Aggravation of left ventricular remodeling by a novel specific endothelin ET(A) antagonist EMD94246 in rats with experimental myocardial infarction.
An endothelin (ET(A)) antagonist reduced mortality and an ET(A) + ET(B) antagonist prevented left ventricular dilatation in rats with large myocardial infarction. This study tested the hypothesis that long-term blockade of the ET(A) receptor would have beneficial effects on left ventricular function and remodeling. Three hours after coronary artery ligation or sham operation in rats, EMD94246 (100 mg/kg/day, n=62) or placebo (n=62) was given by gavage. Eight weeks later, left ventricular hemodynamic measurements were performed and left ventricular volume determined with a double-lumen catheter after KCl-induced cardiac arrest. EMD94246 treatment had no effects on mortality or hemodynamic parameters. In rats with large infarcts, EMD94246 significantly increased left ventricular volume (2.5+/-0.1 vs. 2.2+/-0.1 ml/kg; p < 0.05). The nonpeptide ET(A)-selective antagonist EMD94246 promoted chronic left ventricular dilatation in rats with large myocardial infarction.
Hu
K
K
II. Medizinische Klinik, Klinikum Mannheim der Universität Heidelberg, Germany.
Gaudron
P
P
Schmidt
T J
TJ
Hoffmann
K D
KD
Ertl
G
G
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D005260:Female; D009203:Myocardial Infarction / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects*
D065128:Endothelin Receptor Antagonists; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin