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Spinal Adenosine 2A Receptor Activation is Necessary for Phrenic Long‐Term Facilitation in Carotid‐Denervated Rats
Author(s) -
Perim Raphael R,
Kubilis Paul S,
Mitchell Gordon S
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.731.2
Subject(s) - hypoxia (environmental) , phrenic nerve , intermittent hypoxia , anesthesia , medicine , respiratory system , biology , pharmacology , chemistry , organic chemistry , oxygen , obstructive sleep apnea
Moderate acute intermittent hypoxia (AIH) elicits a long‐lasting increase in phrenic nerve activity, known as phrenic long‐term facilitation (pLTF). pLTF was originally demonstrated by intermittent electrical carotid sinus nerve stimulation, highlighting the pivotal role of carotid chemoafferent neurons in this form of respiratory motor plasticity. Surprisingly, there is still some residual pLTF after carotid body denervation (CBX) through unknown mechanisms. Carotid body‐dependent, serotonin 2 receptor‐induced pLTF is not expected after CBX; thus, a distinct mechanism must account for residual pLTF. Greater hypoxia‐induced hypotension after CBX might further reduce spinal tissue PO 2 more during each hypoxic episode, potentially inducing pLTF via an alternate adenosine‐dependent mechanism. Thus, we tested the hypothesis that adenosine 2A (A2A) receptor activation underlies residual pLTF after CBX. Phrenic nerve activity and spinal tissue PO 2 were measured in vivo during our standard pLTF protocol in urethane anesthetized, male Sprague Dawley rats. The contribution of severe hypoxic hypotension to residual pLTF after CBX was evaluated by preventing the arterial pressure drop during hypoxic episodes via systemic phenylephrine administration. We demonstrate that severe hypoxia‐induced hypotension diminishes spinal tissue oxygenation (at the same arterial PO 2 ) during hypoxic episodes to an extent sufficient to trigger residual pLTF. Preventing hypoxia‐induced hypotension minimizes tissue hypoxia, and residual pLTF is no longer observed. Spinal A2A receptor (MSX‐3; 12 μL, 10 μM), but not a serotonin 2A receptor (Ketanserin, 500 μM, 15 μL), antagonist abolishes residual pLTF after CBX. We conclude that differences in arterial blood pressure regulation impact expression and mechanisms of phrenic motor plasticity, a finding of importance for conditions characterized by hypotension such as anemia or spinal injury, where sympathetic outflow is disrupted by injury. Support or Funding Information Supported by: NIH Grants HL69064, SPARC and University of Florida McKnight Brain Institute This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .