TY - JOUR
T1 - Regulation of free radical outflow from an isolated muscle bed in exercising humans
AU - Bailey, Damian
AU - Young, Ian S.
AU - McEneny, Jane
AU - Lawrenson, Lesley
AU - Kim, Jeannie
AU - Barden, Jeremy
AU - Richardson, Russell S.
PY - 2004/5/13
Y1 - 2004/5/13
N2 - 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 x-phenyl-tert-butylnitrone (PBN) adducts, lipid hydro peroxides (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% andgt; 70% andgt; 25% WR MAX, P andlt; 0.05) consistent with the generation of secondary, lipid-derived oxygen (O2) -centred alkyl and carbon-centred alkyl radicals. Radical outflow appeared to be more intimately associated with predicted decreases in intracellular PO2 (iPO2) as opposed to measured increases in leg O2 uptake, with greater outflow recorded between 25 and 70% WR MAX (P andlt; 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 O2 extraction and flow (25-70% WR MAX P andlt; 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 O2 extraction and flow, exercise-induced free radical generation may also be regulated by changes in iP O2, hydrogen ion generation, norepinephrine autoxidation, peroxidation of damaged tissue, and xanthine oxidase activation.
AB - 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 x-phenyl-tert-butylnitrone (PBN) adducts, lipid hydro peroxides (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% andgt; 70% andgt; 25% WR MAX, P andlt; 0.05) consistent with the generation of secondary, lipid-derived oxygen (O2) -centred alkyl and carbon-centred alkyl radicals. Radical outflow appeared to be more intimately associated with predicted decreases in intracellular PO2 (iPO2) as opposed to measured increases in leg O2 uptake, with greater outflow recorded between 25 and 70% WR MAX (P andlt; 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 O2 extraction and flow (25-70% WR MAX P andlt; 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 O2 extraction and flow, exercise-induced free radical generation may also be regulated by changes in iP O2, hydrogen ion generation, norepinephrine autoxidation, peroxidation of damaged tissue, and xanthine oxidase activation.
KW - electron paramagnetic resonance
KW - spin-trapping
KW - lipid peroxidation
KW - antioxidants
KW - mitochondrial redox
U2 - 10.1152/ajpheart.00148.2004
DO - 10.1152/ajpheart.00148.2004
M3 - Article
C2 - 15155256
VL - 287
SP - H1689 - H1699
JO - AJP - Heart and Circulatory Physiology
JF - AJP - Heart and Circulatory Physiology
SN - 0363-6135
IS - 4
ER -