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Walnuts reduce aortic ET-1 mRNA levels in hamsters fed a high-fat, atherogenic diet

Davis, P., G. Valacchi, E. Pagnin, Q. Shao, H.B. Gross, L. Calo, W. Yokoyama, 2006.  Walnuts reduce aortic ET-1 mRNA levels in hamsters fed a high-fat, atherogenic diet. J.  Nutr. 136(2):428-32

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 ý 10ý15) were fed for 26 wk atherosclerotic, high-fat, hyperlipidemic diets with increasing concentrations of whole walnuts (61ý150 g/kg diet), or a-tocopherol (a-T, 8.1ý81 mg/kg diet) and single diets with either walnut oil (32 g/kg diet) or pure g-tocopherol (g-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 ;6 times normal) occurred in all groups. Aortic CE concentration, a measure of atherosclerotic plaque, was highest in the lowest a-T only group and declined significantly with increasing a-T. The aortic CE of all walnut groups was decreased significantly relative to the lowest a-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 a-T group) but were unaltered in the a-T groups or g-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-1ýdependent mechanisms. The contrasting results between the a-tocopherol or g-tocopherol diets and the walnut diets also make it unlikely that the nonplasma lipid related CVD effects of walnuts are due to their a-tocopherol or g-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. This study was designed to determine the mechanisms behind walnuts’ ability to reduce coronary vascular disease risk. Male Golden Syrian hamsters fed high-fat, hyperlipidemic diets supplemented with either walnuts; alpha-tocopherol, a form of vitamin E; walnut oil; or gamma-tocopherol, the form of vitamin E found in walnuts. Hamsters fed the walnut supplemented diet had the greatest reduction in aortic endothelin, an endothelial cell regulator, and the lowest concentration of aortic cholesterol ester, a measure of arterial plaque development.