In mice of both sexes, repeated contractions of smooth muscle in vivo greatly enhance the response of peripheral airways to methacholine

BALB/c mice from both sexes underwent one of two nebulized methacholine challenges that were preceded by a period of 20 min either with or without tone induced by repeated contractions of the airway smooth muscle. Impedance was monitored throughout and the constant phase model was used to dissociate the impact of tone on conducting airways (RN – Newtonian resistance) versus the lung periphery (G and H – tissue resistance and elastance). The effect of tone on smooth muscle contractility was also tested on excised tracheas. While tone markedly potentiated the methacholine-induced gains in H and G in both sexes, the gain in RN was only potentiated in males. The contractility of female and male tracheas was also potentiated by tone. Inversely, the methacholine-induced gain in hysteresivity (G/H) was mitigated by tone in both sexes. Therefore, the tone-induced muscle hypercontractility impacts predominantly the lung periphery in vivo, but also promotes further airway narrowing in males while protecting against narrowing heterogeneity in both sexes.