title: Antiarrhythmic effects of losartan and enalapril in canine pulmonary vein sleeve preparations.
abstract: BACKGROUND
  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.
authors.affiliation: Masonic Medical Research Laboratory, Utica, New York 13501-1787, USA. sicouris@mmrl.edu
authors.forename: Serge
authors.initials: S
authors.lastname: Sicouri
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Cordeiro
authors.forename: Michael
authors.initials: M
authors.lastname: Talarico
authors.forename: Charles
authors.initials: C
authors.lastname: Antzelevitch
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage*; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects*; D019808:Losartan / Q000008:administration & dosage*; D011667:Pulmonary Veins / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D000889:Anti-Arrhythmia Agents; D004656:Enalapril; D019808:Losartan