Hyperosmolar Solution Effects in Guinea Pig Airways. IV. Lipopolysaccharide-Induced Alterations in Airway Reactivity and Epithelial Bioelectric Responses to Methacholine and Hyperosmolarity

Details

• Personal Author:
  Dortch-Carnes J ; Fedan, Jeffery S. ; Johnston RA ; Kommineni C ; Millecchia LL ; Van Scott MR ; Dortch-Carnes J ; Fedan, Jeffery S. ; Johnston RA ; Kommineni C ; Millecchia LL ; Van Scott MR
• Description:
  We investigated the in vivo and in vitro effects of lipopolysaccharide (LPS) treatment (4 mg/kg i.p.) on guinea pig airway smooth muscle reactivity and epithelial bioelectric responses to methacholine (MCh) and hyperosmolarity. Hyperosmolar challenge of the epithelium releases epithelium-derived relaxing factor (EpDRF). Using a two-chamber, whole body plethysmograph 18 h post-treatment, animals treated with LPS were hyporeactive to inhaled MCh aerosol. This could involve an increase in the release and/or actions of EpDRF, because LPS treatment enhanced EpDRF-induced smooth muscle relaxation in vitro in the isolated perfused trachea apparatus. In isolated perfused tracheas the basal transepithelial potential difference (Vt) was increased after LPS treatment. The increase in Vt was inhibited by amiloride and indomethacin. Concentration-response curves for changes in Vt in response to serosally and mucosally applied MCh were biphasic (hyperpolarization, <3 x 10(-7)M; depolarization, >3 x 10(-7)M); MCh was more potent when applied serosally. The hyperpolarization response to MCh, but not the depolarization response, was potentiated after LPS treatment. In both treatment groups, mucosally applied hyperosmolar solution (using added NaCl) depolarized the epithelium; this response was greater in tracheas from LPS-treated animals. The results of this study indicate that airway hyporeactivity in vivo after LPS treatment is accompanied by an increase in the release and/or actions of EpDRF in vitro. These changes may involve LPS-induced bioelectric alterations in the epithelium. [Description provided by NIOSH]
• Subjects:
  Animals Lung Lung Diseases Methacholine Compounds Occupational Health Respiratory System Safety
• Keywords:
  Airway-obstruction Airway-resistance Animal-studies Bioelectric-effects Cellular-reactions In-vitro-study In-vivo-study Lung-disorders Lung-function Lung-irritants Methacholines Pulmonary-system Throat

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• ISSN:
  0022-3565
• Document Type:
  Text
• Genre:
  Journal Article ; Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Pages in Document:
  37-46
• Volume:
  308
• Issue:
  1
• NIOSHTIC Number:
  nn:20024233
• Citation:
  J Pharmacol Exp Ther 2004 Jan; 308(1):37-46
• Contact Point Address:
  Dr. Jeffrey S. Fedan, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505-2888, USA
• Email:
  jsf2@cdc.gov
• Federal Fiscal Year:
  2004
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease ; Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• 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:f49b08aaaaa312ddeedde8c16c004d2bd55b899e605d469d9592ee3ad5891a98cf117484cbfd785e31e5058add3d271facb0914fe0702ffadc51e05f11fdf8fa
• Download URL:
  https://stacks.cdc.gov/view/cdc/196147/cdc_196147_DS1.pdf
• File Type:
  [PDF - 1.71 MB ]