title: 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 non-plasma 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 non-plasma 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.
authors.affiliation: Department of Nutrition, University of California, Davis, CA 95616, USA. padavis@ucdavis.edu
authors.forename: Paul
authors.initials: P
authors.lastname: Davis
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valacchi
authors.forename: Elisa
authors.initials: E
authors.lastname: Pagnin
authors.forename: Qiming
authors.initials: Q
authors.lastname: Shao
authors.forename: Heidrun B
authors.initials: HB
authors.lastname: Gross
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Calo
authors.forename: Wallace
authors.initials: W
authors.lastname: Yokoyama
mesh_terms: D000821:Animal Feed; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002788:Cholesterol Esters / Q000097:blood; D006224:Cricetinae; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000494:pharmacology*; D019332:Endothelin-1 / Q000235:genetics*; D031324:Juglans / Q000737:chemistry*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008647:Mesocricetus; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D002788:Cholesterol Esters; D004041:Dietary Fats; D019332:Endothelin-1; D008074:Lipoproteins; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase