Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Hyperosmolar solution effects in guinea pig airways. IV. Lipopolysaccharide-induced alterations in airway reactivity and epithelial bioelectric responses to methacholine and hyperosmolarity.

Authors
Johnston-RA; Van Scott-MR; Kommineni-C; Millecchia-LL; Dortch-Carnes-J; Fedan-JS
Source
J Pharmacol Exp Ther 2004 Jan; 308(1):37-46
NIOSHTIC No.
20024233
Abstract
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.
Keywords
Animal-studies; Airway-obstruction; Airway-resistance; Throat; Cellular-reactions; Bioelectric-effects; Methacholines; In-vitro-study; In-vivo-study; Lung-disorders; Lung-irritants; Lung-function; Pulmonary-system
Contact
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
CODEN
JPETAB
Publication Date
20040101
Document Type
Journal Article
Email Address
jsf2@cdc.gov
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0022-3565
NIOSH Division
HELD
Priority Area
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Source Name
Journal of Pharmacology and Experimental Therapeutics
State
WV; NC
TOP