Skip to main content

Advertisement

Log in

Endothelium/nitric oxide mechanism mediates vasorelaxation and counteracts vasoconstriction induced by low concentration of flavanols

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

At relatively low concentrations, flavanols induce inconsistent effects on isolated arterial tone, sometimes explained as being due to a structure–activity relationship. The aim of our study was to investigate the effects of two flavanols at different doses on arterial functional state.

Methods

The effects of two catechins, (−)-epigallocatechin-3-gallate (EGCG) and (−)-epicatechin (EP), on rat-isolated aorta tone were investigated on resting tension and on precontracted preparations, both in the presence and in the absence of endothelium.

Results

At resting tension, endothelium-intact preparations, EGCG and EP (0.01–10 μM), induced a slight concentration-dependent, non-significant contraction. On endothelium-denuded preparations, both EGCG and EP induced a concentration-dependent contraction (significance at 0.1 and 1 μM concentrations of the two compounds, respectively). In phenylephrine (PE) (1 μM) precontracted, endothelium-intact preparations, EGCG and EP (0.01–10 μM), induced a concentration-dependent vasorelaxation, reaching significance at 1 μM concentration of both agonists. On endothelium-denuded preparations, EGCG and EP did not significantly affect PE (0.3 μM)-induced tone. In endothelium-intact precontracted preparations, Nω nitro-l-arginine (L-NNA), a nitric oxide synthase (NOS) activity inhibitor, abolished the vasorelaxant effect of EGCG and EP (0.01–10 μM). At high concentrations, EGCG and EP (100 μM) elicited a marked relaxation. This was significantly larger in the presence than in the absence of endothelium or in the presence of L-NNA.

Conclusions

Our findings highlight the important role played by an endothelium/NO-mechanism in the regulation of basal tone and in both mediating vasorelaxation and counteracting vasoconstriction induced by low concentrations of flavanols in rat thoracic aorta.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Vita JA (2003) Tea consumption and cardiovascular disease: effects on endothelial function. J Nutr 133:3293S–3297S

    CAS  Google Scholar 

  2. Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, Awata S, Nagatomi R, Arai H, Tsuji I (2006) Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan. Am J Clin Nutr 83:355–361

    CAS  Google Scholar 

  3. Widlansky ME, Hamburg NM, Anter E, Holbrook M, Kahn DF, Elliott JG, Keaney JF Jr, Vita JA (2007) Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease. J Am Coll Nutr 2:95–102

    Google Scholar 

  4. Duffy SJ, Keaney JF Jr, Holbrook M, Gokce N, Swerdloff PL, Frei B, Vita JA (2001) Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Circulation 104:151–156

    Article  CAS  Google Scholar 

  5. Schroeter H, Heiss C, Balzer J et al (2006) (−)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. PNAS 103:1024–1029

    Article  CAS  Google Scholar 

  6. Engler MB, Engler MM, Chen CY, Malloy MJ, Browne A, Chiu EY, Kwak HK, Milbury P, Paul SM, Blumberg J, Mietus-Snyder ML (2004) Flavanoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults. J Am Coll Nutr 23:197–204

    CAS  Google Scholar 

  7. Matsui T, Korematsu S, Byun EB, Nishizuka T, Ohshima S, Kanda T (2009) Apple procyanidins induced vascular relaxation in isolated rat aorta through NO/cGMP pathway in combination with hyperpolarization by multiple K+ channel activations. Biosci Biochem Biotechnol 73:2246–2251

    Article  CAS  Google Scholar 

  8. Grassi D, Lippi C, Necozione S, Desideri G, Ferri C (2005) Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am J Clin Nutr 81:611–614

    CAS  Google Scholar 

  9. Grassi D, Desideri G, Necozione S, Lippi C, Casale R, Properzi G, Blumberg JB, Ferri C (2008) Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J Nutr 138:1671–1676

    CAS  Google Scholar 

  10. Corretti MC, Anderson TJ, Benjamin EJ et al (2002) International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 16:257–265

