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Effects of the Galanin Receptor Antagonist M40 on Cardiac Function and Remodeling in Rats with Heart Failure.

AbstractBACKGROUND:
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).
CONCLUSION:
M40 improves cardiac function and attenuates remodeling, suggesting that galanin receptor antagonist may be a potential therapeutic agent for HF.
AuthorsAo Chen, Min Li, Lei Song, Yunhe Zhang, Zhangyuan Luo, Wenzan Zhang, Yingmin Chen, Ben He
JournalCardiovascular therapeutics (Cardiovasc Ther) Vol. 33 Issue 5 Pg. 288-93 (Oct 2015) ISSN: 1755-5922 [Electronic] England
PMID26177027 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2015 John Wiley & Sons Ltd.

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