Resveratrol, a component of red wine, elicits dilation of isolated porcine retinal arterioles: Role of nitric oxide and potassium channels
Resveratrol, a component of red wine, elicits dilation of isolated porcine retinal arterioles: Role of nitric oxide and potassium channels
复制标题
DOI：
10.1167/iovs.07-0094
复制
发表时间：
2007-09-01
影响因子：
4.4
通讯作者：
Kuo, Lih
中科院分区：
文献类型：
--
作者：
Nagaoka, Taiji;Hein, Travis W.;Kuo, Lih
目的.白藜芦醇是一种在葡萄和红葡萄酒中发现的多酚植物抗毒素，已被证明对心血管有益，但其在视网膜微循环中的作用仍不清楚。在这项研究中，白藜芦醇的血管扩张作用的直接影响和潜在的机制进行了检查在视网膜小动脉。分离猪视网膜小动脉，插管，加压，无流动，用于体外研究。通过视频显微镜技术记录白藜芦醇诱导的直径变化。视网膜小动脉（65 +/- 3 μ m）响应白藜芦醇（1-50 μ M）而剂量依赖性地扩张。去除内皮使这种扩张减少了50%。抑制一氧化氮（NO）合酶（通过L-NAME; N-G-硝基-L-精氨酸甲酯）和阻断可溶性鸟苷酸环化酶（通过ODQ; 1H-1，2，4-恶二唑并[4，3-a]喹喔啉-1-酮）产生的抑制作用与剥蚀产生的抑制作用相似。然而，白藜芦醇的反应不受吲哚美辛（环氧合酶抑制剂）和磺胺苯吡唑（环氧合酶抑制剂）。腔内给药细胞外信号调节激酶（ERK）抑制剂（PD 98059），但不是雌激素受体阻滞剂（ICI 182780），也减少了50%的血管舒张。非选择性K+通道阻滞剂，四乙基铵（TEA），和大电导钙激活的K+（BKCa）通道抑制剂，伊比利亚毒素，产生相同的抑制白藜芦醇诱导的扩张。然而，这种扩张对ATP敏感性K+通道和电压门控性K（+）通道抑制剂不敏感。L-NAME和伊比利亚毒素联合应用几乎完全消除白藜芦醇引起的血管舒张作用。白藜芦醇抑制视网膜小动脉内皮依赖性和非内皮依赖性扩张。内皮依赖性扩张是由释放的NO介导的，可能是通过ERK途径激活NO合酶（NOS）和随后激活可溶性鸟苷酸环化酶。平滑肌中BKCa通道的激活有助于白藜芦醇引起的非内皮依赖性舒张。更好地了解白藜芦醇对视网膜血管系统的作用可能有助于揭示其对视网膜血管疾病的治疗潜力。
PURPOSE. Resveratrol, a polyphenolic phytoalexin found in grapes and red wine, has been shown to exert cardiovascular benefits, but its action in the retinal microcirculation remains unknown. In this study, the direct effect and the underlying mechanism of the vasomotor action of resveratrol were examined in retinal arterioles.METHODS. Porcine retinal arterioles were isolated, cannulated, and pressurized without flow for in vitro study. Resveratrolinduced diameter changes were recorded by videomicroscopic techniques.RESULTS. Retinal arterioles (65 +/- 3 mu m) dilated dose dependently in response to resveratrol (1-50 mu M). The removal of the endothelium reduced this dilation by 50%. Inhibition of nitric oxide (NO) synthase (by L-NAME; N-G-nitro-L-arginine methyl ester) and blockade of soluble guanylyl cyclase (by ODQ; 1H-1,2,4-oxadiazolo[4,3-a]quinoxalin-1-one) produced similar inhibition as that produced by denudation. However, the resveratrol response was not affected by indomethacin (a cyclooxygenase inhibitor) and sulfaphenazole (an epoxygenase inhibitor). Intraluminal administration of an extracellular signal-regulated kinase (ERK) inhibitor (PD98059), but not an estrogen receptor blocker (ICI 182780), also reduced vasodilation by 50%. A nonselective K+ channel blocker, tetraethylammonium (TEA), and a large-conductance Ca2+ -activated K+(BKCa) channel inhibitor, iberiotoxin, produced identical inhibition of resveratrol-induced dilation. However, the dilation was insensitive to the inhibitors of ATP-sensitive K+ channels and voltage-gated K (+) channels. Coadministration of L-NAME and iberiotoxin almost abolished the vasodilation induced by resveratrol.CONCLUSIONS. Resveratrol elicits endothelium-dependent and - independent dilation of retinal arterioles. Endothelium-dependent dilation is mediated by the released NO, probably via NO synthase ( NOS) activation by the ERK pathway and the subsequent activation of soluble guanylyl cyclase. The activation of BKCa channels in smooth muscle contributes to the endothelium-independent dilation caused by resveratrol. A better understanding of the action of resveratrol on retinal vasculature may help shed light on its therapeutic potential for retinal vascular disease.