Journal of Applied Physiology, Vol 63, Issue 2 812-819, Copyright © 1987 by American Physiological Society
In vivo functional antagonism between isoproterenol and bronchoconstrictants in the dog
J. W. Jenne, T. K. Shaughnessy, W. S. Druz, C. J. Manfredi and R. E. Vestal
Medical Service, Edward Hines Jr., Veterans Administration Hospital, Hines, Illinois.
The functional antagonism between isoproterenol and methacholine, histamine
and serotonin, as described in vitro in respiratory smooth muscle was
explored in vivo in a canine model. Infusions of isoproterenol were
administered during brief peaks of bronchospasm produced by aerosolized
methacholine and histamine, or during sustained bronchospasm produced by
infused serotonin. In eight mongrel dogs anesthetized with pentobarbital
sodium, the mean protection by infused isoproterenol against methacholine
challenge decreased from 60.6 to 29.1% as the mean lung resistance (RL) was
increased from 78 to 232% over base line by a fourfold increase in
methacholine (P less than 0.002). In six dogs, the mean protection by
isoproterenol against histamine decreased from 55.5 to 26.9% as the
opposing RL increased from 80 to 182% over base line with a fourfold
increase in histamine (P less than 0.02). However, with serotonin infusions
there was only a small 18% mean decrease in protection (P = 0.05),
associated with a correspondingly small 37% mean increase in dose of
serotonin despite a 269% mean increase in resistance (P = 0.02). In all
cases, the loss of protection correlated more closely with the dose of
constrictant than the resistance increase over base line. These findings
demonstrate in vivo functional antagonism between isoproterenol and the
dose of bronchoconstrictant but not necessarily resistance increase per se.
