Difference between revisions of "Boushel 2012 Am J Physiol Regul Integr Comp Physiol"
| Line 5: | Line 5: | ||
|year=2012 | |year=2012 | ||
|journal=Am J Physiol Regul Integr Comp Physiol | |journal=Am J Physiol Regul Integr Comp Physiol | ||
|abstract=Nitric oxide (NO) and prostaglandins (PG) together play a role in regulation blood flow during exercise. NO also regulates mitochondrial oxygen consumption through competitive binding to cytochrome ''c'' oxidase. Indomethacin both uncouples and inhibits the electron transport chain in a concentration-dependent manner, and thus inhibition of NO and PG may regulate both muscle oxygen delivery and utilization. The purpose of this study was to examine the independent and combined effects of NO and PG blockade (L-NMMA and indomethacin respectively) on mitochondrial respiration in human muscle following knee extension (KE) exercise. Mitochondrial respiration was measured ''ex-vivo'' by high resolution respirometry in saponin-permeabilized fibers following 6 min KE in control (CON, n=8), arterial infusion of LNMMA (n=4) and Indo (n=4) followed by combined inhibition of NO and PG (L-NMMA + Indo, n=8). ADP-stimulated | |abstract=Nitric oxide (NO) and prostaglandins (PG) together play a role in regulation blood flow during exercise. NO also regulates mitochondrial oxygen consumption through competitive binding to cytochrome ''c'' oxidase. Indomethacin both uncouples and inhibits the electron transport chain in a concentration-dependent manner, and thus inhibition of NO and PG may regulate both muscle oxygen delivery and utilization. The purpose of this study was to examine the independent and combined effects of NO and PG blockade (L-NMMA and indomethacin respectively) on mitochondrial respiration in human muscle following knee extension (KE) exercise. Mitochondrial respiration was measured ''ex-vivo'' by high-resolution respirometry in saponin-permeabilized fibers following 6 min KE in control (CON, ''n''=8), arterial infusion of LNMMA (''n''=4) and Indo (''n''=4) followed by combined inhibition of NO and PG (L-NMMA + Indo, n=8). ADP-stimulated [[State 3]] respiration with substrates for Complex I (glutamate, malate) was reduced 50% by Indo. State 3 O(2) flux with Complex I and II substrates was reduced less with both Indo (20%) and L-NMMA + Indo (15%) compared to CON. The results indicate that indomethacin reduces State 3 mitochondrial respiration primarily at Complex I of the respiratory chain while blockade of NO by addition of L-NMMA counteracts the inhibition of Indo. This metabolic effect in concert with a reduction of blood flow likely accounts for ''in-vivo'' changes in muscle O<sub>2</sub> consumption during combined blockade of NO and PG. | ||
|keywords=Muscle oxygen delivery and utilization, NO and PG blockade | |keywords=Muscle oxygen delivery and utilization, NO and PG blockade | ||
|mipnetlab=DK Copenhagen Boushel RC, | |mipnetlab=DK Copenhagen Boushel RC, | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
| | |area=Respiration, Pharmacology; toxicology | ||
|organism=Human | |organism=Human | ||
|tissues=Skeletal muscle | |tissues=Skeletal muscle | ||
|preparations=Permeabilized tissue | |preparations=Permeabilized tissue | ||
|injuries=RONS; Oxidative Stress | |||
|couplingstates=LEAK, OXPHOS, ETS | |couplingstates=LEAK, OXPHOS, ETS | ||
|substratestates=CI, CII, CI+II | |substratestates=CI, CII, CI+II | ||
| | |instruments=Oxygraph-2k | ||
}} | }} | ||
Revision as of 07:56, 11 August 2013
| Boushel RC, Fuentes T, Hellsten Y, Saltin B (2012) Opposing effects of nitric oxide and prostaglandin inhibition on muscle mitochondrial VO2 during exercise . Am J Physiol Regul Integr Comp Physiol 303: 94-100. |
Boushel RC, Fuentes T, Hellsten Y, Saltin B (2012) Am J Physiol Regul Integr Comp Physiol
Abstract: Nitric oxide (NO) and prostaglandins (PG) together play a role in regulation blood flow during exercise. NO also regulates mitochondrial oxygen consumption through competitive binding to cytochrome c oxidase. Indomethacin both uncouples and inhibits the electron transport chain in a concentration-dependent manner, and thus inhibition of NO and PG may regulate both muscle oxygen delivery and utilization. The purpose of this study was to examine the independent and combined effects of NO and PG blockade (L-NMMA and indomethacin respectively) on mitochondrial respiration in human muscle following knee extension (KE) exercise. Mitochondrial respiration was measured ex-vivo by high-resolution respirometry in saponin-permeabilized fibers following 6 min KE in control (CON, n=8), arterial infusion of LNMMA (n=4) and Indo (n=4) followed by combined inhibition of NO and PG (L-NMMA + Indo, n=8). ADP-stimulated State 3 respiration with substrates for Complex I (glutamate, malate) was reduced 50% by Indo. State 3 O(2) flux with Complex I and II substrates was reduced less with both Indo (20%) and L-NMMA + Indo (15%) compared to CON. The results indicate that indomethacin reduces State 3 mitochondrial respiration primarily at Complex I of the respiratory chain while blockade of NO by addition of L-NMMA counteracts the inhibition of Indo. This metabolic effect in concert with a reduction of blood flow likely accounts for in-vivo changes in muscle O2 consumption during combined blockade of NO and PG. • Keywords: Muscle oxygen delivery and utilization, NO and PG blockade
• O2k-Network Lab: DK Copenhagen Boushel RC
Labels: MiParea: Respiration, Pharmacology; toxicology"Pharmacology; toxicology" is not in the list (Respiration, Instruments;methods, mt-Biogenesis;mt-density, mt-Structure;fission;fusion, mt-Membrane, mtDNA;mt-genetics, nDNA;cell genetics, Genetic knockout;overexpression, Comparative MiP;environmental MiP, Gender, ...) of allowed values for the "MiP area" property.
Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k
