EFFECT OF TIME-VARYING LOAD ON DEGREE OF BRONCHOCONSTRICTION IN THE DOG

It is well established that the degree of airway smooth muscle shorten ing produced by a given dose of bronchial agonist is greatly affected by lung volume. The airways are tethered by parenchymal attachments, t he tension of which increases progressively with lung volume, thereby presenting a commensurately increasing hindrance to smooth muscle cont raction. Earlier studies (P. F. Dillon, M. O. Aksoy, S. P. Driska, and R. A. Murphy. Science 211: 495-497, 1981) presented evidence that smo oth muscle contraction initially involves rapidly cycling cross bridge s, which then change to noncycling (latch) bridges. They also suggeste d that most of the muscle shortening occurs during the early rapid cro ss-bridge phase. This implies that smooth muscle subject to a given lo ad early in contraction should shorten less than when it is subject to the same load later on. An in vitro study (W. Li and N. L. Stephens. Can. J. Physiol. Pharmacol. 72: 1458-1463, 1994) obtained support for this notion. To test this hypothesis in vivo, we measured the changes in lung impedance at 1 and 6 Hz produced in dogs by a bolus intravenou s injection of methacholine when lung volume was increased for 10 s at different times aRer injection. We found that the changes in mechanic s were greatly inhibited, whereas lung volume was elevated. However, w hen lung volume was returned to its initial level, the lung mechanics continued to change at a rate unaffected by the preceding volume chang e. We conclude that temporary mechanical inhibition of airway smooth m uscle shortening in the normal dog in vivo merely delays an otherwise normal course of contraction.