title: Blockade of angiotensin II improves hyperthyroid induced abnormal atrial electrophysiological properties.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Peilin
authors.initials: P
authors.lastname: Xiao
authors.forename: Chonghan
authors.initials: C
authors.lastname: Gao
authors.forename: Jinqi
authors.initials: J
authors.lastname: Fan
authors.forename: Huaan
authors.initials: H
authors.lastname: Du
authors.forename: Yi
authors.initials: Y
authors.lastname: Long
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Yin
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001552:Benzazepines / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006979:Hyperthermia, Induced; D006980:Hyperthyroidism / Q000150:complications*; D000077405:Irbesartan; D008297:Male; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000502:physiology*; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D014158:Transcription, Genetic; D015431:Weight Loss / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D001713:Biphenyl Compounds; D020746:Calcium Channels, L-Type; D017630:Connexins; D051672:Shal Potassium Channels; D013777:Tetrazoles; D000077405:Irbesartan; C044946:benazepril