Endothelin-A receptor antagonism during acute myocardial infarction in rats

Endothelin levels are increased in rats with experimentally induced myocard ial infarction. The purpose of this study was to determine whether endothel in-A (ETA) receptor antagonism alters ventricular remodeling and the develo pment of heart failure after myocardial infarction (MI). We administered 10 mg/kg/day of A-127722 to rats post-MI for 6 weeks. A hemodynamic study was performed and passive pressure-volume curves obtained. In rats without inf arcts, ETA receptor antagonist (n = 8; vehicle, n = 5) had no effect. Howev er, in rats with infarcts ETA antagonism (n = 14, MI = 35%; vehicle: n = 19 , MI = 32%) reduced systemic arterial and LV systolic (but not end-diastoli c) pressures and shifted the pressure-volume relationship to the right. Bec ause LV mass was not changed, the volume-to-mass ratio was increased and wa s correlated inversely with the ability of the LV to maximally develop pres sure. This increase in volume at low distending pressures was also coupled with a tendency (P < 0.06) for reduced scar thickness, suggesting that earl y initiation of an ETA receptor antagonism increased infarct expansion. The reduction in blood pressure offset the increase in volume such that mall s tresses were unchanged, as was LV mass. The early use of ETA receptor antag onism in the rat model of myocardial infarction did not beneficially alter LV remodeling.