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1 Physiology and Biophysics, Howard University, Washington, District of Columbia, United States
2 Pediatrics, Case Western Reserve University, Cleveland, Ohio, United States
3 Departments of Pediatrics, Medicine, and Anatomy, Case Western Reserve University, Cleveland, Ohio, United States
* To whom correspondence should be addressed. E-mail: smack{at}howard.edu.
Previously we reported that oxytocin (OT)-containing neurons of the hypothalamic paraventricular nucleus (PVN) project to the preBotzinger complex (preBotC) region and phrenic motoneurons innervating the diaphragm (D). The aim of these studies was to determine pathways involved in PVN stimulation-induced changes in upper airway and chest wall pumping muscle activity. In addition, we determined the role of OT-containing neurons in the PVN in mediating increased respiratory output elicited by PVN stimulation. Neuroanatomical experiments, using pseudorabies virus (PRV) as a transneuronal tracer in C8 spinalectomized animals showed that PVN neurons project to hypoglossal motoneurons innervating the genioglossus (GG) muscle. Furthermore, microinjection of the PVN with bicuculline, a GABAA receptor antagonist, significantly increased (P<0.05) peak electromyographic activity of GG (GGEMG) and of DEMG, frequency discharge, and arterial blood pressure (BP) and heart rate. Prior injection of oxytocin antagonist [d-(CH2)5, Tyr(Me)2,Orn8]-vasotocin(OVT) intracisternally or blockade of oxytocin receptors in the preBotC region with oxytocin antagonist L-368,899, diminished GGEMG and DEMG responses and blunted the increase in BP and heart rate to PVN stimulation. These data show that PVN stimulation affects central regulatory mechanisms via the preBotC region controlling both respiratory and cardiovascular functions. The parallel changes induced by PVN stimulation were mediated mainly through an OT-OT receptor signaling pathway.
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