Endothelium/nitric oxide mechanism mediates vasorelaxation and counteracts vasoconstriction induced by low concentration of flavanols
Endothelium/nitric oxide mechanism mediates vasorelaxation and counteracts vasoconstriction induced by low concentration of flavanols
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DOI：
10.1007/s00394-012-0320-x
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发表时间：
2013-02-01
影响因子：
5
通讯作者：
Ferri, Claudio
中科院分区：
文献类型：
--
作者：
Aggio, Annalisa;Grassi, Davide;Ferri, Claudio
在相对较低的浓度下，黄烷醇对孤立动脉张力的影响不一致，有时解释为由于结构-活性关系。本研究旨在探讨两种黄烷醇在不同剂量下对动脉功能状态的影响。研究了两种儿茶素(-)-表没食子儿茶素-3-没食子酸酯（EGCG）和(-)-表儿茶素（EP）对大鼠离体主动脉张力的影响，以及在内皮存在和不存在的情况下对静息张力和预收缩制剂的影响。在静息张力下，内皮完好的制剂，EGCG和EP (0.01-10 μ M)，诱导轻微的浓度依赖性，不显著收缩。在去内皮制剂中，EGCG和EP均诱导浓度依赖性收缩（两种化合物分别在0.1 μ M和1 μ M浓度下具有显著性）。在苯肾上腺素（PE） （1 μ M）预收缩、内皮完整的制剂中，EGCG和EP （0.01-10 μ M）诱导浓度依赖性血管松弛，两种激动剂浓度均为1 μ M时达到显著性。在去内皮制剂中，EGCG和EP对PE （0.3 μ M）诱导的张力无显著影响。在内皮完整预收缩制剂中，一氧化氮合酶（NOS）活性抑制剂N - ω -硝基-l-精氨酸（L-NNA）可消除EGCG和EP （0.01 ~ 10 μ M）的血管松弛作用。高浓度EGCG和EP （100 μ M）可引起明显的松弛。这在有内皮细胞或有L-NNA的情况下明显大于无内皮细胞或有L-NNA的情况下。我们的研究结果强调了内皮/ no机制在大鼠胸主动脉基底张力调节和介导血管松弛和对抗低浓度黄烷醇诱导的血管收缩中发挥的重要作用。
At relatively low concentrations, flavanols induce inconsistent effects on isolated arterial tone, sometimes explained as being due to a structure-activity relationship. The aim of our study was to investigate the effects of two flavanols at different doses on arterial functional state.The effects of two catechins, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin (EP), on rat-isolated aorta tone were investigated on resting tension and on precontracted preparations, both in the presence and in the absence of endothelium.At resting tension, endothelium-intact preparations, EGCG and EP (0.01-10 mu M), induced a slight concentration-dependent, non-significant contraction. On endothelium-denuded preparations, both EGCG and EP induced a concentration-dependent contraction (significance at 0.1 and 1 mu M concentrations of the two compounds, respectively). In phenylephrine (PE) (1 mu M) precontracted, endothelium-intact preparations, EGCG and EP (0.01-10 mu M), induced a concentration-dependent vasorelaxation, reaching significance at 1 mu M concentration of both agonists. On endothelium-denuded preparations, EGCG and EP did not significantly affect PE (0.3 mu M)-induced tone. In endothelium-intact precontracted preparations, N omega nitro-l-arginine (L-NNA), a nitric oxide synthase (NOS) activity inhibitor, abolished the vasorelaxant effect of EGCG and EP (0.01-10 mu M). At high concentrations, EGCG and EP (100 mu M) elicited a marked relaxation. This was significantly larger in the presence than in the absence of endothelium or in the presence of L-NNA.Our findings highlight the important role played by an endothelium/NO-mechanism in the regulation of basal tone and in both mediating vasorelaxation and counteracting vasoconstriction induced by low concentrations of flavanols in rat thoracic aorta.