Effects of aging and exercise training on eNOS uncoupling and reactive oxygen species signaling in the endothelium of skeletal muscle arterioles

The purpose of the first study was to determine the effects of aging and exercise training on endothelial nitric oxide synthase (eNOS) uncoupling in skeletal muscle arterioles. The results of this study confirmed our previous findings that aging impairs endothelium-dependent, NO-mediated vasodilation and tetrahydrobiopterin (BH4) levels in rat skeletal muscle arterioles. Limited availability of BH4, as observed in old sedentary rats, may contribute to eNOS uncoupling, which decreases NO signaling and increases eNOS-derived O2- generation. Exercise training restored BH4 levels and improved flow-induced NO production in arterioles from aged rats. Furthermore, exercise training increased both NO and reactive oxygen species (ROS)-mediated signaling in skeletal muscle arterioles, suggesting that exercise training-induced enhancement of flow-induced vasodilation in skeletal muscle arterioles involves a balance between NO and O2 --derived ROS.;The second study determined the role of O2--derived ROS in mediating endothelium-dependent vasodilation in skeletal muscle arterioles from young and old, sedentary and exercise trained rats. The results of the second study implicated O2- and O2 --derived ROS (H2O2) as necessary signaling molecules required for endothelium-dependent vasodilation in soleus muscle arterioles. The dependence of ACh-induced vasodilation on H2O 2 increased with age and decreased with exercise training. Exercise training contributed to appropriate regulation of the relative production of O2- and H2O2, which must be maintained for robust endothelium-dependent vasodilation to occur in skeletal muscle arterioles