Please use this identifier to cite or link to this item:
Title: Opposing effects of nitric oxide and prostaglandin inhibition on muscle mitochondrial Vo 2 during exercise
Authors: Boushel, Robert
Fuentes, Teresa 
Hellsten, Ylva
Saltin, Bengt
UNESCO Clasification: 241106 Fisiología del ejercicio
Keywords: Contraction
Oxygen Uptake
Issue Date: 2012
Journal: American Journal of Physiology - Regulatory Integrative and Comparative Physiology 
Abstract: 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.
ISSN: 0363-6119
DOI: 10.1152/ajpregu.00044.2012
Source: American Journal of Physiology - Regulatory Integrative and Comparative Physiology [ISSN 0363-6119], v. 303 (1), R94–R100, (Julio 2012)
Appears in Collections:Artículos
Adobe PDF (232,96 kB)
Show full item record


checked on Aug 7, 2022


checked on Oct 17, 2021

Page view(s)

checked on Jul 16, 2022


checked on Jul 16, 2022

Google ScholarTM




Export metadata

Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.