title: Effect of irbesartan on development of atrial fibrosis and atrial fibrillation in a canine atrial tachycardia model with left ventricular dysfunction, association with p53.
abstract: Effects of an angiotensin II receptor blocker, irbesartan (IRB), on the development of atrial fibrosis and atrial fibrillation (AF) were assessed in a canine model of atrial tachycardia remodeling (ATR) with left ventricular dysfunction, together with its possible association with involvement of p53. Atrial tachypacing (400 bpm for 4 weeks) was used to induce ATR in beagles treated with placebo (ATR-dogs, n = 6) or irbesartan (IRB-dogs, n = 5). Non-paced sham dogs served as control (Control-dogs, n = 4). ATR- and IRB-dogs developed tachycardia-induced left ventricular dysfunction. Atrial effective refractory period (AERP) shortened (83 ± 5 ms, p < 0.05), inter-atrial conduction time prolonged (72 ± 2 ms, p < 0.05), and AF duration increased (29 ± 5 s, p < 0.05 vs. baseline) after 4 weeks in ATR-dogs. ATR-dogs also had a larger area of atrial fibrous tissue (5.2 ± 0.5 %, p < 0.05 vs. Control). All these changes, except for AERP, were attenuated in IRB-dogs (92 ± 3 ms, 56 ± 3 ms, 9 ± 5 s, and 2.5 ± 0.7 %, respectively; p < 0.05 vs. ATR for each). In ATR-dogs, p53 expression in the left atrium decreased by 42 % compared with Control-dogs (p < 0.05); however, it was highly expressed in IRB-dogs (+89 % vs. ATR). Transforming growth factor (TGF)-β1 expression was enhanced in ATR-dogs (p < 0.05 vs. Control) but reduced in IRB-dogs (p < 0.05 vs. ATR). Irbesartan suppresses atrial fibrosis and AF development in a canine ATR model with left ventricular dysfunction in association with p53.
authors.affiliation: Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kataoka
authors.affiliation: Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan. knishida@med.u-toyama.ac.jp.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Nishida
authors.affiliation: Department of Legal Medicine, University of Toyama, Toyama, Japan.
authors.forename: Koshi
authors.initials: K
authors.lastname: Kinoshita
authors.affiliation: Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakatani
authors.affiliation: Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tsujino
authors.affiliation: Clinical Research and Ethics Center, University of Toyama, Toyama, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Mizumaki
authors.affiliation: Saiseikai Toyama Hospital, Toyama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kinugawa
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D064752:Atrial Remodeling / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D004452:Echocardiography; D005355:Fibrosis; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D000077405:Irbesartan; D013617:Tachycardia, Supraventricular / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; D016159:Tumor Suppressor Protein p53; D000077405:Irbesartan
keywords: Angiotensin II; Remodeling; TGF-β1; p53