Beneficial effects of olmesartan, a novel angiotensin II receptor type 1 antagonist, upon acute autoimmune myocarditis

Excess amount of cytokine produced by inflammatory stimuli contributes to the progression of myocardial damage in myocarditis. Some angiotensin II receptor type 1 antagonists are reported to inhibit proinflammatory cytokine production in vitro and in vivo. We tested the hypothesis that olmesartan, a...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 2004-04, Vol.259 (1-2), p.217-222
Main Authors: Nimata, Masaomi, Kishimoto, Chiharu, Yuan, Zuyi, Shioji, Keisuke
Format: Article
Language:English
Subjects:
Administration, Oral
Angiotensin II receptors
Angiotensin II Type 1 Receptor Blockers - administration & dosage
Animals
Antihypertensive Agents - administration & dosage
Autoimmune Diseases - chemically induced
Autoimmune Diseases - immunology
Blood pressure
Body weight
Cytokines
Dose-Response Relationship, Drug
Female
Imidazoles - administration & dosage
Interleukin-1 - biosynthesis
Male
Myocarditis - chemically induced
Myocarditis - drug therapy
Myocarditis - immunology
Myocarditis - metabolism
Myocarditis - pathology
Myocardium - metabolism
Myocardium - pathology
Myosins - administration & dosage
Myosins - immunology
Olmesartan Medoxomil
Rats
Rats, Inbred Lew
Receptor, Angiotensin, Type 1 - immunology
Rodents
Swine
Tetrazoles - administration & dosage
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Summary:Excess amount of cytokine produced by inflammatory stimuli contributes to the progression of myocardial damage in myocarditis. Some angiotensin II receptor type 1 antagonists are reported to inhibit proinflammatory cytokine production in vitro and in vivo. We tested the hypothesis that olmesartan, a novel angiotensin II receptor type 1 antagonist, ameliorated experimental autoimmune myocarditis (EAM) in rats attributing to the suppression of inflammatory cytokines in the heart. We orally administered olmesartan 1, 3, and 10 mg/kg/day to rats with EAM for 3 weeks. The results showed that olmesartan decreased blood pressure significantly compared with the untreated group, but markedly reduced the severity of myocarditis by comparing the heart weight/body weight ratio, pericardial effusion scores, macroscopic scores and microscopic scores. Myocardial interleukin (IL)- 1beta expression by western blotting and IL-1beta-positive staining cells by immunohistochemistry were significantly lower in rats with EAM given olmesartan treatment compared with those of rats given vehicle. We conclude that Olmesartan ameliorates acute EAM in rats. The cardioprotection of olmesartan may be due to suppression of inflammatory cytokines dependent of the hemodynamic modifications.
ISSN:0300-8177
1573-4919
DOI:10.1023/B:MCBI.0000021379.82282.53