Effects of long-term enalapril and losartan therapy of heart failure on cardiovascular aldosterone.
Plasma aldosterone escape is found during long-term ACE inhibitor therapy of chronic heart failure. Evidence for aldosterone production in cardiovascular tissues raised the question of whether aldosterone escape occurs or not in these tissues. Rats with infarction-induced chronic heart failure were treated with enalapril (20 mg/kg/d) and losartan (15 mg/kg/d) for 20 weeks. Untreated chronic heart failure and sham-operated rats were used as positive and normal controls, respectively. Ex vivo mesenteric artery and heart perfusion, high performance liquid chromatography, and RIA for aldosterone were performed. Chronic heart failure due to myocardial infarction was associated with tissue-specific activation of cardiovascular aldosterone synthesis. In the mesenteric artery, enalapril significantly inhibited aldosterone production compared to untreated, chronic heart failure rats, and losartan lowered aldosterone production to that of sham rats. In myocardium, enalapril failed to significantly inhibit aldosterone production, and losartan significantly inhibited aldosterone production compared to untreated, chronic heart failure rats. These results provide the first evidence that long-term ACE inhibition therapy induces aldosterone escape in myocardium but not in mesenteric artery of chronic heart failure. The angiotensin II subtype 1 receptor blocker losartan tranquilized aldosterone levels in the cardiovascular tissues of chronic heart failure rats.
Xiu
J C
JC
Department of Cardiology, Nan Fang Hospital, The First Military Medical University, Guangzhou, People's Republic of China.
Wu
P
P
Xu
J P
JP
Guo
Z
Z
Lai
W
W
Zhang
Y
Y
Li
S
S
Li
J
J
Liu
Y
Y
D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D002303:Cardiac Output, Low / Q000188:drug therapy* / Q000378:metabolism*; D006332:Cardiomegaly / Q000517:prevention & control; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism*; D002908:Chronic Disease; D004656:Enalapril / Q000008:administration & dosage* / Q000627:therapeutic use; D019808:Losartan / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008638:Mesenteric Arteries; D009203:Myocardial Infarction / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000450:Aldosterone; D004656:Enalapril; D019808:Losartan