In vitro bronchial responsiveness in two highly inbred rat strains

We investigated methacholine (MCh)-induced bronchoconstriction in explanted airways from Fischer and Lewis rats. Lung explants, 0.5- to 1.0-mm thick, were prepared from agarose-inflated lungs of anesthetized 8- to 12-wk-old male rats. After overnight culture, videomicroscopy was used to record baseline images of the individual airways. Dose-response curves to MCh were then constructed by repeated administration of MCh; airways were reimaged 10 min after each MCh administration. Airway internal luminal area (Ai) was measured at successive MCh concentrations from 10(-9) to 10(-1) M. In addition to the effective concentration leading to 50% of the achieved maximal response, we also determined the effective concentration leading to a 40% reduction in Ai. Both the effective concentration leading to 50% of the achieved maximal response and the concentration leading to a 40% reduction in Ai were significantly lower among Fischer rat airways (P < 0.05). Airway closure was more common among Fischer rat airways (17%) than among those of Lewis rats (7.5%). Responsiveness of Fischer rat airways was more heterogeneous than among Lewis airways; a larger number of Fischer rat airways exhibited high sensitivity to MCh. There was no relationship between responsiveness and baseline Ai in either strain. In a second experiment, we measured the rate of contraction of explanted airways from lungs inflated to 50, 75, and 100% of total lung capacity. The average rate of contraction in the first 15 s was higher in Fischer rat airways at each inflation volume. These data indicate that the hyperresponsiveness of the Fischer rat reflects the responsiveness of individual airways throughout the airway tree and are consistent with the notion that in this model hyperresponsiveness is an intrinsic property of airway smooth muscle.