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.
Keywords: ANOVA, analysis of variance; CHO, Chinese hamster ovary; CNO, clozapine-N-oxide; CVN, cardiac vagal neuron; ChR2, channelrhodopsin; DMNX, dorsal motor nucleus of the vagus; DREADD, designer receptors exclusively activated by designer drug; HF, heart failure; IL, interleukin; LV, left ventricle; LVDP, left ventricle- developed pressure; OXT, oxytocin; PVN, paraventricular nucleus of the hypothalamus; SD, standard deviation; TAC, transascending aortic constriction; heart failure; oxytocin; parasympathetic.
© 2020 The Authors.