The role of hypothalamic paraventricular nucleus oxytocin in stimulating respiratory drive

Abstract

The hypothalamic paraventricular nucleus (PVN) receives a variety of inputs from different stimuli and is an important site for integrating endocrine and autonomic responses including neuronal regulation of chest wall pumping and upper airway dilating muscle activity. Previous studies in our laboratory showed that microinjection of bicuculline, a GABAA receptor antagonist, into the PVN significantly increased electromyographic activity of the diaphragm (Demg) and genioglossus muscle (GGemg) and stimulated respiratory rate. Our data also showed that PVN oxytocin (OT)-containing neurons project to different respiratory-related neuronal cell groups including the preBotzinger complex. Microinjection of OT into this site significantly increased respiratory drive. We tested the hypothesis that stimulation of the PVN partly results in the release of OT that binds to OT receptors and stimulates respiratory activity. Oxytocin receptor antagonist, [d-(CH2)5,Tyr(Me)2,Orn8]-vasotcin(OVT)was administered intracisternally (10 pmol) in anesthetized, vagotomized and mechanically ventilated male rats (n=5). Post injection of OVT, GGemg, Demg, blood pressure and heart rate decreased slightly (p>0.05). There was prolongation of inspiratory duration by 23.5 ± 3.2% (p<0.05) and a slight decrease in expiratory time (4.0 ±2.6%; p>0.05). Bicuculline microinjected unilaterally into the PVN, as compared to control animals, had no effect (p>0.05) on ventilatory parameters as well as arterial blood pressure. These findings indicate that OT is partly involved in stimulating respiratory muscle activity in response to activation of PVN neurons. Supported by NIH NS45859, NINDS/UCRR U54 NS39407, HL50527