Striking Increase of Natriuresis by Low-Dose Spironolactone in Congestive Heart Failure Only in Combination With ACE Inhibition

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Abstract
Background—A marked reduction of overall mortality in patients with severe congestive heart failure (CHF) has been demonstrated by addition of the mineralocorticoid receptor antagonist spironolactone to ACE inhibition. The aim of the present study was to examine a hypothesized interaction of spironolactone and ACE inhibitors in renal electrolyte and volume regulation. Methods and Results—Wistar rats with extensive myocardial infarction or sham operation were treated with either placebo, the ACE inhibitor trandolapril, low-dose spironolactone, or a combination of the 2. Twelve weeks after infarction, rats were housed in metabolic cages. Urinary volume and sodium excretion were significantly increased in CHF rats on a combined treatment with spironolactone and trandolapril (21.2±2.6 mL/d, 2489±320 mmol/d, mean±SD; P<0.05 versus other experimental groups) versus placebo-treated rats (16.7±5.6 mL/d, 1431±458 mmol/d),whereas these parameters were not affected in rats on either spironolactone (16.1±6.6 mL/d, 11...