Proceedings of The Physiological Society
University College Dublin (2009) Proc Physiol Soc 15, PC61
Respiratory muscle plasticity following chronic intermittent hypoxia in male but not female Wistar rats.
J. R. Skelly1, A. Bradford2, K. D. O'Halloran1
1. UCD School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland. 2. Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Upper airway muscle dysfunction is implicated in obstructive sleep apnoea - a debilitating respiratory disorder associated with cardiovascular and neurocognitive impairments. Chronic intermittent hypoxia (CIH), a central feature of sleep apnoea results in oxidative stress/injury and tissue dysfunction. We wished to characterise the effects of CIH on ventilation and pharyngeal dilator muscle function in male and female rats. We tested the hypothesis that sex differences would exist in the effects of CIH on the respiratory system. Adult Wistar rats were exposed to CIH (90s air/90s N2 ; 5%O2 at nadir) or sham treatment for 8 hours/day for 9 days. A subset of animals in both groups received chronic antioxidant treatment in the form of the superoxide scavenger Tempol (1mM in the drinking water). Following treatments, ventilation was assessed by whole body plethysmography. Subsequently, the animals were killed humanely and isometric contractile properties of the sternohyoid (SH) muscle were examined at 35OC under control (95%O2/5%CO2) or hypoxic (95%N2/5%CO2) conditions in vitro. Force-frequency relationship was measured at stimulus frequencies ranging 10-100Hz. In male rats, ventilatory drive (VT /Ti) was significantly increased [2.4±0.1 vs. 2.8±0.2 sham (n=7) vs. CIH (n=7), p<0.001, Student’s t test]. SH peak force was decreased in CIH-treated male rats [23±1 vs. 16±1 N/cm2, sham (n=8) vs. CIH (n=8), p<0.001 ANOVA]. Chronic antioxidant treatment with Tempol ameliorated IH-induced muscle impairment. Conversely, in female rats, CIH treatment had no effect on ventilatory drive or SH peak force [21±1 vs. 20±1 N/cm2, sham (n=8) vs. CIH (n=8), p>0.05 ANOVA]. Additionally, we noted that female SH muscle exhibited greater tolerance to low in vitro PO2 [force at 100Hz was 21.0±1.2 vs. 18.5±2.0 N/cm2, hyperoxia (n=8) vs. hypoxia (n=8), p>0.05 ANOVA] compared to male SH muscle [22.7±0.8 vs. 9.5±0.6 N/cm2, hyperoxia (n=8) vs. hypoxia (n=8), p<0.001 ANOVA]. The main finding of this study is that CIH causes functional plasticity in the respiratory system. We observed CIH-induced muscle dysfunction in male rats - an effect that was ameliorated by antioxidant treatment. Female rats were unaffected by CIH and female SH muscles showed greater hypoxic tolerance in vitro. This suggests a greater antioxidant capacity in females compared to males preventing hypoxic maladaptation both in vivo and in vitro. Our results may have relevance to obstructive sleep apnoea, which is more prevalent in men than pre-menopausal women.
Where applicable, experiments conform with Society ethical requirements