Restoration of Oxytocin Neuron Activity Prevents Hypertension Caused by Chronic Intermittent Hypoxia/Hypercapnia

Abstract

New promising work has indicated oxytocin (OXT) receptor activation is blunted in cardiovascular diseases (CVDs) and OXT receptor activation may be a novel target to increase parasympathetic activity to the heart and treat CVDs. This study tests the hypotheses that the release of OXT from hypothalamic paraventricular (PVN) neurons onto cardiac vagal neurons (CVNs) is diminished with chronic intermittent hypoxia‐hypercapnia (CIH/H), an animal model of OSA, and furthermore that selective activation of PVN OXT neurons can reduce adverse cardiovascular consequences that occur with CIH/H. Optogenetic stimulation of channelrhodopsin expressing PVN fibers evoked large transient increases in Ca2+ in CHO cells stably transfected to express the human recombinant OXT receptor and the red fluorescent calcium indicator, R‐GECO1, dispersed adjacent to CVNs. The release of OXT onto CVNs upon photoactivation of PVN fibers was blunted in animals exposed to 21 days of CIH/H. To examine if restoration of OXT neuron activity can prevent the adverse cardiovascular effects of CIH/H in vivo, we selectively expressed excitatory DREADDs in PVN OXT neurons, and implanted animals with telemetry devices to monitor blood pressure (BP) and EKG activity. Selective chronic activation of PVN OXT neurons decreased resting BP and HR, and perhaps more importantly chronic PVN OXT neuron activation prevented the elevations in BP and HR that occur with CIH/H. These results indicate excitation of parvocellular PVN fibers releases OXT at brainstem CVN targets, and selective activation of OXT neurons in the PVN decreases resting BP and HR, and prevents the elevations in BP and HR that occur after 21 days of CIH/H.