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

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.

journal_name

J Cardiovasc Electrophysiol

journal_title

Journal of cardiovascular electrophysiology

authors

Sicouri S,Cordeiro JM,Talarico M,Antzelevitch C

doi

10.1111/j.1540-8167.2010.01972.x

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

698-705

issue

6

eissn

1045-3873

issn

1540-8167

journal_volume

22

pub_type

杂志文章

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