Journal of Applied Physiology, Vol 75, Issue 5 1996-2002, Copyright © 1993 by American Physiological Society
Interactive effect of inhaled bradykinin with histamine and PGD2 in bronchial asthma
K. Rajakulasingam, G. Gnanakumaran, M. K. Church, P. H. Howarth and S. T. Holgate
Southampton General Hospital, United Kingdom.
Interaction among mediators such as bradykinin (BK), histamine (H), and
prostaglandin (PG) D2 may contribute to reduction in airway caliber in
asthma. Ten stable asthmatic subjects took part in a study to investigate
possible mediator interaction. The provocative concentration of mediator
required to reduce forced expiratory volume in 1 s (FEV1) by 12.5% from the
starting baseline value (PC12.5) and that required to reduce the fall in
FEV1 from 12.5 to 25% (PC25-12.5) of H, BK, and PGD2 were determined. On
three subsequent occasions, subjects inhaled either the vehicle plus BK
PC12.5 or the vehicle plus H or PGD2 PC25-12.5, and FEV1 was measured at
regular time intervals up to 40 min. Predicted time course curves were
calculated from these results. On two additional occasions, interactive
time course studies were undertaken when the subject inhaled BK PC12.5
followed by H or PGD2 PC25-12.5. On a further three visits, the time
courses of individual mediators were studied. When BK was combined with H
and PGD2, the maximum fall in FEV1 and the rate of recovery after
inhalation of the second mediator were not significantly different from
those values of predicted time course responses for the same combination of
mediator. Thus, by employing pharmacologically active concentrations of
inhaled BK, H, and PGD2, which act through separate receptor mechanisms, we
were unable to demonstrate any pharmacological interaction on airway
caliber in asthma.
