Airway Responses to Methacholine in the Guinea Pig Following a Single Dose of Endotoxin: Comparison of In Vitro and In Vivo Data

R.S. Young, A.K. Davey and P.J Nicholls


Inhalation of endotoxin has been shown to be responsible for changes of lung function in man (Rylander and Vesterlund, 1982)1 and other animals including the guinea pig (Broadley et al, 1992)2. As part of a programme to investigate these phenomena the present study compared the in vitro and in vivo effects of a single inhaled dose of endotoxin on the response of the guinea pig to inhaled methacholine.

One hour after exposure of the guinea pigs to a nebulised solution of endotoxin, the airway response (sGaw) to inhaled methacholine was significantly increased indicating a state of hyperreactivity. However 24h post - endotoxin exposure, the response was significantly decreased (hyporeactivity). Isolated tracheal smooth muscle was also found to be significantly more responsive to the contractor actions of methacholine when taken from animals 1 h after endotoxin exposure, the dose - response curve being significantly shifted in a parallel fashion compared to the curve from control tracheal muscle spirals. However, the response of tracheal muscle to methacholine, from guinea pigs 24 h after exposure to endotoxin was no different to that observed in control preparations.

It would appear that the endotoxin - induced airway hyperreactivity seen in the in vivo model is in part, at least, explained by a change in the reactivity of the airway smooth muscle to the muscarinic bronchoconstrictor employed. It is possible that hyporeactivity of the airway is related to factors other than changes of smooth muscle responsiveness to bronchoconstrictors e.g. a change in the normal production of relaxant factors by the epithelium or the influence of a factor present in the pulmonary microvasculature.

Reprinted from Proceedings of the 1994 Beltwide Cotton Conferences pp. 295 - 297
©National Cotton Council, Memphis TN

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Document last modified Sunday, Dec 6 1998