Document Detail

Effects of hard metal on nitric oxide pathways and airway reactivity to methacholine in rat lungs.
MedLine Citation:
PMID:  10373402     Owner:  NLM     Status:  MEDLINE    
To examine whether the development of hard metal (HM)-induced occupational asthma and interstitial lung disease involves alterations in nitric oxide (NO) pathways, we examined the effects of an industrial HM mixture on NO production, interactions between HM and lipopolysaccharide (LPS) on NO pathways, and alterations in airway reactivity to methacholine in rat lungs. HM (2.5 to 5 mg/100 g intratracheal) increased NO synthase (NOS; EC 1.14.23) activity of rat lungs at 24 h without increasing inducible NOS (iNOS) or endothelial NOS (eNOS) mRNA abundance or iNOS, eNOS, or brain NOS (bNOS) proteins. The increase in NOS activity correlated with the appearance histologically of nitrotyrosine immunofluorescence in polymorphonuclear leukocytes (PMN) and macrophages. Intraperitoneal injection of LPS (1 mg/kg) caused up-regulation of iNOS activity, mRNA, and protein at 8 h but not at 24 h. HM at 2.5 mg/100 g, but not at 5 mg/100 g, potentiated the LPS-induced increase in NOS activity, iNOS mRNA, and protein. However, HM decreased eNOS activity at 8 h and eNOS protein at 24 h. Whole body plethysmography on conscious animals revealed that HM caused basal airway obstruction and a marked hyporeactivity to inhaled methacholine by 6-8 h, which intensified over 30-32 h. HM-treatment caused protein leakage into the alveolar space, and edema, fibrin formation, and an increase in the number of inflammatory cells in the lungs and in the bronchoalveolar lavage. These results suggest that a HM-induced increase in NO production by pulmonary inflammatory cells is associated with pulmonary airflow abnormalities in rat lungs.
A Rengasamy; C Kommineni; J A Jones; J S Fedan
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  157     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-07-12     Completed Date:  1999-07-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  178-91     Citation Subset:  IM    
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA.
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MeSH Terms
Air Pollutants / toxicity*
Blotting, Western
Bronchoalveolar Lavage Fluid / chemistry,  cytology
Bronchoconstrictor Agents / administration & dosage,  diagnostic use*
Cell Count
Chromium / toxicity
Cobalt / toxicity
Iron / toxicity
Lung / drug effects*,  metabolism,  pathology,  physiopathology
Metals / toxicity*
Methacholine Chloride / administration & dosage,  diagnostic use*
Nitric Oxide / metabolism*
Nitric Oxide Synthase / biosynthesis,  metabolism
Plethysmography, Whole Body
RNA, Messenger / biosynthesis
Rats, Sprague-Dawley
Respiratory Function Tests
Reverse Transcriptase Polymerase Chain Reaction
Tungsten / toxicity
Tyrosine / analogs & derivatives,  metabolism
Reg. No./Substance:
0/Air Pollutants; 0/Bronchoconstrictor Agents; 0/Metals; 0/RNA, Messenger; 0/Suspensions; 10102-43-9/Nitric Oxide; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; 62-51-1/Methacholine Chloride; 7439-89-6/Iron; 7440-33-7/Tungsten; 7440-47-3/Chromium; 7440-48-4/Cobalt; EC Oxide Synthase

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