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 spironolactone treatment (both p less than 0.05). Plasma hANF before spironolactone was significantly elevated and decreased during spironolactone therapy (p less than 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.
Hensen
J
J
Department of Medicine, University of Colorado School of Medicine, Denver.
Abraham
W T
WT
Dürr
J A
JA
Schrier
R W
RW
D000450:Aldosterone / Q000502:physiology*; D009320:Atrial Natriuretic Factor / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D011188:Potassium / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D012982:Sodium, Dietary / Q000008:administration & dosage; D013148:Spironolactone / Q000494:pharmacology*
D012982:Sodium, Dietary; D013148:Spironolactone; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012964:Sodium; D011188:Potassium