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1 * * Red Wine Polyphenolic Compounds; RWPC RWPC RWPC RWPC RWPC RWPC Fischer 344 Krebs- Henseleit organ bath RWPC RWPC NO N G -nitro-l-arginine L-NNA, M cyclooxygenase diclofenacm mm KCl L-NNA diclofenac mm KCl RWPC NO EDHF EDHF
2 RWPC NO Fischer 344 Henseleit O2, CO2 French Paradox ml organ bath Krebs- 7T-15- Red Wine Polyphenolic Compounds; RWPC mmnacl, KCl RWPC LDL glucose, CaCl2, organ bath ET-1 RWPC RWPC K + K + RWPC NaCl KCl RWPC RWPC RWPC phenylephrine 10-7 M mmmm Krebs-Henseleit 240,,, NaHCO3, MgSO4, KH2 PO4, g KCl mm NaCl mm, KCl mm Krebs-Henseleit M
3 organ bath RWPC phenylephrine 10-7 M NO N G -nitro- RWPC L-arginine L-NNA, M cyclooxygenase phenylephrine diclofenacmrwpc mm KCl phenylephrine PE, 10-7 M ADRIEN BERTEA VIN DE RWPC TEBLE DE FRANCE ROUGE, g /ml phenylephrine Sigma Chemical Co.St.Louis,
4 利 石幡 會田 下田 片野 図２ 内皮細胞無傷および内皮細胞除去標本における RWPC の血管弛緩作用 グラフの縦軸は phenylephrine 10-7 M による最大収縮反応を１ ００ として表し 横軸は RWPC の濃度を表 している Ａ 若齢ラット Ｂ 老齢ラット 内皮細胞無傷標本 内皮細胞除去標本 内は実験例数 **P ０ ０ １ vs. 内皮細胞無傷標本 図３ 内皮細胞無傷標本における RWPC の血管弛緩作用 diclofenac, L-NNA, 30mM KCl の影響 グラフの縦軸は phenylephrine 10-7 M による最大収縮反応を１ ００ として表し 横軸は RWPC の濃度を表 している Ａ 若齢ラット Ｂ 老齢ラット RWPC を単独投与したもの diclofenac 存在下で RWPC を投与したもの L-NNA 存在下で RWPC を投与したもの 30mM KCl 存在下で RWPC を投与したもの diclofenac 10μM L-NNA 100μM およ び 30mM KCl は phenylephrine 10-7M を投 与する１ ５分前 に投与した 内は実験例数 *P ０ ０５ **P ０ ０ １ vs. RWPC 単独投与 36
5 MO, USA, RWPC L-NNA L-NNA Sigma Chemical Co.St.Louis, MO, USA diclofenac Sigma Chemical Co. St.Louis, MO, USA mm KCl mm NaCl.KCl Na HCO3.Mg SO4. KH2 PO4 Student s t-test RWPC Welch s t-test EDHF Mann- Whitney s U test RWPC mm KCl P RWPC PGI2 diclofenacm RWPC diclofenac diclofenac RWPC RWPC PGI 2 RWPC RWPC L-NNA mg /ml RWPC RWPC. glucose.cacl2 NO mm KCl RWPC mm KCl RWPC RWPC mg /ml RWPC RWPC NO RWPC NO L-NNA M
6 RWPC RWPC RWPC EDHF PGI 2 EDHF RWPC NO Andriambeloson RWPC Katano Lamontagne NO PGI2 RWPC cyclooxygenase RWPC RWPC NO PGI2 EDHF NO EDHF PGI2NO L-NNA RWPC RWPC RWPC NO L-NNARWPC cyclooxygenase diclofenac NO mm KCl RWPC Ca 2+ Ca 2+ store Ca 2+ Ca 2+ RWPC NO NO L-NNA diclofenac mm l NO cgmp KCl RWPC NO RWPC mg / l 1 l 19)
7 NO mm KCl RWPC RWPC EDHF 1 RWPC 35-37, 49-50, Renaud S, de Lorgeril M: Wine, alcohol, platelets, and the French paradox for coronary heart disease. The Lancet 1992; 339: cyclooxygenase diclofenac 3 Frankel EN, Kanner J, German JB, Parks E, RWPC Kinsella JE: Inhibition of oxidation of human RWPC low-density lipoprotein by phenolic substances NO PGI 2 in red wine. The Lancet 1993; 341: St Leger AS, Cochrane AL, Moore F: Factors RWPC associated with cardiac mortality in developed NO EDHF PGI2 countries with particular reference to the consumption of wine. The Lancet 1979; 313: Red wine quercetin tannic acid 5 Whitehead TP, Robinson D, Allaway S, Syms J, Hale A: Effect of red wine ingestion on the antioxidant capacity of serum. Clin. Chem. 1995; 41: Demrow HS, Slane PR, Folts JD: Administration of wine and grape juice inhibits in vivo platelet activity and thrombosis in stenosed canine coronary arteries. Circulation 1995; 91: gallic acid catechin epicatechin quercetin 7 Corder R, Douthwaite JA, Lees DM, Khan NQ, Santos A, Wood EG et al.: Endothelin-1 resveratrol delphinidin anthocyanins synthesis reduced by red wine. Nature 2001; : Andriambeloson E, Kleschyov AL, Muller B, Beretz A, Stoclet JC, Andriantsitohaina R: Nitric oxide production and endotheliumdependent vasorelaxation induced by wine polyphenols in rat aorta. Br J Pharmacol 1997; 120: Katano Y, Ishihata A, Morinobu S, Endoh M: Modification by aging of the coronary vascular response to endothelin-1 in the rat isolated
