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.