Losartan but not enalaprilat acutely reduces reperfusion ventricular tachyarrhythmias in hypertrophied rat hearts after low-flow ischaemia

J Pharm Pharmacol. 2004 Apr;56(4):521-8. doi: 10.1211/0022357023178.

Abstract

Based on clinical and experimental studies, angiotensin II receptor blockers and angiotensin converting enzyme inhibitors have been proposed to exert acute anti-arrhythmic effects in heart failure patients. Therefore, the goal of this study was to assess acute anti-arrhythmic effects of losartan and enalaprilat in hypertrophied rat hearts during low-flow ischaemia and reperfusion. In dose-finding experiments in non-hypertrophied isolated perfused hearts, we performed dose-response curves of losartan and enalaprilat studying monophasic action potential duration at 90% repolarisation (MAPD(90%)) and ventricular fibrillation (VF) threshold. Subsequently, we determined the effects of losartan and enalaprilat (in therapeutically relevant concentrations) on ventricular tachyarrhythmias induced by low-flow ischaemia/reperfusion in hearts demonstrating left ventricular (LV) hypertrophy 70 days after aortic banding. We found that neither drug significantly affected MAPD(90%) (1 nM-1 mM) or VF threshold (1 microM losartan and 10 microM enalaprilat) in non-hypertrophied hearts. Similarly in hypertrophied hearts, neither drug significantly affected the incidence or the duration of ventricular tachyarrhythmias (ventricular tachycardia and VF) during low-flow ischaemia. However, 1 microM losartan significantly reduced the duration of ventricular tachyarrhythmias during reperfusion. In conclusion, neither losartan nor enalaprilat is acutely anti-arrhythmic in hypertrophied rat hearts during low-flow ischaemia. During reperfusion, however, losartan but not enalaprilat exerts acute anti-arrhythmic effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Anti-Arrhythmia Agents / administration & dosage
  • Anti-Arrhythmia Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Enalaprilat / administration & dosage
  • Enalaprilat / pharmacology*
  • Heart / drug effects
  • Heart / physiopathology
  • Hypertrophy, Left Ventricular / complications
  • In Vitro Techniques
  • Losartan / administration & dosage
  • Losartan / pharmacology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / complications
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / physiopathology
  • Tachycardia, Ventricular / etiology
  • Tachycardia, Ventricular / prevention & control*
  • Ventricular Fibrillation / etiology
  • Ventricular Fibrillation / physiopathology
  • Ventricular Fibrillation / prevention & control*

Substances

  • Anti-Arrhythmia Agents
  • Enalaprilat
  • Losartan