Pharmacologic responsiveness of rat parenchymal strips, bronchi, and bronchioles

It has been inferred from previous studies that leukotrienes C4 and D4 preferentially exhibit their effects on peripheral airways. Thus we used LTC4 to examine the responsiveness of parenchymal strips, lung preparations often used as in vitro models of airway function, and to compare the responses with those observed in a preparation of isolated peripheral airways. In these studies, the effects of LTC4 on isolated bronchioles of the rat were compared to responses observed in parenchymal strips and primary intrapulmonary bronchi. Parenchymal strips contracted in response to increasing concentrations of LTC4 and to a single concentration of bethanechol. When the maximum responses were normalized to that induced by membrane depolarization, it was found that the parenchymal strip was more responsive to the leukotriene. Primary intrapulmonary bronchi similarly contracted in response to LTC4; however, the intrapulmonary bronchi were much more responsive to bethanechol than to the leukotriene. The bronchioles were not responsive to LTC4 but did contract in response to membrane depolarization and on exposure to bethanechol. When normalized, the responsiveness of the bronchiole to bethanechol was significantly greater than the responsiveness of the bronchi to this agonist. Thus contraction of the rat parenchymal strip to LTC4 cannot be attributed to the direct effects of this agonist on bronchiolar smooth muscle. We conclude that the bronchiole of the rat is not responsive to LTC4 and that the contractions observed in the parenchymal strip in response to this agonist must result from a mechanism other than direct action of LTC4 on peripheral airway smooth muscle.