Irbesartan prevents sodium channel remodeling in a canine model of atrial fibrillation

Activation of the renin-angiotensin system (RAS) plays an important role in atrial electrical remodeling (AER). The purpose of the present study was to evaluate the effects of irbesartan on cardiac sodium current (INa) in a canine model of atrial fibrillation. Eighteen dogs were randomized into sham, pacing or pacing+irbesartan groups (n = 6 in each group). The dogs in the pacing and irbesartan group were paced at 500？bpm for two weeks. Irbesartan (60？mg·kg？1·d？1) was administered orally in the pacing+irbesartan groups. INa was recorded using the whole-cell patch clamp technique from canine atrial myocytes. The expressions of cardiac Na+ channels (Nav1.5) mRNA were semi-quantified by reverse transcription-polymerase chain reaction. Our results showed that INa density and Nav1.5 mRNA expression in the pacing group decreased significantly (p < 0.05 vs. sham). However, rapid atrial pacing had no effects on the half-activation voltage (V1/2act) and half-inactivation voltage (V1/2inact) of INa (p > 0.05 vs. sham). Irbesartan significantly increased INa densities and gene expression and hyperpolarized V1/2act without concomitant changes in V1/2inact. Irbesartan significantly increased INa densities, which contributed to improving intra-atrial conduction and prevented the induction and promotion of AF in atrial pacing dogs