Involvement of bradykinin in endotoxin-induced vascular permeability increase in the skin of rats.
The aim of the present study was to investigate the role of bradykinin as well as that of platelet-activating factor in the endotoxin-induced acute vascular permeability increase in the dorsal skin of rats by use of kininogen-deficient and normal Brown-Norway rats. In the kininogen-deficient rats, the dose-dependent dye exudation induced by endotoxin was about one half of that in the normal rats at any doses of endotoxin tested (0.1-1.0 mg per site), whereas the dose-response curves obtained by bradykinin (1-100 nmol per site), platelet-activating factor (0.1-1 nmol per site) or histamine (50-500 nmol per site) were the same in both rats. This effect induced by endotoxin in the kininogen-deficient rats was not changed by pretreatment with a bradykinin B2 receptor antagonist, HOE140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin, 1 mg kg-1 i.v.), whereas the endotoxin-induced response in the normal rats was attenuated by the receptor antagonist. These responses in both kininogen-deficient and normal rats were significantly inhibited by a selective platelet-activating factor antagonist, TCV309 (3-bromo-5-[N-phenyl-N-[2-[[2-(1,2,3,4,-tetrahydro-2- isoquinolylcarbonyl-oxy)-ethyl]-carbamoyl]-ethyl]carbamoyl]-1-prop yl- pyridinium nitrate, 0.1 mg kg-1 i.v.). These results suggest that bradykinin could be one of the major mediators in the endotoxin-induced vascular permeability increase in rat skin in addition to platelet-activating factor.
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
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Ueno
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T
Tokumasu
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H
Naraba
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Oh-ishi
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D007704:Kininogens / Q000172:deficiency; D008070:Lipopolysaccharides / Q000633:toxicity*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*; D044005:Tetrahydroisoquinolines
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065168:Bradykinin Receptor Antagonists; D004731:Endotoxins; D007546:Isoquinolines; D007704:Kininogens; D008070:Lipopolysaccharides; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D044005:Tetrahydroisoquinolines; C039351:platelet activating factor receptor; C044101:endotoxin, Escherichia coli; C065679:icatibant; D001920:Bradykinin; C067430:TCV 309