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Chronic ( − )-epicatechin improves vascular oxidative and inflammatory status but not hypertension in chronic nitric oxide-deficient rats

  • Manuel Gómez-Guzmán (a1), Rosario Jiménez (a1), Manuel Sánchez (a1), Miguel Romero (a1), Francisco O'Valle (a2), Rocío Lopez-Sepulveda (a1), Ana María Quintela (a1), Pilar Galindo (a1), María José Zarzuelo (a1), Elvira Bailón (a1), Eva Delpón (a3), Francisco Perez-Vizcaino (a3) (a4) and Juan Duarte (a1)...

Abstract

The present study analysed the effects of the flavanol ( − )-epicatechin in rats after chronic inhibition of NO synthesis with NG-nitro-l-arginine methyl ester (l-NAME), at doses equivalent to those achieved in the studies involving human subjects. Wistar rats were randomly divided into four groups: (1) control-vehicle, (2) l-NAME, (3) l-NAME-epicatechin 2 (l-NAME-Epi 2) and (4) l-NAME-epicatechin 10 (l-NAME-Epi 10). Rats were daily given by oral administration for 4 weeks: vehicle, ( − )-epicatechin 2 or 10 mg/kg. Animals in the l-NAME groups daily received l-NAME 75 mg/100 ml in drinking-water. The evolution in systolic blood pressure and heart rate, and morphological and plasma variables, proteinuria, vascular superoxide, reactivity and protein expression at the end of the experiment were analysed. Chronic ( − )-epicatechin treatment did not modify the development of hypertension and only weakly affected the endothelial dysfunction induced by l-NAME but prevented the cardiac hypertrophy, the renal parenchyma and vascular lesions and proteinuria, and blunted the prostanoid-mediated enhanced endothelium-dependent vasoconstrictor responses and the cyclo-oxygenase-2 and endothelial NO synthase (eNOS) up-regulation. Furthermore, ( − )-epicatechin also increased Akt and eNOS phosphorylation and prevented the l-NAME-induced increase in systemic (plasma malonyldialdehyde and urinary 8-iso-PGF) and vascular (dihydroethidium staining, NADPH oxidase activity and p22phox up-regulation) oxidative stress, proinflammatory status (intercellular adhesion molecule-1, IL-1β and TNFα up-regulation) and extracellular-signal-regulated kinase 1/2 phosphorylation. The present study shows for the first time that chronic oral administration of ( − )-epicatechin does not improve hypertension but reduced pro-atherogenic pathways such as oxidative stress and proinflammatory status of the vascular wall induced by blockade of NO production.

