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Euterpe oleracea Mart.-derived polyphenols prevent endothelial dysfunction and vascular structural changes in renovascular hypertensive rats: role of oxidative stress

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Abstract

The consumption of polyphenol-rich foods is associated with a decreased risk of mortality from cardiovascular diseases. Previously, we have demonstrated that the stone of Euterpe oleracea Mart. (açaí) from the Amazon region exerts vasodilator and antioxidant actions. This study examined the effect of açaí stone extract (ASE) on the vascular functional and structural changes and oxidative stress associated with the two-kidney, one-clip (2K-1C) renovascular hypertension. 2K-1C and sham-operated rats were treated with ASE 200 mg/kg/day (or vehicle) for 40 days. Blood pressure was measured by tail plethysmography, and the vascular reactivity was evaluated in the rat isolated mesenteric arterial bed. Mesenteric protein expression of endothelial nitric oxide synthase (eNOS), superoxide dismutase 1 and 2 (SOD1 and SOD2), metalloproteinase 2 (MMP-2), and tissue inhibitor of MMPs (TIMP)-1 was assessed by Western blot; oxidative damage and antioxidant activity by spectrophotometry; MMP-2 levels by gelatin zymography; and structural changes by histological analysis. ASE prevented 2K-1C hypertension and the reduction of acetylcholine-induced vasodilation. The increased levels of malondialdehyde and carbonyl protein were reduced by ASE. SOD, catalase, and glutathione peroxidase activities and the expressions of SOD1 and SOD2, eNOS, and TIMP-1 were decreased in 2K-1C rats and recovered by ASE. In 2K-1C rats, ASE prevented vascular remodeling and the increased expression/levels of MMP-2. These findings indicate that ASE produces antihypertensive effect and prevents the endothelial dysfunction and vascular structural changes in 2K-1C hypertension, probably through mechanisms involving antioxidant effects, NOS activation, and inhibition of MMP-2 activation.

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References

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  PubMed  CAS  Google Scholar 

  • Arribas SM, Hinek A, Gonzalez MC (2006) Elastic fibers and vascular structure in hypertension. Pharmacol Ther 111:771–791

    Article  PubMed  CAS  Google Scholar 

  • Asanuma K, Magid R, Johnson C, Nerem RM, Galis ZS, O’Callaghan CJ, Williams B (2003) Uniaxial strain upregulates matrix-degrading enzymes produced by human vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 284(5):H1778–H1784

    PubMed  CAS  Google Scholar 

  • Bannister JV, Calabrese L (1987) Assays for superoxide dismutase. Meth Biochem Anal 32:279–312

    Article  CAS  Google Scholar 

  • Bouvet C, Gilbert LA, Girardot D, Deblois D, Moreau P (2005) Different involvement of extracellular matrix components in small and large arteries during chronic NO synthase inhibition. Hypertension 45(3):432–437

    Article  PubMed  CAS  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  • Callera GE, Yogi A, Tostes RC, Rossoni LV, Bendhack LM (2004) Ca2 + -activated K + channels underlying the impaired acetylcholine-induced vasodilation in 2K-1C hypertensive rats. J Pharmacol Exp Ther 309(3):1036–42

    Article  PubMed  CAS  Google Scholar 

  • Castro MM, Rizzi E, Figueiredo-Lopes L, Fernandes K, Bendhack LM, Pitol DL, Gerlach RF, Tanus-Santos JE (2008) Metalloproteinase inhibition ameliorates hypertension and prevents vascular dysfunction and remodeling in renovascular hypertensive rats. Atherosclerosis 198(2):320–31

    Article  PubMed  CAS  Google Scholar 

  • Castro MM, Rizzi E, Rodrigues GJ, Ceron CS, Bendhack LM, Gerlach RF, Tanus-Santos JE (2009) Antioxidant treatment reduces matrix metalloproteinase-2-induced vascular changes in renovascular hypertension. Free Radic Biol Med 46(9):1298–307

