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Reduced concentration of myocardial Na+,K+-ATPase in human aortic valve disease as well as of Na+,K+- and Ca2+-ATPase in rodents with hypertrophy

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Abstract

Myocardial Na+,K+-ATPase was studied in patients with aortic valve disease, and myocardial Na+,K+- and Ca2+-ATPase were assessed in spontaneously hypertensive rats (SHR) and hereditary cardiomyopathic hamsters using methods ensuring high enzyme recovery. Na+,K+-ATPase was quantified by [3H]ouabain binding to intact myocardial biopsies from patients with aortic valve disease. Aortic stenosis, regurgitation and a combination hereof were compared with normal human heart and were associated with reductions of left ventricular [3H]ouabain binding site concentration (pmol/g wet weight) of 56, 46 and 60%, respectively (p < 0.01). Na+,K+ and Ca2+-ATPases were quantified by K+- and Ca2+-dependent p-nitrophenyl phosphatase (pNPPase) activity determinations in crude myocardial homogenates from SHR and hereditary cardiomyopathic hamsters. When SHR were compared to age-matched Wistar Kyoto (WKY) rats an increase in heart-body weight ratio of 75% (p < 0.001) was associated with reductions of K+- and Ca2+-dependent pNPPase activities (μmol/min/g wet weight) of 42 (p < 0.01) and 27% (p < 0.05), respectively. When hereditary cardiomyopathic hamsters were compared to age-matched Syrian hamsters an increase in heart-body weight ratio of 69% (p < 0.001) was found to be associated with reductions in K+- and Ca2+-dependent pNPPase activities of 50 (p < 0.001) and 26% (p = 0.05), respectively. The reductions in Na+,K+- and Ca2+-ATPases were selective in relation to overall protein content and were not merely the outcome of increased myocardial mass relative to Na+,K+- and Ca2+-pumps. In conclusion, myocardial hypertrophy is in patients associated with reduced Na+,K+-ATPase concentration and in rodents with reduced Na+,K+- and Ca2+-ATPase concentrations. This may be of importance for development of heart f in hypertrophic heart disease.

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Authors and Affiliations

  1. Department of Medicine B, The Heart Centre, Rigshospitalet, National University Hospital, Blegdamsvej 9, DK-2100, Copenhagen Ø, Denmark

    Jim Stenfatt Larsen, Thomas Andersen Schmidt, Henning surname & Keld Kjeldsen

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  1. Jim Stenfatt Larsen
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  4. Keld Kjeldsen
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Stenfatt Larsen, J., Andersen Schmidt, T., surname, H. et al. Reduced concentration of myocardial Na+,K+-ATPase in human aortic valve disease as well as of Na+,K+- and Ca2+-ATPase in rodents with hypertrophy. Mol Cell Biochem 169, 85–93 (1997). https://doi.org/10.1023/A:1006851411650

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