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Corresponding author

*Corresponding author: J. Duarte, fax +34 958248964, email jmduarte@ugr.es

References

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1 Duffy, SJ, Keaney, JF Jr JF, Holbrook, M, et al. (2001) Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Circulation 104, 151156.
2 Buijsse, B, Feskens, EJ, Kok, FJ, et al. (2006) Cocoa intake, blood pressure, and cardiovascular mortality: the Zutphen Elderly Study. Arch Intern Med 166, 411417.
3 Ding, EL, Hutfless, SM, Ding, X, et al. (2006) Chocolate and prevention of cardiovascular disease: a systematic review. Nutr Metab (Lond) 3, 2.
4 Nagao, T, Hase, T & Tokimitsu, I (2007) A green tea extract high in catechins reduces body fat and cardiovascular risks in humans. Obesity (Silver Spring) 15, 14731483.
5 Deka, A & Vita, JA (2011) Tea and cardiovascular disease. Pharmacol Res 64, 136145.
6 Fisher, ND, Hughes, M, Gerhard-Herman, M, et al. (2003) Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans. J Hypertens 21, 22812286.
7 Hirata, K, Shimada, K, Watanabe, H, et al. (2004) Black tea increases coronary flow velocity reserve in healthy male subjects. Am J Cardiol 93, 13841388, A1386.
8 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, 10241029.
9 Taubert, D, Berkels, R, Roesen, R, et al. (2003) Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA 290, 10291030.
10 Matsuyama, T, Tanaka, Y, Kamimaki, I, et al. (2008) Catechin safely improved higher levels of fatness, blood pressure, and cholesterol in children. Obesity (Silver Spring) 16, 13381348.
11 Grassi, D, Lippi, C, Necozione, S, et al. (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, 611614.
12 Holt, RR, Lazarus, SA, Sullards, MC, et al. (2002) Procyanidin dimer B2 [epicatechin-(4beta-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. Am J Clin Nutr 76, 798804.
13 Keen, CL, Holt, RR, Oteiza, PI, et al. (2005) Cocoa antioxidants and cardiovascular health. Am J Clin Nutr 81, 298S303S.
14 Duarte, J, Perez Vizcaino, F, Utrilla, P, et al. (1993) Vasodilatory effects of flavonoids in rat aortic smooth muscle. Structure–activity relationships. Gen Pharmacol 24, 857862.
15 Huang, Y, Zhang, A, Lau, CW, et al. (1998) Vasorelaxant effects of purified green tea epicatechin derivatives in rat mesenteric artery. Life Sci 63, 275283.
16 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, 4753.
17 Ramirez-Sanchez, I, Maya, L, Ceballos, G, et al. (2010) ( − )-Epicatechin activation of endothelial cell endothelial nitric oxide synthase, nitric oxide, and related signaling pathways. Hypertension 55, 13981405.
18 Steffen, Y, Gruber, C, Schewe, T, et al. (2008) Mono-O-methylated flavanols and other flavonoids as inhibitors of endothelial NADPH oxidase. Arch Biochem Biophys 469, 209219.
19 Luvara, G, Pueyo, ME, Philippe, M, et al. (1998) Chronic blockade of NO synthase activity induces a proinflammatory phenotype in the arterial wall: prevention by angiotensin II antagonism. Arterioscler Thromb Vasc Biol 18, 14081416.
20 Zatz, R & Baylis, C (1998) Chronic nitric oxide inhibition model six years on. Hypertension 32, 958964.
21 Duarte, J, Perez-Palencia, R, Vargas, F, et al. (2001) Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Br J Pharmacol 133, 117124.
22 Esterbauer, H & Cheeseman, KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186, 407421.
23 Duarte, J, Ocete, MA, Perez-Vizcaino, F, et al. (1997) Effect of tyrosine kinase and tyrosine phosphatase inhibitors on aortic contraction and induction of nitric oxide synthase. Eur J Pharmacol 338, 2533.
24 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, 183191.
25 Sanchez, M, Lodi, F, Vera, R, et al. (2007) Quercetin and isorhamnetin prevent endothelial dysfunction, superoxide production, and overexpression of p47phox induced by angiotensin II in rat aorta. J Nutr 137, 910915.
26 Piskula, MK & Terao, J (1998) Accumulation of ( − )-epicatechin metabolites in rat plasma after oral administration and distribution of conjugation enzymes in rat tissues. J Nutr 128, 11721178.
27 Bartunek, J, Weinberg, EO, Tajima, M, et al. (2000) Chronic N(G)-nitro-l-arginine methyl ester-induced hypertension: novel molecular adaptation to systolic load in absence of hypertrophy. Circulation 101, 423429.
28 Li, JM, Gall, NP, Grieve, DJ, et al. (2002) Activation of NADPH oxidase during progression of cardiac hypertrophy to failure. Hypertension 40, 477484.
29 Vaziri, ND (2004) Roles of oxidative stress and antioxidant therapy in chronic kidney disease and hypertension. Curr Opin Nephrol Hypertens 13, 9399.
30 Zhen, J, Lu, H, Wang, XQ, et al. (2008) Upregulation of endothelial and inducible nitric oxide synthase expression by reactive oxygen species. Am J Hypertens 21, 2834.
31 Auch-Schwelk, W, Katusic, ZS & Vanhoutte, PM (1990) Thromboxane A2 receptor antagonists inhibit endothelium-dependent contractions. Hypertension 15, 699703.
32 Duarte, J, Jimenez, R, O'Valle, F, et al. (2002) Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats. J Hypertens 20, 18431854.
33 Belik, J, Gonzalez-Luis, GE, Perez-Vizcaino, F, et al. (2010) Isoprostanes in fetal and neonatal health and disease. Free Radic Biol Med 48, 177188.
34 van Acker, SA, van den Berg, DJ, Tromp, MN, et al. (1996) Structural aspects of antioxidant activity of flavonoids. Free Radic Biol Med 20, 331342.
35 Kumar, N, Kant, R & Maurya, PK (2010) Concentration-dependent effect of ( − )-epicatechin in hypertensive patients. Phytother Res 24, 14331436.
36 Sanchez, M, Galisteo, M, Vera, R, et al. (2006) Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats. J Hypertens 24, 7584.
37 Gonzalez, W, Fontaine, V, Pueyo, ME, et al. (2000) Molecular plasticity of vascular wall during N(G)-nitro-l-arginine methyl ester-induced hypertension: modulation of proinflammatory signals. Hypertension 36, 103109.
38 Nicoletti, A & Michel, JB (1999) Cardiac fibrosis and inflammation: interaction with hemodynamic and hormonal factors. Cardiovasc Res 41, 532543.
39 Brand, K, Page, S, Walli, AK, et al. (1997) Role of nuclear factor-kappa B in atherogenesis. Exp Physiol 82, 297304.
40 Hernandez-Presa, M, Bustos, C, Ortego, M, et al. (1997) Angiotensin-converting enzyme inhibition prevents arterial nuclear factor-kappa B activation, monocyte chemoattractant protein-1 expression, and macrophage infiltration in a rabbit model of early accelerated atherosclerosis. Circulation 95, 15321541.

Keywords

Chronic ( − )-epicatechin improves vascular oxidative and inflammatory status but not hypertension in chronic nitric oxide-deficient rats

  • Manuel Gómez-Guzmán (a1), Rosario Jiménez (a1), Manuel Sánchez (a1), Miguel Romero (a1), Francisco O'Valle (a2), Rocío Lopez-Sepulveda (a1), Ana María Quintela (a1), Pilar Galindo (a1), María José Zarzuelo (a1), Elvira Bailón (a1), Eva Delpón (a3), Francisco Perez-Vizcaino (a3) (a4) and Juan Duarte (a1)...

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