    Article  PubMed  CAS  Google Scholar 

  • Ceron CS, Castro MM, Rizzi E, Montenegro MF, Fontana V, Salgado MC, Gerlach RF, Tanus-Santos JE (2010) Spironolactone and hydrochlorothiazide exert antioxidant effects and reduce vascular matrix metalloproteinase-2 activity and expression in a model of renovascular hypertension. Br J Pharmacol 160(1):77–87

    Article  PubMed  CAS  Google Scholar 

  • Costa CA, Amaral TAS, Carvalho LCRM, Ognibene DT, da Silva AFE, Moss MB, Valença SS, Soares de Moura R, Resende AC (2009) Antioxidant treatment with tempol and apocynin prevents endothelial dysfunction and development of renovascular hypertension. Am J Hypertension 12:1242–1249

    Article  Google Scholar 

  • Curin Y, Andriantsitohaina R (2005) Polyphenols as potential therapeutical agents against cardiovascular disease. Pharmacol Rep 57:97–107

    PubMed  Google Scholar 

  • Draper HH, Squires EJ, Mahmoodi H, Wu J, Agarwal S, Hadley M (1993) A comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials. Free Radic Biol Med 15:353–363

    Article  PubMed  CAS  Google Scholar 

  • Farmand F, Ehdaie A, Roberts CK, Sindhu RK (2005) Lead-induced dysregulation of superoxide dismutases, catalase, glutathione peroxidase, and guanylate cyclase. Environ Res 98:33–39

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Patron C, Radomski MW, Davidge ST (1999) Vascular matrix metalloproteinase-2 cleaves big endotelin-1 yielding a novel vasoconstrictor. Circ Res 85:906–911

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Patron C, Stewart KG, Zhang Y, Koivunen E, Radomski MW, Davidge ST (2000) Vascular matrix metalloproteinase-2-dependent cleavage of calcitonin gene-related peptide promotes vasoconstriction. Cir Res 87:670–676

    Article  CAS  Google Scholar 

  • Fitzpatrick DF, Fleming RC, Bing B, Maggi DA, O'Malley RM (2000) Isolation and characterization of endothelium-dependent vasorelaxing compounds from grape seeds. J Agric Food Chem 48(12):6384–6390

    Article  PubMed  CAS  Google Scholar 

  • Flamant M, Placier S, Dubroca C, Esposito B, Lopes I, Chatziantoniou C, Tedgui A, Dussaule JC, Lehoux S (2007) Role of matrix metalloproteinases in early hypertensive vascular remodeling. Hypertension 50(1):212–218

    Article  PubMed  CAS  Google Scholar 

  • Flohe L, Gunzler WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114–121

    Article  PubMed  CAS  Google Scholar 

  • Galis ZS, Khatri JJ (2002) Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res 90:251–262

    PubMed  CAS  Google Scholar 

  • Gallori S, Bilia AR, Bergonzi MC, Barbosa WLR, Vincieri FF (2004) Polyphenolic constituents of fruit pulp of Euterp oleracea Mart. (Açaí palm). Cromatografia 59:739–743

    CAS  Google Scholar 

  • Goldblatt H, Lynch J, Hamzal RF, Summerville WW (1934) Studies on experimental hypertension: the production of persistent elevation of systolic blood pressure by means of renal ischemia. J Exp Med 59:347–379

    Article  PubMed  CAS  Google Scholar 

  • Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15 N] nitrate in biological fluids. Anal Biochem 126:131–138

    Article  PubMed  CAS  Google Scholar 

  • Grote K, Flach I, Luchtefeld M, Akin E, Holland SM, Drexler H, Schieffer B (2003) Mechanical stretch enhances mRNA expression and pro-enzyme release of matrix metalloproteinase-2 (MMP-2) via NAD(P)H oxidase-derived reactive species. Circ Res 92:e80–e86

    Article  PubMed  CAS  Google Scholar 

  • Higashi Y, Sasaki S, Nakagawa K, Matsuura H, Oshima T, Chayama K (2002) Endothelial function and oxidative stress in renovascular hypertension. N Engl J Med 346:1954–1962

    Article  PubMed  CAS  Google Scholar 

  • Hishikawa K, Oemar BS, Yang Z, Lüscher TF (1997) Pulsatile stretch stimulates superoxide production and activates nuclear factor-kappa B in human coronary smooth muscle. Circ Res 81:797–803

