Activation of Oxytocin Neurons Improves Cardiac Function in a Pressure-Overload Model of Heart Failure

• Published in: JACC. Basic to translational science Vol. 5; no. 5; pp. 484 - 497
• Main Authors: Dyavanapalli, Jhansi, Rodriguez, Jeannette, Rocha dos Santos, Carla, Escobar, Joan B., Dwyer, Mary Kate, Schloen, John, Lee, Kyung-min, Wolaver, Whitney, Wang, Xin, Dergacheva, Olga, Michelini, Lisete C., Schunke, Kathryn J., Spurney, Christopher F., Kay, Matthew W., Mendelowitz, David
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.05.2020; Elsevier
• Subjects: heart failure; oxytocin; parasympathetic; PRECLINICAL RESEARCH; heart failure; oxytocin; IL; ChR2; CNO; DREADD; PVN; LV; OXT; CHO; SD; DMNX; parasympathetic; ANOVA; LVDP; TAC; CVN; HF
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2020.03.007

[Display omitted] •Hypothalamic OXT neurons were chronically activated using a chemogenetic approach in an animal model of HF.•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.•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.•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. 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.