Effect of nitric oxide synthase inhibition on the exchange of glucose and fatty acids in human skeletal muscle

Background: The role of nitric oxide in controlling substrate metabolism in humans is incompletely understood. Methods: The present study examined the effect of nitric oxide blockade on glucose uptake, and free fatty acid and lactate exchange in skeletal muscle of eight healthy young males. Exchange was determined by measurements of muscle perfusion by positron emission tomography and analysis of arterial and femoral venous plasma concentrations of glucose, fatty acids and lactate. The measurements were performed at rest and during exercise without (control) and with blockade of nitric oxide synthase (NOS) with N-G-monomethyl-l-arginine (L-NMMA). Results: Glucose uptake at rest was 0.40 +/- 0.21 mu mol/100 g/min and increased to 3.71 +/- 2.53 mu mol/100 g/min by acute one leg low intensity exercise (p < 0.01). Prior inhibition of NOS by L-NMMA did not affect glucose uptake, at rest or during exercise (0.40 +/- 0.26 and 4.74 +/- 2.69 mu mol/100 g/min, respectively). In the control trial, there was a small release of free fatty acids from the limb at rest (-0.05 +/- 0.09 mu mol/100 g/min), whereas during inhibition of NOS, there was a small uptake of fatty acids (0.04 +/- 0.05 mu mol/100 g/min, p < 0.05). During exercise fatty acid uptake was increased to (0.89 +/- 1.07 mu mol/100 g/min), and there was a non-significant trend (p = 0.10) for an increased FFA uptake with NOS inhibition 1.23 +/- 1.48 mu mol/100 g/min) compared to the control condition. Arterial concentrations of all substrates and exchange of lactate over the limb at rest and during exercise remained unaltered during the two conditions. Conclusion: In conclusion, inhibition of nitric oxide synthesis does not alter muscle glucose uptake during low intensity exercise, but affects free fatty acid exchange especially at rest, and may thus be involved in the modulation of energy metabolism in the human skeletal muscle.