Reactive oxygen species and cerebrovascular diseases

Abstract

In the normal physiologic state, reactive oxygen species (ROS) generation is intentional and important for the functioning of cerebral and systemic circulations. Furthermore, emerging evidence indicates that cerebral arteries generate higher levels of ROS than arteries outside of the brain in the normal physiologic state. As such, it has been proposed that ROS may play a more prominent role in the physiologic regulation of cerebral arteries. There are numerous potential enzymatic sources of ROS in the cerebral vasculature; however, increasing evidence indicates that the family of NADPH oxidases is a major source. Aberrant redox signaling or oxidative stress in the cerebral circulation, usually as a result of excessive production of ROS and reactive nitrogen species (RNS), is a common feature in diverse models of cardiovascular risk factors (e.g., hypertension, hypercholesterolemia) and cerebrovascular disease. Furthermore, oxidative stress is now believed to be an underlying cause of cerebrovascular dysfunction and damage associated with these disease states. In this chapter, we summarize the effects and potential roles of ROS/RNS in modulating cerebral artery function in the normal physiologic state, with a particular focus on their roles in modulating cerebrovascular tone. Furthermore, we will highlight current evidence for the involvement of ROS/RNS in cerebrovascular dysfunction associated with cardiovascular risk factors, stroke, and Alzheimer's disease.