Beneficial effects of adrenomedullin on left ventricular remodeling after myocardial infarction in rats.
OBJECTIVE
We previously reported that plasma adrenomedullin (AM) levels increase in patients with acute myocardial infarction (MI) and AM inhibits growth of rat cardiac myocytes and fibroblasts. The aim of this study was to examine the effects of long-term administration of AM on left ventricular (LV) remodeling, hemodynamic and hormonal parameters in a rat model of MI.


METHODS
Rats with MI induced by left coronary ligation were intravenously infused with 1.0 microg/h of recombinant human AM or saline by osmotic mini-pump. After infusion for 4 weeks, hemodynamic and hormonal studies were performed, and the myocyte size and collagen volume in non-infarct LV area were quantified morphometrically.


RESULTS
When compared with the MI rats infused with saline, continuous infusion of AM reduced the heart weight/body weight (4.4+/-0.2 vs. 3.6+/-0.1 g/kg, P<0.01), myocyte size (922+/-23 vs. 868+/-10 microm(2), P<0.05) and collagen volume fraction of non-infarct LV area (7.6+/-0.8 vs. 4.8+/-0.5%, P<0.05), without affecting the infarct size. The AM infusion had no significant effect on the arterial pressure, but decreased the LV end-diastolic pressure (8.8+/-1.8 vs. 4.4+/-0.5 mmHg, P<0.05) in the MI rats. The plasma level of endogenous rat AM in the MI rats infused with human AM was reduced by 27% (P<0.05), with a slight reduction of plasma atrial natriuretic peptide, compared with the control.


CONCLUSIONS
Continuous administration of AM had beneficial effects on LV remodeling and hemodynamics in MI rats, suggesting the possibility that this peptide could be a useful therapeutic tool for acute MI.
Nakamura
Ryosai
R
First Department of Internal Medicine, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki, Japan.
Kato
Johji
J
Kitamura
Kazuo
K
Onitsuka
Hisamitsu
H
Imamura
Takuroh
T
Marutsuka
Kousuke
K
Asada
Yujiro
Y
Kangawa
Kenji
K
Eto
Tanenao
T
D053607:Adrenomedullin; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D002316:Cardiotonic Agents / Q000097:blood / Q000627:therapeutic use*; D048429:Cell Size / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D006333:Heart Failure / Q000517:prevention & control; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000097:blood / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D020257:Ventricular Remodeling / Q000187:drug effects*
D002316:Cardiotonic Agents; D010455:Peptides; D011994:Recombinant Proteins; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D003094:Collagen