Faculty Collaboration Database

Nitric oxide participates in early events associated with NNMU-induced acute lung injury in rats. Am J Physiol 1999 Feb;276(2):L263-8

Date

02/10/1999

Pubmed ID

9950888

DOI

10.1152/ajplung.1999.276.2.L263

Scopus ID

2-s2.0-0033024262 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

In this study, the biochemical mechanisms by which N-nitroso-N-methylurethane (NNMU) induces acute lung injury are examined. Polymorphonuclear neutrophil infiltration into the lungs first appears in the bronchoalveolar lavage (BAL) fluid 24 h after NNMU injection (10.58 +/- 3.00% of total cells; P < 0.05 vs. control animals). However, NNMU-induced elevation of the alveolar-arterial O2 difference requires 72 h to develop. Daily intraperitoneal injections of the inducible nitric oxide (. NO) synthase (iNOS)-selective inhibitor aminoguanidine (AG) initiated 24 h after NNMU administration improve the survival of NNMU-treated animals. However, AG administration initiated 48 or 72 h after NNMU injection does not significantly improve the survival of NNMU-treated animals. These results suggest that. NO participates in events that occur early in NNMU-induced acute lung injury. BAL cells isolated from rats 24 and 48 h after NNMU injection produce elevated. NO and express iNOS during a 24-h ex vivo culture. AG attenuates. NO production but does not affect iNOS expression, whereas actinomycin D prevents iNOS expression and attenuates. NO production by BAL cells during this ex vivo culture. These results suggest that NNMU-derived BAL cells can stimulate iNOS expression and. NO production during culture. In 48-h NNMU-exposed rats, iNOS expression is elevated in homogenates of whole lavaged lungs but not in BAL cells derived from the same lung. These findings suggest that the pathogenic mechanism by which NNMU induces acute lung injury involves BAL cell stimulation of iNOS expression and. NO production in lung tissue.

Author List

Cruz WS, Corbett JA, Longmore WJ, Moxley MA

Author

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Animals
Arteries
Bronchoalveolar Lavage Fluid
Enzyme Inhibitors
Guanidines
Lung
Lung Diseases
Male
Neutrophils
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nitrosomethylurethane
Oxygen
Pulmonary Alveoli
Rats
Rats, Sprague-Dawley
Therapeutic Irrigation
Time Factors