title: Diet supplementation with rice bran enzymatic extract restores endothelial impairment and wall remodelling of ApoE(-/-) mice microvessels.
abstract: Small mesenteric artery resistance and functionality are key factors for the maintenance of blood homeostasis. We attained to evaluate the effects of a rice bran enzymatic extract (RBEE) on structural, mechanic and myogenic alterations and endothelial dysfunction secondary to atherosclerosis disease.
  
  
  
  Seven week-old ApoE(-/-) mice were fed on standard (ST) or high fat (HF) diets supplemented or not with 1 or 5% RBEE (w/w) for 23 weeks. Wild-type C57BL/6J mice fed on ST diet served as controls. Small mesenteric arteries were mounted in a pressure myograph in order to evaluate structural, mechanical and myogenic properties. Vascular reactivity was assessed in the presence of different combinations of inhibitors: l-NAME, indometacin, apamin and charybdotoxin.
  
  
  
  ApoE(-/-) mice fed on ST and HF diets showed different structural and mechanical alterations, alleviated by RBEE supplementation of ST and HF diets. C57BL/6J was characterized by increased expression of IKCa (199.3%, p = 0.023) and SKCa (133.2%, p = 0.026), resulting in higher EDHF participation (p = 0.0001). However, NO release was more relevant to ApoE(-/-) mice vasodilatation. HF diet reduced the amount of NO released due to 2-fold increase of eNOS phosphorylation in the inhibitory residue Thr495 (p = 0.034), which was fully counteracted by RBEE supplementation (p = 0.028), restoring ACh-induced vasodilatation (p = 0.00006). Dihydroethidium fluorescence of superoxide and picrosirius red staining of collagen were reduced by RBEE supplementation of HF diet by 76.91% (p = 0.022) and 65.87% (p = 0.030), respectively.
  
  
  
  RBEE supplemented diet reduced vessel remodeling and oxidative stress. Moreover, RBEE supplemented diet increased NO release by downregulating p-eNOS(Thr495), thus, protecting the endothelial function.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, C/ Profesor Garcia-Gonzalez 2, 41012 Seville, Spain. Electronic address: cpternero@us.es.
authors.forename: Cristina
authors.initials: C
authors.lastname: Perez-Ternero
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, C/ Profesor Garcia-Gonzalez 2, 41012 Seville, Spain; Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, E-08195 Sant Cugat del Vallés, Barcelona, Spain.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Rodriguez-Rodriguez
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, C/ Profesor Garcia-Gonzalez 2, 41012 Seville, Spain.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Herrera
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, C/ Profesor Garcia-Gonzalez 2, 41012 Seville, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Alvarez de Sotomayor
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001158:Arteries / Q000378:metabolism; D018999:Charybdotoxin / Q000494:pharmacology; D003094:Collagen / Q000737:chemistry; D019587:Dietary Supplements; D004549:Elastin / Q000737:chemistry; D004730:Endothelium, Vascular / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE; D008833:Microcirculation; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000737:chemistry; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D012275:Oryza / Q000737:chemistry*; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D013481:Superoxides / Q000737:chemistry; D066253:Vascular Remodeling; D059289:Vascular Stiffness; D014664:Vasodilation
chemical_list: D013481:Superoxides; D018999:Charybdotoxin; D001030:Apamin; D009569:Nitric Oxide; D003094:Collagen; D004549:Elastin; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin
keywords: ApoE(−/−) mice; Mesenteric arteries; Rice bran enzymatic extract; Structural and mechanic properties; Vascular reactivity