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Reactive oxygen species mediated diaphragm fatigue in a rat model of chronic intermittent hypoxia.
- Source :
-
Experimental physiology [Exp Physiol] 2014 Apr; Vol. 99 (4), pp. 688-700. Date of Electronic Publication: 2014 Jan 17. - Publication Year :
- 2014
-
Abstract
- Respiratory muscle dysfunction documented in sleep apnoea patients is perhaps due to oxidative stress secondary to chronic intermittent hypoxia (CIH). We sought to explore the effects of different CIH protocols on respiratory muscle form and function in a rodent model. Adult male Wistar rats were exposed to CIH (n = 32) consisting of 90 s normoxia-90 s hypoxia (either 10 or 5% oxygen at the nadir; arterial O2 saturation ∼ 90 or 80%, respectively] for 8 h per day or to sham treatment (air-air, n = 32) for 1 or 2 weeks. Three additional groups of CIH-treated rats (5% O2 for 2 weeks) had free access to water containing N-acetyl cysteine (1% NAC, n = 8), tempol (1 mM, n = 8) or apocynin (2 mM, n = 8). Functional properties of the diaphragm muscle were examined ex vivo at 35 °C. The myosin heavy chain and sarco(endo)plasmic reticulum Ca(2+)-ATPase isoform distribution, succinate dehydrogenase and glyercol phosphate dehydrogenase enzyme activities, Na(+)-K(+)-ATPase pump content, concentration of thiobarbituric acid reactive substances, DNA oxidation and antioxidant capacity were determined. Chronic intermittent hypoxia (5% oxygen at the nadir; 2 weeks) decreased diaphragm muscle force and endurance. All three drugs reversed the deleterious effects of CIH on diaphragm endurance, but only NAC prevented CIH-induced diaphragm weakness. Chronic intermittent hypoxia increased diaphragm muscle myosin heavy chain 2B areal density and oxidized glutathione/reduced glutathione (GSSG/GSH) ratio. We conclude that CIH-induced diaphragm dysfunction is reactive oxygen species dependent. N-Acetyl cysteine was most effective in reversing CIH-induced effects on diaphragm. Our results suggest that respiratory muscle dysfunction in sleep apnoea may be the result of oxidative stress and, as such, antioxidant treatment could prove a useful adjunctive therapy for the disorder.
- Subjects :
- Animals
Antioxidants pharmacology
Chronic Disease
Diaphragm drug effects
Diaphragm physiopathology
Disease Models, Animal
Glutathione metabolism
Glycerolphosphate Dehydrogenase metabolism
Hypoxia physiopathology
Male
Myosin Heavy Chains metabolism
Rats, Wistar
Sarcoplasmic Reticulum Calcium-Transporting ATPases metabolism
Sodium-Potassium-Exchanging ATPase metabolism
Succinate Dehydrogenase metabolism
Time Factors
Diaphragm metabolism
Hypoxia metabolism
Muscle Contraction drug effects
Muscle Fatigue drug effects
Oxidative Stress drug effects
Reactive Oxygen Species metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1469-445X
- Volume :
- 99
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Experimental physiology
- Publication Type :
- Academic Journal
- Accession number :
- 24443349
- Full Text :
- https://doi.org/10.1113/expphysiol.2013.076828