Received for publication March 14, 2003.
Revised April 25, 2003.
Accepted for publication October 8, 2003.

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

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). Utilizing 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, since 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 (V_t) was increased after LPS-treatment. The increase in V_t was inhibited by amiloride and indomethacin. Concentration-response curves for changes in V_t in response to serosally- and mucosally- applied MCh were biphasic (hyperpolarization, <3x 10^-7 M; depolarization, >3x10^{- 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 following 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.

Key words: Airway epithelium, Airway reactivity, Electrophysiology, Epithelium-derived relaxing factor, Lipopolysaccharide, Osmolarity

This article has been cited by other articles:

				Y. Jing, J. A. Dowdy, M. R. Van Scott, and J. S. Fedan Hyperosmolarity-Induced Dilation and Epithelial Bioelectric Responses of Guinea Pig Trachea in Vitro: Role of Kinase Signaling J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 186 - 195. [Abstract] [Full Text] [PDF]

				R. W. Balzary and T. M. Cocks Lipopolysaccharide Induces Epithelium- and Prostaglandin E2-Dependent Relaxation of Mouse Isolated Trachea through Activation of Cyclooxygenase (COX)-1 and COX-2 J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 806 - 812. [Abstract] [Full Text] [PDF]