Effects of Hard Metal on Nitric Oxide Pathways and Airway Reactivity to Methacholine in Rat Lungs

Details

• Personal Author:
  Fedan, Jeffery S. ; Jones JA ; Kommineni C ; Rengasamy A
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Asthma Asthma, Occupational Fibrosis Irritants Laboratories Lung Lung Diseases Nitrous Oxide Occupational Health Respiratory System Respiratory Tract Diseases Safety

  More +
• Keywords:
  Airway-obstruction Animal-studies Bronchial-asthma Hard-metals Laboratory-animals Lung-disorders Nitrous-oxides Oxides Pulmonary-congestion Pulmonary-disorders Pulmonary-edema Pulmonary-system-disorders Respiratory-irritants Respiratory-system-disorders

  More +
• ISSN:
  0041-008X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  178-191
• Volume:
  157
• Issue:
  3
• NIOSHTIC Number:
  nn:20027694
• Citation:
  Toxicol Appl Pharmacol 1999 Jun; 157(3):178-191
• Email:
  jsf2@cdc.gov
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:579d930049fb078bc0471d77c4a027b401b4c29bc9185982a31483a3303852bc71f1776187c0526ab98abd51bf03cd84d85ad07c87ba8d248c1d3cf7ad296eb1
• Download URL:
  https://stacks.cdc.gov/view/cdc/197630/cdc_197630_DS1.pdf
• File Type:
  [PDF - 835.44 KB ]