Mechanisms of bradykinin-induced catecholamine release in pithed spontaneously hypertensive rats

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.