Novel Use of 1-methylhistamine as a Biomarker of the Histamine Response to Exercise

Abstract

Histamine is released within skeletal muscle during exercise, promoting a sustained post-exercise vasodilation and contributing to adaptive responses to exercise training. Tracking this response is complicated by the short half-life and localization of histamine, requiring invasive methods such as intramuscular microdialysis or arteriovenous catheterization. Surrogates based on regional blood flow to assess post-exercise vasodilation require skilled use of expensive equipment, such as ultrasonography. These approaches may not be available in many research or athletic settings. Therefore, we explored the use of 1-methylhistamine (1-MH), a primary metabolite of histamine, as a novel biomarker of histamine’s release in response to aerobic and resistance exercise. We hypothesized that urinary 1-MH production would increase following exercise and that it would be positively correlated with post-exercise femoral artery blood flow and vascular conductance. Six healthy (1F, 5M; 22±4y; 24.3±1.9 kg·m2) trained participants (VO2peak: 51.8±7.7 ml·kg−1·min−1; back squat 1-repetition maximum, 1-RM: 1.66±0.27 kg·bodyweight−1) completed two exercise sessions separated by 1-wk: Aerobic, 30-min of cycling exercise at 70% VO2peak; Resistance, 6 sets of 10 repetitions of back squat exercise at 70% 1-RM. Femoral artery blood flow and vascular conductance were measured and venous blood samples were obtained before, immediately after, and throughout 2-h of post-exercise recovery. Urine was collected during the 24-h before and 2-, and 24-h post-exercise. Histamine and 1-MH concentrations were measured via high-performance liquid chromatography. Results are presented as mean ± SD and were compared by repeated-measures ANOVA and Pearson’s correlations. Blood flow increased immediately after exercise vs before (Aerobic: 442±60 vs 184±58 mL·min−1, p<0.05; Resistance: 626±190 vs 194±54 mL·min−1, p<0.05) and remained elevated 30-min into recovery (Aerobic: 273±63, p<0.05; Resistance: 396±99 mL·min−1, p<0.05). The area under the curve for blood flow after exercise tended to be greater following resistance (16117±5504 mL) vs aerobic (8732±5360 mL, p=0.06) exercise. When averaged across exercise modes, urine 1-MH production was elevated 2-h post-exercise vs before (23.6±15.9 vs 9.2±5.9 μg/h, p<0.05). Urine 1-MH production tended to correlate with percent elevation in femoral artery blood flow (r=0.59, p=0.09) and correlated with the percent elevation in vascular conductance following exercise (r=0.53, p<0.05). These results demonstrate that both aerobic and resistance exercise elicit a histamine response and support the utility of urinary 1-MH production as a biomarker of histamine’s release in response to exercise. Supported by NIH grant R01 AG072805. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.