Lung tissue behavior in the mouse during constriction induced by methacholine and endothelin-1

Abstract

Recently, mice have been extensively used to investigate the pathogenesis of pulmonary disease because appropriate murine models, including transgenic mice, are being increasingly developed. However, little information about the lung mechanics of mice is currently available. We questioned whether lung tissue behavior and the coupling between dissipative and elastic processes, hysteresivity (η), in mice would be different from those in the other species. To address this question, we investigated whether tissue resistance (Rti) and η in mice would be affected by varying lung volume, constriction induced by methacholine (MCh) and endothelin-1 (ET-1), and high-lung-volume challenge during induced constriction. From measured tracheal flow and tracheal and alveolar pressures in open-chest ICR mice during mechanical ventilation [tidal volume = 8 ml/kg, frequency (f) = 2.5 Hz], we calculated lung resistance (RL), Rti, airway resistance (Raw), lung elastance (EL), and η (= 2πfRti/EL). Under baseline conditions, increasing levels of end-expiratory transpulmonary pressure decreased Raw and increased Rti. The administration of aerosolized MCh and intravenous ET- 1 increased RL, Rti, Raw, and EL in a dose-dependent manner. Rti increased from 0.207 ± 0.010 to 0.570 ± 0.058 cmH2O·ml-1·s after 10-7 mol/kg ET-1 (P < 0.01). After induced constriction, increasing end-expiratory transpulmonary pressure decreased Raw. However, η was not affected by changing lung volume, constriction induced by MCh and ET-1, or high-lung- volume challenge during induced constriction. These observations suggest that 1) η is stable in mice regardless of various conditions, 2) Rti is an important fraction of RL and increases after induced constriction, and 3) mechanical interdependence may affect airway smooth muscle shortening in this species. In mammalian species, including mice, analysis of η may indicate that both Rti and EL essentially respond to a similar degree.