title: Tempol ameliorates pharyngeal dilator muscle dysfunction in a rodent model of chronic intermittent hypoxia.
abstract: Respiratory muscle dysfunction is implicated in the pathophysiology of obstructive sleep apnea syndrome (OSAS), an oxidative stress disorder prevalent in men. Pharmacotherapy for OSAS is an attractive option, and antioxidant treatments may prove beneficial. We examined the effects of chronic intermittent hypoxia (CIH) on breathing and pharyngeal dilator muscle structure and function in male and female rats. Additionally, we tested the efficacy of antioxidant treatment in preventing (chronic administration) or reversing (acute administration) CIH-induced effects in male rats. Adult male and female Wistar rats were exposed to alternating cycles of normoxia and hypoxia (90 s each; Fi(O(2)) = 5% O(2) at nadir; Sa(O(2)) ∼ 80%) or sham treatment for 8 h/d for 9 days. Tempol (1 mM, superoxide dismutase mimetic) was administered to subgroups of sham- and CIH-treated animals. Breathing was assessed by whole-body plethysmography. Sternohyoid muscle contractile and endurance properties were examined in vitro. Muscle fiber type and cross-sectional area and the activity of key metabolic enzymes were determined. CIH decreased sternohyoid muscle force in male rats only. This was not attributable to fiber transitions or alterations in oxidative or glycolytic enzyme activity. Muscle weakness after CIH was prevented by chronic Tempol supplementation and was reversed by acute antioxidant treatment in vitro. CIH increased normoxic ventilation in male rats only. Sex differences exist in the effects of CIH on the respiratory system, which may contribute to the higher prevalence of OSAS in male subjects. Antioxidant treatment may be beneficial as an adjunct OSAS therapy.
authors.affiliation: Department of Physiology, University College Cork, Western Gateway Building, Western Road, Cork, Ireland.
authors.forename: J Richard
authors.initials: JR
authors.lastname: Skelly
authors.forename: Deirdre
authors.initials: D
authors.lastname: Edge
authors.forename: Christine M
authors.initials: CM
authors.lastname: Shortt
authors.forename: James F X
authors.initials: JF
authors.lastname: Jones
authors.forename: Aidan
authors.initials: A
authors.lastname: Bradford
authors.forename: Ken D
authors.initials: KD
authors.lastname: O'Halloran
mesh_terms: D000818:Animals; D001835:Body Weight; D002908:Chronic Disease; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004195:Disease Models, Animal; D004798:Enzymes / Q000378:metabolism; D005260:Female; D006321:Heart / Q000503:physiopathology; D006400:Hematocrit; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D018995:Myosin Heavy Chains / Q000378:metabolism; D009929:Organ Size; D010609:Pharyngeal Muscles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010991:Plethysmography; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels
chemical_list: D003497:Cyclic N-Oxides; D004798:Enzymes; D013113:Spin Labels; D018995:Myosin Heavy Chains; C001803:tempol