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

Changes in plasma renin activity (PRA) were monitored in six mildly hypertensive men after intravenous doses, in seven separate experiments, of placebo, digoxin, potassium canrenoate, potassium canrenoate with digoxin, furosemide, furosemide with digoxin, and potassium canrenoate with furosemide and digoxin. Potassium canrenoate has been used as a rapid source of canrenone, which has been recently shown to be a competitive antagonist of ouabain at its Na-K-ATPase receptor site. Potassium canrenoate infusion reversed the hyporeninemic effect of digoxin. This result has been taken as evidence that: (1) antialdosteronic drugs can also reverse digoxin effects at extracardiac level and (2) 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. This result indicates that furosemide stimulates renin release by affecting a biochemical system other than that affected by digoxin.