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 anti-arrhythmic and anti-heart failure potentials 
of aliskiren.