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J Physiol Volume 561, Number 2, 623-635, December 1, 2004 DOI: 10.1113/jphysiol.2004.071894
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Influence of nitric oxide synthase inhibition on pulmonary O2 uptake kinetics during supra-maximal exercise in humans

Daryl P Wilkerson1, Iain T Campbell2 and Andrew M Jones1

1 Department of Exercise and Sport Science, Manchester Metropolitan University, Hassall Road, Alsager ST7 2HL, UK
2 Department of Anaesthesia, Wythenshawe Hospital, Manchester M23 9LT, UK

We have recently reported that inhibition of nitric oxide synthase (NOS) with NG-nitro-L-arginine methyl ester (L-NAME) accelerates the ‘phase II’ pulmonary O2 uptake {tjp_543_mu1} kinetics following the onset of moderate and heavy intensity submaximal exercise in humans. These data suggest that the influence of nitric oxide (NO) on mitochondrial function is an important factor in the inertia to aerobic respiration that is evident in the transition from a lower to a higher metabolic rate. The purpose of the present study was to investigate the influence of L-NAME on pulmonary {tjp_543_mu2} kinetics following the onset of supra-maximal exercise, where it has been suggested that O2 availability represents an additional limitation to {tjp_543_mu3} kinetics. Seven healthy young men volunteered to participate in this study. Following an incremental cycle ergometer test for the determination of {tjp_543_mu4}, the subjects returned on two occasions to perform a ‘step’ exercise test from a baseline of unloaded cycling to a work rate calculated to require 105% {tjp_543_mu5}, preceded either by systemic infusion of L-NAME (4 mg kg–1 in 50 ml saline) or 50 ml saline as a control (Con). Pulmonary gas exchange was measured on a breath-by-breath basis throughout the exercise tests. The duration of ‘phase I’ was greater with L-NAME (Con: 14.0 ± 2.1 versus L-NAME: 16.0 ± 1.6 s; P = 0.03), suggestive of a slower cardiovascular adaptation following the onset of exercise. However, the phase II {tjp_543_mu6} time constant was reduced by 44% with L-NAME (Con: 36.3 ± 17.3 versus L-NAME: 20.4 ± 8.3 s; P = 0.01). The accumulation of blood lactate during exercise was also reduced with L-NAME (Con: 4.0 ± 1.1 versus L-NAME: 2.7 ± 2.1 mM; P = 0.04). These data indicate that skeletal muscle NO production represents an important limitation to the acceleration of oxidative metabolism following the onset of supra-maximal exercise in humans.

(Received 14 July 2004; accepted after revision 6 September 2004; first published online 9 September 2004)
Corresponding author A. M. Jones: Department of Exercise and Sport Science, Manchester Metropolitan University, Hassall Road, Alsager ST7 2HL, UK. Email: a.m.jones{at}mmu.ac.uk




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