    Article  PubMed  CAS  Google Scholar 

  • Lee KW, Kang NJ, Oak MH, Hwang MK, Kim JH, Schini-Kerth VB, Lee HJ (2008) Cocoa procyanidins inhibit expression and activation of MMP-2 in vascular smooth muscle cells by direct inhibition of MEK and MT1-MMP activities. Cardiovasc Res 79(1):34–41

    Article  PubMed  CAS  Google Scholar 

  • Lodi F, Cogolludo A, Duarte J, Moreno L, Coviello A, Peral De Bruno M, Vera R, Galisteo M, Jiménez R, Tamargo J, Perez-Vizcaino F (2006) Increased NADPH oxidase activity mediates spontaneous aortic tone in genetically hypertensive rats. Eur J Pharmacol 544:97–103

    Article  PubMed  CAS  Google Scholar 

  • Manea A, Tanase LI, Raicu M, Simionescu M (2010) Jak/STAT signaling pathway regulates nox1 and nox4-based NADPH oxidase in human aortic smooth muscle cells. Arterioscler Thromb Vasc Biol 30(1):105–112

    Article  PubMed  CAS  Google Scholar 

  • Martinez ML, Oh HR, Unsworth EJ, Bregonsio C, Saavedra JM, Stetler-Stevenson WG, Cuttitta F (2004) Matrix metalloproteinase-2 cleavage of adrenomedulin produces a vasoconstrictor out of a vasodilator. Biochem J 383:413–418

    Article  PubMed  CAS  Google Scholar 

  • Martinez MLL, Castro MM, Rizzi E, Fernandes K, Demacq C, Bendhack LM, Gerlach RF, Tanus-Santos JE (2008) Lercanidipine reduces matrix metalloproteinase-2 activity and reverses vascular dysfunction in renovascular hypertensive rats. Eur J Pharmacol 591:224–230

    Article  PubMed  CAS  Google Scholar 

  • Matrisian LM (1994) Matrix metalloproteinase gene expression. Ann NY Acad Sci 732:42–56

    Article  PubMed  CAS  Google Scholar 

  • McGregor DD (1965) The effect of sympathetic nerve stimulation on vasoconstrictor response in perfused mesenteric blood vessels of the rat. J Physiol 177:21–30

    PubMed  CAS  Google Scholar 

  • Montezano AC, Touyz RM (2012) Oxidative stress, Noxs, and hypertension: experimental evidence and clinical controversies. Ann Med 44(Suppl 1):S2–S16

    Article  PubMed  CAS  Google Scholar 

  • Montezano AC, Burger D, Ceravolo GS, Yusuf H, Montero M, Touyz RM (2011) Novel Nox homologues in the vasculature: focusing on Nox4 and Nox5. Clin Sci (Lond) 120(4):131–141

    Article  CAS  Google Scholar 

  • Murphy G, Willenbrock F, Crabbe T, O’Shea M, Ward R, Atkinson S, O’Connell J, Docherty A (1994) Regulation of matrix metalloproteinase activity. Ann NY Acad Sci 732:31–41

    Article  PubMed  CAS  Google Scholar 

  • Niu R, Okamoto T, Iwase K, Nomura S, Mizutani S (2000) Quantitative analysis of matrix metalloproteinases-2 and -9, and their tissue inhibitors-1 and -2 in human placenta throughout gestation. Life Sci 66:1127–1137

    Article  PubMed  CAS  Google Scholar 

  • Okamoto T, Akaike T, Sawa T, Miyamoto Y, van der Vliet A, Maeda H (2001) Activation of matrix metalloproteinases by peroxynitrite induced protein S-glutathiolation via disulfide S-oxide formation. J Biol Chem 276(31):29596–29602

    Article  PubMed  CAS  Google Scholar 

  • Palm F, Onozato M, Welch WJ, Wilcox CS (2010) Blood pressure, blood flow and oxygenation in clipped kidney of chronic 2K,1C rats: effects of tempol and angiotensin blockade. Hypertension 55(2):298–304

