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Role of eNOS in the Regulation of Substrate Metabolism during Exercise
Author(s) -
LeeYoung Robert,
Bracy Deanna,
James Freyja,
Ayala Julio,
Wasserman David
Publication year - 2008
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.22.1_supplement.1235.20
Subject(s) - enos , medicine , endocrinology , chemistry , glycogenolysis , nitric oxide synthase , nitric oxide , metabolism
Endothelial nitric oxide synthase (eNOS) participates in the regulation of a blood flow and muscle mitochondrial function. The functional importance of eNOS was determined in mice with full (−/−) or partial (+/−) deletion of eNOS and wild‐type (+/+) littermates using treadmill exercise to amplify cardiovascular and metabolic responses. Five days after catheterization, 5h fasted mice performed a maximum of 30min of exercise (16m/min). At 5min, 2‐[ 14 C]‐deoxyglucose and [ 3 H]‐bromopalmitic acid were injected into the jugular vein to determine tissue‐specific glucose (Rg) and fatty acid (Rf) uptake. At the end of exercise microspheres were injected into the carotid artery to determine % cardiac output to the gastrocnemius (%Q G ). Running time was impaired in eNOS −/− mice (21±2 vs. 29±1 and 30±0min for eNOS +/− and eNOS +/+ ), as was the increase in %Q G (2±1 vs. 3±1 and 6±1 fold). Muscle and liver glycogenolysis was greatest in eNOS −/− mice, as were plasma lactate levels (11±1 vs. 4±1 and 3±0mM). Despite elevated glycogenolysis eNOS −/− mice were hypoglycemic at the end of exercise (4±1 vs. 11±1 and 14±1mM) due to accelerated muscle glucose uptake (gastrocnemius Rg = 92±31 vs. 23±7 and 20±6μmol/100mg/min). Rf (4.4±1.4 vs. 2.8 ±0.6 and 2.5±0.4 μmol/100mg/min) was also accelerated. In conclusion, eNOS regulates %Q G in a dose dependent manner with ~25% of Q G being eNOS‐independent. Ablation of eNOS markedly increases Rg and Rf. The four‐fold increase in plasma lactate observed in eNOS −/− mice suggests that a high percentage of the substrate consumed by muscle does not undergo mitochondrial oxidation.