Blockade of angiotensin II improves hyperthyroid induced abnormal atrial electrophysiological properties

Previous studies reported that RAS inhibitors prevented atrial fibrillation by improving atrial electrical and structural remodeling. However, the effect of RAS inhibitors on the substrates of atrial fibrillation (AF) underlying hyperthyroid is unclear.

Forty rabbits were assigned to four groups: sham group, thyroxine group, benazepril group and irbesartan group (10 per group). The atrial effective refractory period (AERP) was measured. The physiologic rate adaptation and the AF vulnerability were evaluated. The real-time PCR, Western blot or fluorescent immunohistochemistry was performed to detect the expression of AF related Ca+, K+ channel and gap junction.

No significant difference was found in AERP among the thyroxine group, benazepril group and irbesartan group (75.13±5.41ms vs. 76.63±4.44ms, 79±4.95ms, P=0.28). However, benazepril or irbesartan could reduce AF vulnerability underlying hyperthyroid (75% vs. 37%, 44%, for thyroxine group, benazepril group and irbesartan group, respectively), and significantly improved physiologic rate adaptation of the AERP. Furthermore, both drugs significantly reduced L-Ca(2+) channel related subunits (α1C or α1D) and interstitial fibrosis (17.1±2.2% vs. 12.3±1.8, 11.7±1.2%, P<0.01, for thyroxine group, benazepril group and irbesartan group, respectively), increased lateral/polar connection of Cx43 (1.04±0.16 vs. 1.33±0.29,1.28±0.25, P<0.01, for thyroxine group, benazepril group and irbesartan group, respectively) and improved the abnormal distribution of gap junctions (Cx40, Cx43) underlying hyperthyroid.

Blockade of angiotensin II could improve abnormal atrial electrophysiological properties and further reduce AF vulnerability by extenuating ion channel, gap junction and structural remodeling in experimental thyrotoxic rabbits.