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Expression of mitochondrial regulatory genes parallels respiratory capacity and contractile function in a rat model of hypoxia-induced right ventricular hypertrophy

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Abstract

Chronic hypobaric hypoxia (CHH) increases load on the right ventricle (RV) resulting in RV hypertrophy. We hypothesized that CHH elicits distinct responses, i.e., the hypertrophied RV, unlike the left ventricle (LV), displaying enhanced mitochondrial respiratory and contractile function. Wistar rats were exposed to 4 weeks CHH (11% O2) versus normoxic controls. RV/body weight ratio increased (P < 0.001 vs. control) while RV systolic and developed pressures were higher. However, LV systolic and developed pressures were significantly reduced. Mitochondrial O2 consumption was sustained in the hypertrophied RV, ADP/O increased (P < 0.01 vs. control) and proton leak significantly decreased. Conversely, LV mitochondrial O2 consumption was attenuated (P < 0.05 vs. control) and proton leak significantly increased. In parallel, expression of mitochondrial regulators was upregulated in the hypertrophied RV but not the LV. Our data show that the hypertrophied RV induces expression of mitochondrial regulatory genes linking respiratory capacity and enhanced efficiency to sustained contractile function.

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Acknowledgments

The authors wish to thank Mr. Noel Markgraaff for technical assistance. This work was supported by an NIH-Fogarty R03 TW07344 (to M. F. Essop and W. C. Stanley), the South African Medical Research Council and the South African National Research Foundation (to M.F. Essop).

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Authors and Affiliations

  1. Hatter Heart Research Institute, Department of Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa

    Makhosazane Zungu & M. Faadiel Essop

  2. USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    Martin E. Young

  3. Division of Cardiology, Department of Medicine, University of Maryland-Baltimore, Baltimore, MD, USA

    William C. Stanley

  4. Department of Physiological Sciences, Stellenbosch University, Room 2009, Mike De Vries Building, Merriman Avenue, Stellenbosch, South Africa

    M. Faadiel Essop

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  1. Makhosazane Zungu
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  2. Martin E. Young
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  4. M. Faadiel Essop
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Correspondence to M. Faadiel Essop.

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Zungu, M., Young, M.E., Stanley, W.C. et al. Expression of mitochondrial regulatory genes parallels respiratory capacity and contractile function in a rat model of hypoxia-induced right ventricular hypertrophy. Mol Cell Biochem 318, 175–181 (2008). https://doi.org/10.1007/s11010-008-9867-5

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  • DOI: https://doi.org/10.1007/s11010-008-9867-5

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