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 normorespo nsive and hyperresponsive rats. Specifically, we addressed the questio ns 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 normoresp onsive rats (Sprague-Dawley). We found that, in both strains of rats, contraction to methacholine occurred primarily in the medium- and larg er-sized bronchioles (airways of diameter >0.32 mm) and that, at the h igher methacholine concentrations, the Fisher rats had greater degrees of contraction than did the Sprague-Dawley rats. These results sugges t that the increased airway responsiveness seen in Fisher rats is due to an intrinsic increase in responsiveness (increased contractility) o f their airways, which may be related to amount of smooth muscle, rath er than an increase in airway sensitivity to methacholine. They do not , however, completely rule out the possibility of in vivo species-depe ndent differences in airway-parenchymal interactions.