TY - JOUR
T1 - A circulating inhibitor of (Na+ + K+) ATPase associated with essential hypertension
AU - Hamlyn, John M.
AU - Ringel, Richard
AU - Schaeffer, Juergen
AU - Levinson, Paul D.
AU - Hamilton, Bruce P.
AU - Kowarski, A. Avinoam
AU - Blaustein, Mordecai P.
PY - 1982
Y1 - 1982
N2 - 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.
AB - 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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U2 - 10.1038/300650a0
DO - 10.1038/300650a0
M3 - Article
C2 - 6292738
AN - SCOPUS:0020334656
VL - 300
SP - 650
EP - 652
JO - Nature
JF - Nature
SN - 0028-0836
IS - 5893
ER -