The vascular endothelium is an organ that regulates mass transfer between blood and various tissues around the body. Thus, vascular leak, the exchange of fluid between the vasculature and the interstitium of surrounding tissue, is an essential physiological process. The rate of vascular leak is determined by the tightness of the vascular barrier, which is composed of a monolayer of endothelial cells that form the inner lining of blood vessels. This in turn is regulated by redox-dependent modifications to the cytoskeletons of endothelial cells and the cell–cell junctions between them. Thus, understanding redox-dependent regulation of endothelial barrier function is of significant scientific interest. However, the impetus for this area of inquiry extends well beyond scientific curiosity: In several cardiovascular, renal, and metabolic diseases, oxidative stress leads to pathologically enhancement of vascular leak, contributing to thrombogenesis, and other deleterious effects. Thus, understanding the development and consequences of oxidant-induced pathological vascular leak is of paramount importance to the development of effective therapies. A variety of experimental models and measurement techniques are available for the investigation of oxidant-induced vascular leak in preparations ranging from cells to whole organisms. In this chapter, we discuss the mechanisms underlying oxidant modulation of vascular leak, various experimental models of this phenomenon, and methods to assess structure and function of the vascular endothelium. Particular emphasis is placed on selecting the experimental models and measurement techniques that are most appropriate to the research question under investigation.
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