title: Mineralocorticoid receptor blockade inhibits accelerated atherosclerosis induced by a low sodium diet in apolipoprotein E-deficient mice.
abstract: BACKGROUND
  A low-sodium diet (LSD) was shown to increase both angiotensin II (AngII) and aldosterone levels, and to accelerate atherosclerosis in apolipoprotein E-deficient (E0) mice. The aim of the present study was to examine whether accelerated atherosclerosis in E0 mice fed a LSD is mediated by aldosterone, using the mineralocorticoid receptor blocker, eplerenone (Epl).
  
  
  RESULTS
  Mice were divided into three groups: normal diet (ND), LSD and LSD treated with Epl at 100 mg/kg per day (LSD+Epl) for 10 weeks. LSD significantly enhanced plasma renin and aldosterone levels, which were further increased in mice fed LSD+Epl. The aortic lesion area increased three-fold with LSD, while LSD+Epl significantly reduced the lesion area to values similar to ND. Serum and peritoneal macrophages obtained from LSD-fed mice exhibited pro-atherogenic properties including increased inflammation, oxidation and cholesterol accumulation, which were inhibited in mice fed LSD+Epl. In a J774A.1 macrophage-like cell line stimulated with lipopolysaccharide, Epl was shown to have a direct anti-inflammatory effect.
  
  
  CONCLUSIONS
  In E0 mice, Epl inhibited LSD-accelerated atherosclerosis, despite the elevation of renin and aldosterone levels. It is therefore suggested that the atherogenic action of LSD could be mediated, at least in part, by activation of the mineralocorticoid receptor. In addition, eplerenone may have direct anti-inflammatory actions.
authors.affiliation: Lipid Research Laboratory, Technion - Israel Institute of Technology, Haifa, Israel Rambam Medical Center, Haifa, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Raz-Pasteur
authors.affiliation: Lipid Research Laboratory, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Aviva
authors.initials: A
authors.lastname: Gamliel-Lazarovich
authors.affiliation: Lipid Research Laboratory, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Gantman
authors.affiliation: Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Raymond
authors.initials: R
authors.lastname: Coleman
authors.affiliation: Lipid Research Laboratory, Technion - Israel Institute of Technology, Haifa, Israel Rambam Medical Center, Haifa, Israel skeidar@rambam.health.gov.il.
authors.forename: Shlomo
authors.initials: S
authors.lastname: Keidar
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D015415:Biomarkers / Q000097:blood; D004039:Diet, Sodium-Restricted; D000077545:Eplerenone; D006801:Humans; D007249:Inflammation / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D012083:Renin