Pharmacological Modification of the Airways Response to Inhaled Dust Extract in the Guinea Pig

D.A. Johnson and P.J. Nicholls Welsh


 
ABSTRACT

Specific airways conductance (sGaw), a measure of bronchial airway calibre, was determined in spontaneously breathing unanaesthetized guinea pigs. Baseline sGaw value (0.644+0.142 cm-1 H;,O s-1, n=57), tidal volume (1.8-2.0 ml) and breath frequency (90-100 breaths per minute) were all in the normal physiological range.

In a group of 13 animals, inhalation of cotton dust aqueous extract (in saline) caused a significant (p<0.01) fall in sGaw (i.e. bronchoconstriction) at 1hr (2;1.0%+3.0) and at 2hr (23.0% + 3.0). At 3.5 hours, sGaw had returned to within baseline values. Inhalation of saline alone produced no significant changes in sGaw from baseline value.

A range of drugs capable of modifying the release and/or activity of various endogenous mediators was investigated by pretreating the animals prior to cotton dust challenge. Indomethacin (a cyclo-oxygenase inhibitor) produced a potentiation of the response to dust at 2h but not at 1h. Piriprost (a leukotriene synthesis inhibitor) protected against the response at 1 h but not at 2h. FPL 55712 (a sulphido-peptide leukotriene antagonist) completely protected the animals from the response. Of the other drugs investigated disodium cromoglycate (a mast cell stabilizing drug) was ineffective, and Verapamil (a calcium channel blocker) protected against the response at both 1 and 2hrs.

The results indicate that a bronchoconstriction comparable with that observed in man is produced in the guinea pig upon inhalation of a cotton dust extract. This gives support to the use of this species as an animal model for byssinosis research. The ability of FPL 55712 (and to a lesser extent piriprost) to protect against cotton dust bronchoconstriction suggests that the synthesis and release of Leukotriene metabclites may be implicated in the acute bronchoconstrictor response of the guinea pig to cotton dust.



Reprinted from Cotton Dust: Proceedings--11th Cotton Dust Research Conference 1987 pp. 53 - 56
©National Cotton Council, Memphis TN

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Document last modified Sunday, Dec 6 1998