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concentration can form the superoxide perioxynitrite (OONO). In part the effects <strong>of</strong> these<br />

gases have been covered when reviewing the noxious effects <strong>of</strong> air pollution with particular<br />

reference to the nitrogen oxides in Chapter 2.2. NO and, even more so, NOz are common air<br />

pollutants (Morrow 1984; Anonymous 1995; Anonymous 1996) with inspired NO<br />

concentrations from airway pollution ranging from 20-500ppb in non-polluted areas to<br />

1.5ppm or greater in polluted areas (Aranda and Pearl 2000). As previously mentioned,<br />

cigarette smoke contains NO concentrations in order <strong>of</strong> lOOppm (Norman and Keith 1965), or<br />

higher depending on the cigarette type (Borland and Higenbottam 1987) and cigarette smoke<br />

can inhibit NADPH and myeloperoxidase (Nguyen, Finkelstein et al. 2001). While this does<br />

not result in an acute respiratory event, it might cause an increase risk <strong>of</strong> mutations over time<br />

and thus it contributes to cigarette smoke carcinogenic potential.<br />

With the use <strong>of</strong> nitrous oxide (NzO, "laughing gas") effects were noted when N2O cylinders<br />

were contaminated with NO showing that high NO concentrations could give rise to acute<br />

pulmonary oedema and methamoglobinaemia (Anonymous 1967; Clutton-Brock 1967). High<br />

levels <strong>of</strong> NO were needed to get this response in experiments with animals. For example,<br />

exposure <strong>of</strong> lambs to 80ppm <strong>of</strong> NO for three hours in 2l%o oxygen did not result<br />

methaemoglobinaemia or any <strong>of</strong> the acute problems previously documented (Frostell, Fratacci<br />

et al. 1991). Exposure <strong>of</strong> dogs to 20,000ppm did result in this acute respiratory event with<br />

high morbidity and mortality (Shiel 1967). Inhalation <strong>of</strong> 50ppm <strong>of</strong> NO impairs the<br />

performance <strong>of</strong> learned tasks and prolongs brainstem evoked potential responses in rats,<br />

without significantly elevating methaemoglobin levels (Groll-Knapp, Haider et al. 1988). In<br />

healthy subjects inhaling lOOppm <strong>of</strong> NO for three hours, methaemoglobulin levels increased<br />

by I.77Vo <strong>of</strong> total haemoglobin to a peak at 45 minutes. Serum nitrogen oxides (NOz, NOI)<br />

increased from 36.7 to 124umol L-l at 172 minutes and then declined (Young, Sear et al.<br />

1996). Inhaled NO at 5ppm resulted in thickened alveolar membranes in rabbits (Hugod<br />

1979) and NO at 43ppm and NO2 at 3.6ppm narrowed the surfactant hysteresis, altered<br />

epithelium ultra-structure and caused interstitial atrophy (Hugod 1979). Intermittent NO<br />

exposure over a 9 week period in rats resulted in degeneration <strong>of</strong> interstitial cells and the<br />

interstitial matrix leading to an emphysematous-like destruction <strong>of</strong> alveolar septa (Mercer,<br />

Cosra et al. 1995).<br />

NOz is more toxic and has long been known to cause respiratory damage and fatality<br />

(Kooiker, Schuman et al. 1963: Wagner, 1965 #1030). It was early recognised as a concern in<br />

atmospheric pollution (Kennebeck, Wetherington et al. 1963). NOz has been shown to be<br />

taken up easily by lung lining fluid at a rate related to its speed <strong>of</strong> reaction to glutathione<br />

105

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