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KMID : 1011920140150010006
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International Journal of Arrhythmia
2014 Volume.15 No. 1 p.6 ~ p.19
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Losartan attenuates atrial structural and electrical remodeling in rat ischemic heart failure model: Implications of endothelin for atrial fibrillation
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Cho Kyoung-Im
Lee Soo-Jeong
Cha Tae-Joon
Koo Sang-Ho
Heo Jung-Ho
Kim Hyun-Su
Lee Jae-Woo
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Abstract
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Background: Although endothelin-1 (ET-1) stimulated by angiotensin II contributes to neurohormonal activation and cardiovascular remodeling in congestive heart failure (CHF), its relationship to atrial fibrillation (AF) has not yet been studied. We investigated the relationship between the expression of ET-1, and the development of AF, using an angiotensin receptor blocker (ARB) in a rat model of myocardial infarction (MI)?induced CHF.
Methods: Rats were randomized to one of 3 groups: sham (n=20), MI (n=19), and MI + losartan (n=20, 10 mg/kg/day for 10 weeks). MI was induced by ligation of the left anterior descending coronary artery (LAD). Two days after the MI induction procedure, echocardiography and AF induction studies were performed. Real-time reverse transcription (RT)-polymerase chain reaction (PCR) of ET-1 and western blotting of endothelin receptor A (ETaR) and B (ETbR) were performed, in addition to immunohistochemical analysis of ET-1, ETa, and ETb for localization in left atrial (LA) tissues.
Results: There were significant decreases in ejection fraction (EF) and increases in AF duration in the MI group compared to the sham group, which were attenuated by losartan treatment. ET-1 mRNA expression and ETaR protein density significantly increased, and ETbR protein density decreased in the LA tissue of the MI group compared to the sham group. These changes were improved by losartan treatment. Immunohistochemical experiments demonstrated increased ET-1 and ETaR activity in LA tissue from rats in the MI group, which was attenuated by losartan treatment.
Conclusion: Changes in the endothelin system were associated with increased AF duration, which improved in the losartan treatment group. Our findings suggest a novel AF-preventing effect for ARBs via neurohormonal signaling in CHF.
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KEYWORD
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short QT syndrome, sudden death, ventricular fibrillation
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