Pulmonary Targets of ROS

The responses of any tissue to a strong oxidant stimulus are progressive and range in severity from pertubation of 

It is misleading to consider that ROS are always deleterious, and that to prevent release or action of ail ROS will be of therapeutic value. One could reason that some ROS are released without control or purpose, as by-products of the normal metabolism of eicosanoids, or during oxidative phosphorylation in the mitochondria. However, during normal function, inflammatory ceUs appropriately release ROS both intracellularly into vacuoles and extracellularly in order to kill foreign organisms in host defence. Also, nitric oxide is a radical species whose principal role in the lung appears to be the control of pulmonary vascular tone and platelet function. Nevertheless, there are clear examples where fhistrated phagocytosis could explain an excessive release of ROS in 

Much of the pulmonary NEP activity is believed to reside in the epithelium, as has been demonstrated in the ferret (Borson et al., 1986), and thus it is likely that inhaled ozone would preferentially destroy luminal NEP before affecting any enzymes in the vasculature, which may degrade peptides delivered by the intravenous route. This may explain the route-dependency of BHR after ozone in guinea pigs. Further evidence that the oxidant effects of inhaled ozone are selective is provided by the findings that pressor responses to angiotensin I (which requires conversion by ACE to angiotensin II) were not altered by ozone exposure (Yeadon et eU., 1992). 

Ozone is known to be a powerful oxidant capable of both initiating peroxidation in lipids and reacting with 

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