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Differences in left ventricular cardiomyocyte loss induced by chronic intermittent hypoxia between spontaneously hypertensive and Wistar–Kyoto rats

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Abstract

Rationale

Chronic intermittent hypoxia (CIH) is thought to induce several cardiovascular effects in patients with obstructive sleep apnoea (OSA). However, the effects of CIH on patients with long-standing hypertension are unknown.

Purpose

This prospective study aimed to investigate the influence of combined OSA and hypertension on cardiomyocyte death.

Methods

Wistar–Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were exposed to repetitive hypoxia–reoxygenation cycles (30 s of 5% O2; 45 s of 21% O2) or room air for 6 h/day during the light phase (10 a.m.–4 p.m.) for 10, 20, or 30 days, and the levels of necrosis and apoptosis induced in their left ventricular cardiomyocyte were examined.

Results

CIH increased the accumulation of reactive oxygen species, which induced cardiomyocyte necrosis in WKY and SHR (both p < 0.05). Cardiomyocyte oxidative stress levels by CIH were higher in SHR than in WKY (p < 0.05); therefore, cardiomyocyte necrosis was amplified (p < 0.05). Notably, if a superoxide-scavenging agent is injected beforehand, cardiomyocyte necrosis can be effectively inhibited (p < 0.05). When WKY and SHR are exposed to CIH, increases in mitochondria-released cytochrome c and activation of caspase-3 are found in the cytosolic fraction only in WKY.

Conclusions

CIH causes cardiomyocyte loss in SHR mainly through cardiomyocyte necrosis. In WKY however, CIH simultaneously induces apoptosis and necrosis of cardiomyocytes.

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Acknowledgements

This study was supported by the National Science Council, Taiwan, grant NSC96-2320-B-320-017-MY2 and by Tzu Chi University, Taiwan, grant TCIRP 95004-05.

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Authors and Affiliations

  1. Institute of Medical Sciences, College of Medicine, Tzu Chi University, Hualien, Taiwan

    Tsung-I Chen

  2. Center of Physical Education, Office of General and Basic Education, Tzu Chi University, Hualien, Taiwan

    Tsung-I Chen

  3. Department of Physiology, School of Medicine, Tzu Chi University, No. 701, Sec. 3, Chung-Yang Road,, Hualien, 97004, Taiwan

    Ching-Jung Lai & Kun-Ta Yang

  4. Institute of Physiological and Anatomical Medicine, College of Medicine, Tzu Chi University, Hualien, Taiwan

    Ching-Jung Lai, Chien-Ju Hsieh & Kun-Ta Yang

  5. Department of Physiology and Master’s Program, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Ke-Li Tsai

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Correspondence to Kun-Ta Yang.

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Chen, TI., Lai, CJ., Hsieh, CJ. et al. Differences in left ventricular cardiomyocyte loss induced by chronic intermittent hypoxia between spontaneously hypertensive and Wistar–Kyoto rats. Sleep Breath 15, 845–854 (2011). https://doi.org/10.1007/s11325-010-0448-y

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  • DOI: https://doi.org/10.1007/s11325-010-0448-y

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