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 fully characterized. Earlier studies failed to show complete inhibition by B1- or B2-antagonists of bradykinin-induced catecholamine release, and were impeded by direct stimulatory actions of those substances. Such effects may arise from the involvement of histamine, the release of which is known to be stimulated by bradykinin and kinin-receptor antagonists. The present study was designed to evaluate the significance of B2-receptors and histamine in the bradykinin-induced enhancement of plasma catecholamines in pithed spontaneously hypertensive rats. The effects of bradykinin, the B2-receptor antagonist HOE 140, histamine and the H1-receptor antagonist mepyramine were tested. Administration of histamine dose-dependently increased catecholamine release whereby a marked preference for adrenaline over noradrenaline was seen. The H1-receptor antagonist mepyramine (0.3 mg/kg) prevented this effect. Bradykinin (7.2 microg/kg) enhanced plasma adrenaline and noradrenaline. In doses > or = 10 microg/kg, HOE 140 completely suppressed the bradykinin-induced increase in plasma noradrenaline, while a slight stimulation of adrenaline that even persisted after a high dose of HOE 140 (100 microg/kg), was only abolished by additional administration of mepyramine (0.3 mg/kg). The H1-receptor antagonist at this dose did not influence the effectivity of bradykinin. It is concluded that the bradykinin-induced enhancement of catecholamine release during electrical stimulation is completely (noradrenaline) or predominantly (adrenaline) mediated by B2-receptors. A minor stimulating effect of bradykinin on plasma adrenaline is provoked independently of B2-receptors via histamine acting on H1-receptors.
Dendorfer
A
A
Institute of Pharmacology, Medical University of Lübeck, Germany. dendorfe@medinf.mu-luebeck.de
Fitschen
M
M
Raasch
W
W
Tempel
K
K
Dominiak
P
P
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002395:Catecholamines / Q000097:blood*; D003655:Decerebrate State; D004558:Electric Stimulation; D006632:Histamine / Q000494:pharmacology; D008297:Male; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D014628:Vagotomy
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; C065679:icatibant; D006632:Histamine; D011738:Pyrilamine; D001920:Bradykinin