The Contribution of cocoa additive to cigarette smoking addiction

Page 74 of 207 RIVM report 650270002
Histamine
pressure and heart rate during systemic administration of histamine. Histamine, 0.1
– 11.1 µg/kg/min, lowered blood pressure in a similar dose-dependent fashion in
all three species. In man and in cat this was accompanied by clear dose-dependent
tachycardia whereas in dog the heart rate changes were minimal. Pharmacological
analysis of the depressor responses to histamine in all three species and the
reduction in total peripheral resistance in cat and dog showed that the immediate
responses to histamine in all three species involved H1-receptors and that sustained
responses involved H2 -receptors (27).
In pithed guinea pigs, the general characteristics and origin of the pressor response
to intravenous injection of histamine were examined. Histamine (5-80 µg/kg)
produced a rapid, short-lasting, constant, prominent and dose-dependent pressor
response, followed by a secondary slight and prolonged depressor response. The
vascular response to histamine was accompanied by a marked tachycardia. The
pressor effect of histamine (30 µg/kg) was strongly reduced or abolished in
animals pretreated with nicotine, reserpine, bretylium or 6-hydroxydopamine.
Furthermore, pyrilamine, a histamine H1-receptor antagonist, antagonized in a
dose-dependent manner the pressor response to histamine. On the contrary,
metiamide, a histamine H2 -receptor antagonist, as well as hexamethonium and
atropine, cholinergic antagonists, did not suppress the pressor effect of histamine.
Those experiments provide evidence that in guinea-pigs, the pressor component of
the vascular response to histamine results predominantly from the activation of
histamine H1-receptors in the sympathetic ganglia with consequent release of
noradrenaline at postganglionic sympathetic nerve terminals (28).
heart rate: Histamine is released into the systemic circulation during anaphylaxis
by drugs and by surgical procedures. Studies in animal models have conclusively
demonstrated that released cardiac histamine is a major mediator of arrhythmias
that occur during anaphylaxis and following the administration of histaminereleasing
drugs. Several lines of evidence suggest a similar arrhythmogenic role
for cardiac histamine in humans: (1) The human heart is rich in histamine; (2)
cardiac histamine can be readily released from human heart in vitro by
therapeutic concentrations of drugs; (3) histamine has potent arrhythmogenic
effects on the human heart in vitro. Arrhythmogenic effects of histamine include
enhancement of normal automaticity, induction of abnormal automaticity,
induction of triggered tachyarrhythmias, depression of atrioventricular
conduction, and increase in the vulnerability of the ventricles to fibrillation (24,
29).
Renal system
It is suggested that 1) H1 and H2 receptors are present in the renal vasculature, 2)
changes in intrarenal blood flow distribution are not responsible for histamineinduced
diuresis, and 3) H1 receptors are primarily postglomerular while H2 receptors
exhibit both pre- and postglomerular distribution (30, 31).
diuresis: Histamine, when given intracerebroventricularly (i.c.v.), has been
reported to produce antidiuresis in the rabbit. Histamine (H), 100 µg/kg i.c.v.,
produced antidiuresis with decreases in renal plasma flow and glomerular
filtration rate in urethane-anesthetized rabbits. With larger doses, a tendency
towards increased electrolyte excretion was noted in spite of decreased filtration.