Endothelial dysfunction and reactive oxygen species production in ischemia/reperfusion and nitrate tolerance.
Reactive oxygen species (ROS), as superoxide and its metabolites, have important roles in vascular homeostasis as they are involved in various signaling processes. In many cardiovascular disease states, however, the release of ROS is increased. Uncontrolled ROS production leads to impaired endothelial function and consequently to vascular dysfunction. This review focuses on two clinical conditions associated with elevated ROS levels: ischemia/reperfusion and nitrate tolerance. Injury caused by ischemia/reperfusion is an important limitation of transplantations, and complicates the management of stroke and myocardial infarction. Nitrates, which are used to treat transient myocardial ischemia (angina pectoris), decrease in efficacy in long-term continuous administration. There are several enzyme systems, such as xanthine oxidase, cyclooxygenase, uncoupled endothelial nitric oxide synthase, NAD(P)H oxidase, cytochrome P450 and the mitochondrial electron transport chain, which are responsible for the increased vascular production of superoxide. The contribution of particular ROS producing enzymes and the effect of antioxidant treatment are discussed in both pathological conditions.
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Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovakia. exfakati@savba.sk
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D004361:Drug Tolerance; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D009566:Nitrates / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D014652:Vascular Diseases / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*
D000975:Antioxidants; D009566:Nitrates; D017382:Reactive Oxygen Species; D009569:Nitric Oxide