Angiotensin-(1-7) Prevent Atrial Tachycardia Induced Sodium Channel Remodeling

BackgroundActivation 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 (I-Na) in a canine model of atrial tachycardia. MethodsEighteen 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 g/kg/h) was administered intravenously during pacing. Whole-cell patch clamp techniques were utilized to record I-Na from canine atrial myocytes. Reverse transcription-polymerase chain reaction was used to assess possible underlying changes in cardiac Na+ channels (Nav1.5). ResultsOur results showed that I-Na density and expression of the Nav1.5 mRNA significantly decreased following pacing (P< 0.05 vs sham); however, the half-activation voltage (V-1/2act) and half-inactivation voltage (V-1/2inact) of I-Na were not significantly altered (P > 0.05 vs sham). Ang-(1-7) treatment significantly increased I-Na densities and hyperpolarized V-1/2act without concomitant changes in V-1/2inact but have no effect on the expression of the Nav1.5 gene. ConclusionsAng-(1-7) significantly increased I-Na densities, which contributed to improving intraatrial conduction and decreasing the likelihood of atrial fibrillation maintenance.