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 microg x kg(-1) x 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.
Liu
Enzhao
E
Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China.
Yang
Shengrong
S
Xu
Zhao
Z
Li
Jian
J
Yang
Wansong
W
Li
Guangping
G
D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology / Q000517:prevention & control*; D001483:Base Sequence; D017931:DNA Primers; D004285:Dogs; D005355:Fibrosis / Q000517:prevention & control*; D006325:Heart Atria / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013610:Tachycardia / Q000517:prevention & control*
D017931:DNA Primers; D010446:Peptide Fragments; D000803:Angiotensin I; C118790:angiotensin I (1-7)