title: Effects of the Galanin Receptor Antagonist M40 on Cardiac Function and Remodeling in Rats with Heart Failure.
abstract: BACKGROUND
  Sympathetic activation and parasympathetic withdrawal are important characteristics of heart failure. Recent studies demonstrate that galanin reduces the discharge of acetylcholine and inhibits vagal bradycardia by acting on galanin receptor type 1 (GalR1). We speculated that blocking GalR1 is beneficial for heart failure.
  
  
  METHODS
  Rats with heart failure were induced by myocardial infarction. The rats were injected intraperitoneally with galanin receptor antagonist M40 solution (30 nmol/kg) or saline for 4 weeks. Cardiac function was assessed by echocardiography and brain natriuretic peptide (BNP) in plasma. The ratio of heart weight to body weight (HW/BW), hematoxylin-eosin (HE), and Masson trichrome stain was used to evaluate cardiac remodeling. Tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) in plasma, and sarco(endo)plasmic reticulum Ca(2+) -ATPase (SERCA2) in heart tissue were detected to confirm the mechanism of the cardioprotection effect.
  
  
  RESULTS
  Compared with rats injected with saline, M40 effectively improved cardiac function of contraction; decreased BNP, IL-6, and HW/BW (all P < 0.05); attenuated cardiac fibrosis; and upregulated SERCA2 (P < 0.05).
  
  
  CONCLUSIONS
  M40 improves cardiac function and attenuates remodeling, suggesting that galanin receptor antagonist may be a potential therapeutic agent for HF.
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ao
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jie Sheng (Shanghai) Biological Technology Co., Ltd, Shanghai, China.
authors.forename: Zhangyuan
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Jie Sheng (Shanghai) Biological Technology Co., Ltd, Shanghai, China.
authors.forename: Wenzan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ben
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004396:Coloring Agents; D004195:Disease Models, Animal; D004562:Electrocardiography; D004719:Endomyocardial Fibrosis / Q000517:prevention & control; D004797:Enzyme-Linked Immunosorbent Assay; D019004:Galanin / Q000494:pharmacology*; D006333:Heart Failure / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009206:Myocardium / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009929:Organ Size; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044088:Receptors, Galanin / Q000037:antagonists & inhibitors*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D004396:Coloring Agents; D015850:Interleukin-6; C079517:M40; D010446:Peptide Fragments; D044088:Receptors, Galanin; D014409:Tumor Necrosis Factor-alpha; D020097:Natriuretic Peptide, Brain; D019004:Galanin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human
keywords: Antagonist; Cardiac function; Galanin; Heart failure; M40; Remodeling