Effects of nitrous acid exposure on pulmonary tissues in guinea pigs

Many epidemiological studies on the effects of nitrogen dioxide (NO(2)) on respiratory function may have included nitrous acid (HONO) exposures in their measures, because conventional NO(2) assays detect HONO as NO(2). A few epidemiological studies and human HONO inhalation experiments have associated HONO with decrements in lung functions. However, there have been few HONO exposure experiments in animals. This study aims to develop a HONO generation system for the animal exposure experiments, and to assess the association of HONO exposure with histopathologic alterations in the respiratory tract of guinea pigs. We exposed the guinea pigs to 3.6 ppm HONO with secondary products of 0.3 ppm NO(2) and 1.6 ppm nitric oxide (NO) for 4 weeks (24 h/day). We conducted histopathologic analyses and measured specific airway resistance (sRaw) from 7 h 40 min to 8 h 30 min after the end of HONO exposure. We found pulmonary emphysema-like alterations in the alveolar duct centriacinar regions, distortion of the centriacinar regions of alveolar ducts with extension of the bronchial epithelial cells and smooth muscle cells, and expansion of bronchial epithelial cells, in the HONO exposure. These histopathologic results suggest that a high concentration of HONO with some NO(2) and NO may associate with decrements in lung functions and some respiratory symptoms. Although the increased tendency of the sRaw value was observed in the HONO exposure group, no statistically significant difference was found between the sRaw values from the HONO exposure group and the filtered air group (p = 0.06, student's t-test).