Diffuse alveolar damage in the rat lung after short and long term exposure to nitrogen dioxide

In order to quantify parenchymal, vascular and epithelial changes occurring in the exudative and organizing phase of diffuse alveolar damage (DAD) induced by inhaled NO2 groups of 7 rats were continuously exposed to 5, 10 or 20 ppm NO2 for 3 and 25 days alternatively. AgNOR analysis revealed the highest proliferative activity in the epithelium of the respiratory bronchioles. In this region already after 3d exposure to 5 ppm the maximum AgNOR number was reached. In contrast to long-term exposure after 3d exposure to 5 and 10 ppm NO2 the AgNOR number in the respiratory bronchioles was significantly higher than in central airway epithelia. After long-term exposure to 5 and 10 ppm AgNOR number decreased to normal values or showed no further significant increase, long-term exposure to 20 ppm resulted in a further increase of the AgNOR number. A significant increase of the alveolar circumference and decrease of alveolar surface density was found after an exposure to 20 ppm for 3d and long-term exposure to 10 and 20 ppm NO2, whereas the 5 ppm exposure groups disclosed no significant change of these values. Medial hypertrophy was detected after exposure to 10 and 20 ppm NO2 for 25 days, after the exposure to 5 ppm for 3d and 25d medial thickness was significantly decreased due to vasodilation induced by NO, one of the major reaction products of NO2.