Beneficial effects of olmesartan, an angiotensin II receptor type 1 antagonist, in rats with dilated cardiomyopathy.
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.
Sukumaran
Vijayakumar
V
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603.
Watanabe
Kenichi
K
Veeraveedu
Punniyakoti T
PT
Thandavarayan
Rajarajan A
RA
Gurusamy
Narasimman
N
Ma
Meilei
M
Yamaguchi
Ken'ichi
K
Suzuki
Kenji
K
Kodama
Makoto
M
Aizawa
Yoshifusa
Y
D000804:Angiotensin II / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism; D007093:Imidazoles / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009205:Myocarditis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009218:Myosins; D012333:RNA, Messenger; D051381:Rats; D011917:Rats, Inbred Lew; D013777:Tetrazoles / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D007093:Imidazoles; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D013777:Tetrazoles; D000804:Angiotensin II; C437965:olmesartan; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009218:Myosins