Bronchial responsiveness among inbred mouse strains - Role of airway smooth-muscle shortening velocity

To investigate the relationship between bronchial responsiveness and airway smooth-muscle (ASM) contractile properties, we studied inbred mice with kn own interstrain differences in airway responsiveness. Using oscillatory mec hanics, we confirmed that A/J mice were hyperresponsive to methacholine (MC h) as compared with mice of the C3H/HeJ and C57BL/6J strains. Analysis of r espiratory system resistance and elastance at different flow oscillation fr equencies indicated that interstrain differences in responsiveness are pres ent in both central and peripheral airways of these mice. We used video mic roscopy to measure the rate of contraction of explanted airways, and found that the airways of A/J mice contracted more rapidly than those of C3H/HeJ or C57BL/6J mice. In studies of a fourth strain (Balb/C) of mice, we found both bronchial hyperresponsiveness and increased ASM shortening velocity. T he rank order of responsiveness among strains was the same as that for shor tening velocity (A/J > Balb/C > C3H/HeJ > C57BL/6J). Furthermore, in each s train of mice, shortening velocity correlated with the achieved degree of a irway narrowing and with a greater likelihood of airway closure in individu al airways. In contrast, generation of isometric tension in trachealis, mor phometric measurements of tracheal ASM, tracheal myosin content, and dose-r esponse curves for MCh of explanted intraparenchymal bronchi failed to corr espond to the in vivo phenotype of airway reactivity. These results indicat e that bronchial responsiveness is related to ASM shortening velocity, and underscore the importance of smooth-muscle dynamics in understanding the me chanisms of bronchial responsiveness.