Hypoxia-induced hypotension elicits adenosine-dependent phrenic long-term facilitation after carotid denervation

Raphael R. Perim, Paul S. Kubilis, Yasin B. Seven, Gordon S. Mitchell

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Moderate acute intermittent hypoxia (AIH) elicits a persistent, serotonin-dependent increase in phrenic amplitude, known as phrenic long-term facilitation (pLTF). Although pLTF was originally demonstrated by carotid sinus nerve stimulation, AIH still elicits residual pLTF in carotid denervated (CBX) rats via a distinct, but unknown mechanism. We hypothesized that exaggerated hypoxia-induced hypotension after carotid denervation leads to greater spinal tissue hypoxia and extracellular adenosine accumulation, thereby triggering adenosine 2A receptor (A2A)-dependent pLTF. Phrenic activity, arterial pressure and spinal tissue oxygen pressure were measured in anesthetized CBX rats. Exaggerated hypoxia-induced hypotension after CBX was prevented via intravenous phenylephrine; without the hypotension, spinal tissue hypoxia during AIH was normalized, and residual pLTF was no longer observed. Spinal A2A (MSX-3), but not serotonin 2 receptor (5-HT2) inhibition (ketanserin), abolished residual pLTF in CBX rats. Thus, pLTF regulation may be altered in conditions impairing sympathetic activity and arterial pressure regulation, such as spinal cord injury.

Original languageEnglish (US)
Article number113429
JournalExperimental Neurology
StatePublished - Nov 2020
Externally publishedYes


  • Acute intermittent hypoxia.
  • Carotid body denervation
  • Hypotension
  • Respiratory motor plasticity
  • Tissue hypoxia

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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