Quantitative analysis of parenchymal and vascular alterations in NO2-induced lung injury in rats.
Nitrogen dioxide (NO2), the oxidation product of nitric oxide (NO), is a reactive free radical forming gas, the inhalation of which has been reported to induce severe damage to distal airways. In order to quantify dose and time course of parenchymal and vascular damage, rats were exposed to 5, 10 and 20 ppm NO2 for 3 and 25 days, followed by quantitative histology and morphometry of the lung. Histological investigations of the short-term exposed animals showed structural alterations extending from slight interstitial oedema after exposure to 5 ppm, to epithelial necrosis and interstitial inflammatory infiltration after exposure to 10 ppm, and an additional intra-alveolar oedema after 20 ppm. The pulmonary arteries disclosed no qualitative changes, such as muscularization of intra-acinar vessels. Long-term exposure to 10 ppm and 20 ppm NO2 resulted in emphysema and slight centrilobular interstitial fibrosis. Morphometric analysis revealed the alveolar surface density to be significantly diminished after short-term exposure to 20 ppm NO2 and long-term exposure to 10 and 20 ppm NO2. The medial thickness of pulmonary arteries was significantly increased after short- and long-term exposure to 20 ppm NO2 and long-term exposure to 10 ppm NO2. In the 5 ppm short- and long-term exposure groups the pulmonary arterial medial thickness was significantly decreased compared to controls. Correlation analysis revealed a negative correlation between average medial thickness and alveolar surface density (coefficient of correlation: -0.56). We conclude that the extent of NO2-induced pulmonary parenchymal and vascular alterations are closely related and concentration- and time-dependent.
Barth
P J
PJ
Dept of Pathology, Philipps-Universität Marburg/Lahn, Germany.
Müller
B
B
Wagner
U
U
Bittinger
A
A
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000473:pathology*; D008297:Male; D009585:Nitrogen Dioxide / Q000008:administration & dosage / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000473:pathology; D011651:Pulmonary Artery / Q000473:pathology*; D011656:Pulmonary Emphysema / Q000139:chemically induced* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
D009585:Nitrogen Dioxide