8 perfused heart. Naunyn-Schmiedberg s Arch Pharmacol 1993; 348: Katano Y, Ishihata A, Endoh M: Detrimental adaptation of cardiovascular receptor-mediated regulation with age: Changes in cardiac and coronary vascular responses to endothelin-1 in isolated perfused rat heart. In: Nagano M, Takeda N, Dhalla NS, eds. The Adapted Heart. New York; Raven Press, 1994: Ishihata A, Katano Y, Nakamura M, Doi K, Tasaki K, Ono A: Differential modulation of nitric oxide and prostacyclin release in senescent rat heart stimulated by angiotensinii. Eur J Pharmacol 1999; 382: Lamontagne D, Koing A, Bassenge E, Busse R: Prostacyclin and nitric oxide contribute to the vasodilator action of acetylcholine and bradykinin in the intact rabbit coronary bed. J Cardiovasc Pharmacol 1992; 20: Martin S, Andriambeloson E, Takeda K, Andriantsitohaina R: Red wine polyphenols increase calcium in bovine aortic endothelial cells: a basis to elucidate signalling pathways leading to nitric oxide production. Br J Pharmacol 2002; 135: Fitzpatrick DF, Hirschfield SL, Coffey RG: Endothelium-dependent vasorelaxing activity of wine and other grape products. Am J Physiol 1993; 265: H774-H Ndiaye M, Chataigneau T, Andriantsitohaina R, Stoclet JC, Schini-Kerth VB: Red wine polyphenols cause endothelium-dependent EDHF-mediated relaxations in porcine coronary arteries via a redox-sensitive mechanism. Biochem Biophys Res Commun 2003; 310: Wollny T, Chabielska E, Malinowska- Zaprzalka M, Nazarko J, Rozmyslowicz- Szerminska W, Buczko W: Effects of Bulgarian red and white wines on primary hemostasis and experimental thrombosis in rats. Pol J Pharmacol 2003; 55: Flesch M, Schwarz A, B hm M: Effects of red and white wine on endothelium-dependent vasorelaxation of rat aorta and human coronary arteries. Am J Physiol 1998; 257: H1183-H van Golde PH, van der Westelaken M, Bouma BN, van de Wiel A: Characteristics of piraltin, a polyphenol concentrate, produced by freeze-drying of red wine. Life Sci 2004; 74: Howard A, Chopra M, Thurnham DI, Strain JJ, Fuhrman B, Aviram M: Red wine consumption and inhibition of LDL oxidation: what are the important components? Medical Hypotheses 2002; 59(1):
9 Yamagata Med J (1) Mikako Kaga, Akira Ishihata*, Tomomi Aita, Tomoko Shimoda, Yumi Katano Course of Clinical Nursing, Department of Nursing, *Course of Organ Functions and Controls, Yamagata University School of Medicine, Yamagata, Japan ABSTRACT [Objective] The vasorelaxing effects of the red wine extracts were studied in rat thoracic aorta. [Methods] Aortas were isolated from young (2-3 months) and aged (27 months) F344 rats and the ring preparations with or without endothelium were mounted in Krebs- Henseleit solution to measure the developed tension. The polyphenolic substances were added cumulatively after the contraction with phenylephrine. [Results] Extracts of red wine relaxed the vessels concentration-dependently. These vasorelaxant effects were attenuated by endothelial removal. In young rat, vasorelaxation induced by RWPC was significantly inhibited by L-NNA (100 M), diclofenac (10 M) and 30mM KCl. In aged rat, the inhibition by L-NNA and diclofenac was less than that of young rat, and 30mM KCl potently decreased the relaxation. However, the vasorelaxant responses were preserved even in aged aorta. [Conclusion] RWPC induces vascular relaxation endothelium-dependently not only in young rat but also in aged rat. The relaxation was mediated via NO, prostacyclin and EDHF in young aorta, while EDHF may play an important role in aged aorta. Key words : RWPC, endothelium, NO, EDHF, aging
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226 227 µ 228 Ω 229 230 0 ppb 2000ppb DG subthreshold (µa) 91 ± 59 86 ± 68 max stim. (µa) 755 ± 287 n=37 678 ± 300 max PS (mv) 8.7 ± 3.9 7.7 ± 4.3 n=61 CA1 subthreshold (µa) 36 ± 26 32 ± 13 max stim. (µa)
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