Mechanism of platelet activating factor-induced bronchoconstriction in humans.
The inhalation of platelet activating factor (PAF) produces bronchoconstriction in normal and asthmatic subjects. To identify the mechanism by which PAF-induced bronchoconstriction occurs in humans, bronchoprovocation testing was performed in 7 subjects (3 normal, 4 with mild asthma) after pretreatment with phosphate-buffered saline (PBS), atropine, chlorpheniramine, or indomethacin. We determined the nebulizer concentration of PAF which reduced specific airway conductance (SGaw) 35% (PC35 SGaw) and the slope of the PAF dose-response curve. Atropine produced baseline bronchodilatation (SGaw increased 50%), while chlorpheniramine and indomethacin had no effect on baseline pulmonary function. Atropine increased airway responsiveness to PAF: the PC35 SGaw decreased 40% (p less than 0.05) and the slope of the PAF dose-response curve increased 86% (p less than 0.05). In contrast, chlorpheniramine inhibited the airway response to PAF: the PC35 SGaw increased 87% (p less than 0.05), while the slope of the PAF dose-response curve decreased an insignificant 37%. Indomethacin did not affect either measurement. Chlorpheniramine also prevented the PAF-induced facial flushing and feeling of warmth; atropine and indomethacin did not. These results suggest that PAF-induced bronchoconstriction in humans is mediated at least in part by histamine release, not by cholinergic or cyclooxygenase-dependent mechanisms. Other indirect effects, such as the release of sulfidopeptide leukotrienes, or a direct effect on airway smooth muscle may also contribute to PAF-induced bronchoconstriction. Why atropine heightened the airway response to PAF is unclear.
Smith
L J
LJ
Department of Medicine, Northwestern University Medical School, Chicago, Illinois.
Rubin
A H
AH
Patterson
R
R
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000503:physiopathology; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D002744:Chlorpheniramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D012129:Respiratory Function Tests
D010972:Platelet Activating Factor; D002744:Chlorpheniramine; D001285:Atropine; D007213:Indomethacin