Aerosolized methacholine-induced bronchoconstriction and pulmonary hyperinflation in rats

Abstract

The body plethysmography (BPG) is a useful tool for analyzing pulmonary function in small animals because it simultaneously measures airway resistance (R (aw)) 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 R (aw) 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 R (aw) 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.