Mitochondrial redox control of matrix metalloproteinase signaling in resistance arteries.

The importance of free radicals in the regulation of vascular tone was recognized in the late 1980s, when endothelium-derived relaxing factor was identified to be NO.1,2 More recently, it has become clear that other free radicals, such as superoxide (O2), hydrogen peroxide (H2O2), and peroxynitrite (ONOO-) also modulate vascular reactivity.3,4 However, the exact role of reactive oxygen species (ROS) in the regulation of vascular contraction and relaxation remains elusive because vascular effects of free radicals are heterogeneous. Responses may differ depending on the species studied, the vascular bed under investigation, whether the endothelium is intact or denuded, and if studies are conducted in vitro or in vivo.5,6 Furthermore, vascular actions of ROS may be direct or indirect and responses vary depending on the source of the free radicals and their site of compartmentalization.