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

• Published in: Prostaglandins Vol. 29; no. 2; pp. 313 - 322
• Main Authors: JOHNSON, H. G, STOUT, B. K
• Format: Journal Article
• Language: English
• Published: Stoneham, MA Butterworth-Heinemann 01.02.1985
• Subjects: Animals; Ascaris - immunology; Biological and medical sciences; Bronchi - drug effects; Cardiorespiratory control. Arterial mecano- and chemoreceptor; Diphenhydramine - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Macaca mulatta; Male; SRS-A - pharmacology; Vertebrates: respiratory system; Histamine; Leukotriene; Vertebrata; Bronchoconstriction; Mammalia; Arachidonic acid derivatives; Aerosols; Primates; Bronchomotility; Chemical mediator; Mechanism of action; Respiratory system
• ISSN: 0090-6980
• DOI: 10.1016/0090-6980(85)90211-4

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.