拡張型心筋症モデルマウスにおける自発運動とレニン・アンギオテンシン阻害剤投与の比較

• Published in: 日本薬理学会年会要旨集 p. 3-B-P-216
• Main Authors: 村山, 尚, 三井田, 孝, 柿木, 亮, 森本, 幸生, 杉原, 匡美, 呉林, なごみ, 櫻井, 隆
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: arrhythmia; heart; heart ventricle; その他
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.96.0_3-B-P-216

Dilated cardiomyopathy (DCM) is one of major causes of heart failure (HF). Although exercise is regarded as one of therapies for HF, the effects of exercise on patients with DCM have not been established. A knock-in mouse model of human inherited DCM, TNNT2 ΔK210, shows similar characteristics to DCM patients. We have showed that one of angiotensin receptor blockers (ARB) is effective on cardiac function and electrical remodeling and found that voluntary exercise also improves cardiac function in homozygote model mice (DCM mice). In this study, we examined combination therapy in DCM mice. The DCM mice showed enlarged heart and frequent sudden death with t1/2 of ~70 days. Male DCM mice were divided into 4 groups based on the administration of ARB and voluntary exercise: without drug or exercise (control), oral administration of ARB (ARB), daily exercise (ex), and combined ARB and exercise (comb). The ex and comb groups started wheel running at 1 month of age. Cardiac function was measured with echocardiography at 2.5 months of age. After sacrifice, weights of body, heart, lung, and lower extremity muscles were measured. Gene expressions of HF- and arrhythmia-related genes in myocardium were quantified by qPCR analysis. On echocardiography, the ejection fraction was significantly improved in only comb-group (Cont: 21.7±6.1％(n=6), ARB: 26.9±5.1％(n=6), ex: 27.2±4.5％(n=5), comb: 31.9±3.6％(n=6)). On the other hand, the heart weight/body weight ratio decreased in the ARB and the comb groups. Our results indicate a synergistic effect between ARB and voluntary exercise to cardiac function in DCM.