McCarty Mark F
NutriGuard Research, 1051 Hermes Ave., Encinitas, CA 92024, United States.
Med Hypotheses. 2007;69(6):1367-70. doi: 10.1016/j.mehy.2004.11.050. Epub 2007 Sep 6.
Oxidation of tetrahydrobiopterin by peroxynitrite in oxidant-stressed endothelium compromises nitric oxide synthase (eNOS) activity while amplifying superoxide production; this mechanism contributes prominently to the endothelial dysfunction that characterizes many common clinical disorders. As a physiological peroxynitrite scavenger, gamma-tocopherol may have the potential to protect tetrahydrobiopterin and thus preserve effective eNOS activity. Indeed, in clinical studies, supplemental gamma-tocopherol has enhanced platelet eNOS activity, and a diet high in gamma-tocopherol-rich walnuts has improved endothelium-dependent vasodilation in hypercholesterolemia. In rodents, gamma-tocopherol is reported to increase arterial expression of eNOS while up-regulating an activating phosphorylation of this enzyme. Although epidemiological efforts to link gamma-tocopherol status with coronary risk have yielded inconsistent findings, this does not rule out the possibility that high intakes of this antioxidant could provide clinical protection. The impact of supplemental gamma-tocopherol on compromised endothelium-dependent vasodilation in various disorders merits examination.
在氧化应激的内皮细胞中，过氧亚硝酸盐可氧化四氢生物蝶呤，损害一氧化氮合酶（eNOS）活性，同时增加超氧化物的生成；这一机制在许多常见临床疾病所特有的内皮功能障碍中起主要作用。作为一种生理性过氧亚硝酸盐清除剂，γ-生育酚可能具有保护四氢生物蝶呤从而维持有效eNOS活性的潜力。事实上，在临床研究中，补充γ-生育酚可增强血小板eNOS活性，富含γ-生育酚的核桃含量高的饮食可改善高胆固醇血症患者的内皮依赖性血管舒张功能。在啮齿动物中，据报道γ-生育酚可增加动脉中eNOS的表达，同时上调该酶的激活磷酸化。尽管将γ-生育酚状态与冠心病风险联系起来的流行病学研究结果并不一致，但这并不排除高剂量摄入这种抗氧化剂可能提供临床保护的可能性。补充γ-生育酚对各种疾病中受损的内皮依赖性血管舒张功能的影响值得研究。
