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Lauer N, Suvorava T, Ruther U, Jacob R, Meyer W, Harrison DG, Kojda G: Critical involvement of hydrogen peroxide in exercise-induced up-regulation of endothelial NO synthase. Cardiovasc Res. 2005 Jan 1;65(1):254-62. OBJECTIVE: Recent studies from our groups have indicated that endothelial nitric oxide synthase (eNOS) expression is increased in cell culture by both shear stress and by hydrogen peroxide (H (2) O (2)). In vivo, exercise training, known to increase both endothelial shear stress and oxidative stress, also increases eNOS expression. It is unclear if H (2) O (2) contributes to an increase in eNOS expression in response to exercise training. METHODS: To address this question, we generated mice overexpressing human catalase (hCat) driven by the murine Tie-2 promoter to specifically target this transgene to the endothelium (cat (++)). RESULTS: Vessels of cat (++) expressed significantly higher levels of catalase mRNA and catalase protein and activity but normal levels of eNOS. Exercise alone had no effect on catalase expression in C57BL/6. Wild-type littermates of cat (++) showed an increase in eNOS expression with 3 weeks of exercise (2.53+/-0.42-fold) comparable to C57BL/6 (2.93+/-0.45-fold). In striking contrast, 3 weeks of exercise had no effect on aortic (1.33+/-0.32-fold) and myocardial (1.1+/-0.2-fold) eNOS expression in catalase transgenic mice. CONCLUSIONS: These data suggest that endogenous H (2) O (2) plays a key role in the endothelial adaptation to exercise training by stimulating an up-regulation of eNOS. |
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