title: Spironolactone inhibits the transcardiac extraction of aldosterone in patients with congestive heart failure.
abstract: OBJECTIVE
  The study evaluated the transcardiac extraction or spillover of aldosterone (ALDO) in normal subjects and in patients with congestive heart failure (CHF).
  
  
  BACKGROUND
  Aldosterone promotes collagen synthesis and structural remodeling of target organs such as the heart. Spironolactone, an ALDO receptor antagonist, has recently been reported to reduce the mortality of patients with CHF; however, the effects of spironolactone on the transcardiac gradient of ALDO have not been clarified.
  
  
  METHODS
  We measured plasma ALDO in the aortic root (AO) and coronary sinus (CS) in normal subjects and 113 consecutive CHF patients and also measured plasma procollagen type III aminoterminal peptide (PIIINP) in CS, a biochemical marker of myocardial fibrosis.
  
  
  RESULTS
  Plasma ALDO was significantly lower in the CS than in the AO in normal subjects (n = 15; 61.2 +/- 9.3 vs. 83.1 +/- 11.8 pg/ml, p < 0.0001). In 96 CHF patients who did not receive spironolactone, plasma ALDO was significantly lower in the CS than in the AO (59.3 +/- 3.9 vs. 73.8 +/- 4.9 pg/ml, p < 0.0001). In contrast to the difference in these 96 patients, there was no significant difference in ALDO between the AO and CS in 17 patients who received spironolactone (127.4 +/- 20 vs. 124.0 +/- 19 pg/ml, p = 0.50). Stepwise multivariate analyses showed that spironolactone therapy had an independent and significant negative relationship with the transcardiac gradient of plasma ALDO in patients with CHF. In addition, significant positive correlations were seen between the transcardiac gradient of plasma ALDO and PIIINP (r = 0.565, p < 0.0001) and the left ventricular end-diastolic volume index (r = 0.484, p < 0.0001).
  
  
  CONCLUSIONS
  These results indicate that plasma ALDO is extracted through the heart in normal subjects and in CHF patients who do not receive spironolactone and that spironolactone inhibits the transcardiac extraction of ALDO in CHF patients, suggesting that spironolactone blocks the effects of ALDO on the failing heart in patients with CHF.
authors.affiliation: First Department of Internal Medicine, Shiga University of Medical Science, Seta, Otsu, Japan. tutamoto@belle.shiga-med.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Tsutamoto
authors.forename: A
authors.initials: A
authors.lastname: Wada
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: N
authors.initials: N
authors.lastname: Mabuchi
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Tsutsui
authors.forename: M
authors.initials: M
authors.lastname: Ohnishi
authors.forename: M
authors.initials: M
authors.lastname: Sawaki
authors.forename: M
authors.initials: M
authors.lastname: Fujii
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: H
authors.initials: H
authors.lastname: Horie
authors.forename: Y
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: M
authors.initials: M
authors.lastname: Kinoshita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D001011:Aorta; D003331:Coronary Vessels; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism; D011347:Procollagen / Q000097:blood / Q000378:metabolism; D012016:Reference Values; D013148:Spironolactone / Q000627:therapeutic use*; D013318:Stroke Volume; D016277:Ventricular Function, Left
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D013148:Spironolactone; D000450:Aldosterone