• Irma Rukhadze, Victor B Fenik, Kate E Benincasa, Andrea Price, and Leszek Kubin.
• Department of Animal Biology, University of Pennsylvania, Philadelphia, 19104-6046, USA. rukhadze@vet.upenn.edu
• Am. J. Respir. Crit. Care Med. 2010 Nov 15; 182 (10): 1321-9.

RationalePatients with obstructive sleep apnea (OSA) adapt to the anatomical vulnerability of their upper airway by generating increased activity in upper airway-dilating muscles during wakefulness. Norepinephrine (NE) and serotonin (5-HT) mediate, through α₁-adrenergic and 5-HT₂A receptors, a wake-related excitatory drive to upper airway motoneurons. In patients with OSA, this drive is necessary to maintain their upper airway open. We tested whether chronic intermittent hypoxia (CIH), a major pathogenic factor of OSA, affects aminergic innervation of XII motoneurons that innervate tongue-protruding muscles in a manner that could alter their airway-dilatory action.ObjectivesTo determine the impact of CIH on neurochemical markers of NE and 5-HT innervation of the XII nucleus.MethodsNE and 5-HT terminal varicosities and α₁-adrenergic and 5-HT₂A receptors were immunohistochemically visualized and quantified in the XII nucleus in adult rats exposed to CIH or room air exchanges for 10 h/d for 34 to 40 days.Measurements And Main ResultsCIH-exposed rats had approximately 40% higher density of NE terminals and approximately 20% higher density of 5-HT terminals in the ventromedial quadrant of the XII nucleus, the region that controls tongue protruder muscles, than sham-treated rats. XII motoneurons expressing α₁-adrenoceptors were also approximately 10% more numerous in CIH rats, whereas 5-HT₂A receptor density tended to be lower in CIH rats.ConclusionsCIH-elicited increase of NE and 5-HT terminal density and increased expression of α₁-adrenoceptors in the XII nucleus may lead to augmentation of endogenous aminergic excitatory drives to XII motoneurons, thereby contributing to the increased upper airway motor tone in patients with OSA.

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