Resveratrol provides late-phase cardioprotection by means of a nitric oxide- and adenosine-mediated mechanism

Resveratrol provides late-phase cardioprotection by means of a nitric oxide- and adenosine-mediated mechanism
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DOI:
10.1016/s0014-2999(03)01441-9
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发表时间:
2003-03-28
影响因子:
5
通讯作者:
De Jong, JW
De Jong, JW
中科院分区:
医学2区
文献类型:
--
作者:
Bradamante, S;Barenghi, L;De Jong, JW

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我们使用两个实验模型来证明白藜芦醇(反式-3,4,5-三羟基二苯乙烯)通过一氧化氮和腺苷依赖性机制减轻心脏缺血再灌注损伤。(1)急性离体:与基线相比,在Langendorff灌注的含氧量正常的大鼠心脏中输注白藜芦醇(10 μ M,10分钟)显著增加腺苷释放和冠状动脉流量。30分钟后,低流量缺血,血管舒张,仍然存在于再灌注,被完全废除白藜芦醇加腺苷拮抗剂8-(对磺苯基)茶碱(SPT,50 μ M)管理。(2)体内慢性:大鼠接受含有25 mg/l白藜芦醇的自来水15天或正常水。24小时后,他们的心脏进行Langendorff灌注,并进行60分钟的低流量缺血和再灌注。白藜芦醇治疗的心脏在再灌注时表现出更好的功能恢复和显著的血管舒张,但高能磷酸盐没有变化(P-31核磁共振)。N-G-硝基-L-精氨酸甲酯(L-NAME,30 μ M),一种非选择性的一氧化氮合酶抑制剂,或SPT(50 μ M)在低流量缺血前10分钟给药,取消了这种作用。这表明,长期适度的白藜芦醇消费可能在晚期心脏保护作用中发挥重要作用。(C)2003 Elsevier Science B. V.保留所有权利。
We used two experimental models to prove that resveratrol (trans-3,4,5-trihydroxystilbene) reduces cardiac ischemic-reperfusion injury by means of a nitric oxide- and adenosine-dependent mechanism. (1) Acute ex vivo: resveratrol (10 muM, 10 min) infusion in Langendorff-perfused normoxic rat hearts significantly increased adenosine release and coronary flow compared with baseline. After 30-min low-flow ischemia, vasodilation, still present at reperfusion, was completely abolished by resveratrol plus adenosine antagonist 8-(p-sulfophenyl)theophylline (SPT, 50 muM) administration. (2) Chronic in vivo: rats received tap water containing 25 mg/l resveratrol for 15 days or normal water. Twenty-four hours after, their hearts were Langendorff-perfused and submitted to 60-min low-flow ischemia and reperfusion. The resveratrol-treated hearts showed better functional recovery at reperfusion and significant vasodilation, but no variation in high-energy phosphates (P-31 Nuclear Magnetic Resonance). N-G-nitro-L-arginine methyl ester (L-NAME, 30 muM), a nonselective nitric oxide synthase inhibitor, or SPT (50 muM) administered for 10 min prior to the low-flow ischemia cancelled the effects. This suggests that long-term moderate resveratrol consumption could play an important role in late cardioprotective effects. (C) 2003 Elsevier Science B.V. All rights reserved.