title: Olmesartan, a novel angiotensin II type 1 receptor antagonist, reduces severity of atherosclerosis in apolipoprotein E deficient mice associated with reducing superoxide production.
abstract: OBJECTIVE
  Oxidative stress may play an important role in the development of atherosclerosis. Some angiotensin II type 1 (AT(1)) receptor antagonists have the capacity of reducing oxidative stress in addition to the hemodynamic actions. Accordingly, we assessed the hypothesis that olmesartan, a novel AT(1) receptor antagonist, reduced the severity of atherosclerosis in apolipoprotein (apo) E-deficient mice associated with reducing oxidative stress.
  
  
  RESULTS
  Atherosclerosis was induced in apo E-deficient mice fed a high fat diet. Mice were intraperitoneally treated with an injection of olmesartan (1mg/kg/day) daily over 8 weeks, and were compared with the untreated controls. Blood pressure was not changed significantly by the olmesartan treatment. Fatty streak plaque developed in apo E-deficient mice, and was suppressed in mice that received olmesartan. In addition, olmesartan reduced not only superoxide production but the overload of oxidative stress in aortic walls. There were no significant differences in serum lipid levels between olmesartan-treated and -untreated groups. In vitro study showed that both olmesartan and its active metabolite RNH-6270, an enantiomer of olmesartan, suppressed interferon-γ, macrophage inflammatory protein-2, and thioredoxin (a marker of oxidative stress) concentrations in cultured cells.
  
  
  CONCLUSIONS
  Olmesartan may suppress atherosclerosis via reducing not only superoxide production but also the overload of oxidative stress in this animal model.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shimada
authors.forename: T
authors.initials: T
authors.lastname: Murayama
authors.forename: M
authors.initials: M
authors.lastname: Yokode
authors.forename: T
authors.initials: T
authors.lastname: Kita
authors.forename: M
authors.initials: M
authors.lastname: Fujita
authors.forename: C
authors.initials: C
authors.lastname: Kishimoto
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000037:antagonists & inhibitors / Q000097:blood; D007093:Imidazoles / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology*; D013879:Thioredoxins / Q000037:antagonists & inhibitors / Q000097:blood
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001057:Apolipoproteins E; D015415:Biomarkers; D054426:Chemokine CXCL2; D007093:Imidazoles; D013777:Tetrazoles; D013481:Superoxides; D013879:Thioredoxins; D007371:Interferon-gamma; C437965:olmesartan