Endothelin receptors in the brain modulate autonomic responses and arrhythmogenesis during acute myocardial infarction in rats

Life Sci. 2019 Dec 15;239:117062. doi: 10.1016/j.lfs.2019.117062. Epub 2019 Nov 14.


Aims: Endothelin has been implicated in various processes in the brain, including the modulation of sympathetic responses. The present study examined the pathophysiologic role of brain endothelin-receptors in the setting of acute myocardial infarction, characterized by high incidence of ventricular tachyarrhythmias.

Main methods: We investigated the effects of intracerebroventricular administration of antagonists of endothelin-receptors ETA, ETB, or both, during a 24 h-observation period post-coronary ligation in (n = 70) rats. Continuous recording was performed via implanted telemetry transmitters, followed by arrhythmia-analysis and calculation of autonomic indices derived from heart rate variability. The regional myocardial electrophysiologic properties were assessed by monophasic action potentials and multi-electrode recordings.

Key findings: Sympathetic-activity was decreased and vagal-activity was enhanced after intracerebroventricular ETA-receptor blockade, thus attenuating regional myocardial repolarization inhomogeneity. As a result, the incidence of ventricular tachyarrhythmias was markedly lower in this group. Such effects were also observed after intracerebroventricular blockade of ETB-, or both, ETA- and ETB-receptors, although to a lesser extent.

Significance: ETA-receptors in the brain modulate sympathetic and vagal responses and alter arrhythmogenesis during evolving myocardial necrosis in rats. These findings provide insights into arrhythmogenic mechanisms during acute myocardial infarction and call for further investigation on the role of endothelin in the central autonomic network.

Keywords: Brain endothelin receptors; ET(A)-receptor; ET(B)-receptor; Myocardial infarction; Sympathetic response; Vagal response; Ventricular tachyarrhythmias.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Arrhythmias, Cardiac / complications
  • Arrhythmias, Cardiac / metabolism
  • Autonomic Nervous System / metabolism
  • Brain / metabolism
  • Brain / physiology
  • Endothelin Receptor Antagonists / metabolism
  • Endothelin Receptor Antagonists / pharmacology
  • Endothelin-1 / pharmacology
  • Endothelins / metabolism
  • Endothelins / pharmacology*
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Male
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology*
  • Myocardium / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Endothelin A / metabolism
  • Receptor, Endothelin B / metabolism
  • Receptors, Endothelin / metabolism*
  • Receptors, Endothelin / physiology
  • Sympathetic Nervous System / drug effects
  • Tachycardia, Ventricular / metabolism
  • Tachycardia, Ventricular / physiopathology


  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Endothelins
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Receptors, Endothelin