Aldosterone in congestive heart failure: Analysis of determinants and role in sodium retention

In patients with congestive heart failure (CHF), the role of aldosterone in the abnormal sodium (Na⁺) retention and the determinants of plasma aldosterone (PA) including plasma atrial natriuretic factor (hANF), plasma renin activity (PRA), and plasma potassium (K⁺) have not been fully elucidated. We therefore studied the effect of the specific aldosterone antagonist, spironolactone, on urinary Na⁺ and K⁺ excretion and plasma hormone responses in 6 Na⁺-retaining CHF patients. After withdrawal of diuretics 4 days prior to the study, the CHF patients were placed on a Na⁺ intake of 100 mmol/day for 9 days. Spironolactone. 200 mg p.o. bid. was administered for the last 4 days of the 9-day study period. PRA and norepinephrine increased with spirinolactone treatment (both p < 0.05). Plasma hANF before spironolactone was significantly elevated and decreased during spironolactone therapy (p < 0.05). Urinary Na+ excretion significantly increased during spironolactone administration and the positive Na⁺ balance was reversed in the CHF patients. Moreover, the urine Na⁺:K⁺ concentration ratio significantly increased during spironolactone administration. Analysis of the relationship between PA. plasma K⁺. PRA, and plasma hANF indicated that PRA is the primary determinant of PA in patients with CHF. Thus, the present results indicate that the renin-angiotensin-aldosterone system is an important mediator of Na⁺ retention in CHF, as evidenced by the reversal of the positive Na⁺ balance with a specific aldosterone antagonist. This natriuretic effect can be demonstrated in the presence of potential antinatriuretic influences including stimulation of the renin-angiotensin and sympathetic nervous systems and a decrease in plasma hANF.