Nitric oxide (NO) is a small, uncharged, highly reactive free radical that is synthesized from L-arginine by nitric oxide synthase (NOS) and may participate in acute and chronic lung injury. To help elucidate the role of NO in the pathogenesis of lung diseases, an animal model for NO- induced lung damage was developed. NO production was evaluated in male Sprague-Dawley rats after administration of either endotoxin or vehicle. Inducible NOS RNA was detected by Northern analysis, only in RNA extracted from lungs of animals injected with endotoxin but not in RNA from control animals. Alveolar macrophages isolated from lavage fluid of animals injected with endotoxin and cultured for 24 hours produced greater amounts of nitrite, an end-product of NO production, than did macrophages isolated from control animals. Nitrite was also found to be higher in lavage fluid from animals treated with endotoxin compared to lavage fluid from control animals. Morphologic evaluation of lung tissues showed inflammatory changes in animals injected with endotoxin.
Tesauro, M; Thompson, W C; Rogliani, P et al. (2000) Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci U S A 97:2832-5 |
Rivera-Nieves, J; Thompson, W C; Levine, R L et al. (1999) Thiols mediate superoxide-dependent NADH modification of glyceraldehyde-3-phosphate dehydrogenase. J Biol Chem 274:19525-31 |
Novoradovsky, A; Brantly, M L; Waclawiw, M A et al. (1999) Endothelial nitric oxide synthase as a potential susceptibility gene in the pathogenesis of emphysema in alpha1-antitrypsin deficiency. Am J Respir Cell Mol Biol 20:441-7 |