title: Chronic nitric oxide synthase inhibition does not impair upper airway muscle adaptation to chronic intermittent hypoxia in the rat.
abstract: Nitric oxide (NO) is an important modulator of striated muscle function. Nitric oxide synthase (NOS) expression and activity is altered by hypoxia and NO is implicated in respiratory muscle remodeling following chronic sustained hypoxia. We sought to determine if NO is implicated in upper airway dilator muscle adaptation to chronic intermittent hypoxia (CIH). Thirty-two adult male Wistar rats (284±13, mean±SD) were exposed to alternating bouts of hypoxia (90 s; 5% O2 at the nadir) and normoxia (210 s; 21% O2) for 12 cycles per hour, 8h/day for 3 weeks. Sham animals were exposed to normoxia in parallel. Half of the animals in both groups received the nNOS inhibitor-L-NNA (2mM) in the drinking water throughout the study (N=8 for all groups). Sternohyoid (pharyngeal dilator) muscle contractile and endurance properties were determined ex vivo. Sternohyoid muscle myosin heavy chain (MHC) isoform composition and cross-sectional area was determined by fluorescence microscopy. Chronic nNOS blockade did not alter sternohyoid muscle peak force or force-frequency relationship in sham or CIH-treated animals. In contrast, chronic nNOS blockade significantly decreased sternohyoid muscle endurance with equivalent effects in sham and CIH-treated rats. Our results suggest that NO is an important modulator of sternohyoid muscle endurance. However, our data provide no evidence to suggest that NO is implicated in upper airway muscle adaptation to CIH.
authors.affiliation: Health Sciences Centre, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Fiona B
authors.initials: FB
authors.lastname: McDonald
authors.affiliation: Health Sciences Centre, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland; Department of Physiology, School of Medicine, University College Cork, Cork, Ireland.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Edge
authors.affiliation: Department of Physiology, School of Medicine, University College Cork, Cork, Ireland. Electronic address: k.ohalloran@ucc.ie.
authors.forename: Ken D
authors.initials: KD
authors.lastname: O'Halloran
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D002908:Chronic Disease; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018995:Myosin Heavy Chains / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D010609:Pharyngeal Muscles / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D018995:Myosin Heavy Chains
keywords: chronic intermittent hypoxia; neuronal nitric oxide synthase; nitric oxide; sternohyoid; upper airway muscle