Walnuts Reduce Aortic ET-1 mRNA Levels in Hamsters Fed a High-Fat, Atherogenic Diet
2006
Davis, Paul | Valacchi, Giuseppe | Pagnin, Elisa | Shao, Qiming | Gross, Heidrun B. | Calo, Lorenzo | Yokoyama, Wallace
Walnut consumption is associated with reduced coronary vascular disease (CVD) risk; however, the mechanisms responsible remain incompletely understood. Recent clinical studies suggested that these mechanisms involve nonplasma lipid-related effects on endothelial function. Male Golden Syrian hamsters (12 groups, n = 10-15) were fed for 26 wk atherosclerotic, high-fat, hyperlipidemic diets with increasing concentrations of whole walnuts (61-150 g/kg diet), or [alpha]-tocopherol ([alpha]-T, 8.1-81 mg/kg diet) and single diets with either walnut oil (32 g/kg diet) or pure [gamma]-tocopherol ([gamma]-T; 81 mg/kg diet) added. Aortic endothelin 1 (ET-1), an important endothelial regulator, was assayed as mRNA. Aortic cholesterol ester (CE) concentration along with other vascular stress markers (Cu/Zn and Mn superoxide dismutase, biliverdin reductase) and plasma lipid concentrations were determined. Hyperlipidemia (plasma LDL cholesterol [approximately]6 times normal) occurred in all groups. Aortic CE concentration, a measure of atherosclerotic plaque, was highest in the lowest [alpha]-T only group and declined significantly with increasing [alpha]-T. The aortic CE of all walnut groups was decreased significantly relative to the lowest [alpha]-T only group but showed no dose response. The diets did not produce changes in the other vascular stress markers, whereas aortic ET-1 mRNA levels declined dramatically with increasing dietary walnuts (to a 75% reduction in the highest walnut content group compared with the lowest [alpha]-T group) but were unaltered in the [alpha]-T groups or [gamma]-T group. The study results are consistent with those of human walnut feeding studies and suggest that the mechanisms underlying those results are mediated in part by ET-1-dependent mechanisms. The contrasting results between the [alpha]-tocopherol or [gamma]-tocopherol diets and the walnut diets also make it unlikely that the nonplasma lipid-related CVD effects of walnuts are due to their [alpha]-tocopherol or [gamma]-tocopherol content. Finally, the results indicate that the walnut fat compartment is a likely location for the components responsible for the reduced aortic CE concentration.
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