Antihypertensive Effect of Canrenone in a Model Where Endogenous Ouabain-Like Factors are Present

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Abstract
Summary: The effect of canrenone, an antialdosterone and partial ouabain-agonist drug, was studied in rats that developed volume expansion and hypertension after renal mass reduction and excess Na+ intake (RRM-salt). The RRM-salt was characterized by: (1) increased endogenous “digitalis-like” compounds in plasma [cross reactivity with digoxin-antibodies (57.5 ± 5.0 vs. 42.1 ± 3.8 pg/ml, p < 0.02); inhibition of kidney Na+,K+-ATPase activity (135 ± 5 vs. 154 ± 5 μmol/mg/h, p < 0.01); and inhibition of Na+ extrusion from normal erythrocytes (5.96 ± 0.40 vs. 7.68 ± 0.34 mmol/L cells/h, p < 0.01)]; (2) reduced Na+,K+-pump activity (7.34 ± 0.29 vs. 10.88 ± 0.41 mmol/L cells/h, p < 0.001) and increased Na+ content (4.66 ± .08 vs. 4.16 ± 0.11 mmol/L cells, p < 0.01) in erythrocytes; and (3) low plasma renin activity (2.1 ± 0.9 vs. 12.6 ± 1.6 ng/ml/h). Ninety minutes after the administration to RRM-salt of a single oral dose of 60 mg/kg of canrenone, the systolic blood pressure decreased by 36 ± 4 mm Hg (mean ± SEM). Chronic canrenone administration (60 mg/kg/day) resulted in a marked antihypertensive effect associated to a correction of volume expansion, a decrease in endogenous “digitalis- like” compounds, and a partial recovery of Na+,K+ -pump activity and Na+ content in erythrocytes. Our results suggest that the antihypertensive effect in RRM-salt rats results, at least in part, from antagonism with endogenous “digitalis-like” compounds.

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