シガ ツヨシ   Tsuyoshi Shiga
  志賀 剛
   所属   医学部 医学科(東京女子医科大学病院)
   職種   客員教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Influence of beta-blockers on the myocardial mRNA expressions of circadian clock- and metabolism-related genes.
掲載誌名 正式名:Journal of the American Society of Hypertension : JASH
略  称:J Am Soc Hypertens
ISSNコード:18787436
掲載区分国外
出版社 Official Journal of the American Society of Hypertension
巻・号・頁 7(2),107-117頁
著者・共著者 USHIJIMA Kentarou†, MAEKAWA Tomohiro, ISHIKAWA-KOBAYASHI Eiko, ANDO Hitoshi, SHIGA Tsuyoshi, FUJIMURA Akio
発行年月 2013/03
概要 Daily rhythms are regulated by a master clock-system in the suprachiasmatic nucleus and by a peripheral clock-system in each organ. Because norepinephrine is one of the timekeepers for the myocardial circadian clock that influences cardiac metabolism, it is speculated that a beta-blocker may affect the circadian clock and metabolism in heart tissue. In this study, thirty mg/kg/day of propranolol (a lipophilic beta-blocker) or atenolol (a hydrophilic beta-blocker) was given orally to Wistar rats for 4 weeks. The mRNA expressions of Bmal1 and E4BP4 in heart tissue were suppressed by the beta-blockers. However, the mRNA expressions of these clock genes in the suprachiasmatic nucleus were unchanged. Myocardial mRNA expressions of lactate dehydrogenase a and pyruvate dehydrogenase kinase 4 were also suppressed by the beta-blockers. In addition, ATP content in heart tissue was significantly elevated by the beta-blockers throughout 24 hours. The effects of propranolol and atenolol did not differ significantly. This study showed for the first time that a beta-blocker affects myocardial clock gene expression. Propranolol and atenolol increased ATP content in heart tissue throughout 24 hours. The influences of beta-blockers may be negligible on the SCN, and may be independent of lipid solubility on heart tissue. It is well known that these drugs exert a protective effect against myocardial ischemia, which may be mediated by an increase in the preservation of myocardial ATP.
DOI 10.1016/j.jash.2012.12.007
PMID 23394803