Reactive oxygen species and vascular signal transduction mechanisms.

Sources of reactive O2 species in the vessel wall that potentially contribute to the control of vascular tone include NADPH oxidases, arachidonic acid metabolizing enzymes, xanthine oxidase, nitric oxide synthase and mitochondria. Specific physiological stimuli (such as changes in PO2) as well as pathophysiological stimuli control the production of reactive O2 species by many of these sources. Certain key reactive O2 species activate specific signalling mechanisms that control vascular tone, often through processes involving the metabolism of these species. The production of prostaglandins and cyclic GMP are some of the most sensitive systems regulated by hydrogen peroxide; whereas the conversion of nitric oxide (NO) to peroxynitrite (ONOO-) and inhibition of the stimulation of the cytosolic form of guanylate cyclase are processes that are very sensitive to superoxide anion (O2.-). High levels of NO production readily result in the formation of significant amounts of ONOO-, because NO competes with superoxide dismutase for the metabolism of cellular O2.- and thereby activates additional signalling mechanisms such as regulation through thiol nitrosation. As the levels of individual reactive O2 species increase, other signalling mechanisms likely to participate in vascular responses to oxidant injury seem to become activated. Thus, evidence is developing to support the concept that reactive O2 species are important contributors to the control of vascular tone.