A quantitative receptor assay for "digitalis-like" compounds in serum. Demonstration of raised concentrations in essential hypertension and correlation with arterial blood pressure.

The influence of serum from patients with essential hypertension on [3H]ouabain binding to isolated (Na+ +K+)-ATPase and on the reactivity with digoxin-specific antibodies was investigated. [3H]Ouabain binding to (Na+ +K+)-ATPase was significantly decreased (P less than 0.001) by sera of 18 hypertensive patients (34.9 +/- 1.5 pmol/U) as compared with 22 normotensive controls (43.8 +/- 1.2 pmol/U). The factor, whose concentration is increased in the serum of patients with essential hypertension, competed with [3H]ouabain at isolated (Na+ +K+)-ATPase. Therefore, it was possible to quantify this "digitalis-like" factor with a receptor assay in ouabain equivalents. Three times higher mean serum levels were found in hypertensive patients (234.8 +/- 48.7 nM) than in normotensive controls (76.3 +/- 9.3 nM). Deproteinization of the sera by ultrafiltration through steroid-adsorbing membranes and by boiling of acidified sera for 10 min led to a significant reduction of the inhibitory activity and to the complete loss of a difference between the sera of normotensives and hypertensives. After deproteinization by boiling for 15 min, sera of normotensives showed levels of "digitalis-like" compounds of 16.53 +/- 2.15 nM and hypertensives of 41.65 +/- 8.41 nM (P less than 0.05). Though significantly elevated concentrations of "digitalis-like" factor were measured with the receptor assay, no significant increase of digoxin-like activity could be detected with digoxin-specific antibodies in untreated serum.