Canrenoate reversal of inhibitory effects of digoxin on basal and furosemide-stimulated renin secretion

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Abstract
Changes in plasma renin activity (PRA) were monitored in 6 mildly hypertensive men after i.v. doses, in 7 separate experiments, of placebo, digoxin, potassium canrenoate, potassium canrenoate with digoxin, furosemide, furosemide with digoxin and potassium canrenoate with furosemide and digoxin. Potassium canrenoate was used as a rapid source of canrenone, a competitive antagonist of ouabain at its Na-K-ATPase receptor site. Potassium canrenoate infusion reversed the hyporeninemic effect of digoxin. Evidently, antialdosteronic drugs can also reverse digoxin effects at extracardiac level, and the Na-K-ATPase system is involved in the renin secretory mechanism. A seemingly identical reversal of the hyporeninemic effect of digoxin was induced by furosemide, which, when given alone, stimulated renin secretion. The simultaneous administration of potassium canrenoate, digoxin and furosemide induced an increase in PRA on the same order as that after furosemide alone. Appparently, furosemide stimulates renin release by affecting a biochemical system other than that affected by digoxin.