Dexamethasone Reduces Tachykinin but Not ACh Airway Hyperreactivity After O3

Details

• Personal Author:
  Chodimella V ; Lang Z ; Murlas CG
• Description:
  We investigated whether dexamethasone pretreatment affected the acute increase in airway reactivity produced by high-level ozone exposure. Reactivity to intravenous IV substance P (SP), IV acetylcholine (ACh), or aerosolized capsaicin (CAP) before and 1 hr after ozone exposure (3 ppm for 2 hr) was determined by measuring specific airway resistance in anesthetized, spontaneously breathing guinea pigs, half of whom had been pretreated for 2 days pre-ozone with dexamethasone (2 mg/kg intramuscularly [IM] daily). The amount of IV SP, IV ACh, or inhaled capsaicin necessary to increase baseline specific airway resistance by 100% (ED200ACh or ED2OOSP) or 35% (ED135CAP) was determined by interpolation from dose-response curves. Compared to their pre-ozone status on the day of exposure, we found that dexamethasone-pretreated animals manifested significantly less of an increase in airway reactivity postozone to IV SP or inhaled CAP than did untreated animals. Changes in logEDs of the pretreated group were 0.18 +/- 0.03 (mean +/- SE) for SP and 2.20 +/- 0.11 for CAP compared to 0.27 +/- 0.04 and 3.38 +/- 0.34, respectively, for the untreated groups post-ozone (p < 0.05 and n = 4 for each). In contrast, dexamethasone pretreatment had no effect on IV ACh reactivity postozone: changes in logED2OOACh were 0.27 +/- 0.08 and 0.28 +/- 0.04 for the pretreated and untreated groups, respectively (n = 4). In animals pretreated with captopril to block possible dexamethasone stimulation of angiotensin-converting enzyme synthesis that could influence tachykinin reactivity, we found that the corticosteroid effect on post-ozone SP reactivity was as marked as that seen in animals without captopril (n = 4). Because these reactivity studies were consistent with the possibility that dexamethasone may ameliorate ozone-induced, tachykinin hyperreactivity by stimulating airway neutral endopeptidase (NEP), we measured NEP activity by high-performance liquid chromatography (HPLC) of each tracheal homogenate made from other groups of animals. Homogenates from ozone-exposed, dexamethasone-pretreated animals demonstrated significantly greater NEP activity (81 +/- 24%) than that from ozone-exposed, untreated animals (p < 0.05, n = 5). We conclude that corticosteroid pretreatment reduces the acute increase in airway reactivity to exogenous and endogenous tachykinins caused by ozone. This reduction may be at least partly due to stimulation of airway NEP activity, perhaps most of which is nonmucosal in that ozone acutely inactivates mucosal NEP. [Description provided by NIOSH]
• Subjects:
  Animals Asthma Asthma, Occupational Enzymes Occupational Health Ozone Respiratory System Safety
• Keywords:
  Airway Smooth Muscle Animal Studies Author Keywords: Airway Resistance Bronchoconstriction Corticosteroids Dose Response Enkephalinase Enzymatic Effects Enzyme Activity Guinea Pig Metalloendopeptidase Substance P Receptors

  More +
• ISSN:
  0341-2040
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Illinois ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  109-121
• Volume:
  171
• Issue:
  2
• NIOSHTIC Number:
  nn:20058986
• Citation:
  Lung 1993 Mar-Apr; 171(2):109-121
• Contact Point Address:
  Christopher G. Murlas, Lung Cell Biology Laboratories and Departments of Medicine and Immunology, Rush University, 1653 West Congress Parkway, Chicago, IL 60612, USA
• CAS Registry Number:
  Ozone (CAS RN 10028-15-6)
• Federal Fiscal Year:
  1993
• Performing Organization:
  Rush University Medical Center, Chicago, Illinois
• Peer Reviewed:
  True
• Start Date:
  19880301
• Source Full Name:
  Lung
• End Date:
  19920229
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7bc5e084889f6a59956f2b3790c664a7a402cda8394bb7f215f7c646510439a0b90085f5b65fa29ec1b8f7aac7fe740e0e96ca6d41109bed8253f29a0a1b396c
• Download URL:
  https://stacks.cdc.gov/view/cdc/223326/cdc_223326_DS1.pdf
• File Type:
  [PDF - 709.26 KB ]