Critical involvement of hydrogen peroxide in exercise-induced up-regulation of endothelial NO synthase

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 (H2O2). In vivo, exercise training, known to increase both endothelial shear stress and oxidative stress, also increases eNOS expression. It is unclear if H2O2 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 H2O2 plays a key role in the endothelial adaptation to exercise training by stimulating an up-regulation of eNOS. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.