Redox balance in the aging microcirculation: new friends, new foes, and new clinical directions.

Cardiovascular aging is associated with a decline in the function of the vascular endothelium. Considerable evidence indicates that age-induced impairment of endothelium-dependent vasodilation results from a reduction in the availability of nitric oxide (NO(•) ). NO(•) can be scavenged by reactive oxygen species (ROS), in particular by superoxide radical (O(2) (•-) ), and age-related increases in ROS have been demonstrated to contribute to reduced endothelium-dependent vasodilation in numerous large artery preparations. In contrast, emerging data suggest that ROS may play a compensatory role in endothelial function of the aging microvasculature. The primary goal of this review is to discuss reports in the literature which indicate that ROS function as important signaling molecules in the aging microvasculature. Emphasis is placed upon discussion of the emerging roles of hydrogen peroxide (H(2) O(2) ) and peroxynitrite (ONOO(•-) ) in the aging microcirculation. Overall, existing data in animal models suggest that maintenance in the balance of ROS is critical to successful microvascular aging. The limited work that has been performed to investigate the role of ROS in human microvascular aging is also discussed, and the need for future investigations of ROS signaling in older humans is considered.