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Nutrition and Disease

Walnuts Reduce Aortic ET-1 mRNA Levels in Hamsters Fed a High-Fat, Atherogenic Diet^1,2

Paul Davis^*,3, Giuseppe Valacchi, Elisa Pagnin^**, Qiming Shao, Heidrun B. Gross^*, Lorenzo Calo^** and Wallace Yokoyama

^* Department of Nutrition and Department of Internal Medicine, University of California, Davis, Davis, CA 95616; ^** Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, 35128 Padova, Italy; and Western Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Albany, CA, 94710

³ To whom correspondence should be addressed. E-mail: padavis{at}ucdavis.edu.

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

KEY WORDS: • walnuts • endothelin • hamsters • tocopherol • atherosclerosis

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