Reactive Oxygen Species Mediate Central Cardiorespiratory Network Responses to Acute Intermittent Hypoxia

• Published in: Journal of neurophysiology 2007-03, Vol.97 (3), p.2059-2066
• Main Authors: Griffioen, Kathleen J. S, Kamendi, Harriet W, Gorini, Christopher J, Bouairi, Evguenia, Mendelowitz, David
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; GABA Antagonists - pharmacology; Glutamic Acid - metabolism; Glutamic Acid - pharmacology; Glycine Agents - pharmacology; Hypoxia - pathology; In Vitro Techniques; Inhalation - drug effects; Inhalation - physiology; Medulla Oblongata - cytology; Membrane Potentials - drug effects; Membrane Potentials - physiology; Membrane Potentials - radiation effects; Nerve Net - drug effects; Nerve Net - physiopathology; Neurons - drug effects; Neurons - metabolism; Oxygen - pharmacology; Patch-Clamp Techniques - methods; Pyridazines - pharmacology; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Strychnine - pharmacology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00975.2006

Department of Pharmacology and Physiology, George Washington University, Washington, District of Columbia Submitted 12 September 2006; accepted in final form 1 November 2006 Although oxidative stress and reactive oxygen species generation is typically associated with localized neuronal injury, reactive oxygen species have also recently been shown to act as a physiological signal in neuronal plasticity. Here we define an essential role for reactive oxygen species as a critical stimulus for cardiorespiratory reflex responses to acute episodic hypoxia in the brain stem. To examine central cardiorespiratory responses to episodic hypoxia, we used an in vitro medullary slice that allows simultaneous examination of rhythmic respiratory-related activity and synaptic neurotransmission to cardioinhibitory vagal neurons. We show that whereas continuous hypoxia does not stimulate excitatory neurotransmission to cardioinhibitory vagal neurons, acute intermittent hypoxia of equivalent duration incrementally recruits an inspiratory-evoked excitatory neurotransmission to cardioinhibitory vagal neurons during intermittent hypoxia. This recruitment was dependent on the generation of reactive oxygen species. Further, we demonstrate that reactive oxygen species are incrementally generated in glutamatergic neurons in the ventrolateral medulla during intermittent hypoxia. These results suggest a neurochemical basis for the pronounced bradycardia that protects the heart against injury during intermittent hypoxia and demonstrates a novel role of reactive oxygen species in the brain stem. Address for reprint requests and other correspondence: K.J.S. Griffioen, Dept. of Pharmacology and Physiology, George Washington University, 2300 Eye St. N.W., Washington, D.C. 20037 (E-mail: kgriff{at}gwu.edu )