    Article  Google Scholar 

  11. Rice-Evans CA, Miller NJ, Paganga G (1996) Structure-antioxidant activity relationships of flavanoids and phenolic acids. Free Radic Biol Med 20:933–956

    Article  CAS  Google Scholar 

  12. Richelle M, Tavazzi I, Enslen M, Offord EA (1999) Plasma kinetics in man of epicatechin from black chocolate. Eur J Clin Nutr 53:22–26

    Article  CAS  Google Scholar 

  13. Auger C, Kim JH, Chabert P, Chaabi M, Anselm E, Lanciaux X, Lobstein A, Schini-Kerth VB (2010) The EGCg-induced redox-sensitive activation of endothelial nitric oxide synthase and relaxation are critically dependent on hydroxyl moieties. Biochem Biophys Res Commun 393:162–167

    Article  CAS  Google Scholar 

  14. Ramirez-Sanchez I, Maya L, Ceballos G, Villarreal F (2010) (−)-Epicatechin activation of endothelial cell endothelial nitric oxide synthase, nitric oxide, and related signaling pathways. Hypertension 55:1398–1405

    Article  CAS  Google Scholar 

  15. Moore RJ, Jackson KG, Minihane AM (2009) Green tea (Camellia sinensis) catechins and vascular function. Br J Nutr 102:1790–1802

    Article  CAS  Google Scholar 

  16. Duarte J, Vizcaino P, Zarzuelo A, Jimenez J, Tamargo J (1993) Vasodilatator effects of quercetin in isolated rat vascular smooth muscle. Eur J Pharmacol 239:1–7

    Article  CAS  Google Scholar 

  17. Herrera MD, Zarzuelo A, Jimenez J, Marhuenda E, Duarte J (1996) Effects of flavonoids on rat aortic smooth muscle contractility: structure-activity relationships. Gen Pharmac 27:273–277

    Article  CAS  Google Scholar 

  18. Chan ECH, Pannangpetch P, Woodman OL (2000) Relaxation to flavones and flavonols in rat isolated thoracic aorta: mechanism of action and structure-activity relationships. J Cardiovasc Pharmacol 35:326–333

    Article  CAS  Google Scholar 

  19. Woodman OL, Meeker WF, Boujaoude M (2005) Vasorelaxant and antioxidant activity of flavanols and flavones: structure-activity relationships. J Cardiovasc Pharmacol 46:302–309

    Article  CAS  Google Scholar 

  20. Sanae F, Miyaichi Y, Kizu H, Hayashi H (2002) Effect of catechins on vascular tone in rat aortic thoracic aorta with endothelium. Life Sci 71:2553–2562

    Article  CAS  Google Scholar 

  21. 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  Google Scholar 

  22. Lorenz M, Urban J, Engelhardt U, Baumann G, Stangl K, Stangl V (2009) Green and black tea are equally potent stimuli of NO production and vasodilation: new insights into tea ingredients involved. Basic Res Cardiol 104:100–110

    Article  CAS  Google Scholar 

  23. Lim DY, Lee ES, Park HG, Kim BC, Hong SP, Lee EB (2003) Comparison of green tea extract and epigallocatechin gallate on blood pressure and contractile responses of vascular smooth muscle of rats. Arch Pharm Res 26:214–223

    Article  CAS  Google Scholar 

  24. Angus JA, Wrigth CE (2000) Techniques to study the pharmacodynamics of isolated large and small blood vessel. J Pharmacol Toxicol Methods 44:395–407

    Article  CAS  Google Scholar 

  25. Nishimura K, Ota M, Ito K (1991) Existence of two components in the tonic contraction of rat aorta mediated by α1-adrenoceptor activation. Br J Pharmacol 102:215–221

    Article  CAS  Google Scholar 

  26. Ajay M, Gilani AH, Mustafa MR (2003) Effects of flavonoids on vascular smooth muscle of the isolated rat thoracic aorta. Life Sci 74:603–612

