Relaxation of tracheal smooth muscle is impaired in innate airway hyperresponsiveness

The current study was designed to determine whether the nonspecific in vivo airway hyperresponsiveness of the inbred Fisher F-344 rat strain is associated with impaired spontaneous relaxation of airway smooth muscle. Strips of the posterior portion of the trachea from 10 adult Fisher and 10 adult Lewis rats were electrically stimulated at pH 7.4, 2.5 mM Ca(2+)concentration, at 37 degrees C. Both isotonic and isometric relaxations of tracheal smooth muscle (TSM) were investigated. Half time for isotonic relaxation at preload was markedly prolonged in Fisher rats (8.33+/-3.21 s) compared with Lewis rats (3.53+/-0.54 s; p<0.001). Maximum lengthening velocity at preload and peak rate of isometric tension decline were significantly decreased in Fisher rats compared with Lewis rats. The ratio of shortening velocity to lengthening velocity at preload, as well as the ratio of the isometric peak rates of tension development to tension decline were higher in Fisher rat TSM than in Lewis rat TSM. These differences were associated with a six-fold higher expression of myosin light chain kinase in Fisher rats than in Lewis rats. In Fisher rats, these results suggest that innate airway hyperresponsiveness is associated with both a reduced level and a slower rate of TSM spontaneous relaxation, promoting maintenance of airway constriction.