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H 1 /H 2 histamine receptor blockade lowers substrate‐dependent mitochondrial H 2 O 2 emission in deep gastrocnemius muscle following a bout of prolonged exercise
Author(s) -
Davidson Laura R.,
Wallace Helen Elizabeth,
Bell Mackenzie CW.,
Brebner Karen,
Kane Daniel A.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.618.11
Subject(s) - medicine , endocrinology , skeletal muscle , chemistry , gastrocnemius muscle , histamine receptor , pharmacology , biochemistry , antagonist , biology , receptor
Prolonged exercise increases oxidative metabolism in skeletal muscle mitochondria, which is facilitated, in part, by increased blood flow and delivery of nutrients and oxygen. Histamine mediates many acute exercise responses, including sustained vasodilation and associated delivery of substrates to muscle. We tested the hypothesis that H 1 and H 2 histamine receptor blockade would attenuate exercise‐induced changes in skeletal muscle mitochondrial function. Adult male Wistar rats (75–94 days old; 441.2 ± 39.5 g) were randomly assigned to one of three groups ( n = 12/group): exercise, in the form of one hour of continuous treadmill running at 20 cm/sec (Group 1); mass‐specific oral gavage with H 1 antagonist fexofenadine (7.11 mg/kg) and H 2 antagonist ranitidine (3.95 mg/kg) one hour prior to the same exercise protocol (Group 2); control, which received neither antihistamines nor exercise (Group 3). An hour post exercise, mitochondrial function was assessed in saponin‐permeabilized myofibers from deep gastrocnemius (mixed fiber types) and soleus (oxidative) skeletal muscle. A sequential substrate‐inhibitor titration protocol was used to examine multiple mitochondrial metabolic pathways (i.e., malate + octanoyl‐carnitine, ADP, lactate + NAD + , pyruvate, glutamate, succinate, inhibitors of antioxidant defense glutathione peroxidase and thioredoxin). Substrate‐dependent oxygen consumption ( J O 2 ; high‐resolution respirometry) was not different between treatments; however, H 1 and H 2 histamine receptor blockade significantly decreased hydrogen peroxide emission (mH 2 O 2 ; fluorometric monitoring of Amplex Red oxidation) in deep gastrocnemius fibres ( P < .05). Given the widespread and routine use of antihistamines, further research into the effects of these antagonists on mitochondrial function, in the context of exercise, is warranted. Support or Funding Information The 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 .