| RRC ID |
203
|
| 著者 |
Yuan Z, Nimata M, Okabe TA, Shioji K, Hasegawa K, Kita T, Kishimoto C.
|
| タイトル |
Olmesartan, a novel AT1 antagonist, suppresses cytotoxic myocardial injury in autoimmune heart failure.
|
| ジャーナル |
Am J Physiol Heart Circ Physiol
|
| Abstract |
Some ANG II receptor type 1 (AT(1)) antagonists are reported to inhibit proinflammatory cytokine production in vitro and in vivo. However, the effects of the drugs on autoimmune diseases are unknown. We tested the hypothesis that olmesartan, a novel AT(1) antagonist, ameliorated experimental autoimmune myocarditis (EAM) in rats attributed to the suppression of inflammatory cytokines as well as to the immunomodulatory action of the heart. We administered olmesartan orally at does of 1, 3, and 10 mg.kg(-1).day(-1) to rats with EAM for 3 wk. The results showed that olmesartan decreased blood pressure significantly compared with the untreated group and markedly reduced the severity of myocarditis associated with the decrease of myocardial macrophage, CD4(+), and CD8(+) T-cell expression by comparison of heart wt-to-body wt ratios, pericardial effusion scores, and macroscopic and microscopic scores. Numbers of myocardial interleukin-1beta (IL-1beta)-positive-staining cells (obtained by immunohistochemistry) and quantities of IL-1beta expression (obtained by Western blotting) were significantly lower in rats with EAM given olmesartan treatment compared with rats given vehicle. Cardiac myosin-specific, delayed-type hypersensitivity was significantly lower in olmesartan-treated rats than in control rats. The cytotoxic activities of lymphocytes in rats with EAM treated with olmesartan were reduced compared with untreated control rats. In vitro study showed that both olmesartan and its active metabolite RNH-6270 suppressed IL-1beta production in U-937 cells and cultured myocytes. Olmesartan ameliorates acute EAM in rats. The cardioprotection of olmesartan may be due to suppression of inflammatory cytokines as well as to suppressive effects of cytotoxic myocardial injury in addition to hemodynamic modifications.
|
| 巻・号 |
289(3)
|
| ページ |
H1147-52
|
| 公開日 |
2005-9-1
|
| DOI |
10.1152/ajpheart.00078.2005
|
| PII |
00078.2005
|
| PMID |
15879491
|
| MeSH |
Angiotensin II Type 1 Receptor Blockers / pharmacology*
Animals
Autoimmune Diseases / drug therapy*
Autoimmune Diseases / pathology
Blood Pressure / drug effects
Body Weight
Cardiomyopathies / drug therapy
Cardiomyopathies / immunology
Cardiomyopathies / pathology
Disease Models, Animal
Heart Failure / drug therapy*
Heart Failure / immunology
Heart Failure / pathology
Heart Rate / drug effects
Imidazoles / pharmacology*
Interleukin-1 / metabolism
Lymphocytes / drug effects
Lymphocytes / pathology
Myocarditis / drug therapy
Myocarditis / immunology
Myocarditis / pathology
Myocardium / metabolism
Myocardium / pathology
Myosins
Olmesartan Medoxomil
Organ Size
Rats
Rats, Inbred Lew
Receptor, Angiotensin, Type 1 / metabolism*
Tetrazoles / pharmacology*
|
| IF |
3.864
|
| 引用数 |
36
|
|
WOS 分野
|
CARDIAC & CARDIOVASCULAR SYSTEMS
PHYSIOLOGY
PERIPHERAL VASCULAR DISEASE
|
| リソース情報 |
| ラット |
|
