Inhibition of nitric oxide synthase by L-NAME speeds phase II pulmonary VO2 kinetics in the transition to moderate-intensity exercise in man

There is evidence that the rate at which oxygen uptake (To) 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 (V)over dot(O2) by nitric oxide and result in a speeding of (V)over dot(O2) 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(-1) in 50 ml saline over 60 min). Pulmonary gas exchange was measured breath-by-breath and (V)over dot(O2) 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 (V)over dot(O2) (means S.E.M. 797 +/- 32 vs. 794 +/- 29), the duration of phase 1 (15.4 +/- 0.8 vs. 17.2 +/- 0.6), or the steady-state increment in (V)over dot(O2) above baseline (1000 +/- 83 vs. 990 +/- 85 ml min(-1)), respectively. However, the phase II time constant of the II, 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 (V)over dot(O2) 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 (V)over dot(O2) by nitric oxide at cytochrome c oxidase, although other mechanisms for the effect Of L-NAME on (V)over dot(O2) kinetics remain to be explored.