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Altered tension cost in (TG(mREN-2)27) rats overexpressing the mouse renin gene

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Abstract

The present study aimed to characterize cardiac hypertrophy induced by activation of the renin–angiotensin system in terms of functional alterations on the level of the contractile proteins, employing transgenic rats harboring the mouse renin gene (TGR(mREN2)27). Ca2+-dependent tension and myosin ATPase activity were measured in skinned fiber preparations obtained from TGR(mREN2)27 and from age-matched Sprague–Dawley rats (SPDR). Western blots for troponin I (TnI) and troponin T (TnT) were performed and the phosphorylation status of TnI were evaluated in myocardial preparations. TnT and myosin heavy chain (MHC) isoforms were analyzed by RT-PCR. The pCa/tension relationship was shifted to the right in TGR(mREN2)27 compared to SPDR as indicated by increased Ca2+-concentrations required for half maximal activation of tension (SPDR 5.80, 95% confidence limits 5.77–5.82 vs. TGR(mREN2)27 5.69, 95% confidence limits 5.67–5.72, pCa units), while maximal developed tension was unaltered. Even more pronounced was the shift in the relationship between pCa and myosin–ATPase (SPDR 6.01, 95% confidence limits 5.99–6.03 vs. TGR(mREN2)27 5.77, 95% confidence limits 5.73–5.79, pCa units). The maximal myosin–ATPase activity was reduced in TGR(mREN2)27 compared to SPDR, respectively (211.0 ± 28.77 μmol ADP/s vs. 271.6 ± 43.66 μmol ADP/s, P < 0.05). Tension cost (ATPase activity/tension) was significantly reduced in TGR(mREN2)27. The β-MHC expression was significantly increased in TGR(mREN2)27. There was no isoform shift for TnT (protein and mRNA), as well as TnI, and no alteration of the phosphorylation of TnI in TGR(mREN2)27 compared to SPRD. The present study demonstrates that cardiac hypertrophy, induced by an activation of the renin–angiotensin system, leads to adapting alterations on the level of the contractile filaments, which reduce tension cost.

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Acknowledgment

This study was supported by the Else-Kröner-Fresenius-Stiftung as well as by the Deutsche Forschungsgemeinschaft DFG.

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Authors and Affiliations

  1. Laboratory of Muscle Research and Molecular Cardiology, Department of Internal Medicine III, University of Cologne, Joseph-Stelzmann-Str. 9, 50924, Cologne, Germany

    Carsten Zobel, Persephone Zavidou-Saroti, Birgit Bölck, Klara Brixius, Hannes Reuter, Konrad Frank, Holger Diedrichs, Jochen Müller-Ehmsen & Robert H. G. Schwinger

  2. Department of Molecular and Cellular Sport Medicine, German Sports University, Carl-Diem-Weg 6, 50933, Cologne, Germany

    Wilhelm Bloch

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  1. Carsten Zobel
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  2. Persephone Zavidou-Saroti
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  3. Birgit Bölck
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  4. Klara Brixius
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  5. Hannes Reuter
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  10. Robert H. G. Schwinger
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Correspondence to Carsten Zobel.

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Zobel, C., Zavidou-Saroti, P., Bölck, B. et al. Altered tension cost in (TG(mREN-2)27) rats overexpressing the mouse renin gene. Eur J Appl Physiol 99, 121–132 (2007). https://doi.org/10.1007/s00421-006-0323-5

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