Serotonin inhibition of 1-methylxanthine metabolism parallels its vasoconstrictor activity and inhibition of oxygen uptake in perfused rat hindlimb

The effect of serotonin (5‐HT) on the metabolism of infused 1‐methylxanthine (1‐MX), a putative substrate of capillary endothelial xanthine oxidase (XO), and on the distribution of infused fluorescent microspheres (15 μm) by the artificially constant‐flow perfused rat hindlimb preparation was investigated. 1‐MX (5–100 μM) caused a slight inhibition of oxygen uptake (V˙O2) but was not vasoactive, either alone or with 5‐HT. 1‐MX was converted to 1‐methylurate (1‐MU) and this conversion was inhibited by allopurinol and xanthine. 5‐HT (0.35 μM), which caused vasoconstriction and decreased V˙O2, also inhibited the conversion of 1‐MX, indicated by a lowered venous perfusate steady‐state 1‐MU:1‐MX ratio from 1.14 ± 0.02 to 0.71 ± 0.02 (P