Effect of histamine-receptor antagonism on leg blood flow during exercise

Abstract

Histamine mediates vasodilation during inflammatory and immune responses, as well as following endurance exercise. During exercise, intramuscular histamine concentration increases, and its production, appears related to exercise intensity and duration. However, whether histamine contributes to exercise hyperemia and promotes exercise blood flow in an intensity- or duration-dependent pattern is unknown. The purpose of this study was to compare leg blood flow across a range of exercise intensities, before and after prolonged exercise, with and without histamine-receptor antagonism. It was hypothesized that combined oral histamine H1/H2-receptor antagonism would decrease leg blood flow, and the effect would be greater at higher intensities and following prolonged exercise. Sixteen (7F, 9M) volunteers performed single-leg knee-extension exercise after consuming either placebo or combined histamine H1/H2-receptor antagonists (Blockade). Exercise consisted of two graded protocols at 20, 40, 60, and 80% of peak power, separated by 60 min of knee-extension exercise at 60% of peak power. Femoral artery blood flow was measured by ultrasonography. Femoral artery blood flow increased with exercise intensity up to 2,660 ± 97 mL/min at 80% of peak power during Placebo (P < 0.05). Blood flow was further elevated with Blockade to 2,836 ± 124 mL/min (P < 0.05) at 80% peak power (9.1 ± 4.8% higher than placebo). These patterns were not affected by prolonged exercise (P = 0.13). On average, femoral blood flow during prolonged exercise was 12.7 ± 2.8% higher with Blockade vs. Placebo (P < 0.05). Contrary to the hypothesis, these results suggest that histamine receptor antagonism during exercise, regardless of intensity or duration, increases leg blood flow measured by ultrasonography.NEW & NOTEWORTHY Leg blood flow during exercise was increased by taking antihistamines, which block the receptors for histamine, a molecule often associated with inflammatory and immune responses. The elevated blood flow occurred over exercise intensities ranging from 20 to 80% of peak capacity and during exercise of 60 min duration. These results suggest that exercise-induced elevations in histamine concentrations are involved in novel, poorly understood, and perhaps complex ways in the exercise response.

Keywords: antihistamine; endurance exercise; histamine; regional blood flow.

Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Fig. 1.

Study time line. After ingestion of placebo or blockade (Rx), subjects performed 3-min stages of knee extension at 20, 40, 60, and 80% of peak power. Subjects next performed a 60-min bout of sustained moderate-intensity (60% of peak power) knee-extension exercise. Finally, subjects repeated the 3-min stages of knee extension at 20, 40, 60, and 80% of peak power. All exercise was performed at a rate of 60 contractions per minute. The 60-min bout of sustained exercise was separated from the graded stages of exercise by 20 min of seated rest. Each open arrow (⇓) represents a time point where blood flow, blood pressure, heart rate, and cardiac output were measured. Solid arrows indicate points where V̇o2, ventilation, muscle tissue oxygenation index, tissue pH, and rating of perceived exertion were measured.

Fig. 2.

Hemodynamic and local muscle responses to graded exercise. Heart rate, mean arterial pressure, femoral blood flow, femoral vascular conductance, muscle tissue oxygenation index, and intramuscular pH in response to increasing power output before (PRE; circles) and after (POST; squares) 60 min of sustained moderate-intensity exercise with either Placebo (open symbols) or histamine receptor antagonism (Blockade, solid symbols). *P < 0.05, exercise vs. resting at specified power output. a denotes P < 0.05 main effect for Post vs. Pre, and b denotes P < 0.05, main effect for Blockade vs. Placebo. Solitary regression lines for a variable indicate the absence of differences between Placebo and Blockade and PRE and POST. Multiple regression lines indicate models differed P < 0.05 across experimental conditions. n = 16 except for blood flow and conductance, where n = 14.

Fig. 3.

Whole body metabolic and perception of effort responses to graded exercise. Oxygen uptake (V̇o2), ventilation, respiratory exchange ratio, and rating of perceived exertion in response to increasing power output before (PRE; circles) and after (POST; squares) 60-min sustained moderate-intensity exercise with either placebo (open symbols) or histamine receptor antagonism (blockade, solid symbols). *P < 0.05, exercise vs. resting at specified power output; a denotes P < 0.05, main effect for Post vs. Pre. Solitary regression lines for a variable indicate the absence of differences between Placebo and Blockade and PRE and POST. Multiple regression lines indicate models differed P < 0.05 across experimental conditions. n = 16.

Fig. 4.

Hemodynamic and local muscle responses to sustained moderate-intensity exercise. Heart rate, mean arterial pressure, femoral blood flow, femoral vascular conductance, muscle tissue oxygenation index, and intramuscular pH in response to 60 min of sustained moderate-intensity exercise with either Placebo (open symbols) or histamine receptor antagonism (Blockade, solid symbols). b denotes P < 0.05, main effect for blockade vs. placebo. Solitary regression lines for a variable indicate the absence of differences between placebo and blockade. Multiple regression lines indicate models differed P < 0.05 across experimental conditions. n = 16 except for blood flow and conductance, where n = 14.

Fig. 5.

Whole body metabolic and perception of effort responses to sustained moderate-intensity exercise. Oxygen uptake (V̇o2), ventilation, respiratory exchange ratio, and rating of perceived exertion in response to 60 min of sustained moderate-intensity exercise with either placebo (open symbols) or histamine receptor antagonism (blockade, solid symbols). *P < 0.05, exercise vs. resting at specified power output. Solitary regression lines for a variable indicate the absence of differences between placebo and blockade. n = 16.