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A circulating inhibitor of (Na+ + K+) ATPase associated with essential hypertension

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Abstract

The aetiology of essential hypertension, a disease prevalent in cultured societies, is unknown. However, much evidence suggests that abnormal sodium metabolism has a critical role—this has led to the hypothesis that an increase in the circulating concentration of an inhibitor of (Na+ + K+) ATPase is responsible for the increased peripheral vascular resistance in essential hypertension1. Evidence for relatively high levels of a Na+ pump inhibitor in essential hypertension has come from bioassay and cytochemical assays of plasma and urine from normotensive and hypertensive individuals2,3. There is also evidence for increased plasma levels of a Na+ pump inhibitor in some animal models (for example, renal and deoxycorticosterone acetate (DOCA) models) of hypertension4. Nevertheless, direct biochemical determination of (Na+ + K+) ATPase inhibition by this substance has not yet been reported. We demonstrate here, with a kinetic (Na+ + K+) ATPase assay, a highly significant correlation between levels of a plasma inhibitor of (Na+ + K+)ATPase activity and mean arterial blood pressure (MAP) in normotensive and hypertensive individuals. These data provide evidence for the involvement of a circulating Na+ pump inhibitor in the genesis of essential hypertension. Moreover, our assay methods may be useful for the isolation and characterization of this inhibitor.

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Authors and Affiliations

  1. Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, Maryland, 21201, USA

    John M. Hamlyn, Juergen Schaeffer & Mordecai P. Blaustein

  2. Cardiology Division, Department of Pediatrics, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, Maryland, 21201, USA

    Richard Ringel

  3. Endocrinology Division, Department of Pediatrics, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, Maryland, 21201, USA

    Paul D. Levinson & A. Avinoam Kowarski

  4. Endocrinology and Metabolism Section, Veterans Administration Baltimore Hospital, 3900 Loch Raven Boulevard, Baltimore, Maryland, 21218, USA

    Bruce P. Hamilton

Authors
  1. John M. Hamlyn
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  2. Richard Ringel
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  3. Juergen Schaeffer
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  4. Paul D. Levinson
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  5. Bruce P. Hamilton
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  6. A. Avinoam Kowarski
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  7. Mordecai P. Blaustein
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Hamlyn, J., Ringel, R., Schaeffer, J. et al. A circulating inhibitor of (Na+ + K+) ATPase associated with essential hypertension. Nature 300, 650–652 (1982). https://doi.org/10.1038/300650a0

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