TY - JOUR
T1 - Beneficial effects of olmesartan, an angiotensin II receptor type 1 antagonist, in rats with dilated cardiomyopathy
AU - Sukumaran, Vijayakumar
AU - Watanabe, Kenichi
AU - Veeraveedu, Punniyakoti T.
AU - Thandavarayan, Rajarajan A.
AU - Gurusamy, Narasimman
AU - Meilei, Ma
AU - Yamaguchi, Ken'ichi
AU - Suzuki, Kenji
AU - Kodama, Makoto
AU - Aizawa, Yoshifusa
N1 - Funding Information:
This research was supported by a Yujin Memorial Grant, Ministry of Education, Culture, Sports, Science and Technology, Japan, and by a grant from the Promotion and Mutual Aid Corporation for Private Schools, Japan. We thank Wawaimuli Arozal, Flori Ratna Sari, Hiroko Shimazaki, Sayaka Egawa, Fuji Tomohiko, Kana Kawadura, Yoshiyasu Kobayashi and Yuhki for their assistance in this research work. We also express our sincere gratitude to Dr Masaki Nagata (Division of Oral and Maxillofacial Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan) for help with the RT-PCR analysis in this study.
PY - 2010/11
Y1 - 2010/11
N2 - Favorable effects of angiotensin II type 1 receptor blockers on patients with ischemic or idiopathic dilated cardiomyopathy (DCM) have already been suggested by several human trials, but their effects on DCM remain unknown. Hence, we investigated the effect of olmesartan on myocardial remodeling in a rat model in which myosin-induced experimental autoimmune myocarditis (EAM) might develop into DCM. EAM was elicited in Lewis rats by immunization with cardiac myosin, and 28 d after immunization, the surviving Lewis rats were divided into two groups and treated with either olmesartan (10 mg/kg/d) or vehicle. Age-matched normal rats without immunizations were also used. After four weeks of treatment, we investigated the effects of olmesartan on cardiac function, inflammatory cytokines and cardiac remodeling in EAM rats. Myocardial functional parameters measured by hemodynamic and echocardiographic analyses were significantly improved by the treatment with olmesartan compared with those of vehicle-treated rats. Olmesartan significantly reduced cardiac fibrosis as well as hypertrophy and its molecular markers (left ventricular [LV] mRNA expressions of transforming growth factor beta1, collagen-I and -III, and atrial natriuretic peptide) compared with those of vehicle-treated rats. Increased myocardial mRNA expressions of proinflammatory cytokines (interleukin [IL]-6, IL-1β), monocyte chemoattractant protein-1 and matrix metalloproteinases (MMP-2 and -9) were also suppressed by the treatment with olmesartan in rats with DCM. Further, the plasma level of angiotensin II was significantly increased in olmesartan-treated rats. These findings demonstrate that olmesartan treatment significantly improved LV function and ameliorated the progression of cardiac remodeling in rats with DCM after EAM.
AB - Favorable effects of angiotensin II type 1 receptor blockers on patients with ischemic or idiopathic dilated cardiomyopathy (DCM) have already been suggested by several human trials, but their effects on DCM remain unknown. Hence, we investigated the effect of olmesartan on myocardial remodeling in a rat model in which myosin-induced experimental autoimmune myocarditis (EAM) might develop into DCM. EAM was elicited in Lewis rats by immunization with cardiac myosin, and 28 d after immunization, the surviving Lewis rats were divided into two groups and treated with either olmesartan (10 mg/kg/d) or vehicle. Age-matched normal rats without immunizations were also used. After four weeks of treatment, we investigated the effects of olmesartan on cardiac function, inflammatory cytokines and cardiac remodeling in EAM rats. Myocardial functional parameters measured by hemodynamic and echocardiographic analyses were significantly improved by the treatment with olmesartan compared with those of vehicle-treated rats. Olmesartan significantly reduced cardiac fibrosis as well as hypertrophy and its molecular markers (left ventricular [LV] mRNA expressions of transforming growth factor beta1, collagen-I and -III, and atrial natriuretic peptide) compared with those of vehicle-treated rats. Increased myocardial mRNA expressions of proinflammatory cytokines (interleukin [IL]-6, IL-1β), monocyte chemoattractant protein-1 and matrix metalloproteinases (MMP-2 and -9) were also suppressed by the treatment with olmesartan in rats with DCM. Further, the plasma level of angiotensin II was significantly increased in olmesartan-treated rats. These findings demonstrate that olmesartan treatment significantly improved LV function and ameliorated the progression of cardiac remodeling in rats with DCM after EAM.
KW - Angiotensin II
KW - Cardiac remodeling
KW - Dilated cardiomyopathy
KW - Fibrosis
KW - Olmesartan
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U2 - 10.1258/ebm.2010.010016
DO - 10.1258/ebm.2010.010016
M3 - Article
C2 - 20876084
AN - SCOPUS:78049322900
SN - 1535-3702
VL - 235
SP - 1338
EP - 1346
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 11
ER -