Resiniferatoxin reduces ventricular arrhythmias in heart failure via selectively blunting cardiac sympathetic afferent projection into spinal cord in rats.
Eur J Pharmacol
; 867: 172836, 2020 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-31811858
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arritmias Cardíacas
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Bloqueio Nervoso Autônomo
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Diterpenos
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Gânglios Simpáticos
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Insuficiência Cardíaca
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2020
Tipo de documento:
Article