Effects of nitric oxide synthase inhibition by L-NAME on oxygen uptake kinetics in isolated canine muscle in situ

Nitric oxide (NO) has an inhibitory action on O-2 uptake (Vo(2)) at the level of the mitochondrial respiratory chain. The aim of this study was to evaluate the effects of NO synthase (NOS) inhibition on muscle Vo(2) kinetics. Isolated canine gastrocnemius muscles in situ (n = 6) were studied during transitions from rest to 4-min of electrically stimulated contractions corresponding to similar to 60% of the muscle peak Vo(2) Two conditions were compared: (i) Control (CTRL) and (ii) L-NAME, in which the NOS inhibitor L-NAME (20 mg kg(-1)) was administered. In both conditions the muscle was pump-perfused with constantly elevated blood flow (Q), at a level measured during a preliminary contraction trial with spontaneous self-perfused Q. A vasodilatory drug was also infused. Arterial and venous O-2 concentrations were determined at rest and at 5-7 s intervals during the transition. Vo(2), was calculated by Fick's principle. Muscle biopsies were obtained at rest and during contractions. Muscle force was measured continuously. Phosphocreatine hydrolysis and the calculated substrate level phosphorylation were slightly (but not significantly) lower in L-NAME than in CTRL. Significantly (P < 0.05) less fatigue was found in L-NAME versus CTRL. The time delay (TDf) and the time constant (tau(f)) of the 'fundamental' component of kinetics were not significantly different between CTRL (TDf 7.2 +/- 1.2 s; and tau(f) 10.6 +/- 1.3, S.E.M.) and L-NAME (TDf 9.3 +/- 0.6; and tau(f) 10.4 +/- 1.0). Contrary to our hypothesis, NOS inhibition did not accelerate muscle Vo(2) kinetics. The down-regulation of mitochondrial respiration by NO does not limit the kinetics of adjustment of oxidative metabolism at exercise onset.