Leukotriene B4 potentiates airway muscle responsiveness in vivo and in vitro

We studied the effects of leukotriene B4 (LTB4) on guinea pig airway muscle responsiveness in vivo and in vitro. Responsiveness in vivo was assessed by measuring specific airway resistance (SRaw) upon intravenous acetylcholine infusion in 5 unanesthetized, spontaneously breathing guinea pigs. We found that aerosolized LTB4, in a concentration that itself had no effect on baseline SRaw, caused a substantial increase in bronchial reactivity to i.v. ACh within 8 min of its administration. Responsiveness in vitro was assessed by measuring isometric contraction of the guinea pig trachealis upon stimulation by either chemical or electrical field stimuli. These studies in vitro showed that a concentration of LTB4 that itself did not cause contraction, potentiated airway muscle contraction to ACh and KCl, but not to norepinephrine. This effect of LTB4 was substantially reduced by nifedipine. Our data suggests that amounts of LTB4 that are themselves non-contractile in vivo or in vitro, may directly potentiate the responsiveness of airway smooth muscle to other bronchoconstrictors.