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http://dx.doi.org/10.4062/biomolther.2011.19.4.477

Inhibitory Effects of Polyphenol-Rich Fraction Extracted from Rubus coreanum M on Thoracic Aortic Contractility of Spontaneously Hypertensive Rats  

Lim, Hyo-Jeong (Department of Internal Medicine, College of Medicine, Seoul National University)
Min, Seon-Young (Department of Pharmacology, College of Medicine, Chosun University)
Woo, Eun-Ran (Department of Pharmacognosy, College of Pharmacy, Chosun University)
Lim, Dong-Yoon (Department of Pharmacology, College of Medicine, Chosun University)
Publication Information
Biomolecules & Therapeutics / v.19, no.4, 2011 , pp. 477-486 More about this Journal
Abstract
The purpose of the present study was to investigate whether polyphenol-rich fraction extracted from fruit wine of Rubus coreanum M (PCRC) can affect the contractility of the thoacic aortic strips isolated from spontaneously hypertensive rats (SHRs), and to clarify its mechanism of action. PCRC (200-800 ${\mu}g/mL$) concentration-depenedently blocked phenylephrine (10 ${\mu}M$)-induced contractile responses of the isolated aortic strips of SHRs. PCRC (400 ${\mu}g/mL$), added in to bath medium, also depressed the contractile active tension evoked by both phenylephrine (3 and 10 ${\mu}M$) and high potassium (25 and 56 mM). In the simultaneous presence of PCRC (400 ${\mu}g/mL$) and L-NAME (a selective inhibitor of NO synthase, 300 ${\mu}M$), the contractile responses evoked by phenylephrine and high $K^+$ were recovered to considerable level of the corresponding control contractility compared with those effects of PCRC-treatment alone. However, in the simultaneous presence of indomethacin (10 ${\mu}M$, a selective cyclooxygenase inhibitor) and PCRC (400 ${\mu}g/mL$), they were not affected. In the endothelium-denuded aortic strips by CHAPS-treatment, PCRC did not affect the contractile responses induced by phenylephrine or high potassium. Interestingly, PCRC (1.0, 3.0 and 10.0 mg/kg/30 min, i.v., respectively) dose-dependently suppressed norepiphrine-induced vasopressor responses in anesthetized SHRs. Collectively, we concluded that PCRC causes vasorelaxation in the thoracic aortic strips with intact endothelium of SHRs at least partly by the increased NO production through the activation of NO synthase of vascular endothelium, but not through the activation of cyclooxygenase. These results suggest that PCRC might be helpful to prevent or alleviate cardiovascular diseases, including hypertension.
Keywords
PCRC; Vasorelaxation; NO production; NO Synthase; Thoracic aorta; SHRs;
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1 Andriambeloson, E., Stoclet, J.C. and Andriantsitohaina, R. (1999) Mechanism of endothelial nitric oxide-dependent vasorelaxation induced by wine polyphenols in rat thoracic aorta. J. Cardiovasc. Pharmacol. 33, 248-254.   DOI
2 Benito, S., Lopez, D., Saiz, M. P., Buxaderas, S., Sanchez, J., Puig- Parellada, P. and Mitjavila, M. T. (2002) A flavonoid-rich diet increases nitric oxide production in rat aorta. Br. J. Pharmacol. 135, 910-916.   DOI
3 Zenebe, W. and Pechanova, O. (2002) Effect of red wine polyphenolic compounds on the cardiovascular system. Bratisl. Lek. Listy 103, 159-165.
4 Zenebe, W., Pechanova, O. and Andriantsitohaina, R. (2003) Red wine polyphenols induce vasorelaxation by increased nitric oxide bioactivity. Physiol. Res. 52, 425-432.
5 Zou, J. G., Wang, Z. R., Huang, Y. Z., Cao, K. J. and Wu, J. M. (2003) Effect of red wine and wine polyphenol resveratrol on endothelial function in hypercholesterolemic rabbits. Int. J. Mol. Med. 11, 317-320.
6 Triggle, D. J., Zheng, W., Hawthorn. M., Kwon, Y. W., Wei, X. Y., Joslyn, A., Ferrante, J. and Triggle, A. M. (1989) Calcium channels in smooth muscle: properties and regulation. Ann. NY. Acad. Sci. 560, 215-229.   DOI
7 Soares de Moura, R., Costa Viana, F. S., Souza, M. A. V., Kovary, K., Guedes, D. C., Oliviera, E. P., Rubenich, L. M., Carvalho, L. C., Oliveira, R. M., Tano, T. and Gusmao Correia, M. L. (2002) Antihypertensive, vasodilator and antioxidant effects of vinifera grapeskin extract. J. Pharm. Pharmacol. 54, 1515-1520.   DOI   ScienceOn
8 Spedding, M. and Paoletti, R. (1992) Classifi cation of calcium channels and the sites of action of drugs modifying channel function. Pharmacol. Rev. 44, 363-376.
