A. Dendorfer et al., Mechanisms of bradykinin-induced catecholamine release in pithed spontaneously hypertensive rats, IMMUNOPHARM, 44(1-2), 1999, pp. 99-104
Kinins have the potential to modulate the sympathetic system. However, the
kinin receptor subtypes and secondary mediators involved in vivo are not fu
lly characterized. Earlier studies failed to show complete inhibition by B-
1- or B-2-antagonists of bradykinin-induced catecholamine release, and were
impeded by direct stimulatory actions of those substances. Such effects ma
y arise from the involvement of histamine, the release of which is known to
be stimulated by bradykinin and kinin-receptor antagonists. The present st
udy was designed to evaluate the significance of B-2-receptors and histamin
e in the bradykinin-induced enhancement of plasma catecholamines in pithed
spontaneously hypertensive rats. The effects of bradykinin. the B-2-recepto
r antagonist HOE 140, histamine and the H-1-receptor antagonist mepyramine
were tested. Administration of histamine dose-dependently increased catecho
lamine release whereby a marked preference for adrenaline over noradrenalin
e was seen. The H-1-receptor antagonist mepyramine (0.3 mg/kg) prevented th
is effect. Bradykinin (7.2 mu g/kg) enhanced plasma adrenaline and noradren
aline. In doses greater than or equal to 10 mu g/kg, HOE 140 completely sup
pressed the bradykinin-induced increase in plasma noradrenaline, while a sl
ight stimulation of adrenaline that even persisted after a high dose of HOE
140 (100 mu g/kg), was only abolished by additional administration of mepy
ramine (0.3 mg/kg). The H-1-receptor antagonist at this dose did not influe
nce the effectivity of bradykinin. It is concluded that the bradykinin-indu
ced enhancement of catecholamine release during electrical stimulation is c
ompletely (noradrenaline) or predominantly (adrenaline) mediated by B-2-rec
eptors. A minor stimulating effect of bradykinin on plasma adrenaline is pr
ovoked independently of B-2-receptors via histamine acting on H-1-receptors
. (C) 1999 Elsevier Science B.V.,All rights reserved.