    Article  PubMed  CAS  Google Scholar 

  • Pozo-Insfran DD, Brenes CH, Talcott ST (2004) Phytochemical composition and pigment stability of Açai (Euterpe oleracea Mart.). J Agric Food Chem 52(6):1539–1545

    Article  PubMed  Google Scholar 

  • Ray R, Murdoch CE, Wang M, Santos CX, Zhang M, Alom-Ruiz S, Anilkumar N, Ouattara A, Cave AC, Walker SJ, Grieve DJ, Charles RL, Eaton P, Brewer AC, Shah AM (2011) Endothelial Nox4 NADPH oxidase enhances vasodilatation and reduces blood pressure in vivo. Arterioscler Thromb Vasc Biol 31(6):1368–1376

    Article  PubMed  CAS  Google Scholar 

  • Rocha AP, Carvalho LC, Sousa MA, Madeira SV, Sousa PJ, Tano T, Schini-Kerth VB, Resende AC, Soares de Moura R (2007) Endothelium-dependent vasodilator effect of Euterpe oleracea Mart. (Açaí) extracts in mesenteric vascular bed of the rat. Vascul Pharmacol 46(2):97–104

    Article  PubMed  CAS  Google Scholar 

  • Rocha AP, Resende AC, Souza MAV, Carvalho LCRM, Sousa PJC, Tano T, Criddle DN, Porto LC, Valença SS, Soares de Moura R (2008) Antihypertensive effects and antioxidant action of a hydro-alcoholic extract obtained from fruits of Euterpe oleracea Mart. (Açaí). J Pharmacol Toxicol 3(6):435–448

    Article  CAS  Google Scholar 

  • Rodrigues RB, Lichtenthaler R, Zimmermann BF, Papagiannopoulos M, Fabricius H, Marx F, Maia JG, Almeida O (2006) Total oxidant scavenging capacity of Euterpe oleracea Mart. (acai) seeds and identification of their polyphenolic compounds. J Agric Food Chem 54:4162–4167

    Article  PubMed  CAS  Google Scholar 

  • Schröder K, Zhang M, Benkhoff S, Mieth A, Pliquett R, Kosowski J, Kruse C, Luedike P, Michaelis UR, Weissmann N, Dimmeler S, Shah AM, Brandes RP (2012) Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase. Circ Res 110(9):1217–1225

    Article  PubMed  Google Scholar 

  • Schulz R (2007) Intracellular targets of matrix metalloproteinase-2 in cardiac disease: rationale and therapeutic approaches. Annu Rev Pharmacol Toxicol 47:211–242

    Article  PubMed  CAS  Google Scholar 

  • Singleton VL, Rossi JA (1965) Colorimetry of total phenolics with phosphomolybdic–phosphotungstic acid reagents. Am J Enol Vitic 16:144–158

    CAS  Google Scholar 

  • Soares De Moura R, Costa Viana FS, Souza MA, Kovary K, Guedes DC, Oliveira EP, Rubenich LM, Carvalho LC, Oliveira RM, Tano T, Gusmão Correia ML (2002) Antihypertensive, vasodilator and antioxidant effects of a vinifera grape skin extract. J Pharm Pharmacol 54(11):1515–1520

    Article  PubMed  CAS  Google Scholar 

  • Soares de Moura R, Ferreira TS, Lopes AA, Pires KMP, Nesi R, Resende AC, Sousa PJDC, da Silva AJR, Borges RM, Porto LC, Valença SS (2012) Effects of Euterpe oleracea Mart. (açaí) extract in acute lung inflammation induced by cigarette smoke in the mouse. Phytomedicine 19(3-4):262–269

    Article  Google Scholar 

  • Stoclet JC, Chataigneau T, Ndiaye M, Oak MH, El Bedoui J, Chataigneau M, Schini-Kerth VB (2004) Vascular protection by dietary polyphenols. Eur J Pharmacol 500(1–3):299–313

