Aerosolized methacholine-induced bronchoconstriction and pulmonary hyperinflation in rats

The body plethysmography (BPG) is a useful tool for analyzing pulmonary function in small animals because it simultaneously measures airway resistance (Raw) and functional residual capacity (FRC). We previously described a BPG with the enclosed environment maintained at body temperature and water vapor-saturated. We found dose-dependent increases in Raw in response to inhaled methacholine (Mch) with no apparent increase in FRC in intratracheally intubated rats without paralysis. To resolve this apparent inconsistency in clinical observations, we repeated the study using a newly developed BPG that allowed us to shorten the interval between Mch-inhalation and measurements by about two-thirds. Using Mch concentrations of 0, 0.5, 1.0, 2.0 and 4.0 mg/ml each for 2 min, both parameters increased in a dose-dependent fashion with FRC (mean ± SE) values of 3.77 ± 0.16, 4.43 ± 0.26, 4.75 ± 0.34, 5.02 ± 0.49 and 5.34 ± 0.38 ml and Raw values of 18.6 ± 3.9, 21.6 ± 4.9, 35.0 ± 6.9, 49.0 ± 8.8 and 65.7 ± 8.8 ml/s/Pa, respectively. Immediate measurement after Mch-inhalation demonstrated profound bronchoconstriction associated with dose-dependent increases in FRC.