Methacholine induced bronchoconstriction and airway smooth muscle
in the guinea pig.
Saez, A. Opazo, Tao Du, N. S. Wang, and J. G. Martin.
Meakins-Christie Laboratories and the Department of Pathology,
Royal Victoria Hospital, the Respiratory Health Network of Centres of
Excellence, McGill University, Montreal, Quebec, Canada
APStracts 2:0433A, 1995.
We examined the role of airway smooth muscle (ASM) as a determinant of
the site and extent of methacholine (MCh)-induced airway narrowing in
anesthetized and mechanically ventilated Hartley strain guinea pigs.
The site of airway narrowing was determined in animals (n=4)
bronchoconstricted to 75%, 60%, 40% or 15% of the maximal lung
resistance (Rmax) induced by aerosolized MCh and compared to a saline
challenged control animal. The lungs were frozen with liquid nitrogen
and the airway luminal size and ASM were determined by morphometry.
The median luminal area of each animal was significantly inversely
correlated to its lung resistance (r = -0.95; p<0.01). However,
there was no correlation between the degree of narrowing of any given
airway and the quantity of ASM in that airway. The relationship
between the amount of ASM and responsiveness to MCh was studied in
different animals (n=13). The concentration of MCh required to reach
50% of the maximal response (EC50) showed a 254-fold difference but
there was only a 3.6-fold range of Rmax among different animals.
There was no correlation between Rmax and ASM. However, there was a
significant inverse correlation between the logEC50 and ASM (r=-.541,
p<0.05) in intraparenchymal cartilaginous airways. The logEC50
also correlated well with the median internal perimeter of the
intraparenchymal airways (r=0.72, p<0.05). In conclusion,
morphometric measurements of airway narrowing are correlated with
pulmonary resistance. Variability in the quantity of airway smooth
muscle does not appear to be a determinant of the heterogeneity of
airway narrowing or of maximal bronchoconstriction among normal
guinea pigs. However the sensitivity to MCh is associated with airway
size and differences in the amount of ASM in intraparenchymal
cartilaginous airways.
Received 28 October 1994; accepted in final form 27 September
1995.
APS Manuscript Number A1109-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95