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In vivo evaluation of airway and pulmonary tissue response to inhaled methacholine in the rat
Author(s) -
Sakae R. S.,
Martins M. A.,
Criado P. M. P.,
Zin W. A.,
Saldiva P. H. N.
Publication year - 1992
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550120404
Subject(s) - methacholine , airway , in vivo , medicine , airway hyperresponsiveness , inhalation , lung , anesthesia , respiratory disease , biology , microbiology and biotechnology
The current study was designed to assess the methacholine dose‐response behaviour of the airways and pulmonary parenchyma with the aid of alveolar capsules. The experiments were performed in eight adult female Wistar rats (155–250 g). The animals were anaesthetized with sodium pentobarbital (30 mg kg −1 i.p.) and mechanically ventilated. Measurements of tracheal ( p tr ) and alveolar ( p A ) pressures and the pressure change across the airway ( p aw ) were performed prior to and after exposing rats to aerosols generated from sequentially increasing concentrations of methacholine chloride solution (2, 4, 8, 16, 32, 64 and 128 mg ml −1 ) through the breathing circuit. Baseline p aw and p A mean (± SD) values (6.44 ± 2.06 and 8.25 ± 3.44 cmH 2 O, respectively) were not statistically different ( P = 0.220). The increases in p tr and p A were significant during the dose‐response study ( P = 0.001), whereas p aw was not increased. The increase in p A was significantly higher than that of p aw ( P < 0.001). The relationship between the mean (± SE) values of p tr and p A could be well described by a straight line ( r = 0.990, P < 0.001). There were also significant correlations based on regression equations between p tr and p aw ( r = 0.947, P < 0.001) and p A and p aw ( r = 0.913, P = 0.004). These findings suggest that the pulmonary tissue of rats is a major component responsible for the increase in lung impedance observed after methacholine challenge. In addition, airway and pulmonary parenchyma pressure changes were correlated, suggesting that both lung regions have a similar sensitivity to the agonist. Our results indicate that the response of peripheral tissues should be considered during bronchial challenge protocols in rats.