Journal of Applied Physiology, Vol 65, Issue 5 1944-1949, Copyright © 1988 by American Physiological Society
Histamine tachyphylaxis in canine airways despite prostaglandin synthesis inhibition
P. J. Antol, S. J. Gunst and R. E. Hyatt
Division of Thoracic Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905.
Tachyphylaxis to aerosolized histamine was studied in dogs anesthetized
with thiamylal after pretreatment with prostaglandin synthesis inhibitors.
Three consecutive histamine dose-response curves were obtained in nine dogs
pretreated with 5 mg/kg indomethacin; two of these nine were also
pretreated with 10 mg/kg indomethacin. Seven of the nine dogs were
pretreated with 4 mg/kg sodium meclofenamate; four of these seven were also
pretreated with 12 mg/kg. All dogs had tachyphylaxis at high concentrations
of histamine regardless of inhibitor used. Pretreatment with indomethacin
while the dogs were under alpha-chloralose-urethan anesthesia gave similar
results. Histamine tachyphylaxis was also studied both in the presence and
in the absence of indomethacin in tracheal smooth muscle strips obtained
from seven additional dogs. A decrease in the median effective dose to
histamine was observed in the indomethacin-treated strips, but
tachyphylaxis to histamine remained. We conclude that prostaglandin
synthesis inhibition does not reverse histamine tachyphylaxis either in
vivo or in vitro. Thus the mechanism of histamine tachyphylaxis remains
unexplained.
