Oxidative stress plays a crucial role in sickle cell disease (SCD) physiopathology. Given that chronic physical activity is known to decrease reactive oxygen species (ROS) and increase nitric oxide (NO) bioavailability in healthy subjects and in patients with cardiovascular or inflammatory pathologies, modulating these factors involved in the severity of the pathology could also be beneficial in SCD. This study aimed to determine if 8 weeks of increased physical activity (PA) by voluntary wheel running affects the hypoxia/reoxygenation (H/R) responses by reducing oxidative stress and increasing NO synthesis in sickle SAD mice. Nitrite/nitrate (NOx) concentrations, NOS3 mRNA expression and phosphorylated-endothelial nitric oxide synthase immunostaining were increased in the lungs of the PA groups after H/R stress. Moreover, lipid peroxidation in the heart was decreased in PA SAD mice. The improvement of antioxidant activity at rest and the decrease in haemolysis may explain this reduced oxidative stress. These results suggest that physical activity probably diminishes some deleterious effects of H/R stress in SAD mice and could be protective against vascular occlusions.
