Airway responses to aerosolized leukotriene D4 (LTD4) in normal and Ascaris reactor primates

Normal and Ascaris reactor primates were compared for their bronchial pulmonary response to aerosolized leukotriene D4 (LTD4). When 10 micrograms/ml LTD4 was aerosolized (total amount delivered to endotracheal tube was 1.0 micrograms) into the lungs of 6 normal primates, a small increase in total lung resistance (RL) was noted (4.4 +/- 4.5% increase, in 19 separate challenges). However, a larger effect was seen in compliance (27.6 +/- 15.8% decrease, n = 19). Ascaris reactors (n=4) demonstrated a larger RL effect than normals with almost an identical Cdyn change (RL 36.1 +/- 27.7% increase, Cdyn 32.8 +/- 18.8% decrease n = 12). When the pharmacological blockers diphenhydramine, 0.5 mg/kg and atropine, 0.5 mg/kg were administered iv separately before LTD4 challenge, significant antagonist activity was seen. Diphenhydramine inhibited the LTD4 response in normal primates (RL 64.2 +/- 44.3% and Cdyn 50.5 +/- 40.9% n = 6) and in reactors (RL 47.8 +/- 43.1% and Cdyn 19.2 +/- 20.8% n = 4). Atropine inhibited normals (RL 100% and Cdyn 73.1 +/- 32.7% n = 2) and reactors (RL 96.3 +/- 7.7 and Cdyn 47.4 +/- 35.1% n = 3). These results indicate that the LTD agonist action is partially mediated through histamine, primarily acting on lung resistance (large airways) and, in addition, may have a reflex atropine-sensitive component. The difference between the response of normal and reactor primates to LTD4 is primarily a histamine-mediated large airway response.