Olmesartan, an AT1 antagonist, attenuates oxidative stress, endoplasmic reticulum stress and cardiac inflammatory mediators in rats with heart failure induced by experimental autoimmune myocarditis

Vijayakumar Sukumaran, Kenichi Watanabe, Punniyakoti T. Veeraveedu, Narasimman Gurusamy, Meilei Ma, Rajarajan A. Thandavarayan, Arun Lakshmanan, Ken'ichi Yamaguchi, Kenji Suzuki, Makoto Kodama

Research output: Contribution to journalArticle

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Abstract

Studies have demonstrated that angiotensin II has been involved in immune and inflammatory responses which might contribute to the pathogenesis of immune-mediated diseases. Recent evidence suggests that oxidative stress may play a role in myocarditis. Here, we investigated whether olmesartan, an AT1R antagonist protects against experimental autoimmune myocarditis (EAM) by suppression of oxidative stress, endoplasmic reticulum (ER) stress and inflammatory cytokines. EAM was induced in Lewis rats by immunization with porcine cardiac myosin, were divided into two groups and treated with either olmesartan (10 mg/kg/day) or vehicle for a period of 21 days. Myocardial functional parameters measured by hemodynamic and echocardiographic analyses were significantly improved by the treatment with olmesartan compared with those of vehicle-treated rats. Treatment with olmesartan attenuated the myocardial mRNA expressions of proinflammatory cytokines, [Interleukin (IL)-1β, monocyte chemoattractant protein-1, tumor necrosis factor-α and interferon-γ)] and the protein expression of tumor necrosis factor-α compared with that of vehicle-treated rats. Myocardial protein expressions of AT1R, NADPH oxidase subunits (p47phox, p67phox, gp91phox) and the expression of markers of oxidative stress (3-nitrotyrosine and 4-hydroxy-2-nonenal), and the cardiac apoptosis were also significantly de creased by the treatment with olmesartan compared with those of vehicle-treated rats. Fur-thermore, olmesartan treatment down-regulated the myocardial expressions of glucose regulated protein-78, growth arrest and DNA damage-inducible gene, caspase-12, phospho-p38 mito-gen-activated protein kinase (MAPK) and phospho-JNK. These findings suggest that olmesartan protects against EAM in rats, at least in part via suppression of oxidative stress, ER stress and in-flammatory cytokines.

Original languageEnglish
Pages (from-to)154-157
Number of pages4
JournalInternational Journal of Biological Sciences
Volume7
Issue number2
Publication statusPublished - 15 Mar 2011
Externally publishedYes

Fingerprint

myocarditis
Endoplasmic Reticulum Stress
Myocarditis
heart failure
endoplasmic reticulum
antagonists
Oxidative Stress
oxidative stress
Heart Failure
protein
rats
cytokines
tumor necrosis factors
tumor
caspase-12
protein synthesis
Cytokines
immunization
angiotensin II
Tumor Necrosis Factor-alpha

Keywords

  • Endoplasmic reticulum stress
  • Experimental autoimmune myocarditis
  • Inflammation
  • Olmesartan
  • Oxidative stress

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology

Cite this

Olmesartan, an AT1 antagonist, attenuates oxidative stress, endoplasmic reticulum stress and cardiac inflammatory mediators in rats with heart failure induced by experimental autoimmune myocarditis. / Sukumaran, Vijayakumar; Watanabe, Kenichi; Veeraveedu, Punniyakoti T.; Gurusamy, Narasimman; Ma, Meilei; Thandavarayan, Rajarajan A.; Lakshmanan, Arun; Yamaguchi, Ken'ichi; Suzuki, Kenji; Kodama, Makoto.

In: International Journal of Biological Sciences, Vol. 7, No. 2, 15.03.2011, p. 154-157.

Research output: Contribution to journalArticle

Sukumaran, Vijayakumar ; Watanabe, Kenichi ; Veeraveedu, Punniyakoti T. ; Gurusamy, Narasimman ; Ma, Meilei ; Thandavarayan, Rajarajan A. ; Lakshmanan, Arun ; Yamaguchi, Ken'ichi ; Suzuki, Kenji ; Kodama, Makoto. / Olmesartan, an AT1 antagonist, attenuates oxidative stress, endoplasmic reticulum stress and cardiac inflammatory mediators in rats with heart failure induced by experimental autoimmune myocarditis. In: International Journal of Biological Sciences. 2011 ; Vol. 7, No. 2. pp. 154-157.
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