Diet supplementation with rice bran enzymatic extract restores endothelial impairment and wall remodelling of ApoE−/− mice microvessels

•RBEE diet supplementation reduced microvessel hypertrophy.•RBEE reduced microvessel stiffness by decreasing collagen content and stiffness.•RBEE reduced microvessel superoxide production.•RBEE improved endothelium impairment by reducing p-eNOSThr495 expression.•NO was the major responsible for vasorelaxation in ApoE−/− and EDHF in C57BL/6J mice.

Background and aimsSmall 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.MethodsSeven 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.ResultsApoE−/− 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.ConclusionRBEE supplemented diet reduced vessel remodeling and oxidative stress. Moreover, RBEE supplemented diet increased NO release by downregulating p-eNOSThr495, thus, protecting the endothelial function.

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