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A Novel Angiotensin Type I Receptor Antagonist, Fimasartan, Prevents Doxorubicin-induced Cardiotoxicity in Rats
Journal of Korean Medical Science ; : 559-568, 2015.
Article in English | WPRIM | ID: wpr-99852
ABSTRACT
Angiotensin receptor blockers (ARBs) have organ-protective effects in heart failure and may be also effective in doxorubicin-induced cardiomyopathy (DOX-CMP); however, the efficacy of ARBs on the prevention of DOX-CMP have not been investigated. We performed a preclinical experiment to evaluate the preventive effect of a novel ARB, fimasartan, in DOX-CMP. All animals underwent echocardiography and were randomly assigned into three groups treated daily with vehicle (DOX-only group, n=22), 5 mg/kg of fimasartan (Low-fima group, n=22), and 10 mg/kg of fimasartan (High-fima group, n=19). DOX was injected once a week for six weeks. Echocardiography and hemodynamic assessment was performed at the 8th week using a miniaturized conductance catheter. Survival rate of the High-fima group was greater (100%) than that of the Low-fima (75%) and DOX-only groups (50%). Echocardiography showed preserved left ventricular (LV) ejection fraction in the High-fima group, but not in the DOX-only group (P=0.002). LV dimensions increased in the DOX-only group; however, remodeling was attenuated in the Low-fima and High-fima groups. Hemodynamic assessment showed higher dP/dt in the High-fima group compared with the DOX-only group. A novel ARB, fimasartan, may prevent DOX-CMP and improve survival rate in a dose-dependent manner in a rat model of DOX-CMP and could be a treatment option for the prevention of DOX-CMP.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pyrimidines / Tetrazoles / Biphenyl Compounds / Echocardiography / Doxorubicin / Survival Rate / Ventricular Function, Left / Rats, Sprague-Dawley / Receptor, Angiotensin, Type 1 / Angiotensin Receptor Antagonists Limits: Animals Language: English Journal: Journal of Korean Medical Science Year: 2015 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pyrimidines / Tetrazoles / Biphenyl Compounds / Echocardiography / Doxorubicin / Survival Rate / Ventricular Function, Left / Rats, Sprague-Dawley / Receptor, Angiotensin, Type 1 / Angiotensin Receptor Antagonists Limits: Animals Language: English Journal: Journal of Korean Medical Science Year: 2015 Type: Article