Hypothalamic OXT neurons were chronically activated using a chemogenetic approach in an animal model of HF.
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Synaptic release of OXT onto parasympathetic autonomic targets was reduced in animals with HF but restored with daily treatment consisting of activation of OXT neurons.
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Long-term daily OXT neuron activation increased parasympathetic activity to the heart and reduced mortality, cardiac inflammation, and fibrosis and improved critical longitudinal in vivo indices of cardiac function.
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The benefits in cardiac function and autonomic balance in HF closely tracked the study-designed differences in initiation of OXT neuron activation in different groups.
Summary
This work shows long-term restoration of the hypothalamic oxytocin (OXT) network preserves OXT release, reduces mortality, cardiac inflammation, fibrosis, and improves autonomic tone and cardiac function in a model of heart failure. Intranasal administration of OXT in patients mimics the short-term changes seen in animals by increasing parasympathetic—and decreasing sympathetic—cardiac activity. This work provides the essential translational foundation to determine if approaches that mimic paraventricular nucleus (PVN) OXT neuron activation, such as safe, noninvasive, and well-tolerated intranasal administration of OXT, can be beneficial in patients with heart failure.
designer receptors exclusively activated by designer drug
HF
heart failure
IL
interleukin
LV
left ventricle
LVDP
left ventricle- developed pressure
PVN
paraventricular nucleus of the hypothalamus
OXT
oxytocin
SD
standard deviation
TAC
transascending aortic constriction
Cited by (0)
This work was supported by an American Autonomic Society postdoctoral fellowship (to Dr. Dyavanapalli), a predoctoral fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES) (to Dr. Rocha dos Santos), AHA SDG 18CDA34080353 (to Dr. Schunke), and NIH R01HL133862 (to Drs. Mendelowitz and Kay). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Scienceauthor instructions page.
