Proceedings of The Physiological Society
University College Dublin (2009) Proc Physiol Soc 15, PC60
The superoxide scavenger Tempol improves pharyngeal dilator muscle function in old obese male rats
J. R. Skelly1, K. D. O'Halloran1
1. UCD School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland.
Age, obesity and male sex are major risk factors for the development of obstructive sleep apnoea/hypopnoea syndrome (OSAS). Pharyngeal dilator muscle dysfunction is implicated in the pathophysiology of OSAS. We wished to examine the effects of acute hypoxia on contractile properties of an upper airway dilator muscle in old obese male rats. Furthermore, we wished to test the hypothesis that Tempol, a superoxide scavenger, would protect against hypoxia-induced impairment of pharyngeal dilator muscle function. Old (18-20 month), obese (902±33g), male rats were killed by cervical spinal cord transection under 5% isoflurane. Sternohyoid (SH) muscles were dissected and removed for study. Isometric contractile and endurance properties were examined in physiological salt solution at 35OC under either hyperoxic (95%O2/5%CO2) or hypoxic (95%N2/5%CO2) conditions in vitro. Experiments were carried out in the absence (control) or presence of Tempol (10mM). Muscles were set to optimum length (i.e. length producing maximum isometric force). Force was measured in response to electrical field stimulation at stimulus frequencies ranging from 10-100Hz and was expressed as a function of muscle cross-sectional area (i.e. specific force). We also examined muscle performance in response to repeated stimulation (40Hz, 300ms, every 2 seconds for 2 minutes). Hypoxia was associated with significant decreases in SH muscle force [peak force was 27±2 vs. 18±1, mean±SEM N/cm2, hyperoxia (n=8) vs. hypoxia (n=8), p<0.05 ANOVA]. Tempol rescued force in hypoxia-treated muscle strips [peak force = 24±2 N/cm2, (n=8), p<0.05 vs. hypoxia]. Interestingly, the positive inotropic effect of Tempol was also observed in hyperoxia [32±2 N/cm2, (n=8), p<0.05 vs. hyperoxia] suggesting that the inotropic effect was not dependent on the bath PO2, and was more likely related to a beneficial effect of scavenging of free radicals produced by endogenous metabolism and muscle contraction. We observed improved muscle performance during the fatigue trial under both hyperoxic and hypoxic conditions, owing largely to increased force potentiation during the early phase of the trial in Tempol-treated muscles [e.g. 8±1 vs. 15±2 N/cm2, hypoxia (n=8) vs. hypoxia+Tempol (n=8) at 20s of the 2min trial, p<0.05]. In summary, the main finding of this study was that Tempol has a significant positive inotropic effect on SH muscle in old obese male rats. Pharmacotherapy is considered a viable clinical option in the treatment of OSAS and agents that improve pharyngeal dilator muscle function might prove useful, since these muscles play a pivotal role in the maintenance of pharyngeal airway calibre. We conclude that antioxidant treatment may be beneficial as an adjunct therapy in the treatment of OSAS.
Where applicable, experiments conform with Society ethical requirements