Effects of H1/H2 histamine receptor blockade on mitochondrial function in rodent brain following prolonged exercise

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Exercise has been shown to stimulate histamine release, which mediates vasodilation in exercising tissue and is sustained post‐exercise. Blockade of H1 and H2 receptors with antihistamine drugs attenuates this effect in skeletal muscle. Research examining the effects of exercise‐related histamine action on cellular level processes is relatively sparse. There also remains limited understanding of the impacts of histamine receptor blockade on non‐exercising tissue, such as the brain. To this end, 36 adult male Wistar rats (75–94 days old, 441.2 ± 39.5 g body wt) were randomly assigned to three groups: (1) given H1 and H2 receptor antagonists fexofenadine (7.11 mg/kg) and ranitidine (3.95 mg/kg) via oral gavage 1 hr prior to treadmill exercise (1 hr, 20 cm/s); (2) completed the exercise without drug, and (3) control. All groups received body mass‐proportional oral gavage volumes (water or antihistamines). One hour post‐exercise, mitochondrial function was assessed in saponin‐permeabilized prefrontal cortex and dorsal hippocampus brain sub‐regions. There was no effect of exercise or drug treatment on mitochondrial substrate‐dependent oxygen consumption (JO2; high‐resolution respirometry), or in mitochondrial hydrogen peroxide emission (mH2O2; fluorometric monitoring of Amplex Red oxidation) in permeabilized prefrontal cortex or the dorsal hippocampus. These results suggest negligible effects of oral H1/H2 antagonists on mitochondrial metabolism in brain following exercise. This supports prior evidence suggesting the effects of H1/H2 inhibition remain localized in exercising muscle. Other studies report systemic increases in histamine levels following exercise, however, which suggests further research may reveal a relationship between histamine receptor blockade and cellular processes in non‐exercising tissues.Support or Funding InformationThe Natural Sciences and Engineering Research Council of Canada (NSERC), The Nova Scotia Health Research Foundation (NSHRF), and Canada Foundation for Innovation (CFI)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.