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

Abstract

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 α-tocopherol (α-T, 8.1-81 mg/kg diet) and single diets with either walnut oil (32 g/kg diet) or pure γ-tocopherol (γ-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 α-T only group and declined significantly with increasing α-T. The aortic CE of all walnut groups was decreased significantly relative to the lowest α-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 α-T group) but were unaltered in the α-T groups or γ-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 α-tocopherol or γ-tocopherol diets and the walnut diets also make it unlikely that the nonplasma lipid-related CVD effects of walnuts are due to their α-tocopherol or γ-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. © 2006 American Society for Nutrition.