Methacholine responsiveness of proximal and distal airways of monkeys and rats using videomicrometry

Rat and monkey are species that are used in models of human airway hyperresponsiveness. However, the wall structures of rat and monkey airways are different from each other, with that of the monkey more closely resembling that of humans. We hypothesized that differences in wall structure would explain differences in airway responsiveness. Using videomicrometry, we measured airway luminal area in lung slices to compare proximal and distal airway responsiveness to methacholine in the rat and monkey. The airway type was then histologically identified. Proximal airways of the young rat and monkey were equally responsive to methacholine. In contrast, respiratory bronchioles of monkeys were less responsive than were their proximal bronchi, whereas the distal bronchioles of rats were more responsive than their proximal bronchioles. Both proximal and distal airways of younger monkeys were more responsive than those of older monkeys. Airway heterogeneity in young monkeys was greatest with regard to degree of airway closure of respiratory bronchioles. We conclude that responsiveness to methacholine varies with airway wall structure and location.