9 Stein, J. H., Keevil, J. G., Wiebe, D. A., Aeschlimann S. and Folts, J. D. (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.   DOI   ScienceOn
10 Tallarida, R. J. and Murray, R. B. (1987) Manual of pharmacologic calculation with computer programs. 2nd Ed. Speringer-Verlag, New York.
11 Wada, A., Takara, H., Izumi, F., Kobayashi, H. and Yanagihara, N. (1985) Influx of $^{22}Na$ through acetylcholine receptor-associated Na channels: relationship between $^{22}Na$ influx, $^{45}Ca$ influx and secretion of catecholamines in cultured bovine adrenal medullary cells. Neuroscience 15, 283-292.   DOI
12 Yu, B. S., Ko, W. S. and Lim, D. Y. (2008) Inhibitory mechanism of polyphenol compounds isolated from red wine on catecholamine release in the perfused rat adrenal medulla. Biomolecules & Therapeutics 16, 147-160.   DOI
13 Yu, B. S., Na, D. M. and Lim, D. Y. (2009) Polyphenols of Rubus coreanum inhibit catecholamine secretion from the perfused adrenal medulla of SHRs. Korean J. Physiol. Pharmacol. 13, 517-526, 2009.   과학기술학회마을   DOI
14 Ndiaye, M., Chataigneau, T., Andriantsitohaina, J. C. S. and Schini- Kerth, V. B. (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.   DOI
15 Nevala, R., Korpela, R. and Vapaatalo, H. (1998) Plant derived estrogens relax rat mesenteric artery in vitro. Life Sci. 63, 95-100.
16 Palmer, R. M. J., Ferrige, A. G. and Moncada, S. (1987) Nitric oxide release account for the biology activity of endotheliumderived relaxing factor. Nature 327, 524-526.   DOI
17 Sarr, M., Chataigneau, M., Martins, S., Schott, C., El Bedoui, J., Oak, M. H., Muller, B., Chataigneau, T. and Schini-Kerth, V. B. (2006) Red wine polyphenols prevent angiotensin II-induced hypertension and endothelial dysfunction in rats: role of NADPH oxidase. Cardiovasc. Res. 71, 794-802.   DOI
18 Pechanova, O., Bernatova, I., Babal, P., Martinez, M. C., Kysela, S., Stvrtina, S. and Andriantsitohaina, R. (2004) Red wine polyphenols prevent cardiovascular alterations in L-NAME-induced hypertension. J. Hypertens. 22, 1551-1559.   DOI
19 Radomski, M. W., Palmer, R. M. J. and Moncada, S. (1987) The antiaggregating properties of vascular endothelium adhesion to vascular endothelium. Lancet. 2, 1057-1058.
20 Ryman, T., Brandt, L., Anderson, K. E. and Mellergard, P. (1989) Regional and species differences in vascular reactivity to extracellular potassium. Acta. Physiol. Scand. 136, 151-159.   DOI
21 Schwartz, A. and Taira, N. (1983) Calcium channel-blocking drugs: a novel intervention for the treatment of cardiac disease. Circ. Res. 52, I1-2.   DOI   ScienceOn
22 Scott-Burden, T. and Vanhoutte, P. M. (1994) Regulation of smooth muscle cell growth by endothelium-derived factors. Tex. Heart Inst. J. 21, 91-97.
23 Landmesser, U. and Drexler, H. (2007) Endothelial function and hypertension. Curr. Opin. Cardiol. 22, 316-320.   DOI
24 Lee, J. W. and Do, J. H. (2000) Chemical compound and volatile flavor of Rubus coreanum. Korean J. Food & Nutr. 13, 453-459.
