Inhibition of Nitric Oxide Synthase by l-NAME Speeds Phase II Pulmonary VÌO2 Kinetics in the Transition to Moderate-Intensity Exercise in Man
There is evidence that the rate at which oxygen uptake ( VÌ O 2 ) rises at the transition to higher metabolic rates within the moderate exercise intensity domain is modulated by oxidative enzyme inertia, and also that nitric oxide regulates mitochondrial function through competitive inhibition of c...
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Published in | The Journal of physiology Vol. 552; no. 1; p. 265 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
The Physiological Society
01.10.2003
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Online Access | Get full text |
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Summary: | There is evidence that the rate at which oxygen uptake ( VÌ O 2 ) rises at the transition to higher metabolic rates within the moderate exercise intensity domain is modulated by oxidative
enzyme inertia, and also that nitric oxide regulates mitochondrial function through competitive inhibition of cytochrome c oxidase in the electron transport chain. We therefore hypothesised that inhibition of nitric oxide synthase (NOS) by nitro-L-arginine
methyl ester ( l -NAME) would alleviate the inhibition of mitochondrial VÌ O 2 by nitric oxide and result in a speeding of VÌ O 2 kinetics at the onset of moderate-intensity exercise. Seven males performed square-wave transitions from unloaded cycling
to a work rate requiring 90 % of predetermined gas exchange threshold with and without prior intravenous infusion of l -NAME (4 mg kg â1 in 50 ml saline over 60 min). Pulmonary gas exchange was measured breath-by-breath and VÌ O 2 kinetics were determined from the averaged response to four exercise bouts performed in each condition using a mono-exponential
function following elimination of the phase I response. There were no significant differences between the control and l -NAME conditions for baseline VÌ O 2 (means ± s.e.m . 797 ± 32 vs. 794 ± 29), the duration of phase I (15.4 ± 0.8 vs. 17.2 ± 0.6), or the steady-state increment in VÌ O 2 above baseline (1000 ± 83 vs. 990 ± 85 ml min â1 ), respectively. However, the phase II time constant of the VÌ O 2 response was significantly smaller following l -NAME infusion (22.1 ± 2.4 vs. 17.9 ± 2.3; P < 0.05). These data indicate that inhibition of NOS by l -NAME results in a significant (19 %) speeding of pulmonary VÌ O 2 kinetics in the transition to moderate-intensity cycle exercise in man. At least part of the intrinsic inertia to oxidative
metabolism at the onset of moderate-intensity exercise may result from competitive inhibition of mitochondrial VÌ O 2 by nitric oxide at cytochrome c oxidase, although other mechanisms for the effect of l -NAME on VÌ O 2 kinetics remain to be explored. |
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ISSN: | 0022-3751 1469-7793 |
DOI: | 10.1113/jphysiol.2003.045799 |