Hydrogen Peroxide Promotes Endothelial Dysfunction by Decreasing Nitric Oxide Bioavailability in Experimental Diabetes Mellitus

Oxidative stress is the major pathophysiological mechanism that underlies the progression of both cardiovascular and metabolic diseases. The individual contribution of reactive oxygen species (ROS) to diabetes mellitus (DM)-related endothelial dysfunction is partially elucidated. While superoxide has been unequivocally involved in the progression of endothelial dysfunction, less it is known about the contribution of hydrogen peroxide (H2O2). The present study was purported to assess the amount of H2O2 generated in murine vessels in the presence of diabetes and to characterize its effects on vascular function, respectively. To this aim we isolated aortas from rats with streptozotocin-induced DM, measured the H2O2 production using the ferrous oxidation-xylenol orange (FOX) assay, and performed organ bath studies of vascular reactivity. Our data showed that in diabetic vessels: i) basal ROS production was comparable to the one generated after ex vivo stimulation with lipopolysaccharide and angiotensin Hand ii) the amount of H2O2 generated in the vascular wall decreased relaxation via the impairment of NO signaling. In conclusion, metabolic abnormalities associated to diabetes elicit constant H2O2 overproduction with the subsequent impairment of NO signaling and endothelial dysfunction. Ongoing studies are addressing the sources of vascular H2O2 as well as the means to counteract its generation.