Circulating endogenous digitalis-like factor(s) (EDLF) in man is derived from the adrenals and its secretion is ACTH-dependent.

Adrenal origin and ACTH-dependent secretion of endogenous digitalis-like factor(s) (EDLF) was investigated. Twelve normal weight normotensive subjects (normal group) and 10 patients with Addison's disease (Addison group) were subjected to prolonged ACTH stimulation with 1 mg tetracosactin-depot im. Blood sampling was at 0 and 240 min. Digitalis-like reactivity was monitored in plasma extracts (combined organic solvent solid phase method) by digoxin and ouabain radioimmunoassay (RIAD and RIAO, respectively). 3H-ouabain concentration on erythrocytes (OBS) was also determined. Na+, K+-ATPase inhibition by normal plasma extract was tested by measuring Vmax and Km of 86Rb+-transport into human erythrocytes. In the normal group basal median plasma concentrations RIAD (0.07 nmol/l) and RIAO (0.89 nmol/l) increased significantly after ACTH administration (median 0.31 and 1.83, respectively; Wilcoxon, p<0.01). In contrast, in the Addison group no plasma RIAD and RIAO reactivity was detected before or after ACTH administration with minor exceptions. The OBS remained unchanged in the Addison group at 0 and 240 min; in the normal group there was a significant decline at 240 min (Wilcoxon, p<0.05) implying increase in circulating EDLF after ACTH stimulation. In the 86Rb+-transport experiments, 2 nmol/l ouabain or 2 nmol/l plasma-extracted ouabain reactivity both significantly impaired substrate affinity equally increasing Km without affecting Vmax. In men, the adrenals may produce and secrete EDLF, whose secretion appears to be ACTH-dependent.