title: In vivo evaluation of airway and pulmonary tissue response to inhaled methacholine in the rat.
abstract: 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 (ptr) and alveolar (pA) 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 pA mean (+/- SD) values (6.44 +/- 2.06 and 8.25 +/- 3.44 cmH2O, respectively) were not statistically different (P = 0.220). The increases in ptr and pA were significant during the dose-response study (P = 0.001), whereas p(aw) was not increased. The increase in pA was significantly higher than that of p(aw) (P less than 0.001). The relationship between the mean (+/- SE) values of ptr and pA could be well described by a straight line (r = 0.990, P less than 0.001). There were also significant correlations based on regression equations between ptr and p(aw) (r = 0.947, P less than 0.001) and pA 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.
authors.affiliation: Laboratório de Poluição Atmosférica Experimental, FMUSP, São Paulo, Brazil.
authors.forename: R S
authors.initials: RS
authors.lastname: Sakae
authors.forename: M A
authors.initials: MA
authors.lastname: Martins
authors.forename: P M
authors.initials: PM
authors.lastname: Criado
authors.forename: W A
authors.initials: WA
authors.lastname: Zin
authors.forename: P H
authors.initials: PH
authors.lastname: Saldiva
mesh_terms: D000280:Administration, Inhalation; D000399:Air Pressure; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008168:Lung / Q000187:drug effects*; D008688:Methacholine Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects*
chemical_list: D008688:Methacholine Compounds