Objective     To investigate the effect of renin angiotensin system (RAS) on thyroxine-induced atrial electrical remodeling and ion channel remodeling in experimental hyperthyroid rabbits and the effect of RAS blocker on thyroxine-induced atrial remodeling.      Methods     Forty New Zealan

d white rabbits were assigned to four groups (n=10): a normal control group

a thyroxine group

a benazepril group

and an irbesartan group. In the thyroxine group

benazepril group

and irbesartan group

levothyroxine (L-Thy) was given to the rabbits by intraperitoneal injection to establish a rabbit model of hyperthyroidism

and benazepril and irbesartan were administered orally in combination with L-Thy in the benazepril group and irbesartan group

respectively. Four weeks later

burst stimulation was used to induce atrial fibrillation (AF). Electrophysiological testing was performed to measure atrial effective refractory period (AERP) and evaluate AERP frequency adaptability and AF vulnerability. Real-time PCR was used to measure the mRNA expression levels of L-Ca

2+

channel-related subunits (Cav1.2 and Cav1.3)  and Ito channel-related subunits (kv1.4

kv4.2

and kv4.3). Western blot was used to measure the protein expression levels of Cav1.2 and kv4.2.      Results     No significant difference was found in AERP among the thyroxine group (75.13±5.41 ms)

benazepril group (76.63±4.44 ms)

and irbesartan group (79.00±4.95 ms) (P0.05). Benazepril or irbesartan could significantly decrease AF vulnerability and significantly increase AERP frequency adaptation. The protein expression of L-Ca

2+

channel-related subunit Cav1.2 was significantly increased in the benazepril group (1.15±0.24) and irbesartan group (1.08±0.17)

as compared with that in the thyroxine group (0.56±0.11) (P0.01). Benazepril and irbesartan did not markedly inhibit the effect of L-Thy on the mRNA and protein expression of Ito channel-related subunits (P0.05).      Conclusion     RAS may play an important role in thyroxine-induced atrial electrical remodeling and ion channel remodeling. Benazepril or irbesartan may reduce thyroxine-induced atrial electrical remodeling and ion channel remodeling and the increase of AF vulnerability attributed to thyroxine.