Aggravation of left ventricular remodeling by a novel specific endothelin ET(A) antagonist EMD94246 in rats with experimental myocardial infarction

J Cardiovasc Pharmacol. 1998 Sep;32(3):505-8. doi: 10.1097/00005344-199809000-00024.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Endothelin Receptor Antagonists*
  • Female
  • Myocardial Infarction / etiology
  • Myocardial Infarction / physiopathology*
  • Rats
  • Rats, Wistar
  • Receptor, Endothelin A
  • Receptors, Endothelin / physiology
  • Ventricular Function, Left / drug effects*

Substances

  • Endothelin Receptor Antagonists
  • Receptor, Endothelin A
  • Receptors, Endothelin