Angiotensin-(1-7) prevents atrial fibrosis and atrial fibrillation in long-term atrial tachycardia dogs

Renin-angiotensin system (RAS) is activated in the fibrillating atria. Angiotensin-(1-7) [Ang-(1-7)] counterbalances the actions of angiotensin II (Ang II). To investigate the effects of Ang-(1-7) on the long-term atrial tachycardia-induced atrial fibrosis and atrial fibrillation (AF) vulnerability, eighteen dogs were assigned to sham group, paced group, or paced + Ang-(1-7) group, 6 dogs in each group. Rapid atrial pacing at 500 bpm was maintained for 14 days, but dogs in the sham group were instrumented without pacing. During the pacing, Ang-(1-7) (6 μg· kg− 1 ·h− 1) was given intravenously. After pacing, atrial mRNA expression of ERK1/ERK2 and atrial fibrosis were assessed, the inducibility and duration of AF were measured. Compared with sham, ERK1/ERK2 mRNA expression was increased in the paced group (P < 0.05). Atrial tissue from the paced dogs showed a large amount of interstitial fibrosis, and the inducible rate of AF was increased at various BCLs in paced dogs (P < 0.01). Compared with the paced group, Ang-(1-7) prevented the increase of ERK1/ERK2 mRNA expression (P < 0.01 and P < 0.05, respectively), and attenuated the interstitial fibrosis (P < 0.01). Inducibility and duration of AF were reduced by Ang-(1-7) at various BCLs. In conclusion, Ang-(1-7) reduced AF vulnerability in chronic paced atria, and antifibrotic actions contributed to its preventive effects on AF.