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Endothelin-A Receptor Antagonism during Acute Myocardial Infarction in Rats

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Abstract

Endothelin levels are increased in rats with experimentally induced myocardial infarction. The purpose of this study was to determine whether endothelin-A (ETA) receptor antagonism alters ventricular remodeling and the development 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 infarcts, ETA receptor antagonist (n=8; vehicle, n = 5) had no effect. However, in rats with infarcts ETA antagonism (n = 14, MI = 35%; vehicle: n = 19, MI = 32%) reduced systemic arterial and LV systolic (but not end-diastolic) pressures and shifted the pressure-volume relationship to the right. Because LV mass was not changed, the volume-to-mass ratio was increased and was correlated inversely with the ability of the LV to maximally develop pressure. This increase in volume at low distending pressures was also coupled with a tendency (P < 0.06) for reduced scar thickness, suggesting that early initiation of an ETA receptor antagonism increased infarct expansion. The reduction in blood pressure offset the increase in volume such that wall stresses were unchanged, as was LV mass. The early use of ETA receptor antagonism in the rat model of myocardial infarction did not beneficially alter LV remodeling.

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Authors and Affiliations

  1. Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Janice M. Pfeffer

  2. Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Peter V. Finn, Leonardo A.M. Zornoff & Marc A. Pfeffer

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  1. Janice M. Pfeffer
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  2. Peter V. Finn
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  3. Leonardo A.M. Zornoff
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  4. Marc A. Pfeffer
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Pfeffer, J.M., Finn, P.V., Zornoff, L.A. et al. Endothelin-A Receptor Antagonism during Acute Myocardial Infarction in Rats. Cardiovasc Drugs Ther 14, 579–587 (2000). https://doi.org/10.1023/A:1007890126061

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