Antiarrhythmic effects of losartan and enalapril in canine pulmonary vein sleeve preparations

J Cardiovasc Electrophysiol. 2011 Jun;22(6):698-705. doi: 10.1111/j.1540-8167.2010.01972.x. Epub 2010 Dec 16.

Abstract

Introduction: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II-receptor blockers (ARBs) are prototypes of "upstream" therapy for the management of atrial fibrillation (AF). Ectopic activity arising from the PV sleeves plays a prominent role in the development of AF.

Methods: Transmembrane action potentials were recorded from canine superfused left superior or inferior PV sleeves using standard microelectrode techniques. Acetylcholine (ACh, 1 μM), isoproterenol (1 μM), high calcium ([Ca(2+)](o) = 5.4 mM) or a combination was used to induce early or delayed afterdepolarizations (EADs or DADs) and triggered activity.

Results: The ARB losartan (1 μM, n = 5) and the ACE inhibitor enalapril (10 μM, n = 5) produced no significant change in action potential duration, maximum rate of rise of action potential upstroke (V(max)), action potential amplitude or take-off potential at basic cycle lengths of 200 to 2000 ms. Losartan (1 μM) and enalapril (10-20 μM) markedly attenuated or suppressed EADs and DAD-induced triggered activity elicited by exposure of the PV sleeves to ACh, isoproterenol or high calcium following rapid pacing in 6 of 6 (losartan) and 4 of 5 (enalapril) PV sleeve preparations. Neither losartan nor enalapril altered Ca(2+) or K(+) channel currents in enzymatically-dissociated atrial myocytes at these concentrations.

Conclusions: Our data suggest that in addition to their "upstream" effects to reduce atrial structural remodeling, ACE inhibitors and ARBs exert a "direct" antiarrhythmic effect by suppressing triggers responsible for the genesis of AF and other atrial arrhythmias.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / administration & dosage
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Enalapril / administration & dosage*
  • Heart Conduction System / drug effects
  • Heart Conduction System / physiopathology*
  • Heart Rate / drug effects*
  • Losartan / administration & dosage*
  • Pulmonary Veins / drug effects
  • Pulmonary Veins / physiopathology*

Substances

  • Anti-Arrhythmia Agents
  • Enalapril
  • Losartan