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Clinical and Experimental Nephrology
Published in: Clinical and Experimental Nephrology 6/2015

01-12-2015 | Original Article

Olmesartan protects endothelial cells against oxidative stress-mediated cellular injury

Authors: Daisuke Kadowaki, Makoto Anraku, Moe Sakaya, Sumio Hirata, Toru Maruyama, Masaki Otagiri

Published in: Clinical and Experimental Nephrology | Issue 6/2015

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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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Metadata
Title
Olmesartan protects endothelial cells against oxidative stress-mediated cellular injury
Authors
Daisuke Kadowaki
Makoto Anraku
Moe Sakaya
Sumio Hirata
Toru Maruyama
Masaki Otagiri
Publication date
01-12-2015
Publisher
Springer Japan
Published in
Clinical and Experimental Nephrology / Issue 6/2015
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-015-1111-5

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