title: Diaphragm muscle remodeling in a rat model of chronic intermittent hypoxia.
abstract: Respiratory muscle remodeling occurs in human sleep apnea--a common respiratory disorder characterized by chronic intermittent hypoxia (CIH) due to recurrent apnea during sleep. We sought to determine if CIH causes remodeling in rat sternohyoid (upper airway dilator) and diaphragm muscles. Adult male Wistar rats were exposed to CIH (n=8), consisting of 90 sec of hypoxia (5% at the nadir; SaO₂ ~80%)/90 sec of normoxia, 8 hr per day, for 7 consecutive days. Sham animals (n=8) were exposed to alternating air/air cycles in parallel. The effect of CIH on myosin heavy-chain (MHC) isoform (1, 2a, 2x, 2b) distribution, sarcoplasmic reticulum calcium ATPase (SERCA) isoform distribution, succinate dehydrogenase activity, glycerol phosphate dehydrogenase activity, and Na⁺/K⁺ ATPase pump content was determined. Sternohyoid muscle structure was unaffected by CIH treatment. CIH did not alter oxidative/glycolytic capacity or the Na⁺/K⁺-ATPase pump content of the diaphragm. CIH significantly increased the areal density of MHC 2b fibers in the rat diaphragm, and this was associated with a shift in SERCA proteins from SERCA2 to SERCA1. We conclude that CIH causes a slow-to-fast fiber transition in the rat diaphragm after just 7 days of treatment. Respiratory muscle functional remodeling may drive aberrant functional plasticity such as decreased muscle endurance, which is a feature of human sleep apnea.
authors: UCD School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. c.short@ucc.ie
authors: Christine M
authors: CM
authors: Shortt
authors: Anne
authors: A
authors: Fredsted
authors: Aidan
authors: A
authors: Bradford
authors: Ken D
authors: KD
authors: O'Halloran
mesh_terms: D000818:Animals; D003964:Diaphragm / Q000378:metabolism*; D004195:Disease Models, Animal; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D000860:Hypoxia / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; 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; D013997:Time Factors
chemical_list: D005993:Glycerolphosphate Dehydrogenase; D013385:Succinate Dehydrogenase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; D000254:Sodium-Potassium-Exchanging ATPase
keywords: chronic intermittent hypoxia; diaphragm dysfunction; myosin heavy chain isoform distribution; obstructive sleep apnea; respiratory muscles
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