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

•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.