A Novel Angiotensin Type I Receptor Antagonist, Fimasartan, Prevents Doxorubicin-induced Cardiotoxicity in Rats.
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.
Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. ; Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Sung-A
0000-0001-5124-605X
SA
Chang
Department of Biomedical Science, Jungwon University, Goesan-gun, Korea.
Byung-Kwan
BK
Lim
Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
You Jung
YJ
Lee
Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Mi-Kyung
MK
Hong
Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. ; Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jin-Oh
JO
Choi
Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. ; Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Eun-Seok
0000-0002-9946-5611
ES
Jeon
D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D004317:Doxorubicin / Q000633:toxicity*; D004452:Echocardiography; D006439:Hemodynamics; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry / Q000378:metabolism*; D015996:Survival Rate; D013777:Tetrazoles / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D011743:Pyrimidines; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D004317:Doxorubicin; C558933:fimasartan
Angiotensin Receptor Blocker; Doxorubicin-induced Cardiomyopathy