title: Olmesartan protects endothelial cells against oxidative stress-mediated cellular injury.
abstract: BACKGROUND
  The primary cause of death of hemodialysis (HD) patients is cardiovascular disease, and increased oxidative stress has been proposed to be involved in the disease pathogenesis. In this study, we examined the effect of olmesartan on oxidative stress induced by angiotensin II, lipopolysaccharide, indoxyl sulfate, advanced oxidation protein products (AOPP) or hydrogen peroxide (H2O2), which are known to be present at higher concentrations in the blood of HD patients, using human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  Oxidative stress was evaluated by measuring the mean fluorescence intensity of CM-H2DCFCA, an ROS-sensitive fluorescent dye, in HUVECs. HUVECs were incubated with each of the above compounds in the presence or absence of olmesartan. Moreover, these oxidant-stimulated cells were also treated with the reactive oxygen species (ROS) inhibitor N-acetyl-cysteine (NAC), NADPH oxidase inhibitor diphenylene iodonium (DPI) or PKC inhibitor calphostin C. In addition, we investigated the effects of olmesartan on cytotoxicity and vascular endothelial growth factor (VEGF) secretion, which is involved in vascular inflammation in HUVECs induced by AOPP or H2O2.
  
  
  RESULTS
  The treatment of these oxidant-stimulated cells with olmesartan resulted in a significant reduction in intracellular ROS production to an extent that was nearly equivalent to that of NAC, DPI or calphostin C. Furthermore, olmesartan reduced the cytotoxicity and VEGF secretion induced by AOPP or H2O2.
  
  
  CONCLUSIONS
  These results demonstrated that the antioxidant activity of olmesartan might contribute to both its vasculoprotective and anti-hypertensive effects.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.|Center for Clinical Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Japan.|Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kadowaki
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto, 860-0082, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Anraku
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.
authors.forename: Moe
authors.initials: M
authors.lastname: Sakaya
authors.affiliation: Center for Clinical Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Japan.|Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Hirata
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan. tomaru@gpo.kumamoto-u.ac.jp.|Center for Clinical Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Japan. tomaru@gpo.kumamoto-u.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto, 860-0082, Japan. otagirim@ph.sojo-u.ac.jp.|DDS Research Institute, Sojo University, 4-22-1 Ikeda, Kumamoto, 860-0082, Japan. otagirim@ph.sojo-u.ac.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D007093:Imidazoles; D016877:Oxidants; D017382:Reactive Oxygen Species; D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; C437965:olmesartan; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D011493:Protein Kinase C
keywords: Antioxidant; Endothelial cell; Hemodialysis; Olmesartan; Oxidative stress