title: Sleep fragmentation impairs ventilatory long-term facilitation via adenosine A1 receptors.
abstract: Sleep fragmentation (SF), a primary feature of obstructive sleep apnoea (OSA), impairs hippocampal long-term potentiation and causes cognitive/attention deficits. However, its influence upon respiratory control has hardly been studied. This study examined the effect of SF on ventilatory long-term facilitation (LTF, a persistent augmentation of respiratory activity after episodic hypoxia) and the hypoxic ventilatory response (HVR), and investigated the role of adenosine A1 receptors in these SF effects in conscious adult male Sprague-Dawley rats. SF, confirmed by sleep architecture recordings, was achieved by periodic, forced locomotion in a rotating drum (30 s rotation/90 s stop for 24 h). LTF, elicited by five episodes of 5 min poikilocapnic hypoxia (10% O2) with 5 min intervals, was measured by plethysmography. Resting ventilation and metabolic rate were unchanged, HVR was reduced (150.6 +/- 3.5% versus 110.4 +/- 12.3%) and LTF was eliminated (22.6 +/- 0.5% versus -0.1 +/- 1.3%) shortly after 24 h SF. The SF-induced impairments were SF duration dependent, and completely reversible as HVR (< 24 h) and LTF (< 48 h) returned spontaneously to their pre-SF values. The SF-impaired HVR was improved (130.3 +/- 4.2%) and SF-eliminated LTF was restored (19.6 +/- 0.9%) by systemic injection of the adenosine A1 receptor antagonist 8-CPT (2.5 mg kg(-1)) approximately 30 min before LTF elicitation. Both HVR and LTF were also similarly impaired by 24 h total sleep deprivation or 24 h repeated cage tapping-induced SF, but not by a 24 h locomotion control protocol for SF. Collectively, these data suggest that: (1) 24 h SF impairs LTF and poikilocapnic HVR; (2) these impairments require A1 receptors; and (3) SF of OSA may exacerbate OSA via impaired ventilatory control mechanisms.
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: McGuire
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Tartar
authors.forename: Ying
authors.initials: Y
authors.lastname: Cao
authors.forename: Robert W
authors.initials: RW
authors.lastname: McCarley
authors.forename: David P
authors.initials: DP
authors.lastname: White
authors.forename: Robert E
authors.initials: RE
authors.lastname: Strecker
authors.forename: Liming
authors.initials: L
authors.lastname: Ling
mesh_terms: D000818:Animals; D001481:Basal Metabolism / Q000502:physiology; D001831:Body Temperature; D003345:Corticosterone / Q000097:blood; D006339:Heart Rate; D000860:Hypoxia; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D015656:Respiratory Mechanics / Q000502:physiology*; D012892:Sleep Deprivation / Q000378:metabolism*
chemical_list: D043682:Receptor, Adenosine A1; D003345:Corticosterone
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