25 Leffl er, C. W., Mirro, R., Shibata, M., Parfenova, H., Armstead, W. M. and Zuckerman, S. (1993) Effects of indomethacin on cerebral vasodilator responses to arachidonic acid and hypercapnia in newborn pigs. Pediatr. Res. 33, 609-614.   DOI   ScienceOn
26 Mizutani, K., Ikeda, K., Kawai Y. and Yamori, Y. (1999) Extract of wine phenolics improves aortic biomechanical properties in stroke-prone spontaneously hypertensive rats (SHRSP). J. Nutr. Sci. Vitaminol. 45, 95-106.   DOI
27 Li, H. F., Li, W., Zheng, T. Z., Qu, S. Y. and Zhang, C. L. (2002) A study of the mechanisms involved in relaxation induced by 17 $\beta$-estradiol in the isolated rabbit aorta. Arch. Gynecol. Obstet. 266, 101-104.   DOI
28 Li, H. F., Tian, Z. F., Qiu, X. Q., Wu, J. X., Zhang, P. and Jia, Z. J. (2006) A Study of mechanisms involved in vasodilatation induced by resveratrol in isolated porcine coronary artery. Physiol. Res. 55,365-372.
29 Martin, S., Andriambeloson, E., Takeda, K. and Andriantsitohaina, R. (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.   DOI
30 Moncada, S., Palmer, R. M. J. and Higgs, E. A. (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 43, 109-142.
31 Moore, P., Kal-Swayeh, O. A., Chong, N. W., Evans, R. A. and Gibson, A. (1990) L-NG-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro. Br. J. Pharmacol. 99, 408-412.   DOI   ScienceOn
32 Formica, J. V. and Regelson, W. (1995) Review of the biology of quercetin and related biofl avonoids. Food Chem. Toxicol. 33, 1061-1080.   DOI
33 Freis, E. D., Mackay, J. C. and Oliver, W. F. (1951) The effect of "sympatholytic" drugs on the cardiovascular responses to epinephrine and norepinephrine in man. Circulation 3, 254-259.   DOI   ScienceOn
34 Johns, A., Leijten, P., Yamamoto, H, Hwang, K. and van Breemen C. (1987) Calcium regulation in vascular smooth muscle contractility. Am. J. Cardiol. 59, 18A-23A.   DOI
35 Hashimoto, M., Kim, S., Eto, M., Iijima, K., Ako, J., Yoshizumi, M., Akishita, M., Kondo, K., Itakura, H., Hosoda, K., Toba K. and Ouchi, Y. (2001) Effect of acute intake of red wine on flow-mediated vasodilatation of the brachial artery. Am. J. Cardiol. 88, 1457-1460.   DOI
36 Hertog, M. G. L., Feskens, E. J. M. and Kromhout, D. (1997) Antioxidant flavonols and coronary heart disease risk: ten year follow-up of the Zutphen elderly study. Lancet. 349, 699.
37 Jimenez, R., López-Sepulveda, R., Kadmiri, M., Romero, M., Vera, R., Sanchez, M., Vargas, F., O'Valle, F., Zarzuelo, A., Duenas, M., Santos-Buelga, C. and Duarte, J. (2007) Polyphenols restore endothelial function in DOCA-salt hypertension: role of endothelin-1 and NADPH oxidase. Free Radic. Biol. Med. 43, 462-473.   DOI
38 Kee, Y. W. and Lim, D. Y. (2007) Influence of polyphenolic compounds isolated from Rubus coreanum on catecholamine release in the rat adrenal medulla. Arch. Pharm. Res. 30, 1240-1251.   과학기술학회마을   DOI
39 Keli, S. O., Hertog, M. G. L., Feskens, E. J. M. and Kromhout, D. (1996) Flavonoids, antioxidant vitamins and risk of stroke. The Zutphen elderly study. Arch. Intern. Med. 156, 637-642.   DOI
40 Kim, J. M., Park, K. O. and Baik, Y. H. (1989) Effects of antiepileptic drugs on contractile responses of vascular smooth muscles. Chonnam J. Med. Sci. 2, 50-59.
41 Cortijo, J., Perpina, M. and Esplugues, J. (1986) Pharmacological characterization of the effects of verapamil and nifedipine on isolated guinea-pig lung parenchymal strip. Gen. Pharmacol. 17, 211-217.   DOI
42 Dube, G. P., Baik, Y. H., Van Breemen, C. and Schwartz, A. (1988) Effects of isosorbide dinitrate and diltiazem on $Ca^{2+}$ flux and contraction in artery. European J. Pharmacol. 145, 39-47.   DOI
43 Derek, D., Pearson, D. A. and German, J. B. (1997) Endothelial cell basal PGI2 release is stimulated by wine in vitro: one mechanism that may mediate the vasoprotective effects of wine. J. Nutr. Biochem. 8, 647-651.   DOI
44 Diebolt, M., Bucher, B. and Andriantsitohaina, R. (2001) Wine polyphenols decrease blood pressure, improve NO vasodilatation, and induce gene expression. Hypertension 38, 159-165.   DOI   ScienceOn
45 Dube, G. P., Baik, Y. H. and Schwartz, A. (1985) Effects of novel calcium channel agonist dihydropyridine analogue, Bay K 9644, on pig coronary artery: Biphasic mechanical response and paradoxical potentiation of contraction by diltiazem and nimodipine. J. Cardiovasc. Pharmacol. 7, 377-389.   DOI
46 Fitzpatrick, D. F., Fleming, R. C., Bing, B., Maggi, D. A. and O'Malley, R. (2000) Isolation and characterization of endothelium-dependent vasorelaxing compounds from grape seeds. J. Agric. Food Chem. 48, 6384-6390.   DOI
47 Fitzpatrick, D. F., Hirschfi eld, S. L. and Coffey, R. G. (1993) Endothelium-dependent vasorelaxing activity of wine and other grape products. Am. J. Physiol. 265, H77-78.
