Site of methacholine reactivity in the peripheral airways: analysis using lung explants

We used a recently developed lung explant technique to investigate the partitioning of airway contractility in the bronchioles of normoresponsive and hyperresponsive rats. Specifically, we addressed the questions 1) whether airway response to methacholine varied with airway size and 2) whether airways from rats known to be innately hyperresponsive to methacholine (Fisher) would have responses different from normoresponsive rats (Sprague-Dawley). We found that, in both strains of rats, contraction to methacholine occurred primarily in the medium- and larger-sized bronchioles (airways of diameter > 0.32 mm) and that, at the higher methacholine concentrations, the Fisher rats had greater degrees of contraction than did the Sprague-Dawley rats. These results suggest that the increased airway responsiveness seen in Fisher rats is due to an intrinsic increase in responsiveness (increased contractility) of their airways, which may be related to amount of smooth muscle, rather than an increase in airway sensitivity to methacholine. They do not, however, completely rule out the possibility of in vivo species-dependent differences in airway-parenchymal interactions.