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. Karim M, McCormick K, Kappagoda CT (2000) Effects of cocoa extracts on endothelium-dependent relaxation. J Nutr 130:2105S–2108S

    CAS  PubMed  Google Scholar 

  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 130:53–56

    CAS  PubMed  Google Scholar 

  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 282:13736–13745

    Article  CAS  PubMed  Google Scholar 

  60. Kim SH, Kang KW, Kim KW et al (2000) Procyanidins in crataegus extract evoke endothelium-dependent vasorelaxation in rat aorta. Life Sci 67:121–131

    Article  CAS  PubMed  Google Scholar 

  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 280:7460–7468

    Article  CAS  PubMed  Google Scholar 

  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 369:206–211

    Article  CAS  PubMed  Google Scholar 

  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 106:1614–1617

    Article  CAS  PubMed  Google Scholar 

  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 45:1035–1045

    Article  CAS  PubMed  Google Scholar 

  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 55:365–372

    CAS  PubMed  Google Scholar 

  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 20:1021–1027

    Article  CAS  PubMed  Google Scholar 

  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 279:6190–6195

    Article  CAS  PubMed  Google Scholar 

  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 46:406–416

    Article  CAS  PubMed  Google Scholar 

  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 135:1579–1587

    Article  CAS  PubMed  Google Scholar 

  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 73:2246–2251

    Article  CAS  PubMed  Google Scholar 

  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 104:14855–14860

    Article  CAS  PubMed  Google Scholar 

  72. Michell BJ, Griffiths JE, Mitchelhill KI et al (1999) The Akt kinase signals directly to endothelial nitric oxide synthase. Curr Biol 9:845–848

    Article  CAS  PubMed  Google Scholar 

  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 28:1263–1269

    Article  CAS  PubMed  Google Scholar 

  74. Mombouli JV, Vanhoutte PM (1999) Endothelial dysfunction: from physiology to therapy. J Mol Cell Cardiol 31:61–74

    Article  CAS  PubMed  Google Scholar 

  75. Mukamal KJ, Maclure M, Muller JE et al (2002) Tea consumption and mortality after acute myocardial infarction. Circulation 105:2476–2481

    Article  PubMed  Google Scholar 

  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 50:5191–5196

    Article  CAS  PubMed  Google Scholar 

  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 19:455–457

    CAS  PubMed  Google Scholar 

  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 310:371–377

    Article  CAS  PubMed  Google Scholar 

  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 142:1131–1136

    Article  CAS  PubMed  Google Scholar 

  80. Nicholson SK, Tucker GA, Brameld JM (2008) Effects of dietary polyphenols on gene expression in human vascular endothelial cells. Proc Nutr Soc 67:42–47

    Article  CAS  PubMed  Google Scholar 

  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 74:418–425

    CAS  PubMed  Google Scholar 

  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 61:294–302

    Article  CAS  PubMed  Google Scholar 

  83. Palmer RM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526

    Article  CAS  PubMed  Google Scholar 

  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 22:145–147

    Article  CAS  PubMed  Google Scholar 

  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–R775

    CAS  PubMed  Google Scholar 

  86. Perez-Vizcaino F, Duarte J, Jimenez R et al (2009) Antihypertensive effects of the flavonoid quercetin. Pharmacol Rep 61:67–75

    CAS  PubMed  Google Scholar 

  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 105:209–215

    Article  PubMed  Google Scholar 

  88. Robak J, Gryglewski RJ (1988) Flavonoids are scavengers of superoxide anions. Biochem Pharmacol 37:837–841

    Article  CAS  PubMed  Google Scholar 

  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 46:97–104

    Article  CAS  PubMed  Google Scholar 

  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 71:794–802

    Article  CAS  PubMed  Google Scholar 

  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 252:581–585

    CAS  PubMed  Google Scholar 

  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 103:1024–1029

    Article  CAS  PubMed  Google Scholar 

  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 28:703–711

    Article  CAS  PubMed  Google Scholar 

  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 54:1515–1520

    Article  CAS  Google Scholar 

  95. Sofi F, Cesari F, Abbate R et al (2008) Adherence to Mediterranean diet and health status: meta-analysis. BMJ 337:a1344

    Article  PubMed  Google Scholar 

  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 1:1017–1020

    Article  CAS  PubMed  Google Scholar 

  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 100:1050–1055

    CAS  PubMed  Google Scholar 

  98. Stoclet JC, Kleschyov A, Andriambeloson E et al (1999) Endothelial no release caused by red wine polyphenols. J Physiol Pharmacol 50:535–540

    CAS  PubMed  Google Scholar 

  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 40:701–713

    Article  CAS  PubMed  Google Scholar 

  100. Taubert D, Berkels R, Roesen R et al (2003) Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA 290:1029–1030

    Article  PubMed  Google Scholar 

  101. Taylor SG, Weston AH (1988) Endothelium-derived hyperpolarizing factor: a new endogenous inhibitor from the vascular endothelium. Trends Pharmacol Sci 9:272–274

    Article  CAS  PubMed  Google Scholar 

  102. Torel J, Cillard J, Cillard P (1986) Antioxidant activity of flavonoids and reactivity with peroxy radical. Phytochemistry 25:383–385

    Article  CAS  Google Scholar 

  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 314:1300–1309

    Article  CAS  PubMed  Google Scholar 

  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) 112:183–191

    Article  CAS  Google Scholar 

  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 106:1652–1658

    Article  CAS  PubMed  Google Scholar 

  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 12:97–104

    Article  CAS  PubMed  Google Scholar 

  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 41:471–478

    Article  CAS  PubMed  Google Scholar 

  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–S186

    Article  CAS  PubMed  Google Scholar 

  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 34:224–228

    Article  CAS  PubMed  Google Scholar 

  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 26:95–102

    CAS  PubMed  Google Scholar 

  111. Xu PH, Long Y, Dai F et al (2007) The relaxant effect of curcumin on porcine coronary arterial ring segments. Vascul Pharmacol 47:25–30

    Article  CAS  PubMed  Google Scholar 

  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) 54:95–98

    Article  CAS  Google Scholar 

  113. Yamamoto M, Suzuki A, Jokura H et al (2008) Glucosyl hesperidin prevents endothelial dysfunction and oxidative stress in spontaneously hypertensive rats. Nutrition 24:470–476

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, 74, route du Rhin, 67401, Illkirch, France

    Valérie B. Schini-Kerth, Cyril Auger, Jong-Hun Kim, Nelly Étienne-Selloum & Thierry Chataigneau

Authors
  1. Valérie B. Schini-Kerth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cyril Auger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jong-Hun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nelly Étienne-Selloum
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thierry Chataigneau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Valérie B. Schini-Kerth.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schini-Kerth, V.B., Auger, C., Kim, JH. et al. Nutritional improvement of the endothelial control of vascular tone by polyphenols: role of NO and EDHF. Pflugers Arch - Eur J Physiol 459, 853–862 (2010). https://doi.org/10.1007/s00424-010-0806-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-010-0806-4

Keywords

Search

Navigation