Am. J. Respir. Crit. Care Med., Vol 149, No. 6, Jun 1994, 1494-1498.
In vivo, in vitro correlation of acetylcholine airway responsiveness in sensitized guinea pigs. The role of modified epithelial functions
Y Masaki, M Munakata, M Amishima, Y Homma and Y Kawakami
First Department of Medicine and Health Center, School of Medicine, Hokkaido University, Sapporo, Japan.
Many attempts have failed to correlate in vivo airway responsiveness with
in vitro airway smooth muscle functions. We have reexamined this relation
by taking account of airway epithelial functions in guinea pigs sensitized
with inhaled ovalbumin (OA). In vivo responses were assessed by the
provocative concentration of acetylcholine (ACh) required to double the
airway opening pressure (PC200) under mechanical ventilation. In vitro
responses were measured in a perfused whole- tracheal preparation. The
negative logarithm of the molar concentration of ACh required to produce a
10% reduction in diameter was calculated both for epithelial-side
stimulation (PC10(in)) and for serosal-side stimulation (PC10(out)).
OA-sensitized guinea pigs showed significantly smaller log PC200 than
control animals (0.51 +/- 0.07 and 0.81 +/- 0.10, respectively, p <
0.01). In in vitro study, there were variable differences in PC10(in) and
PC10(out) in each animal. The difference in sensitivity between epithelial-
and serosal-side stimulation (PC10(in- out)) showed a significant
correlation in PC10(in) (r = 0.82, n = 9, p < 0.01) but not to PC10(out)
(r = 0.39, p > 0.1), indicating that the variation in PC10(in-out)
resulted from the changes in PC10(in). For in vivo-in vitro correlation,
log PC200 correlated significantly with PC10(in) (r = 0.68, n = 9, p <
0.05) but not with PC10(out) (r = 0.18, p > 0.1). These results indicate
that the sensitization by inhalation of OA produces increased airway
responsiveness to ACh in vivo and that this airway responsiveness may be
related, at least in part, to the altered airway epithelial functions.
