Influence of nitric oxide synthase inhibition on pulmonary O2 uptake kinetics during supra-maximal exercise in humans.
We have recently reported that inhibition of nitric oxide synthase (NOS) with N(G)-nitro-L-arginine methyl ester (L-NAME) accelerates the 'phase II' pulmonary O2 uptake (VO2) 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 VO2 kinetics following the onset of supra-maximal exercise, where it has been suggested that O2 availability represents an additional limitation to VO2 kinetics. Seven healthy young men volunteered to participate in this study. Following an incremental cycle ergometer test for the determination of VO2max, 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% VO2max, 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 VO2 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.
Wilkerson
Daryl P
DP
Department of Exercise and Sport Science, Manchester Metropolitan University, Hassall Road, Alsager ST7 2HL, UK.
Campbell
Iain T
IT
Jones
Andrew M
AM
D000328:Adult; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005080:Exercise Test / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010100:Oxygen / Q000493:pharmacokinetics; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D005082:Physical Exertion / Q000187:drug effects / Q000502:physiology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000502:physiology*; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester