Electromechanical effects of the direct renin inhibitor (aliskiren) on the pulmonary vein and atrium

Chin Feng Tsai, Yao Chang Chen, Yung Kuo Lin, Shih Ann Chen, Yi Jen Chen

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17 Citations (Scopus)

Abstract

Activation of the atrial renin-angiotensin system plays an important role in the pathophysiology of atrial fibrillation (AF). The pulmonary vein (PV) and left atrium (LA) are important trigger and substrate for the genesis of AF. We investigate the effects of a direct renin inhibitor, aliskiren, on the PV and LA arrhythmogenic activity and the underlying electromechanical mechanisms. Conventional microelectrodes were used to record action potentials and contractility in isolated rabbit PVs and LA tissues before and after the administration of aliskiren (0.1, 1, 3 and 10 μM). By the whole-cell patch clamp and indo-1 fluorimetric ratio techniques, ionic currents and intracellular calcium transient were studied in isolated single PV and LA cardiomyocyte before and after the administration of aliskiren (3 μM). Aliskiren (0.1, 1, 3 and 10 μM) reduced PV firing rate in a concentration-dependent manner (6, 10, 14 and 17%) and decreased PV diastolic tension, which could be attenuated in the presence of 100 μM L-N G-Nitroarginine Methyl Ester (L-NAME). Aliskiren induced PV automatic rhythm exit block causing slow and irregular PV activity with variable pauses. Aliskiren increased PV and LA contractility, which could be abolished by pre-treating with 0.1 μM ryanodine. Aliskiren (3 μM) decreased L-type calcium currents, but increased reverse-mode of Na +/Ca 2+ exchanger currents, intracellular calcium transients, and sarcoplasmic reticulum calcium content in PV and LA cardiomyocytes. Pretreatment with renin, losartan or angiotensin II did not alter the effect of aliskiren on sarcolemmal calcium flux. In conclusion, aliskiren reduces PV arrhythmogenic activity with a direct vasodilatory property and has a positive inotropic effect on cardiomyocytes. These findings may reveal the antiarrhythmic and anti-heart failure potentials of aliskiren.

Original languageEnglish
Pages (from-to)979-993
Number of pages15
JournalBasic Research in Cardiology
Volume106
Issue number6
DOIs
Publication statusPublished - Nov 2011

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Keywords

  • Aliskiren
  • Arrhythmia
  • Calcium transient
  • Pulmonary vein

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

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