Influence of L-NAME on pulmonary O2 uptake kinetics during heavy-intensity cycle exercise

We hypothesized that inhibition of nitric oxide synthase (NOS) by N-G-nitro-L-arginine methyl ester (L-NAME) would alleviate the inhibition of mitochondrial oxygen uptake ((V) over dotO(2)) by nitric oxide and result in a speeding of phase II pulmonary (V) over dotO(2) kinetics at the onset of heavy-intensity exercise. Seven men performed square-wave transitions from unloaded cycling to a work rate requiring 40% of the difference between the gas exchange threshold and peak (V) over dotO(2) with and without prior intravenous infusion of L-NAME (4 mg/kg in 50 ml saline over 60 min). Pulmonary gas exchange was measured breath by breath, and (V) over dotO(2) kinetics were determined from the averaged response to two exercise bouts performed in each condition. There were no significant differences between the control (C) and L-NAME conditions (L) for baseline (V) over dotO(2), the duration of phase I, or the amplitude of the primary (V) over dotO(2) response. However, the time constant of the (V) over dotO(2) response in phase II was significantly smaller (mean +/- SE: C: 25.1 +/- 3.0 s; L: 21.8 +/- 3.3 s; P < 0.05), and the amplitude of the (V) over dotO(2) slow component was significantly greater (C: 240 +/- 47 ml/min; L: 363 +/- 24 ml/min; P < 0.05) after L-NAME infusion. These data indicate that inhibition of NOS by L-NAME results in a significant (13%) speeding of (V) over dotO(2) kinetics and a significant increase in the amplitude of the (V) over dotO(2) slow component in the transition to heavy-intensity cycle exercise in men. The speeding of the primary component (V) over dotO(2) kinetics after L-NAME infusion indicates that at least part of the intrinsic inertia to oxidative metabolism at the onset of heavy-intensity exercise may result from inhibition of mitochondrial (V) over dotO(2) by nitric oxide. The cause of the larger (V) over dotO(2) slow-component amplitude with L-NAME requires further investigation but may be related to differences in muscle blood flow early in the rest-to-exercise transition.