In vitro and in vivo effect of @entity1855 on XXXX airway responsiveness to leukotriene D4.

@entity1 @entity1855 @entity460 @entity2701 @entity2710
The mechanism by which leukotriene D4 (LTD4) induces airway narrowing in @entity1 is unclear. We have investigated this by examining the effect of the @entity460 channel blocker @entity1855 on the sensitivity of in vitro preparations of @entity1 bronchi to LTD4 and @entity2710 , and on the bronchoconstriction induced in normal subjects by these agonists in vivo. In vitro smooth muscle sensitivity was assessed by the concentration of LTD4 and @entity2710 causing a 50% of maximum contraction (EC50) and as the maximum @entity2701 generated. @entity1855 did not alter baseline @entity2701 or the response to LTD4 but did inhibit contractile responses to @entity2710 . In vivo studies were performed in six normal subjects; they inhaled increasing concentrations of LTD4 (0.4-50 micrograms/ml) or @entity2710 (2-64 mg/ml). Airway responsiveness in vivo was expressed as the provocation concentration (PC) of agonist producing a 35% fall in specific airways conductance (PC35sGaw) and a 30% fall in flow at 30% of vital capacity (PC30 V30(p)). @entity1855 did not alter baseline sGaw or V30(p). One subject did not respond to LTD4 on either day. In contrast to the in vitro results, @entity1855 produced a greater than 10 fold reduction in LTD4 induced bronchoconstriction, but had no effect on @entity2710 induced bronchoconstriction. These results suggest that in normal subjects bronchoconstriction induced by inhaled LTD4 is due to a combination of direct and indirect mechanisms.
