The Microcirculation and Oxidative Stress

Abstract

Microvascular dysfunction appears to play a key role in the pathogenesis of many pathologies, such as hypertension, diabetes, ischemia-reperfusion or sepsis. One of the main players in microcirculatory regulation is the endothelium. Indeed, many studies outline the fundamental role of the endothelium in vascular tone regulation, vascular pro-anticoagulant balance, and vessel wall permeability modulation. Many stimuli are able to induce endothelial dysfunction, including pro-inflammatory cytokines, hypoxia, and oxidative stress. Among the causes of endothelial dysfunction, oxidative stress has been the most extensively investigated. The endothelium represents both a source and a target for reactive oxygen species (ROS) released into the microcirculation. Rather than contribute to oxidative stress, endogenous endothelial systems for ROS generation may have normal physiological signal functions, generating ‘second messengers’ that regulate endothelial cell growth/proliferation, endothelial cell barrier function, vasorelaxation, and vascular remodeling. However, in pathologies such as sepsis or hemorrhagic shock, the imbalance between the production of ROS and their effective removal by non-enzymatic and enzymatic antioxidant systems may induce endothelial dysfunction with alteration of vascular tone, increased cell adhesion properties (leukocyte and platelet adhesion), and increased vascular wall permeability, leading to a pro-coagulant state.