Adequate glutathione levels are necessary to prevent hypoxia‐induced inflammation in trained rats

Abstract

Systemic hypoxia (Hx) produces microvascular inflammation in several tissues, including skeletal muscle. This inflammatory response results in an increase in leukocyte-endothelial adherence (LEA) and an increase in vascular permeability during Hx. The response to Hx is absent in exercised trained (ET) rats. Our objective was to investigate the role of glutathione (GSH), an endogenous antioxidant, on the protective effect of exercise training (5 weeks treadmill exercise). Total GSH levels were measured in ET and untrained (UT) rat liver, blood, cremaster, and biceps femoris. In addition, buthionine sulfoximine (BSO) was used to deplete endogenous GSH to determine if GSH was necessary to prevent Hx-induced inflammation. GSH levels were not elevated in ET liver (2.9±0.1 vs. 2.9±0.2μmol/g in UT, P > 0.05), blood (1.1±0.1 vs. 1.0±0.1μmol/ml in UT, P > 0.05), cremaster (0.7±0.1 vs. 0.8±0.1μmol/g in UT, P > 0.05), and biceps femoris (0.5±0.1 vs. 0.5±0.1μmol/g in UT, P > 0.05). However, BSO depletion of GSH in ET rats produced increases in LEA (2.2±0.4 during Hx vs. 18.4±2.1 leukocytes per 100μm venule during Hx with BSO, P<0.05) and vascular permeability (0.11±0.02 during Hx vs. 0.53±0.05 extra/intravascular FITC-albumin ratio during Hx with BSO, P<0.05). Therefore, exercise training does not significantly elevate GSH levels in liver, blood, cremaster, or biceps femoris, but adequate GSH levels are necessary to prevent Hx-induced inflammation from occurring in ET cremaster venules. Supported by National Heart, Lung, and Blood Institute Grants HL-39443 and HL-64195.