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

• Published in: Experimental neurology Vol. 333; p. 113429
• Main Authors: Perim, Raphael R., Kubilis, Paul S., Seven, Yasin B., Mitchell, Gordon S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2020
• Subjects: Acute intermittent hypoxia; Adenosine - metabolism; Animals; Arterial Pressure; Blood Gas Analysis; Carotid Body; Carotid body denervation; Denervation; Hypotension; Hypotension - etiology; Hypotension - metabolism; Hypoxia - complications; Ketanserin - pharmacology; Long-Term Potentiation - drug effects; Male; Phenylephrine - pharmacology; Phrenic Nerve - physiopathology; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A2A - metabolism; Respiratory motor plasticity; Serotonin 5-HT2 Receptor Antagonists - pharmacology; Spinal Cord - pathology; Tissue hypoxia; AIH; PtO2; Tissue hypoxia; Acute intermittent hypoxia; DMSO; Respiratory motor plasticity; 5-HT2; Hypotension; A2A; PaO2; CBX; Carotid body denervation; pLTF
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2020.113429

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.