Increased metabolism of infused 1-methylxanthine by working muscle

Exogenous substrates for capillary endothelial enzymes have potential as markers for changes in capillary recruitment (albeit nutritive flow). The metabolism of infused 1-methylxanthine (1-MX) to 1-methylurate (1-MU) by capillary endothelial xanthine oxidase of the constant-flow perfused rat hindlimb was shown previously to decrease with oxygen uptake (V̇(o2)) when nutritive flow was decreased. In the present study, the metabolism of 1-MX was investigated under conditions when V̇(o2) and nutritive flow are known to increase during muscle contraction. The constant-flow red blood cell-perfused rat hindlimb at 37°C was used with sciatic nerve stimulation, and perfusate samples from whole hindlimb and working muscles taken for analysis of oxygen, lactate, 1-MX and 1-MU. Flow to muscle was assessed separately using fluorescent microspheres and was found to increase 2.3-fold to the working muscles while flow to the non-working leg muscles decreased to compensate. The activity of xanthine oxidase of whole muscle extracts was not altered by contraction. Samples from the vein draining the working muscles, and microsphere measurements of flow, indicated increased V̇(o2) (5.5-fold to 249.2 ± 43.1 μmol h-1 g-1, P < 0.001), and 1-MX conversion (2.5-fold to 1.87 ± 0.25 μmol h-1 g-1, P < 0.01) (SEM are shown). It is concluded that as 1-MX metabolism parallels V̇(o2), this substrate may be a useful indicator of changes in capillary (nutritive) surface area in muscle.