Stimulation of the hypothalamic paraventricular nucleus modulates cardiorespiratory responses via oxytocinergic innervation of neurons in pre-Botzinger complex.
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 GABA(A) receptor antagonist, significantly increased (P < 0.05) peak electromyographic activity of GG (GG(EMG)) and of D(EMG), frequency discharge, and arterial blood pressure (BP) and heart rate. Prior injection of OT antagonist [d-(CH(2))(5),Tyr(Me)(2),Orn(8)]-vasotocin intracisternally or blockade of OT receptors in the pre-BötC region with OT antagonist l-368,899, diminished GG(EMG) and D(EMG) 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.
Mack
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Department of Physiology and Biophysics, Howard University College of Medicine, Washington, DC 20059, USA. Smack@Howard.edu
Wu
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Haxhiu
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D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001892:Camphanes / Q000494:pharmacology; D003964:Diaphragm / Q000294:innervation / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D011558:Herpesvirus 1, Suid; D007002:Hypoglossal Nerve / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology*; D010120:Oxytocics / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000502:physiology*; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D014668:Vasotocin / Q000494:pharmacology
D001892:Camphanes; D018756:GABA Antagonists; D010120:Oxytocics; D010879:Piperazines; D018045:Receptors, Oxytocin; C086206:L 368899; D014668:Vasotocin; D001640:Bicuculline