Bradykinin-induced oedema formation proceeds from B2 receptor stimulation and is potentiated by concomitantly released prostaglandins.
Bradykinin, a stimulator of B1 and B2 receptors, significantly increased PGI2 synthesis and fluid extravasation, as assessed by the increase of organ weight when injected intraarterially into the artificially perfused rabbit hindquarters preparation. Diclofenac pretreatment prevented PGI2 synthesis and significantly reduced fluid extravasation. Oedema formation and PGI2 synthesis were also significantly reduced by a simultaneous infusion of papaverine. Selective stimulation of B1-type receptors with des-Arg9-bradykinin was not accompanied by edema formation nor PGI2 synthesis but by a significant rise in vascular resistance. The combined application of bradykinin and the selective B1 receptor antagonist des-Arg9-[Leu8]-bradykinin also resulted in oedema formation and PGI2 synthesis, the extent, however, being significantly reduced in comparison to the application of bradykinin only. The data suggest that bradykinin-induced oedema proceeds from B2 receptor stimulation and is potentiated by simultaneous stimulation of B1 receptors. The kinin-induced fluid extravasation seems to be augmented by concomitantly generated prostaglandins.
Neppl
H
H
Division of Clinical Pathophysiology and Experimental Medicine/Department of Internal Medicine, Justus-Liebig University, Giessen, Germany.
Neuhof
H
H
Afflerbach
F
F
Llach Puig Neppl
J
J
Berghöfer
A
A
D000818:Animals; D001920:Bradykinin / Q000633:toxicity*; D002199:Capillary Permeability / Q000187:drug effects; D004008:Diclofenac / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism / Q000502:physiology*; D011817:Rabbits; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects
D011453:Prostaglandins; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D004008:Diclofenac; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D001920:Bradykinin