Effect of Ozone Treatment on Airway Reactivity and Epithelium-Derived Relaxing Factor in Guinea Pigs

Details

• Personal Author:
  Cutler D ; Dey RD ; Dortch-Carnes J ; Fedan, Jeffery S. ; Frazer DG ; Goldsmith WT ; Hubbs A ; Johnston RA ; Millecchia LL ; Orsini L ; Rengasamy A ; Reynolds JS ; Watson D ; Yuan LX
• Description:
  Ozone (O(3)) is toxic to respiratory epithelium and causes airway inflammation and hyperreactivity. To evaluate the role of the epithelium in the development of hyperreactivity, we examined in guinea pigs the effects of inhaled O(3) (3 ppm for 1 h; 0-24 h after exposure) on 1) reactivity to inhaled methacholine (MCh), 2) reactivity of the isolated, perfused trachea (IPT) to MCh, 3) epithelium-derived relaxing factor (EpDRF)-mediated relaxations of IPT induced by mucosal hyperosmolar solutions, 4) neurogenic contraction and relaxation responses, 5) transepithelial potential difference, and 6) microscopic analysis of nitrotyrosine immunofluorescence, substance P fiber density, and tracheal morphology. At 0 h, O(3) caused hyperreactivity to inhaled MCh and mucosally but not serosally applied MCh in IPT (only in the presence of the epithelium) and a decrease in transepithelial potential difference. Inhibition of EpDRF-induced relaxation responses occurred at 2 h. All of these changes returned to control by 12 to 18 h. O(3) had no effect on neurogenic responses. Nitrotyrosine immunofluorescence appeared in the trachea at 0 h in detached epithelial cell ghosts and in intrapulmonary airways by 6 h. Substance P fiber density was elevated in smooth muscle at 0 and 18 h but not in epithelium or lamina propria of intrapulmonary and extrapulmonary bronchi. Loss of cilia and mucosubstances in the mucosa occurred at 0 h; the epithelium became markedly attenuated over 12 to 24 h. A reversible increase in epithelial permeability and a decrease in EpDRF production may contribute to O(3)-induced hyperreactivity to MCh. [Description provided by NIOSH]
• Subjects:
  Animals Hazardous Substances Laboratories Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Airway Obstruction Animal Studies Laboratory Animals Pulmonary System Disorders Respiratory System Disorders Toxins
• ISSN:
  0022-3565
• 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
• Volume:
  293
• Issue:
  3
• NIOSHTIC Number:
  nn:20020666
• Citation:
  J Pharmacol Exp Ther 2000 Jun; 293(3):724-734
• Email:
  jsf2@cdc.gov
• CAS Registry Number:
  Ozone (CAS RN 10028-15-6)
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Pharmacology and Experimental Therapeutics
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:95f684e27f262aeb912109569dc74e9ee138c7590db3314321a11a50c2d3b63f1a866424c58df0dc09f4f2f44a53749107b95fef0af4984c5ae5f04b122a6dc6
• Download URL:
  https://stacks.cdc.gov/view/cdc/198350/cdc_198350_DS1.pdf
• File Type:
  [PDF - 1.41 MB ]