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Telmisartan ameliorates experimental autoimmune myocarditis associated with inhibition of inflammation and oxidative stress.

Abstract：

:Excess cytokine produced by inflammatory stimuli contributes to the progression of myocardial damage in myocarditis. Angiotensin-II has been shown to play a pivotal role in the pathophysiology of various organs, especially the cardiovascular system. Some angiotensin II type 1 receptor antagonists are reported to inhibit proinflammatory cytokine production in vitro and in vivo. We investigated whether telmisartan, an angiotensin II type 1 receptor antagonist protects against experimental autoimmune myocarditis by suppression of inflammatory cytokines and oxidative stress. Experimental autoimmune myocarditis was induced in Lewis rats by immunization with porcine cardiac myosin. The rats were divided into two groups and treated with either telmisartan (10mg/kg/day) or vehicle for 21days. Age-matched normal rats without immunization were also included in this study. Myocardial functional parameters were significantly improved by treatment with telmisartan compared with vehicle-treated rats. Increased myocardial mRNA expressions of inflammatory cytokines [interleukin (IL-6), IL-1β, tumor necrosis factor-α and interferon-γ] were also suppressed by telmisartan treatment compared with vehicle-treated rats. Myocardial protein expressions of NADPH oxidase subunits p47phox, Nox-4, and gp91phox, myocardial levels of 8-hydroxydeoxyguanosine and 4-hydroxy-2-nonenal, and myocardial apoptosis were also significantly decreased by telmisartan treatment compared with vehicle-treated rats. Further, telmisartan significantly decreased endoplasmic reticulum stress markers in experimental autoimmune myocarditis rats. These findings suggest that telmisartan protects against experimental autoimmune myocarditis in rats, at least in part by suppressing inflammatory cytokines and oxidative stress; however, further investigations are needed before clinical use.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Sukumaran V,Watanabe K,Veeraveedu PT,Ma M,Gurusamy N,Rajavel V,Suzuki K,Yamaguchi K,Kodama M,Aizawa Y

doi

10.1016/j.ejphar.2010.10.081

subject

Has Abstract

pub_date

2011-02-10 00:00:00

pages

126-35

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(10)01132-5

journal_volume

652

pub_type

杂志文章

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