    Article  PubMed  CAS  Google Scholar 

  • Tian XY, Wong WT, Leung FP, Zhang Y, Wang YX, Lee HK, Ng CF, Chen ZY, Yao X, Au CL, Lau CW, Vanhoutte PM, Cooke JP, Huang Y (2012) Oxidative stress-dependent cyclooxygenase-2-derived prostaglandin f(2α) impairs endothelial function in renovascular hypertensive rats. Antioxid Redox Signal 16(4):363–373

    Article  PubMed  CAS  Google Scholar 

  • Ulker S, McMaster D, McKeown PP, Bayraktutan U (2003) Impaired activities of antioxidant enzymes elicit endothelial dysfunction in spontaneous hypertensive rats despite enhanced vascular nitric oxide generation. Cardiovasc Res 59(2):488–500

    Article  PubMed  CAS  Google Scholar 

  • Vaziri ND, Oveisi F, Ding Y (1998) Role of increased oxygen free radical activity in the pathogenesis of uremic hypertension. Kidney Int 53:1748–1754

    Article  PubMed  CAS  Google Scholar 

  • Viappiani S, Nicolescu AC, Holt A, Sawicki G, Crawford BD, Leon H, van Mulligen T, Schulz R (2009) Activation and modulation of 72 kDa matrix metalloproteinase-2 by peroxynitrite and glutathione. Biochem Pharmacol 77(5):826–834

    Article  PubMed  CAS  Google Scholar 

  • Weidig P, McMaster D, Bayraktutan U (2004) High glucose mediates pro-oxidant and antioxidant enzyme activities in coronary endothelial cells. Diabetes Obes Metab 6(6):432–441

    Article  PubMed  CAS  Google Scholar 

  • Welch WJ, Mendonca M, Aslam S, Wilcox CS (2003) Roles of oxidative stress and AT1 receptors in renal hemodynamics and oxygenation in the postclipped 2K,1C kidney. Hypertension 41:692–696

    Article  PubMed  CAS  Google Scholar 

  • Widder JD, Chen W, Dikalov S, Thony B, Hatakeyama K, Harrison DG (2007) Regulation of tetrahydrobiopterin biosynthesis by shear stress. Cir Res 101(8):830–838

    Article  CAS  Google Scholar 

  • Xu S, Shriver AS, Jagadeesha DK, Chamseddine AH, Szőcs K, Weintraub NL, Griendling KK, Bhalla RC, Miller FJ Jr (2012) Increased expression of Nox1 in neointimal smooth muscle cells promotes activation of matrix metalloproteinase-9. J Vasc Res 49(3):242–248

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was conducted with grants from the National Council of Scientific and Technological Development (CNPq) and Rio de Janeiro State Research Agency (FAPERJ). The authors of this manuscript are grateful to Mr. Marcelo Augusto Vieira de Sousa for technical assistance.

Conflict of interest

Roberto Soares de Moura is inventor of a patent PCT/BR2007/000178 that may support the development of a product. The other authors state no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Institute of Biology, Rio de Janeiro State University, Av. 28 de Setembro, 87, Rio de Janeiro, 20 551-030, Brazil

    Cristiane Aguiar da Costa, Paola Raquel Braz de Oliveira, Graziele Freitas de Bem, Lenize Costa Reis Marins de Cavalho, Andréa Fernandes Emiliano da Silva, Roberto Soares de Moura & Angela Castro Resende

  2. Laboratory of Technology in Drug Production, State University of the West, Rio de Janeiro, Brazil

    Dayane Teixeira Ognibene

  3. Department of Pharmacology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Samuel dos Santos Valença & Karla Maria Pereira Pires

  4. Department of Pharmacy, Federal University of Pará, Belém, Brazil

    Pergentino José da Cunha Sousa

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  1. Cristiane Aguiar da Costa
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  2. Paola Raquel Braz de Oliveira
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  3. Graziele Freitas de Bem
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Correspondence to Angela Castro Resende.

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da Costa, C.A., de Oliveira, P.R.B., de Bem, G.F. et al. Euterpe oleracea Mart.-derived polyphenols prevent endothelial dysfunction and vascular structural changes in renovascular hypertensive rats: role of oxidative stress. Naunyn-Schmiedeberg's Arch Pharmacol 385, 1199–1209 (2012). https://doi.org/10.1007/s00210-012-0798-z

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