Effects of perindopril on aldosterone production in the failing human heart.
The present study was designed to examine whether the production of aldosterone from the heart is suppressed by angiotensin-converting enzyme (ACE) inhibition in patients with heart failure. Forty-one patients with left ventricular systolic dysfunction were randomly divided into either the perindopril group (n = 21, perindopril 4 mg/day) or the placebo group (n = 20). Plasma levels of aldosterone and ACE activity were measured in the anterior interventricular vein, coronary sinus, and aortic root during cardiac catheterization. The levels of aldosterone as well as ACE activity were significantly higher at the anterior interventricular vein and the coronary sinus than at the aortic root in the placebo group (aldosterone: 92.1 +/- 9.0 vs 70.6 +/- 8.3 pg/ml [p <0.001]; 90.3 +/- 9.2 vs 70.6 +/- 8.3 pg/ml [p <0.001], respectively; ACE activity: 13.6 +/- 0.8 vs 12.2 +/- 0.7 IU/L [p <0.001], 13.4 +/- 0.8 vs 12.2 +/- 0.7 IU/L [p <0.001], respectively). On the other hand, there were no differences in the levels of aldosterone or ACE activity between the anterior interventricular vein and aortic root or between the coronary sinus and aortic root (aldosterone: 68.1 +/- 8.4 vs 69.9 +/- 9.4 pg/ml [p = NS]; 67.3 +/- 8.9 vs 69.9 +/- 9.4 pg/ml [p = NS], respectively; ACE activity: 9.7 +/- 0.8 vs 9.9 +/- 0.8 IU/L [p = NS]; 9.8 +/- 0.8 vs 9.9 +/- 0.8 IU/L, respectively) in the perindopril group. The levels of aldosterone as well as ACE activity were significantly lower at the anterior interventricular vein and coronary sinus in the perindopril group than in the placebo group. The difference in the level of aldosterone between the anterior interventricular vein and aortic root (Delta aldosterone [anterior interventricular vein - aortic root]) had a significant positive correlation with that of ACE activity (Delta ACE [anterior interventricular vein - aortic root]) (r = 0.536, p <0.001), whereas ACE activity in the aortic root had no significant correlation with either the aldosterone levels in the aortic root or Delta aldosterone (anterior interventricular vein - aortic root). Perindopril suppressed cardiac aldosterone production by mainly suppressing cardiac ACE activity in patients with heart failure. Thus, aldosterone production is activated in the failing ventricle and is suppressed by perindopril mainly via the suppression of cardiac ACE activity in patients with heart failure.
Mizuno
Yuji
Y
Division of Cardiovascular Medicine, Kumamoto Aging Research Institute, Kumamoto, Japan. aldo@poppy.ocn.ne.jp
Yasue
Hirofumi
H
Yoshimura
Michihiro
M
Fujii
Hiromi
H
Yamamoto
Nobuyasu
N
Nakayama
Masafumi
M
Harada
Eisaku
E
Sakamoto
Tomohiro
T
Nakamura
Shota
S
Ito
Teruhiko
T
Shimasaki
Yukio
Y
Ogawa
Hisao
H
Saito
Yoshihiko
Y
Nakao
Kazuwa
K
D000450:Aldosterone / Q000096:biosynthesis* / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D006328:Cardiac Catheterization; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism; D020913:Perindopril / Q000627:therapeutic use*; D013223:Statistics as Topic; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000150:complications / Q000188:drug therapy
D000806:Angiotensin-Converting Enzyme Inhibitors; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A; D020913:Perindopril