Catecholamine effects on cardiac remodelling, oxidative stress and fibrosis in experimental heart failure.
The aim of the study was to assess the relationships between oxidative stress, cardiac remodelling and fibrosis on an experimental model of heart failure with adrenergic stimulation. Large myocardial infarction (approximately 50% of the left ventricle myocardium) was obtained by ligation of the left coronary artery of normotensive male Wistar rats. Sham animals were submitted to left thoracotomy without coronary ligation. In order to perform cardiac stimulation by catecholamines, mini-osmotic pumps were implanted in animals 10 weeks after surgery to deliver noradrenalin for a 2-week period. At the end of this period, the following investigations were performed: haemodynamics, morphometry, fibrosis quantification, plasma and tissue catecholamine assay and oxidative stress status. Coronary ligation induced dilatation of left ventricle with compensatory hypertrophy of the right ventricle and of the remaining left ventricle myocardium. This remodelling process was associated in non-infarcted myocardium with increased collagen infiltration and increased oxidative stress. Ten weeks after surgery, the chronic administration of noradrenalin for 2 weeks did not increase oxidative stress. Noradrenalin, however, induced inotropic stimulation and myocardial hypertrophy, but to a lesser extent in infarcted rats compared to sham rats. Our results suggest that noradrenalin infusion to levels in excess of those seen post-infarction is associated with fibrosis and oxidative stress. Moreover, noradrenalin in infarcted animals caused additional fibrosis without further increasing oxidative stress. The mechanism of catecholamine-induced fibrosis may thus involve different processes such as ischaemia, increased mechanical stress, cytokines and neurohormones.
Bonnefont-Rousselot
Dominique
D
Laboratoire de Biochimie B, Coeur et Vaisseaux, Groupe Hospitalier Pitié-Salpêtrière (AP-HP), 47 boulevard de l'Hôpital, 75651 Paris Cedex 13, France. dominique.rousselot@psl.ap-hop-paris.fr
Mahmoudi
Allal
A
Mougenot
Nathalie
N
Varoquaux
Odile
O
Le Nahour
Gilles
G
Fouret
Pierre
P
Lechat
Philippe
P
D000818:Animals; D004195:Disease Models, Animal; D004452:Echocardiography; D005355:Fibrosis; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D009638:Norepinephrine