AT1 receptor blockade prevents cardiac dysfunction after myocardial infarction in rats.
Myocardial infarction (MI) can induce severe alterations of contractile function that can, in turn, lead to heart failure. In a previous study, we have demonstrated that TNF-alpha was involved in cardiac contractile dysfunction 7 days after coronary artery ligation in rats. Since Angiotensin II type 1 (AT1) receptor can be involved in TNF-alpha production, we have investigated whether early short-term treatment with irbesartan, an AT1 receptor blocker, is able to limit TNF-alpha production within the heart and to improve cardiac function and geometry following MI in rats. Male Wistar rats were subjected to permanent coronary artery ligation and received either a placebo or irbesartan (50 mg/kg/day) per os daily from day 3 to day 6 after surgery. On day 7, cardiac TNF-alpha was significantly reduced in MI rats receiving irbesartan (p < 0.05). Moreover, irbesartan improved residual LV end-diastolic pressure under both basal conditions and after volume overload (p < 0.01). In addition, a significant leftward shift of the pressure-volume curve in the irbesartan-treated group was found versus placebo. Finally, infarct expansion index was also significantly improved by irbesartan (p < 0.01). In conclusion, early, short-term AT1 receptor blockade limits post-infarct cardiac TNF-alpha production and diminishes myocardial alterations observed 7 days after MI in the rat.
Berthonneche
Corinne
C
Laboratoire NVMC, IFRT 130 Ingénierie pour le Vivant, Université Joseph Fourier, Grenoble, France.
Sulpice
Thierry
T
Tanguy
Stéphane
S
O'Connor
Stephen
S
Herbert
Jean-Marc
JM
Janiak
Philippe
P
de Leiris
Joël
J
Boucher
François
F
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D000077405:Irbesartan; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D000077405:Irbesartan