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Altered circadian rhythm of cardiac β3-adrenoceptor activity following myocardial infarction in the rat

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Abstract

Circadian rhythms influence the incidence of adverse cardiac events but the underlying mechanisms are not well defined. We sought to investigate the role of the β3-adrenoceptor (β3-AR) in cardiac circadian disorders and arrhythmia severity after myocardial infarction (MI). MI was created by ligating the left anterior descending coronary artery of the rat heart in situ. Circadian variations of the myocardial expressions of β3-AR and clock genes Bmal1 and Npas2 were examined by real time reverse transcription polymerase chain reaction, Western blot and immunohistochemistry. Electrocardiograms and myocardial contraction were recorded in vivo and/or ex vivo. Ventricular tachyarrhythmias were induced by isoprenaline. Normal rats showed circadian oscillations in both the myocardial transcriptional expression of β3-AR and the β3-AR-induced positive chronotropic and negative inotropic cardiac effects. However, these circadian rhythms were significantly blunted or even abolished in rats with either acute MI (within 24 h) or healed MI (14 days after coronary ligation). The nocturnal level of β3-AR protein was higher in MI rats than in normal rats. In contrast, the circadian oscillations of the transcripts of Bmal1 and Npas2 in the myocardium were significantly augmented in rats with either acute MI or healed MI. BRL37344, a preferential β3-AR selective agonist, reduced the occurrence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in rats with either acute MI or healed MI. We conclude that circadian rhythms of myocardial β3-AR activities are disturbed after MI and β3-AR activation offers anti-arrhythmic protection.

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Acknowledgments

This study was supported by grants from the national Natural Science Foundation of China (NSFC) (30125016, 30370565 and 30670863 to J.-M.C.), the National Basic Research Program (973 Program) funded by the Ministry of Science and Technology (MOST) of China (2006CB503800 and 2006CB933202 to J.-M.C.), and Canadian Institutes of Health Research (W. R.). We thank Dr. Robert M. Carey for language editing of the manuscript.

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences, School of Basic Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China

    Lan Zhou, Peng Zhang, Wei Hao & Ji-Min Cao

  2. Division of Cardiology, Department of Medicine, Peking Union Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China

    Zhongwei Cheng & Quan Fang

  3. Department of Biology, Lakehead University, Thunder Bay, ON, Canada

    Rui Wang

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  1. Lan Zhou
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  2. Peng Zhang
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  4. Wei Hao
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  7. Ji-Min Cao
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Correspondence to Quan Fang or Ji-Min Cao.

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L. Zhou and P. Zhang contributed equally to this work.

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Zhou, L., Zhang, P., Cheng, Z. et al. Altered circadian rhythm of cardiac β3-adrenoceptor activity following myocardial infarction in the rat. Basic Res Cardiol 106, 37–50 (2011). https://doi.org/10.1007/s00395-010-0110-7

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  • DOI: https://doi.org/10.1007/s00395-010-0110-7

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