Resveratrol is a plant-derived phytoalexin with antioxidant, anti-inflammatory and cardio-protective properties and may be a promising therapeutic intervention strategy in cardiovascular disease. Here, we investigated the acute direct effects of trans-resveratrol (RV), on acetylcholine (ACh)-induced and flow-mediated dilation (FMD) of isolated pressurized femoral arteries of young (4-month-old) and old (26-month-old) mice. Vessel exposure to RV enhanced ACh (0.01-1.0 mM)-induced dilation (p < 0.05), but not FMD (@ 5-10 μL⋅min-1) (p < 0.05) in both young and old mice. After RV incubation, acute nitric oxide (NO) production by cultured endothelial cells was increased in response to 0.01 mM ACh, but reduced by flow (5-10 μL⋅min-1; p < 0.05). In isolated femoral arteries from endothelial nitric oxide synthase knockout (eNOS-/-) mice, RV had no overall effect on FMD, but potentiated ACh induced dilation, that was completely abolished by potassium channel blockers, Apamin and Tram 34 (p < 0.01). We demonstrate that the non-metabolised form of RV stimulates ACh-induced dilation via the NO and EDHF pathways, but not FMD by interaction with the cyclo-oxygenase pathway. Our findings have important implications in the use of RV (for both young and aged) under 'normal' non-diseased physiological states.

中文翻译：

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白藜芦醇对离体股动脉扩张反应的差异作用。

白藜芦醇是一种植物来源的植物抗毒素，具有抗氧化，抗炎和保护心脏的特性，可能是心血管疾病中一种有希望的治疗干预策略。在这里，我们研究了白藜芦醇（RV）对乙酰胆碱（ACh）诱导的和年轻的（4个月大）和年老的（26岁）的加压股动脉的血流介导的扩张（FMD）的急性直接影响。个月大）的小鼠。在年轻和老年小鼠中，暴露于RV的血管均增强了ACh（0.01-1.0 mM）诱导的扩张（p <0.05），但未增强FMD（@ 5-10μL⋅min-1）（p <0.05）。RV孵育后，对0.01 mM ACh的响应，培养的内皮细胞产生的急性一氧化氮（NO）产量增加​​，但流量降低（5-10μL⋅min-1; p <0.05）。在来自内皮一氧化氮合酶基因敲除（eNOS-/-）小鼠的股动脉中，RV对口蹄疫没有总体影响，但增强的ACh诱导的扩张被钾通道阻滞剂，Apamin和Tram 34完全消除（p <0.01）。我们证明RV的非代谢形式通过NO和EDHF途径刺激ACh诱导的扩张，但通过与环加氧酶途径的相互作用刺激FMD。我们的发现对在“正常”非疾病生理状态下使用RV（无论年龄大小）具有重要意义。