Proceedings of The Physiological Society

University of Manchester (2010) Proc Physiol Soc 19, PC26

Poster Communications

Chronic hypoxia increases rat diaphragm muscle endurance and Na+-K+ ATPase pump content

C. McMorrow1, A. Fredsted2, J. Carberry1, R. O'Connell1, A. Bradford3, J. Jones1, K. O'Halloran1

1. School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. 2. Physiology and Biophysics, Aarhus University, Aarhus, Denmark. 3. Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.


Skeletal muscle has enormous capacity for re-modelling as evident in various physiological and pathophysiological settings. Chronic hypoxia (CH) - a feature of respiratory disease - is known to affect skeletal muscle structure and function. Surprisingly, there is a general paucity of information concerning the effects of CH on respiratory muscle despite the clinical relevance. We sought to examine the effects of CH on respiratory muscle structure and function and determine if nitric oxide (NO) is implicated in respiratory muscle adaptation to CH exposure. Male Wistar rats were exposed to chronic hypobaric hypoxia (ambient pressure = 380mmHg) for 1-6 weeks. Sternohyoid and diaphragm muscle contractile and endurance properties were assessed in vitro. Respiratory muscle fibre type and size, density of fibres expressing SERCA2 protein, and Na+-K+ ATPase pump content were determined. Muscle succinate dehydrogenase (SDH) and nitric oxide synthase (NOS) enzyme activities were also assessed. Acute and chronic blockade of NOS was employed to determine whether NO is critically involved in functional re-modelling in CH muscles. CH improved diaphragm, but not sternohyoid, fatigue tolerance in a time-dependent fashion. After 6 weeks of CH, fatigue index was 53±4% vs. 70±2%, mean±SEM, normoxia (n=6) vs. CH (n=6), P<0.05, ANOVA. This adaptation was not attributable to fibre transitions, increased oxidative capacity, increased NADPH diaphorase activity or increased density of fibres expressing SERCA2 (17±1% vs. 19±1%, normoxia vs. CH). However, Na+-K+ ATPase pump content was significantly increased in CH diaphragms (370±7 vs. 458±12 oubain binding sites occupied pmol/g wet weight, P<0.05). Acute NOS inhibition in vitro did not affect CH diaphragm fatigue index. However, chronic NOS inhibition attenuated CH-induced increases in diaphragm Na+-K+ ATPase pump content and blocked CH-induced increase in muscle endurance. This study provides novel insight into mechanisms involved in CH-induced muscle plasticity. The results may have relevance to respiratory disorders characterized by CH such as COPD where respiratory muscle re-modelling is known to occur.

Where applicable, experiments conform with Society ethical requirements