Document Detail

Regulation of free radical outflow from an isolated muscle bed in exercising humans.
MedLine Citation:
PMID:  15155256     Owner:  NLM     Status:  MEDLINE    
Incremental knee extensor (KE) exercise performed at 25, 70, and 100% of single-leg maximal work rate (WR(MAX)) was combined with ex vivo electron paramagnetic resonance (EPR) spectroscopic detection of alpha-phenyl-tert-butylnitrone (PBN) adducts, lipid hydroperoxides (LH), and associated parameters in five males. Blood samples were taken from the femoral arterial and venous circulation that, when combined with measured changes in femoral venous blood flow, permitted a direct examination of oxidant exchange across a functionally isolated contracting muscle bed. KE exercise progressively increased the net outflow of LH and PBN adducts (100% > 70% > 25% WR(MAX), P < 0.05) consistent with the generation of secondary, lipid-derived oxygen (O(2))-centered alkoxyl and carbon-centered alkyl radicals. Radical outflow appeared to be more intimately associated with predicted decreases in intracellular Po(2) (iPo(2)) as opposed to measured increases in leg O(2) uptake, with greater outflow recorded between 25 and 70% WR(MAX) (P < 0.05 vs. 70-100% WR(MAX)). This bias was confirmed when radical venoarterial concentration differences were expressed relative to changes in the convective components of O(2) extraction and flow (25-70% WR(MAX) P < 0.05 vs. 70-100% WR(MAX), P > 0.05). Exercise also resulted in a net outflow of other potentially related redox-reactive parameters, including hydrogen ions, norepinephrine, myoglobin, lactate dehydrogenase, and uric acid, whereas exchange of lipid/lipoproteins, ascorbic acid, and selected lipid-soluble anti-oxidants was unremarkable. These findings provide direct evidence for an exercise intensity-dependent increase in free radical outflow across an active muscle bed that was associated with an increase in sarcolemmal membrane permeability. In addition to increased mitochondrial electron flux subsequent to an increase in O(2) extraction and flow, exercise-induced free radical generation may also be regulated by changes in iPo(2), hydrogen ion generation, norepinephrine autoxidation, peroxidation of damaged tissue, and xanthine oxidase activation.
Damian M Bailey; Ian S Young; Jane McEneny; Lesley Lawrenson; Jeannie Kim; Jeremy Barden; Russell S Richardson
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Publication Detail:
Type:  Journal Article     Date:  2004-05-20
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  287     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-16     Completed Date:  2004-11-09     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1689-99     Citation Subset:  IM    
Depts. of Anesthesiology and Surgery, Colorado Center for Altitude Medicine and Physiology, University of Colorado Health Sciences Center, PO Box 6508, Mail Stop F524, Aurora, CO 80111, USA.
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MeSH Terms
Antioxidants / metabolism
Blood Flow Velocity / physiology
Carbon Dioxide / blood
Catecholamines / blood
Electron Spin Resonance Spectroscopy
Exercise / physiology*
Free Radicals / metabolism
Lipid Peroxidation / physiology*
Lipoproteins, LDL / blood
Middle Aged
Mitochondria / metabolism
Muscle Contraction / physiology
Muscle, Skeletal / metabolism*
Oxidative Stress / physiology
Oxygen / blood
Reg. No./Substance:
0/Antioxidants; 0/Catecholamines; 0/Free Radicals; 0/Lipoproteins, LDL; 124-38-9/Carbon Dioxide; 7782-44-7/Oxygen

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