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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+Show Affiliations

Pathology and Physiology Branch, National Institute of Occupational Safety and Health, Morgantown, WV 26505, USA.

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

10553264

Citation

Mercer, R R.. "Morphometric Analysis of Alveolar Responses of F344 Rats to Subchronic Inhalation of Nitric Oxide." Research Report (Health Effects Institute), 1999, pp. 1-15; discussion 17-9.
Mercer RR. Morphometric analysis of alveolar responses of F344 rats to subchronic inhalation of nitric oxide. Res Rep Health Eff Inst. 1999.
Mercer, R. R. (1999). Morphometric analysis of alveolar responses of F344 rats to subchronic inhalation of nitric oxide. Research Report (Health Effects Institute), (88), 1-15; discussion 17-9.
Mercer RR. Morphometric Analysis of Alveolar Responses of F344 Rats to Subchronic Inhalation of Nitric Oxide. Res Rep Health Eff Inst. 1999;(88)1-15; discussion 17-9. PubMed PMID: 10553264.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Morphometric analysis of alveolar responses of F344 rats to subchronic inhalation of nitric oxide. A1 - Mercer,R R, PY - 1999/11/30/pubmed PY - 1999/11/30/medline PY - 1999/11/30/entrez SP - 1-15; discussion 17-9 JF - Research report (Health Effects Institute) JO - Res Rep Health Eff Inst IS - 88 N2 - 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. SN - 1041-5505 UR - https://www.unboundmedicine.com/medline/citation/10553264/Morphometric_analysis_of_alveolar_responses_of_F344_rats_to_subchronic_inhalation_of_nitric_oxide_ DB - PRIME DP - Unbound Medicine ER -