Nitric oxide and reactive oxygen species in vascular injury.
Nitric oxide (.NO), a free radical species produced by several mammalian cell types, plays a role in regulation of vascular, neurological and immunological signal transduction and function. The role of .NO in cytotoxic events is acquiring increased significance. The high rate of production and broad distribution of sites of production of .NO, combined with its facile direct and indirect reactions with metalloproteins, thiols and various oxygen radical species, assures that .NO will play a central role in regulating vascular, physiological and cellular homoeostasis, as well as critical intravascular free radical and oxidant reactions. At the same time, there are contradictions as to whether .NO mediates or limits free-radical-mediated tissue injury, and uncertainty regarding its mechanisms of action. .NO has been portrayed as a pathogenic mediator during ischaemia-reperfusion, and inflammatory and septic tissue injury. In contrast, cell-, metal- and oxidant-induced lipoprotein oxidation events, as well as hepatic, cerebrovascular, pulmonary and myocardial inflammatory and ischaemia-reperfusion injury studies, show convincingly that stimulation of endogenous .NO production or exogenous administration of .NO-donating molecules can serve a protective role by inhibition of often oxidant-related mechanisms. The final outcome of toxic versus tissue-protective reactions of .NO will depend on several factors, including sites and relative concentrations of individual reactive species and their diffusion distances. The following sections address these issues and conclude with a proposal as to how .NO serves as a central regulator of oxidant reactions and diverse free radical-related disease processes.
Rubbo
H
H
Department of Anesthesiology, University of Alabama at Birmingham 35233, USA.
Tarpey
M
M
Freeman
B A
BA
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D017382:Reactive Oxygen Species
D017382:Reactive Oxygen Species; D009569:Nitric Oxide