Journal of Applied Physiology, Vol 80, Issue 2 437-444, Copyright © 1996 by American Physiological Society
Methacholine-induced bronchoconstriction and airway smooth muscle in the guinea pig
A. Opazo Saez, T. Du, N. S. Wang and J. G. Martin
Meakins-Christie Laboratories and Department of Pathology, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
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 guinea pigs. The sites of airway
narrowing and ASM were determined in animals (n = 4) bronchoconstricted to
75, 60, 40, or 15% of the maximal lung resistance (RL,max) induced by
aerosolized MCh and compared with a saline-challenged animal. The median
luminal area of each animal was significantly inversely correlated to the
percentage of RL,max (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 of any given airway. The relationship between the amount of
ASM and responsiveness to MCh was studied in different animals (n = 13).
The range of the concentration of MCh required to reach 50% of RL,max
(EC50) varied by 254-fold, but the RL,max had only a 3.6-fold range. There
was no correlation between RL,max and ASM. However, there was a correlation
between the log EC50 and ASM (r = -0.541; P<0.05) in intraparenchymal
cartilaginous airways. In conclusion, morphometric measurements of airway
narrowing are correlated with pulmonary resistance. Variability in the
quantity of ASM 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 differences in the
amount of ASM in intraparenchymal cartilaginous airways.
