Cerebral vascular effects of reactive oxygen species: Recent evidence for a role of NADPH-oxidase

1. Reactive oxygen species (ROS) are a diverse family of molecules that are produced throughout the vascular wall. Many ROS, such as the superoxide anion (O-.(2)-) and hydrogen peroxide (H2O2), are now known to act as cellular signalling molecules within blood vessels. In particular, these molecules can exert powerful effects on vascular tone. 2. Cerebral arteries are relatively unusual in their responsiveness to ROS. Unlike in many systemic vessels, both O-.(2)- and H2O2 can cause vasodilatation in the cerebral microcirculation. 3. Reactive oxygen species can be produced in the vasculature via a variety of mechanisms; however, it appears that the primary source of O-.(2)- within blood vessels is the enzyme NADPH-oxidase. 4. In cerebral vessels, activation of NADPH-oxidase causes both O-.(2)- production and vasodilatation, indicating that NADPH-oxidase-derived ROS may have a functional role in the regulation of cerebral vascular tone. 5. Elevated levels of NADPH-oxidase activity and expression occur in cardiovascular disease states such as hypertension, atherosclerosis and subarachnoid haemorrhage. 6. Thus, ROS may contribute to the regulation of cerebral vascular tone during both physiological and pathological conditions.