Acute histamine-induced flux of airway liquid: role of
neuropeptides.
Yager, Deborah, M. A. Martins, H. Feldman, R. D. Kamm, and J. M.
Drazen.
Respiratory Biology Program, Department of Environmental Science
and Physiology, Harvard School of Public Health, Boston,
Massachusetts 02115, Combined Program in Pulmonary and Critical Care
Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston,
Massachusetts 02115, New England Research Institute, Watertown,
Massachusetts 02172 and Department of Mechanical Engineering,
Massachusetts Institute of Technology, Cambridge, Massachusetts
02139
APStracts 2:0513A, 1995.
The role of capsaicin-sensitive neuropeptides in the accumulation of
airway wall liquid observed 30 seconds after histamine infusion was
investigated in guinea pigs. Two groups were studied, normal animals
and animals whose endogneous neuropeptides had been depleted by
capsaicin pretreatment. A rapid intravenous infusion of either saline
or 11 mg/kg histamine resulted in marked but similar changes in
pulmonary mechanics in both normal and capsaicin pretreated animals.
To assess liquid accumulation in airway wall compartments, the lungs
were frozen 30 seconds after histamine infusion; airways from these
lungs, 0.15 - 2.44 mm in internal perimeter, were imaged by low
-temperature scanning electron microscopy. There was no difference in
average airway surface liquid thickness (hASL) in normal or capsaicin
pretreated airways in response to saline. In capsaicin pretreated
animals, histamine infusion was associated with a significantly
decreased hASL (hASL,cap11/hASL,cap0 = 0.58, p < 0.04).
Capsaicin pretreatment, without histamine exposure, caused
significant increases in epithelial and submucosal areas
(Aepi,cap0/Aepi,norm0 = 1.23, p < 0.06; Asub,cap0/Asub,norm0 =
1.40, p < 0.01). Histamine infusion in capsaicin pretreated
animals was associated with liquid shifts from epithelium to lamina
propria and from submucosa to adventitia; however, the total wall
area was of similar if not dimished size relative to that in
capsaicin pretreated animals without histamine treatment. In
contrast, histamine infusion in normal animals resulted in
significant increases in the areas of the epithelial and lamina
propria compartments (Aepi,norm11/Aepi,norm0 = 1.25, p < 0.05;
Alp,norm11/Alp,norm0 = 2.19, p < 0.001) as well as a substantial
increase in adventitial area which was significantly attenuated by
capsaicin pretreatment (Aadv,cap11/Aadv,norm11 = 0.40, p <
0.001). The resulting total wall area was more than twice that in
normal animals without histamine treatment. Our data indicate that
histamine induced accumulation of liquid in the epithelium, lamina
propria and adventitia of normal airways is rapid in onset, most
likely derives from a leaky bronchial microvasculature and is
mediated by the secondary release of neurokinins.
Received 31 March 1995; accepted in final form 10 November 1995.
APS Manuscript Number A355-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95