48 Fitzpatrick, D. F., Hirschfi eld, S. L., Ricci, T., Jantzen, P. and Coffey, R. G. (1995) Endothelium-dependent vasorelaxation caused by various plant extracts. J. Cardiovasc. Pharmacol. 26, 90-95.   DOI
49 Flesch, M., Schwarz, A. and Bolun, 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.
50 Bernatova, I., Pechaoova, O., Babal, P., Kysela, S., Stvrtina, S. and Andriantsitohaina, R. (2002) Wine polyphenols improve cardiovascular remodelling and vascular function in NO-defi cient hypertension. Am. J. Physiol. 282, H942-H948.
51 Bolton, T. M. (1979) Mechanisms of action of transmitters and other substances on smooth muscle. Physiol. Rev. 3, 606-718.
52 Bouloumie, A., Bauersachs, J. and Linz, W. (1997) Endothelial dysfunction coincides with an enhanced nitric oxide synthase expression and superoxide anion production. Hypertension 30, 934-941.   DOI   ScienceOn
53 Burns, J., Gardner, P. T., O'Neil, J., Crawford, S., Morecroft, I., McPhail, D. B., Lister, C., Matthews, D., MacLean, M. R., Lean, M. E., Duthie, G. G. and Crozier, A. (2000) Relationship among antioxidant activity, vasodilation capacity, and phenolic content of red wines. J. Agric. Food Chem. 48, 220-230.   DOI
54 Caderni, G., De Filippo, C., Luceri, C., Salvadori, M., Giannini, A., Biggeri, A., Remy, S., Cheynier, V. and Dolara, P. (2000) Effects of black tea, green tea and wine extracts on intestinal carcinogenesis induced by azoxymethane in F344 rats. Carcinogenesis 21, 1965-1969.   DOI
55 Cho, Y. J. (2005) Comparison of physiological activities between hotwater and ethanol extracts of Bokbunja (Rubus coreanum F.). Korean J. Food & Nutr. 34, 790-796.   DOI
56 Constantine, J. W., Mcshane, W. K., Scriabine, A. and Hess, H. J. (1973) Analysis of the hypotensive action of prazosin. In Hypertension: Mechanisms and Management (G. Onesti, Ed.), pp. 429. Grume & Stratton, New York.
57 Corder, R., Douthwaite, J. A., Lees, D. M., Khan, N. Q., Viseu Dos Santos, A. C., Wood, E. G. and Carrier, M. J. (2001) Endothelin-1 synthesis reduced by red wine. Nature 414, 863-864.   DOI
58 Aldini, G., Carini, M., Piccoli, A., Rossoni, G. and Facino, R. M. (2003) Procyanidins from grape seeds protect endothelial cells from peroxynitrite damage and enhance endothelium-dependent relaxation in human artery: new evidences for cardio-protection. Life Sci. 73, 2883-2898.   DOI
59 Cornish, E. J., Goldie, R. G., Krstew, E. V. and Miller, R. C. (1983) Effect of indomethacin on responses of sheep isolated coronary artery to arachidonic acid. Clin. Exp. Pharmacol. Physiol. 10, 171-517.   DOI
60 Ablad, B., Borg, K. O., Carlsson, E., Johnson, G., Malmfors, L. and Regardh, C. G. (1975) A survey of the pharmacological properties of metoprolol in animals and man. Acta. Pharmacol. Toxicol. 36, 7-23.
61 Andriambeloson, E., Magnier, C. and Haan-Archipoff, G. (1998) Lobstein Natural dietary polyphenolic compounds cause endotheliumdependent vasorelaxation in rat thoracic aorta. J. Nutr. 128, 2324-2333.