title: Morphometric analysis of alveolar responses of F344 rats to subchronic inhalation of nitric oxide.
abstract: Nitric oxide (NO)*, the principal airborne pollutant generated from combustion processes such as gas stoves, tobacco smoke, and burning of fossil fuels, is being tested as a therapeutic agent in clinical trials. A prior morphometric study of rats exposed for 9 weeks to 0.5 parts per million (ppm) NO demonstrated focal degeneration of the alveolar interstitium and increased numbers of fenestrated alveolar septa (Mercer et al. 1995). The limited size and distribution of defects in this NO exposure did not alter alveolar surface area or other morphometric indicators of lung function, but were of interest as the responses to inhaled NO appeared to differ from those produced by other oxidants such as ozone (O3) and nitrogen dioxide (NO2). Nitric oxide exposures at the same concentration and duration as prior morphometric studies of O3 and NO2 were necessary in order to make a comparison. This was the purpose of the current study in which F344 rats were exposed for 6 weeks to air, 2 ppm NO, or 6 ppm NO. Following exposure, the lungs of NO- and air-exposed rats were preserved and prepared for electron microscopy. The lungs of replicate groups were lavaged and analyzed for protein content and antioxidants. Ultrastructural alterations due to exposure were determined by quantitative morphometric analyses and serial-section counts of the number of alveolar fenestrae. In contrast to the prior study of NO, there was no significant difference in the number of alveolar fenestrae/lung between control and NO-exposed groups. Morphometric analysis of the 6 ppm NO-exposure group demonstrated a significant increase from controls in the percentage of epithelial basement membrane covered by type II epithelial cells and a significant increase in the number of type II epithelial cells and airspace macrophages. At 2 ppm, only the percentage of epithelial basement membrane covered by type II epithelial cells was significant. No significant differences were found in lavage protein or in lavage ascorbic acid or glutathione content between clean-air controls and NO-exposed groups. Overall, the proinflammatory responses by type II epithelial cells and airspace macrophages following inhaled NO were comparable to those of O3 and NO2. These results, derived from experiments using significantly higher concentrations than in the prior study, demonstrate that inhaled NO produces a pattern of injury similar to that of other oxidants.
authors.affiliation: Pathology and Physiology Branch, National Institute of Occupational Safety and Health, Morgantown, WV 26505, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Mercer
mesh_terms: D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000633:toxicity*; D009585:Nitrogen Dioxide / Q000633:toxicity; D010126:Ozone / Q000633:toxicity; D010974:Platelet Aggregation / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000393:Air Pollutants; D009569:Nitric Oxide; D010126:Ozone; D009585:Nitrogen Dioxide