Reperfusion-induced arrhythmias are suppressed by inhibition of the angiotensin II type 1 receptor

Cardiology. 2003;99(2):61-7. doi: 10.1159/000069722.

Abstract

We examined antiarrhythmic effects of drugs, including renin-angiotensin system (RAS) inhibitors, on reperfusion arrhythmias in rats in vivo. Anesthetized rats were subjected to 5 min of coronary occlusion and 30 min of reperfusion. Arrhythmia scores, calculated as the product of the type of arrhythmia (1 for ventricular tachycardia, 2 for ventricular fibrillation) and its duration (in seconds), were adopted to evaluate the severity of arrhythmias. Reperfusion arrhythmias were suppressed by Na(+)/H(+) exchange inhibitor, Na(+)/Ca(2+) exchange inhibitor and L-type Ca channel antagonist by more than 90%. Angiotensin-converting enzyme inhibitor and angiotensin II (Ang II) type 1 receptor (AT(1)) antagonist also modestly (by 60-70%) but significantly decreased reperfusion arrhythmias. These effects were not reversed by co-administration of bradykinin B(2) receptor antagonist or AT(2) antagonist, respectively. Effects of superoxide dismutase (SOD) were also examined, but SOD proved ineffective. Effects of Na(+)/H(+) exchange inhibitor, Na(+)/Ca(2+) exchange inhibitor and L-type Ca channel antagonist suggest a causative relationship of Ca overload in reperfusion arrhythmias. These transport systems are known to be activated by Ang II. Thus, the antiarrhythmic action of RAS inhibitors might be attributable to the inhibition of the action of Ang II via AT(1).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Anti-Arrhythmia Agents / therapeutic use*
  • Arrhythmias, Cardiac / drug therapy*
  • Arrhythmias, Cardiac / epidemiology
  • Arrhythmias, Cardiac / etiology*
  • Blood Pressure / drug effects
  • Calcium Channels / metabolism
  • Calcium Channels, L-Type / therapeutic use
  • Disease Models, Animal
  • Heart Ventricles / pathology
  • Incidence
  • Male
  • Models, Cardiovascular
  • Myocardial Infarction / pathology
  • Myocardial Reperfusion / adverse effects*
  • Myocardial Reperfusion Injury / drug therapy
  • Myocardial Reperfusion Injury / epidemiology
  • Myocardial Reperfusion Injury / etiology
  • Rats
  • Rats, Wistar
  • Receptor, Angiotensin, Type 1
  • Receptors, Angiotensin / therapeutic use*
  • Renin-Angiotensin System / drug effects
  • Risk Factors
  • Sodium Channels / metabolism
  • Treatment Outcome

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Anti-Arrhythmia Agents
  • Calcium Channels
  • Calcium Channels, L-Type
  • Receptor, Angiotensin, Type 1
  • Receptors, Angiotensin
  • Sodium Channels