Myocardial infarction causes sex-dependent dysfunction in vagal sensory glutamatergic neurotransmission that is mitigated by 17ß-estradiol.
JCI Insight
; 9(14)2024 Jun 17.
Article
en En
| MEDLINE
| ID: mdl-38885308
ABSTRACT
Parasympathetic dysfunction after chronic myocardial infarction (MI) is known to predispose ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]). VT/VF after MI is more common in males than females. The mechanisms underlying the decreased vagal tone and the associated sex difference in the occurrence of VT/VF after MI remain elusive. In this study, using optogenetic approaches, we found that responses of glutamatergic vagal afferent neurons were impaired following chronic MI in male mice, leading to reduced reflex efferent parasympathetic function. Molecular analyses of vagal ganglia demonstrated reduced glutamate levels, accompanied by decreased mitochondrial function and impaired redox status in infarcted males versus sham animals. Interestingly, infarcted females demonstrated reduced vagal sensory impairment, associated with greater vagal ganglia glutamate levels and decreased vagal mitochondrial dysfunction and oxidative stress compared with infarcted males. Treatment with 17ß-estradiol mitigated this pathological remodeling and improved vagal neurotransmission in infarcted male mice. These data suggest that a decrease in efferent vagal tone following MI results from reduced glutamatergic afferent vagal signaling that may be due to impaired redox homeostasis in the vagal ganglia, which subsequently leads to pathological remodeling in a sex-dependent manner. Importantly, estrogen prevents pathological remodeling and improves parasympathetic function following MI.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nervio Vago
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Transmisión Sináptica
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Ácido Glutámico
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Estradiol
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Infarto del Miocardio
Límite:
Animals
Idioma:
En
Revista:
JCI Insight
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Estados Unidos