title: Valsartan Reduced Atrial Fibrillation Susceptibility by Inhibiting Atrial Parasympathetic Remodeling through MAPKs/Neurturin Pathway.
abstract: OBJECTIVE
  Angiotensin II receptor blockers (ARBs) have been proved to be effective in preventing atrial structural and electrical remodelinq in atrial fibrillation (AF). Previous studies have shown that parasympathetic remodeling plays an important role in AF. However, the effects of ARBs on atrial parasympathetic remodeling in AF and the underlying mechanisms are still unknown.
  
  
  METHODS
  Canines were divided into sham-operated, pacing and valsartan + pacing groups. Rats and HL-1 cardiomyocytes were divided into control, angiotensin II (Ang II) and Ang II + valsartan groups, respectively. Atrial parasympathetic remodeling was quantified by immunocytochemical staining with anti-choline acetyltransferase (ChAT) antibody. Western blot was used to analysis the protein expression of neurturin.
  
  
  RESULTS
  Both inducibility and duration were increased in chronic atrial rapid-pacing canine model, which was significantly inhibited by the treatment with valsartan. The density of ChAT-positive nerves and the protein level of neurturin in the atria of pacing canines were both increased than those in sham-operated canines. Ang II treatment not only induced atrial parasympathetic remodeling in rats, but also up-regulated the protein expression of neurturin. Valsartan significantly prevented atrial parasympathetic remodeling, and suppressed the protein expression of neurturin. Meanwhile, valsartan inhibited Ang II -induced up-regulation of neurturin and MAPKs in cultured cardiac myocytes. Inhibition of MAPKs dramatically attenuated neurturin up-regulation induced by Ang II.
  
  
  CONCLUSIONS
  Parasympathetic remodeling was present in animals subjected to rapid pacing or Ang II infusion, which was mediated by MAPKs/neurturin pathway. Valsartan is able to prevent atrial parasympathetic remodeling and the occurrence of AF via inhibiting MAPKs/neurturin pathway.
authors.affiliation: Cardiovascular Department, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Geng
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhao
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Yun
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.forename: Sen
authors.initials: S
authors.lastname: Yan
authors.forename: Xue
authors.initials: X
authors.lastname: Ding
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Li
authors.forename: Dingyu
authors.initials: D
authors.lastname: Wang
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Li
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Pan
authors.forename: Yongtai
authors.initials: Y
authors.lastname: Gong
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Tan
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000517:prevention & control*; D004285:Dogs; D005260:Female; D020935:MAP Kinase Signaling System; D008297:Male; D051101:Neurturin / Q000378:metabolism*; D051381:Rats; D000068756:Valsartan / Q000494:pharmacology*
chemical_list: D051101:Neurturin; D000068756:Valsartan