title: Sleep fragmentation attenuates the hypercapnic (but not hypoxic) ventilatory responses via adenosine A1 receptors in awake rats.
abstract: Sleep fragmentation (SF) and intermittent hypoxia and hypercapnia are the primary events associated with obstructive sleep apnea (OSA). We previously found that SF eliminates ventilatory long-term facilitation and attenuates poikilocapnic hypoxic ventilatory responses (HVR). This study examined the effect of SF on isocapnic HVR and hypercapnic ventilatory responses (HCVR), and investigated the time course of and the role of adenosine A1 receptors in these SF effects in conscious adult male Sprague-Dawley rats. SF was achieved by periodic, forced locomotion in a rotating drum (30 s rotation/90 s stop for 24 h). Ventilation during baseline, isocapnic hypoxia (11% O₂ plus 4% CO₂) and hypercapnia (6% CO₂) was measured using plethysmography. About 1h after 24h SF, resting ventilation, arterial blood gases and isocapnic HVR (control: 169.3 ± 11.5% vs. SF: 170.0 ± 10.3% above baseline) were not significantly changed, but HCVR was attenuated (control: 172.8 ± 17.5% vs. SF: 129.5 ± 9.6%; P = 0.003). This attenuated HCVR then returned spontaneously to the control level ∼4 h after SF (168.9 ± 12.1%). This HCVR attenuation was also reversed (184.0 ± 17.5%) by systemic injection of the adenosine A1 receptor antagonist 8-CPT (2.5 mg/kg) shortly after SF, while 8-CPT at this dose had little effect on HCVR in control rats (169.9 ± 11.8%). Collectively, these results suggest that: (1) 24 h SF does not change isocapnic HVR but causes an attenuation of HCVR; and (2) this attenuation lasts for only a few hours and requires activation of adenosine A1 receptors.
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Cao
authors.forename: Atul
authors.initials: A
authors.lastname: Malhotra
authors.forename: Liming
authors.initials: L
authors.lastname: Ling
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis / Q000379:methods; D006935:Hypercapnia / Q000188:drug therapy / Q000503:physiopathology*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D010991:Plethysmography / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects; D012892:Sleep Deprivation / Q000503:physiopathology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014851:Wakefulness
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D043682:Receptor, Adenosine A1; C053907:8-cyclopentyl-1,3-dimethylxanthine; D013806:Theophylline