Increased metabolism of infused 1-methylxanthine by working muscle

Exogenous substrates for capillary endothelial enzymes have potential as ma rkers for changes in capillary recruitment (albeit nutritive flow). The met abolism of infused 1-methylxanthine (1-MX) to 1-methylurate (1-MU) by capil lary endothelial xanthine oxidase of the constant-flow perfused rat hindlim b was shown previously to decrease with oxygen uptake (Vo(2)) when nutritiv e flow was decreased. In the present study, the metabolism of 1-MX was inve stigated under conditions when Vo(2) and nutritive flow are known to increa se during muscle contraction. The constant-flow red blood cell-perfused rat hindlimb at 37 degrees C was used with sciatic nerve stimulation, and perf usate samples from whole hindlimb and working muscles taken for analysis of oxygen, lactate, 1-MX and 1-MU. Flow to muscle was assessed separately usi ng fluorescent microspheres and was found to increase 2.3-fold to the worki ng muscles while flow to the non-working leg muscles decreased to compensat e. The activity of xanthine oxidase of whole muscle extracts was not altere d by contraction. Samples from the Vein draining the working muscles, and m icrosphere measurements of flow, indicated increased lie, (5.5-fold to 249. 2 +/- 43.1 mu mol h(-1) g(-1), P < 0.001), and 1-MX conversion (2.5-fold to 1.87 +/- 0.25 mu mol h(-1) g(-1). P < 0.01) (SEM are shown). It is conclud ed that as 1-MX metabolism parallels Vo(2), this substrate may be a useful indicator of changes in capillary (nutritive) surface area in muscle.