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J Appl Physiol 102: 189-199, 2007. First published July 20, 2006; doi:10.1152/japplphysiol.00522.2006 Free Article
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Stimulation of the hypothalamic paraventricular nucleus modulates cardiorespiratory responses via oxytocinergic innervation of neurons in pre-Bötzinger complex

S. O. Mack,1 M. Wu,1 P. Kc,2 and M. A. Haxhiu2,3,4

1Department of Physiology and Biophysics, Howard University College of Medicine, Washington, District of Columbia; and 2Department of Pediatrics, 3Medicine, and 4Anatomy, Case Western Reserve University, Cleveland, Ohio

Submitted 8 May 2006 ; accepted in final form 10 July 2006

Previously we reported that oxytocin (OT)-containing neurons of the hypothalamic paraventricular nucleus (PVN) project to the pre-Bötzinger complex (pre-BötC) 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 OT antagonist [D-(CH2)5,Tyr(Me)2,Orn8]-vasotocin intracisternally or blockade of OT receptors in the pre-BötC region with OT 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 pre-BötC region controlling both respiratory and cardiovascular functions. The parallel changes induced by PVN stimulation were mediated mainly through an OT-OT receptor signaling pathway.

transneuronal labeling; pseudorabies virus; diaphragm and genioglossus electromyographic activity; arterial pressure; heart rate


Address for reprint requests and other correspondence: S. O. Mack, Dept. of Physiology and Biophysics, Howard Univ. College of Medicine, Washington, DC 20059 (e-mail: Smack{at}Howard.edu)




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