Superoxide scavengers improve rat pharyngeal dilator muscle performance.
Obstructive sleep apnea is a common disorder associated with upper airway muscle dysfunction. Agents that improve respiratory muscle performance may be useful as an adjunct therapy. The aim of this study was to examine the effects of antioxidants on rat pharyngeal dilator muscle performance. Adult male Wistar rats were killed humanely and isometric contractile properties of isolated sternohyoid muscle strips were examined in physiological salt solution at 35 degrees C in vitro. Muscle strips were incubated in tissue baths under hyperoxic (95%O(2)/5%CO(2)) or hypoxic (95%N(2)/5%CO(2)) conditions in the absence (control) or presence of the antioxidants: N-acetylcysteine (10 mM), Tiron (10 mM), or Tempol (10 mM). Force-frequency relationship was determined in response to supramaximal stimulation (10-100 Hz in increments of 10-20 Hz, train duration: 300 ms). Isometric force was also recorded during repetitive muscle stimulation (40 Hz, 300 ms every 2 s for 2 min). Under hyperoxic conditions, Tiron and Tempol, but not N-acetylcysteine, significantly increased sternohyoid muscle force and caused a left-shift in the force-frequency relationship. In addition, Tempol had a significant positive inotropic effect over the initial 90 seconds of repeated muscle activation. Hypoxia caused a significant decrease in sternohyoid muscle force. Under hypoxic conditions, Tempol-incubated muscles generated significantly higher forces compared with control muscles and showed improved performance in the early phase of the fatigue trial. This study illustrates that superoxide scavengers increase upper airway muscle force and that this effect persists under hypoxic conditions. We conclude that antioxidant treatment may be beneficial as a therapy in obstructive sleep apnea.
Skelly
J Richard
JR
UCD School of Medicine and Medical Science, Room C228, Health Sciences Centre, University College Dublin, Belfield, Dublin 4, Ireland.
Bradford
Aidan
A
Jones
James F X
JF
O'Halloran
Ken D
KD
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004558:Electric Stimulation; D016166:Free Radical Scavengers / Q000494:pharmacology*; D018496:Hyperoxia / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D053580:Muscle Strength / Q000187:drug effects*; D010609:Pharyngeal Muscles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D013113:Spin Labels; D013481:Superoxides; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; C001803:tempol; D000111:Acetylcysteine