Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Opposing effects of nitric oxide and prostaglandin inhibition on muscle mitochondrial Vo(2) during exercise

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Absent increase in vertebral artery blood flow during l-arginine infusion in hypertensive men

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Erythropoiesis with endurance training: dynamics and mechanisms

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Impact of TGF-β inhibition during acute exercise on Achilles tendon extracellular matrix

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Coupling between arterial and venous cerebral blood flow during postural change

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Carotid baroreflex function at the onset of cycling in men

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Reduced skeletal-muscle perfusion and impaired ATP release during hypoxia and exercise in individuals with type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Effect of endurance versus resistance training on local muscle and systemic inflammation and oxidative stress in COPD

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations
Nitric oxide (NO) and prostaglandins (PG) together play a role in regulating blood flow during exercise. NO also regulates mitochondrial oxygen consumption through competitive binding to cytochrome-c oxidase. Indomethacin uncouples and inhibits the electron transport chain in a concentration-dependent manner, and thus, inhibition of NO and PG synthesis 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 synthesis blockade (L-NMMA and indomethacin, respectively) on mitochondrial respiration in human muscle following knee extension exercise (KEE). Specifically, this study examined the physiological effect of NO, and the pharmacological effect of indomethacin, on muscle mitochondrial function. Consistent with their mechanism of action, we hypothesized that inhibition of nitric oxide synthase (NOS) and PG synthesis would have opposite effects on muscle mitochondrial respiration. Mitochondrial respiration was measured ex vivo by high-resolution respirometry in saponin-permeabilized fibers following 6 min KEE in control (CON; n = 8), arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA; n = 4) and Indo (n = 4) followed by combined inhibition of NOS and PG synthesis (L-NMMA + Indo, n = 8). ADP-stimulated state 3 respiration (OXPHOS) 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 with CON. The results indicate that indomethacin reduces state 3 mitochondrial respiration primarily at complex I of the respiratory chain, while blockade of NOS by L-NMMA counteracts the inhibition by Indo. This effect on muscle mitochondria, in concert with a reduction of blood flow accounts for in vivo changes in muscle O(2) consumption during combined blockade of NOS and PG synthesis.
Original languageEnglish
JournalAmerican Journal of Physiology: Regulatory, Integrative and Comparative Physiology
Volume303
Issue number1
Pages (from-to)R94-100
ISSN0363-6119
DOIs
Publication statusPublished - 2012

    Research areas

  • Electron Transport Chain Complex Proteins, Exercise, Humans, Indomethacin, Male, Mitochondria, Muscle, Muscle, Skeletal, Nitric Oxide, Oxygen, Oxygen Consumption, Prostaglandin Antagonists, Regional Blood Flow, Young Adult, omega-N-Methylarginine

ID: 36795729