Acute intermittent hypoxia increases both phrenic and sympathetic nerve activities in the rat

Exp Physiol. 2007 Jan;92(1):87-97. doi: 10.1113/expphysiol.2006.035758. Epub 2006 Nov 30.


The respiratory system expresses multiple forms of plasticity, defined as alterations in the breathing pattern that persist or develop after a stimulus. Stimulation of breathing with intermittent hypoxia (IH) elicits long-term facilitation (LTF), a type of plasticity in which respiratory motor activity progressively increases in anaesthetized animals, even after the stimuli have ceased and blood gases have normalized. It is unknown whether the sympathetic nervous system similarly expresses IH-induced plasticity, but we predicted that IH would evoke LTF in sympathetic nerve activity (SNA) because respiratory and sympathetic control systems are coupled. To test this idea, we recorded splanchnic (sSNA) and phrenic nerve activities (PNA) in equithesin-anaesthetized rats. Animals were exposed to 10 45 s episodes of 8% O(2)-92% N(2), separated by 5 min intervals of 100% O(2), and recordings were continued for 60 min following the last hypoxic exposure. Cycle-triggered averages of integrated PNA and sSNA from periods preceding, and 5 and 60 min following the hypoxic stimuli were compared. Intermittent hypoxia significantly increased both sSNA and PNA. Treatment with methysergide (3 mg kg(-1), i.v.) 20 min before the intermittent hypoxic exposures prevented the increases in integrated PNA and sSNA 60 min after IH, indicating a role of serotonergic pathways in this form of plasticity. No increases in PNA and sSNA occurred at comparable times (60 and 120 min) in rats not exposed to hypoxia. The increased sSNA was not simply tonic, but was correlated with respiratory bursts, and occurred predominantly during the first half of expiration. These findings support the hypothesis that sympathorespiratory coupling may underlie the sustained increase in SNA associated with the IH that occurs during sleep apnoea.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Animals
  • Disease Models, Animal
  • Hypoxia / physiopathology*
  • Long-Term Potentiation*
  • Male
  • Methysergide / pharmacology
  • Neuronal Plasticity
  • Phrenic Nerve / metabolism
  • Phrenic Nerve / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Mechanics
  • Respiratory Muscles / innervation
  • Respiratory System / innervation
  • Serotonin / metabolism
  • Serotonin Antagonists / pharmacology
  • Sleep Apnea Syndromes / physiopathology
  • Splanchnic Nerves / physiopathology
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / physiopathology*
  • Time Factors


  • Serotonin Antagonists
  • Serotonin
  • Methysergide