Adrenomedullin administration immediately after myocardial infarction ameliorates progression of heart failure in rats.
BACKGROUND
Adrenomedullin (AM) is expressed in cardiac tissue, and plasma AM levels increase in patients with acute myocardial infarction (MI). This study was performed to determine whether AM administration immediately after acute MI inhibits progression of heart failure in rats.


RESULTS
Rats were infused with 1.0 microg/h IP AM or saline over 7 days immediately after MI inducted by left coronary ligation and were examined 9 weeks after MI. Compared with the saline infusion, AM infusion significantly improved survival (59% versus 81%; P<0.05) and body weight gain (32%; P<0.01) and reduced heart weight (-28%; P<0.01), lung weight (-26%; P<0.01), left ventricular (LV) end-diastolic pressure (11.4+/-2.0 versus 4.0+/-0.6 mm Hg, mean+/- SEM; P<0.01), collagen volume fraction of noninfarcted LV (-39%; P<0.05), and plasma levels of endogenous rat AM (-38%; P<0.05) without affecting infarct size. To investigate the mechanism of AM actions, another series of MI rats infused with AM were killed on day 7. AM infusion had no effect on organ weights and hemodynamic parameters on day 7 of MI but significantly reduced urinary excretion of isoprostane (-61%; P<0.01) and noninfarcted LV mRNA levels of ACE (-31%; P<0.05) and p22-phox (-30%; P<0.05).


CONCLUSIONS
AM administration during the early period of MI improved the survival and ameliorated progression of LV remodeling and heart failure. This beneficial effect was accompanied by reductions in oxidative stress and ACE mRNA expression in noninfarcted LV in the AM infusion period.
Nakamura
Ryosai
R
First Department of Internal Medicine, Miyazaki Medical College, Kiyotake, Miyazaki 889-1692, Japan.
Kato
Johji
J
Kitamura
Kazuo
K
Onitsuka
Hisamitsu
H
Imamura
Takuroh
T
Cao
Yuanning
Y
Marutsuka
Kousuke
K
Asada
Yujiro
Y
Kangawa
Kenji
K
Eto
Tanenao
T
D053607:Adrenomedullin; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D006333:Heart Failure / Q000209:etiology / Q000517:prevention & control*; D006439:Hemodynamics / Q000187:drug effects; D008026:Ligation; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D023421:Models, Animal; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009252:NADPH Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D019255:NADPH Oxidases; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis / Q000235:genetics; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
D026901:Membrane Transport Proteins; D010455:Peptides; D010750:Phosphoproteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D053607:Adrenomedullin; C075750:8-epi-prostaglandin F2alpha; D000450:Aldosterone; D015237:Dinoprost; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase; D007703:Peptidyl-Dipeptidase A