γ‐Tocopherol supplementation attenuates arterial dysfunction in db/db mice (260.8)

γ‐Tocopherol (γ‐T) prevents endothelial dysfunction evoked by acute hyperglycemia. We hypothesized that γ‐T supplementation would attenuate arterial dysfunction induced by chronic hyperglycemia. Wild‐type (WT) mice were fed a diet with no γ‐T and db/db mice were fed 0 or 500 mg/kg γ‐T for 8 wk. Db/db mice had higher (p<0.05) plasma glucose and liver malondialdehyde (MDA) vs. WT animals. Compared to db/db controls, db/db mice fed γ‐T had higher (p<0.05) plasma γ‐T and hepatic levels of its metabolite γ‐carboxyethyl‐hydroxychroman (γ‐CEHC), and reduced (p<0.05) hepatic MDA, while plasma glucose was similar between groups. Relaxation to acetylcholine in precontracted femoral arteries was impaired in db/db controls vs. WT animals, and γ‐T reduced the severity of impairment in db/db mice. Arterial responses to sodium nitroprusside were similar among groups. p‐eNOSS1177 / total eNOS was lower (p<0.05) in arteries from db/db controls vs. WT and db/db mice fed γ‐T. In human aortic endothelial cells exposed (24 h) to 25 mM glucose, 3 µM γ‐CEHC prevented (p<0.05) glucose‐induced increases in reactive oxygen species, and decreases in p‐eNOSS1177 / total eNOS and nitrates + nitrites. These data suggest that γ‐T, either directly and/or indirectly through γ‐CEHC, protects against arterial dysfunction evoked by chronic hyperglycemia, potentially by lowering oxidative stress and improving NO bioavailability. Grant Funding Source : UU‐VPR‐0981