In vitro bronchial responsiveness in two highly inbred rat strains

Wang, C. G., J. J. Almirall, C. S. Dolman, R. J. Dandurand,and D. H. Eidelman. In vitro bronchial responsiveness in twohighly inbred rat strains. J. Appl.Physiol. 82(5): 1445-1452, 1997.We investigatedmethacholine (MCh)-induced bronchoconstriction in explanted airwaysfrom Fischer and Lewis rats. Lung explants, 0.5- to 1.0-mm thick, wereprepared from agarose-inflated lungs of anesthetized 8- to 12-wk-oldmale rats. After overnight culture, videomicroscopy was used to recordbaseline images of the individual airways. Dose-response curves to MChwere then constructed by repeated administration of MCh; airways werereimaged 10 min after each MCh administration. Airway internal luminalarea(A_i)was measured at successive MCh concentrations from10⁹ to10¹ M. Inaddition to the effective concentration leading to 50% of the achievedmaximal response, we also determined the effective concentrationleading to a 40% reduction inA_i.Both the effective concentration leading to 50% of the achievedmaximal response and the concentration leading to a 40% reduction inA_iwere significantly lower among Fischer rat airways(P < 0.05). Airway closure was morecommon among Fischer rat airways (17%) than among those of Lewis rats(7.5%). Responsiveness of Fischer rat airways was more heterogeneousthan among Lewis airways; a larger number of Fischer rat airwaysexhibited high sensitivity to MCh. There was no relationship betweenresponsiveness and baselineA_iin either strain. In a second experiment, we measured the rate ofcontraction of explanted airways from lungs inflated to 50, 75, and100% of total lung capacity. The average rate of contraction in thefirst 15 s was higher in Fischer rat airways at each inflation volume.These data indicate that the hyperresponsiveness of the Fischer rat reflects the responsiveness of individual airways throughout the airwaytree and are consistent with the notion that in this model hyperresponsiveness is an intrinsic property of airway smooth muscle.