    Article  CAS  Google Scholar 

  27. Shen JZ, Zheng XF, Wei EQ, Kwan CY (2003) Green tea catechins evoke a phasic contraction in rat aorta via H2O2-mediated multiple-signalling pathways. Clin Exp Pharmacol Physiol 30:88–95

    Article  CAS  Google Scholar 

  28. Schrammel A, Behrends S, Schmidt K, Koesling D, Mayer B (1996) Characterization of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one as a heme-site inhibitor of nitric oxide-sensitive guanylyl cyclase. Mol Pharmacol 50:1–6

    CAS  Google Scholar 

  29. Alvarez-Castro E, Campos-Tomoil M, Orallo F (2004) (−)-Epigallocatechin-3-gallate induces contraction of the rat aorta by a calcium influx-dependent mechanism. Naunyn-Schmiedeberg’s Arch Pharmacol 369:496–506

    Article  CAS  Google Scholar 

  30. Loke WM, Hodgson JM, Proudfoot JM, McKinley AJ, Puddey IB, Croft KD (2008) Pure dietary flavonoids quercetin and (−)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am J Clin Nutr 88:1018–1025

    CAS  Google Scholar 

  31. Huang Y, Chan NW, Lau CW, Yao XQ, Chan FL, Chen ZY (1999) Involvement of endothelium/nitric oxide in vasorelaxation induced by purified green tea (−)epicatechin. Biochim Biophys Acta 1427:322–328

    Article  CAS  Google Scholar 

  32. Kim JA, Formoso G, Li Y, Potenza MA, Marasciulo FL, Montagnani M, Quon MJ (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  Google Scholar 

  33. Alvarez E, Campos-Toimil M, Justiniani-Basaran H, Lugnier C, Orallo F (2006) Study the of the mechanisms involved in the vasorelaxation induced by (−)- epigallocatechin-3-gallate in rat aorta. Br J Pharmacol 147:269–280

    Article  CAS  Google Scholar 

  34. Chen ZY, Law WI, Yao XQ, Lau CW, Ho WK, Huang Y (2000) Inhibitory effects of purified green tea epicatechins on contraction and proliferation of arterial smooth muscle cells. Acta Pharmacol Sin 21:835–840

    CAS  Google Scholar 

  35. Martin W, Furchgott RF, Villani GM, Jothianandan D (1986) Depression of contractile responses in rat aorta by spontaneously released endothelium-derived relaxing factor. J Pharmacol Exp Ther 237:529–538

    CAS  Google Scholar 

  36. Chen ZY, Su YL, Lau WI, Huang Y (1999) Endothelium-dependent contraction and direct relaxation induced by baicalein in rat mesenteric artery. Euro J Pharmacol 374:41–47

    Article  CAS  Google Scholar 

  37. Wyse GD (1990) On the “normalization” of active developed force of isolated helical strips of muscular and elastic arteries for variation in wall thickness. J Pharmacol Methods 4:313–326

    Article  Google Scholar 

  38. Li Z, Wang Y, Vanhoutte PM (2011) Epigallocatechin Gallate elicits contractions of the isolated aorta of the aged spontaneously hypertensive rat. Basic Clin Pharmacol Toxicol 109(1):47–55

    Article  CAS  Google Scholar 

  39. Gendron ME, Théorêt JF, Mamarbachi AM et al (2010) Late chronic catechin antioxidant treatment is deleterious to the endothelial function in aging mice with established atherosclerosis. Am J Physiol Heart Circ Physiol 298(6):H2062–H2070

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Davide Grassi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aggio, A., Grassi, D., Onori, E. et al. Endothelium/nitric oxide mechanism mediates vasorelaxation and counteracts vasoconstriction induced by low concentration of flavanols. Eur J Nutr 52, 263–272 (2013). https://doi.org/10.1007/s00394-012-0320-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-012-0320-x

Keywords

Navigation