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

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 individuals^2,3. 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.