Histamine Increases the Skeletal Muscle Blood Flow Response to Resistance Exercise

Blood flow is important for maintaining oxygen delivery to and metabolite washout from exercising muscle. Histamine contributes to blood flow responses during and following aerobic exercise, but it is not clear if it is also contributing to resistance exercise responses. If histamine increases blood flow during resistance exercise, it may aid in the matching of oxygen supply to oxygen demand. Conversely, histamine receptor blockade may disrupt the balance of oxygen supply and demand within the exercising muscle, possibly slowing recovery and reoxygenation during rest. Therefore, we investigated the effect of histamine-receptor blockade (combined oral H 1 - and H 2 -receptor antagonism with fexofenadine and famotidine, versus placebo) on femoral artery blood flow (using Doppler ultrasound) and local skeletal muscle oxygenation (SmO 2 , via non-invasive near infrared spectroscopy) during back squat exercise utilizing short inter-set rest. We hypothesized that compared to placebo, blockade would decrease blood flow and vascular conductance during recovery from exercise and lead to greater reductions of SmO 2 during exercise. In this double-blind placebo-controlled experiment, ten well-trained participants (4F, 6M, 22±2.9 y; 24.3±3.6 kg·m -2 ; 1-repetition maximum, 1.5±0.3 kg·bodyweight -1 ) completed six sets of ten repetitions at 70% of their 1-repetition maximum with two minutes rest between sets on two different occasions (blockade and placebo). Femoral artery blood flow and vascular conductance were determined before set one and immediately after set six. The change in SmO 2 (Δ) was determined for each set from pre- to end-set and the slope of reoxygenation (%SmO 2 ·s -1 ) was determined during recovery between sets. Values are reported as means [95% CI]. Femoral artery blood flow and vascular conductance was lower after exercise in blockade (693 [508,879] mL·min -1 ) vs placebo (894 [733,1056] mL·min -1 , p<0.05) as was vascular conductance (blockade 9 [6,12] mL·min -1 ·mmHg -1 vs placebo 12 [9,15] mL·min -1 ·mmHg -1 , p < 0.05). The end-set SmO 2 was lower in blockade (27 [12,42] %) vs placebo (37 [17,56] %, p<0.05) driving greater ΔSmO 2 within sets during blockade (52 [38,65] ΔSmO 2 %) vs placebo (44 [28,60] ΔSmO 2 %, p<0.05), and indicating greater tissue desaturation observed with blockade. There was a reduced rate of reoxygenation in blockade (2.1 [1.5,2.7] %SmO 2 ·s -1 ) vs placebo (2.5 [1.6,3.5] %SmO 2 ·s -1 , p<0.05). These data indicate a reduction in skeletal muscle blood flow during and following resistance exercise when histamine’s receptors are blocked, akin to measurements following aerobic exercise. In addition to demonstrating that histamine increases the muscle blood flow response during resistance exercise, this work highlights histamine’s actions on local tissue perfusion and oxygenation during exercise and suggests that antihistamines may delay recovery between sets of resistance exercise during an exercise session. Supported by NIH R01 AG072805, the Wu Tsai Human Performance Alliance and the Joe and Clara Tsai Foundation, and the Eugene and Clarissa Evonuk Memorial Graduate Fellowship. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.