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Olmesartan protects endothelial cells against oxidative stress-mediated cellular injury

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Clinical and Experimental Nephrology Aims and scope Submit manuscript

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.

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Conflict of interest

All of the authors have declared that there are no competing interests.

Author information

Authors and Affiliations

  1. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan

    Daisuke Kadowaki, Moe Sakaya & Toru Maruyama

  2. Center for Clinical Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Japan

    Daisuke Kadowaki, Sumio Hirata & Toru Maruyama

  3. Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Japan

    Daisuke Kadowaki & Sumio Hirata

  4. Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto, 860-0082, Japan

    Makoto Anraku & Masaki Otagiri

  5. DDS Research Institute, Sojo University, 4-22-1 Ikeda, Kumamoto, 860-0082, Japan

    Masaki Otagiri

Authors
  1. Daisuke Kadowaki
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  2. Makoto Anraku
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  3. Moe Sakaya
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  4. Sumio Hirata
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  5. Toru Maruyama
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  6. Masaki Otagiri
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Corresponding authors

Correspondence to Toru Maruyama or Masaki Otagiri.

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Kadowaki, D., Anraku, M., Sakaya, M. et al. Olmesartan protects endothelial cells against oxidative stress-mediated cellular injury. Clin Exp Nephrol 19, 1007–1014 (2015). https://doi.org/10.1007/s10157-015-1111-5

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  • DOI: https://doi.org/10.1007/s10157-015-1111-5

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