Angiotensin-(1-7) prevent atrial tachycardia induced sodium channel remodeling

Abstract

Background Activation of the renin-angiotensin system plays an important role in atrial electrical remodeling; angiotensin-(1-7) (Ang-(1-7)) counterbalances the actions of angiotensin II. The aim of this study was to determine the effects of Ang-(1-7) on cardiac sodium current (INa) in a canine model of atrial tachycardia. Methods Eighteen dogs were randomly assigned to sham, pacing, or pacing + Ang-(1-7) groups (n = 6 in each group). Rapid atrial pacing (500 beats/min) was maintained for 2 weeks, while the dogs in the sham group were not paced. Ang-(1-7) (6 μg/kg/h) was administered intravenously during pacing. Whole-cell patch clamp techniques were utilized to record INa from canine atrial myocytes. Reverse transcription-polymerase chain reaction was used to assess possible underlying changes in cardiac Na+ channels (Nav1.5). Results Our results showed that INa density and expression of the Nav1.5 mRNA significantly decreased following pacing (P < 0.05 vs sham); however, the half-activation voltage (V1/2act) and half-inactivation voltage (V1/2inact) of INa were not significantly altered (P > 0.05 vs sham). Ang-(1-7) treatment significantly increased INa densities and hyperpolarized V1/2act without concomitant changes in V1/2inact but have no effect on the expression of the Nav1.5 gene. Conclusions Ang-(1-7) significantly increased INa densities, which contributed to improving intraatrial conduction and decreasing the likelihood of atrial fibrillation maintenance.