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 co pollutants resulting. from combustion processes such as the burning of fossil fuels and tobacco smoke. The relative toxicity of these two po llutants has not been adequately addressed. Separate low level exposur es to each of these two poUutants were carried out to allow comparison s of relative health risks. EXPERIMENTAL DESIGN: Male rats were expose d 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 perfus ion of fixative and were embedded for sectioning. The number of fenest rations in alveolar septa of the lung was determined by using serial s ections 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 gr oup, there were 99 +/- 42 x 10(3) fenestrae per lung. The number of fe nestrae per lung in the controls (9 +/- 9 x 10(3)) was not statistical ly different from zero. The number of fenestrae in the NO group was si gnificantly greater than that in the control or NO2 groups. Analyses o f total parenchymal cells per lung demonstrated a statistically signif icant 29% reduction in the number of interstitial cells in the NO grou p. 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 mu m ve rsus 0.32 +/- 0.02 mu m in controls) but not in the NO2 group (0.29 +/ - 0.02 mu m). Epithelial cell thickness did not differ between groups. CONCLUSIONS: Focal degeneration of interstitial cells, interstitial m atrix, and connective tissue fibers is the principal injury resulting from low level NO exposure. NO is significantly more potent than NO2 i n the production of these defects in the interstitial spaces of alveol ar septa. Although limited in number and size, the formation of fenest rae by atrophy of the interstitial spaces is similar to the initial st eps in an emphysema-like destruction of alveolar septa.