Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats
Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats
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DOI：
10.1097/01.hjh.0000198029.22472.d9
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发表时间：
2006-01-01
影响因子：
4.9
通讯作者：
Duarte, J
中科院分区：
文献类型：
--
作者：
Sánchez, M;Galisteo, M;Duarte, J
背景与目的一些研究发现，在高血压动物模型中，长期服用黄酮类化合物槲皮素可降低血压并恢复内皮功能障碍。我们假设内皮型一氧化氮合酶（eNOS）的增加和/或烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶蛋白表达和活性的降低，槲皮素对自发性高血压大鼠（SHR）血管内皮功能的改善可能与活性氧的减少有关。（5周龄）用槲皮素（10 mg/kg）或媒介物处理13周。结果槲皮素能降低SHR血压和心率的升高，增强乙酰胆碱诱导的内皮依赖性主动脉血管舒张，并能抑制血管内皮细胞的增殖，抑制血管内皮细胞的凋亡，抑制血管内皮细胞的增殖，抑制血管内皮细胞的凋亡。但对硝普钠诱导的内皮非依赖性反应无影响。然而，槲皮素对内皮依赖性血管收缩和主动脉血栓素132的产生没有影响。与WKY相比，SHR的eNOS和p47（phox）蛋白表达上调，caveolin-1蛋白表达下调，NADPH诱导的超氧化物生成增加，但eNOS活性降低。慢性槲皮素治疗阻止了SHR的所有这些变化。在WKY，槲皮素对血压、内皮功能或蛋白质的表达或活性无影响。结论增强eNOS活性和减少NADPH氧化酶介导的超氧阴离子（O-2（-））产生以及减少p47（phox）表达可能是槲皮素改善内皮功能和抗高血压作用的重要机制。
Background and objective Several studies have found that chronic treatment with the dietary flavonoid quercetin lowers blood pressure and restores endothelial dysfunction in hypertensive animal models. We hypothesized that increased endothelial nitric oxide synthase (eNOS) and/or decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase protein expression and activity, and reduced reactive oxygen species might be involved in the improvement of endothelial function induced by quercetin in sponataneously hypertensive rats (SHR).Design and methods Male SHR and Wistar-Kyoto (WKY) rats (5 weeks old) were treated with quercetin (10 mg/kg) or vehicle for 13 weeks. Changes in vascular expression of eNOS, caveolin-1 and p47(phox) were analysed by Western blot, eNOS activity by conversion of [H-3]arginine to L-[H-3]citrulline, and NADPH oxidase activity by NADPH-enhanced chemoluminescence of lucigenin.Results In SHR, quercetin reduced the increase in blood pressure and heart rate and enhanced the endothelium-dependent aortic vasodilation induced by acetylcholine, but had no effect on the endothelium-independent response induced by nitroprusside. However, quercetin had no effect on endothelium-dependent vasoconstriction and aortic thromboxane 132 production. Compared to WKY, SHR showed upregulated eNOS and p47(phox) protein expression, downregulated caveolin-1 expression, increased NADPH-induced superoxide production but, paradoxically, eNOS activity was reduced. Chronic quercetin treatment prevented all these changes in SHR. In WKY, quercetin had no effect on blood pressure, endothelial function or the expression or activity of the proteins analysed.Conclusions Enhanced eNOS activity and decreased NADPH oxidase-mediated superoxide anion (O-2(-)) generation associated with reduced p47(phox) expression appear to be essential mechanisms for the improvement of endothelial function and the anti hypertensive effects of chronic quercetin.