Influence of beta-blockers on the myocardial mRNA expressions of circadian clock- and metabolism-related genes

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• 作者：Kentarou Ushijima ; PhD^a ; ¹ ; Tomohiro Maekawa ; MPAS^a ; ¹ ; Eiko Ishikawa-Kobayashi ; MPAS^a ; Hitoshi Ando ; MD ; PhD^a ; Tsuyoshi Shiga ; MD ; PhD^b ; Akio Fujimura ; MD ; PhD^a ; ^{akiofuji@jichi.ac.jp}
• 关键词：Atenolol ; ATP ; daily rhythm ; propranolol
• 刊名：Journal of the American Society of Hypertension
• 出版年：2013
• 出版时间：March-April, 2013
• 年：2013
• 卷：7
• 期：2
• 页码：107-117
• 全文大小：1297 K

文摘

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.