Affordable Access

deepdyve-link
Publisher Website

Resiniferatoxin reduces ventricular arrhythmias in heart failure via selectively blunting cardiac sympathetic afferent projection into spinal cord in rats.

Authors
  • Wu, Yong1
  • Hu, Zhengtao1
  • Wang, Deguo2
  • Lv, Kun3
  • Hu, Nengwei4
  • 1 Department of Gerontology, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, PR China; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, Anhui, 241001, PR China. , (China)
  • 2 Department of Gerontology, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, PR China; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, Anhui, 241001, PR China. Electronic address: [email protected] , (China)
  • 3 Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, Anhui, 241001, PR China. , (China)
  • 4 Department of Gerontology, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, PR China; Department of Physiology and Neurobiology, Zhengzhou University School of Medicine, Zhengzhou, 450001, PR China; Department of Pharmacology & Therapeutics and Institute of Neuroscience, Trinity College, Dublin 2, Ireland. Electronic address: [email protected] , (China)
Type
Published Article
Journal
European journal of pharmacology
Publication Date
Dec 04, 2019
Volume
867
Pages
172836–172836
Identifiers
DOI: 10.1016/j.ejphar.2019.172836
PMID: 31811858
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Excessive sympathetic activity is associated with heart failure and ventricular arrhythmias, which regulated by enhanced cardiac sympathetic afferent reflex, which can be blunted by resiniferatoxin, a selective receptor agonist of transient vanilloid potential 1 (TRPV1) + primary sensory afferents. The present study is aimed to determine whether intrathecal resiniferatoxin application affect cardiac sympathetic tone and electrophysiology, furtherly create a new effective strategy to prevent lethal arrhythmias in chronic heart failure. Four weeks after coronary artery occlusion to induce heart failure in rats, RTX (2μg/10 μl) or vehicle was injected intrathecally into the T2/T3 interspace. Cardiac sympathetic nerve activities (CSNA) and cardiac electrophysiology were evaluated two weeks later. Intrathecal resiniferatoxin significantly and selectively abolished the afferent markers expression (TRPV1 and calcitonin gene-related peptide) in dorsal horn and reduced overactivated CSNA. Electrophysiological studies revealed that resiniferatoxin administration intrathecally significantly reversed the prolongation of action potential duration (APD) and APD alternan, reduced the inducibilities of ventricular arrhythmias. Moreover, the over-activated calcium handling related protein CaMKII and RyR2 in heart failure was reversed by resiniferatoxin administration. In conclusion, these results firstly demonstrate that central chemo-ablation of the TRPV1+ afferents in spinal cord prevent heart from ventricular arrhythmias in heart failure via selectively blunting cardiac sympathetic afferent projection into spinal cord, which suggest a novel promising therapeutic method for anti-arrhythmia in heart failure. Copyright © 2019. Published by Elsevier B.V.

Report this publication

Statistics

Seen <100 times