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Oxidative capacity interacts with oxygen delivery to determine maximal O 2 uptake in rat skeletal muscles in situ
Author(s) -
Hepple Russell T.,
Hagen Jason L.,
Krause Dan J.
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2001.013649
Subject(s) - oxidative phosphorylation , in situ , oxygen , chemistry , skeletal muscle , oxygen delivery , biophysics , vo2 max , medicine , biology , biochemistry , anatomy , heart rate , organic chemistry , blood pressure
Based on proportional changes in V̇ O2,max with alterations in O 2 delivery, it is widely held that O 2 availability limits V̇ O2,max . In contrast, reductions in V̇ O2,max are also seen when mitochondrial oxidative capacity is reduced. Taken collectively, these prior results are consistent with the notion that there is not a single‐step limitation to V̇ O2,max . We used a pump‐perfused rat hindlimb model to test the hypothesis that combining moderate reductions in O 2 delivery and mitochondrial oxidative capacity would yield a greater reduction in V̇ O2,max than seen when performing each intervention independently, demonstrating an interaction between O 2 supply and mitochondrial oxidative capacity in determining V̇ O2,max . Four groups of animals were studied: two in high O 2 delivery conditions (hindlimb O 2 delivery: 88 ± 1 μmol O 2 min −1 ; mean ± s.e.m. ) and two in moderately reduced O 2 delivery conditions (66 ± 2 μmol O 2 min −1 ). One group at each level of O 2 delivery was treated with 0.1 μM myxothiazol to reduce mitochondrial oxidative capacity via competitive inhibition of NADH cytochrome c reductase. V̇ O2,max in control animals (no myxothiazol) was 29 % lower in the moderately reduced O 2 delivery group (592 ± 24 mmol O 2 min −1 (100 g) −1 ); P < 0.05 ) than in the high O 2 delivery group (833 ± 63 μmol O 2 min −1 (100 g) −1 ). Similarly, V̇ O2,max was reduced by 29 % (594 ± 22 μmol O 2 min −1 (100 g) −1 ); P < 0.05 ) in myxothiazol‐treated animals in high O 2 delivery conditions compared to control animals in high O 2 delivery conditions. When myxothiazol treatment was combined with moderately reduced O 2 delivery, V̇ O2,max was reduced by an additional 18 % (484 ± 21 μmol O 2 min −1 (100 g) −1 ); P < 0.05 ) compared to either intervention performed independently. These results show that O 2 supply and mitochondrial oxidative capacity interact to determine V̇ O2,max .