title: Chronic hypoxia increases rat diaphragm muscle endurance and sodium-potassium ATPase pump content.
abstract: The effects of chronic hypoxia (CH) on respiratory muscle are poorly understood. The aim of the present study was to examine the effects of CH on respiratory muscle structure and function, and to determine whether nitric oxide is implicated in respiratory muscle adaptation to CH. Male Wistar rats were exposed to CH for 1-6 weeks. Sternohyoid and diaphragm muscle contractile properties, muscle fibre type and size, the density of fibres expressing sarco/endoplasmic reticulum calcium-ATPase (SERCA) 2 and sodium-potassium ATPase (Na+,K+-ATPase) pump content were determined. Muscle succinate dehydrogenase (SDH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) dehydrogenase activities were also assessed. Acute and chronic blockade of nitric oxide synthase (NOS) was employed to determine whether or not NO is critically involved in functional remodelling in CH muscles. CH improved diaphragm, but not sternohyoid, fatigue tolerance in a time-dependent fashion. This adaptation was not attributable to increased SDH or NADPH dehydrogenase activities. The areal density of muscle fibres and relative area of fibres expressing SERCA2 were unchanged. Na+,K+-ATPase pump content was significantly increased in CH diaphragm. Chronic NOS inhibition decreased diaphragm Na+,K+-ATPase pump content and prevented CH-induced increase in muscle endurance. This study provides novel insight into the mechanisms involved in CH-induced muscle plasticity. The results may be of relevance to respiratory disorders characterised by CH, such as chronic obstructive pulmonary disease.
authors.affiliation: University College Dublin School of Medicine and Medical Science, C228 Health Sciences Centre, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: C
authors.initials: C
authors.lastname: McMorrow
authors.forename: A
authors.initials: A
authors.lastname: Fredsted
authors.forename: J
authors.initials: J
authors.lastname: Carberry
authors.forename: R A
authors.initials: RA
authors.lastname: O'Connell
authors.forename: A
authors.initials: A
authors.lastname: Bradford
authors.forename: J F X
authors.initials: JF
authors.lastname: Jones
authors.forename: K D
authors.initials: KD
authors.lastname: O'Halloran
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002908:Chronic Disease; D003964:Diaphragm / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D018763:Muscle Fatigue / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010807:Physical Endurance / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: C506948:Atp2a2 protein, rat; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D013385:Succinate Dehydrogenase; D009252:NADPH Dehydrogenase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase