Effects of prolonged exposure to low doses of nitric oxide or nitrogen dioxide on the alveolar septa of the adult rat lung.

BACKGROUND

Nitric oxide (NO) and nitrogen dioxide (NO2) are common copollutants resulting from combustion processes such as the burning of fossil fuels and tobacco smoke. The relative toxicity of these two pollutants has not been adequately addressed. Separate low level exposures to each of these two pollutants were carried out to allow comparisons of relative health risks.

EXPERIMENTAL DESIGN

Male rats were exposed to either NO or NO2 for 9 weeks at 0.5 ppm with twice daily, 1-hour spikes to 1.5 ppm. Lungs from five rats in each exposed group and from rats from a clean air control group were preserved by vascular perfusion of fixative and were embedded for sectioning. The number of fenestrations in alveolar septa of the lung was determined by using serial sections to directly count the number of fenestrae in a known volume of lung.

RESULTS

The average number of fenestrae was 328 +/- 156 x 10(3) (mean +/- SE, n = 5) per lung in the NO group. In the NO2 exposure group, there were 99 +/- 42 x 10(3) fenestrae per lung. The number of fenestrae per lung in the controls (9 +/- 9 x 10(3)) was not statistically different from zero. The number of fenestrae in the NO group was significantly greater than that in the control or NO2 groups. Analyses of total parenchymal cells per lung demonstrated a statistically significant 29% reduction in the number of interstitial cells in the NO group. There were no significant differences in the numbers of other types of cells between the control and exposed groups. The thickness of the interstitial space was reduced in the NO group (0.24 +/- 0.02 microns versus 0.32 +/- 0.02 microns in controls) but not in the NO2 group (0.29 +/- 0.02 microns). Epithelial cell thickness did not differ between groups.

CONCLUSIONS

Focal degeneration of interstitial cells, interstitial matrix, and connective tissue fibers is the principal injury resulting from low level NO exposure. NO is significantly more potent than NO2 in the production of these defects in the interstitial spaces of alveolar septa. Although limited in number and size, the formation of fenestrae by atrophy of the interstitial spaces is similar to the initial steps in an emphysema-like destruction of alveolar septa.