Mast cell degranulation and de novo histamine formation contribute to sustained postexercise vasodilation in humans

In humans, acute aerobic exercise elicits a sustained postexercise vasodilation within previously active skeletal muscle. This response is dependent on activation of histamine H-1 and H-2 receptors, but the source of intramuscular histamine remains unclear. We tested the hypothesis that interstitial histamine in skeletal muscle would be increased with exercise and would be dependent on de novo formation via the inducible enzyme histidine decarboxylase and/or mast cell degranulation. Subjects performed 1 h of unilateral dynamic kneeextension exercise or sham (seated rest). We measured the interstitial histamine concentration and local blood flow (ethanol washout) via skeletal muscle microdialysis of the vastus lateralis. In some probes, we infused either alpha-fluoromethylhistidine hydrochloride (alpha-FMH), a potent inhibitor of histidine decarboxylase, or histamine H-1/H-2-receptor blockers. We also measured interstitial tryptase concentrations, a biomarker of mast cell degranulation. Compared with preexercise, histamine was increased after exercise by a change (Delta) of 4.2 +/- 1.8 ng/ml (P < 0.05), but not when alpha-FMH was administered (Delta-0.3 +/- 1.3 ng/ml, P < 0.9). Likewise, local blood flow after exercise was reduced to preexercise levels by both alpha-FMH and H-1/H-2 blockade. In addition, tryptase was elevated during exercise by -6.8 +/- 1.1 ng/ml (P < 0.05). Taken together, these data suggest that interstitial histamine in skeletal muscle increases with exercise and results from both de novo formation and mast cell degranulation. This suggests that exercise produces an anaphylactoid signal, which affects recovery, and may influence skeletal muscle blood flow during exercise.