Journal of Applied Physiology, Vol 60, Issue 3 791-797, Copyright © 1986 by American Physiological Society
Suppression of pulmonary and systemic vascular histamine H2-receptors in allergic sheep
T. Ahmed and M. King
We have previously demonstrated a depression of airway H2-receptor function
in sheep allergic to Ascaris suum antigen. To investigate whether this is a
generalized defect, we studied the H1- and H2- histamine receptor functions
in the pulmonary and systemic circulations of allergic and nonallergic
sheep. Pulmonary arterial pressure, and cardiac output were measured for
calculation of pulmonary vascular resistance (PVR) and systemic vascular
resistance (SVR) before and immediately after a rapid intrapulmonary
infusion of histamine (10 micrograms/kg), with and without pretreatment
with H1- (chlorpheniramine) and H2- (metiamide) antagonists. Histamine
alone increased mean PVR to 435 and 401% of base line and decreased mean
SVR by 51 and 54% in the nonallergic and allergic sheep, respectively (P
less than 0.001). In the nonallergic sheep following pretreatment with
chlorpheniramine (selective H2 stimulation) or metiamide (selective H1
stimulation), histamine decreased SVR by 18 and 36%, respectively,
suggesting that approximately two-thirds of the vasodepressor response was
mediated by H1-receptors and one-third by H2-receptors. Combined H1- and
H2-antagonists completely blocked the histamine response. In allergic sheep
the histamine-induced decrease in SVR was primarily mediated by
H1-receptors, because the response was blocked by H1-antagonist,
chlorpheniramine, and the H2-antagonist, metiamide, had no effect. In the
pulmonary circulation selective H1-stimulation caused a similar increase in
PVR in allergic (365%) and nonallergic sheep (424%), whereas selective
H2-stimulation caused a significant decrease in PVR in the nonallergic
group (14%) but not in the allergic group.(ABSTRACT TRUNCATED AT 250 WORDS)
