Kinin B2 and B1 receptor-mediated vasoactive effects in rabbit synovium.
Blood flow in response to bradykinin (BK, B2 receptor agonist) and desArg9 BK (B1 receptor agonist) was measured by laser Doppler flowmetry, as a reversal of noradrenaline (50 nmol)-induced decreased blood flow, in the synovium of the anaesthetised rabbit. Either a pretreatment (-6 h) of the cytokines IL-1beta (10 pmol) plus TNFalpha (10 pmol) or saline was injected intra-articularly. BK increased blood flow irrespective of pretreatment, whereas desArg9BK increased blood flow only in the cytokine-pretreated joints. The B2 antagonist HOE 140 reversed (p < 0.01) only the BK responses, and the B1 antagonist desArg9Leu8BK only reversed desArg9BK responses (p < 0.001). A nitric oxide synthase inhibitor, (L-NAME, 10 micromol kg(-1)), reversed the effects of the kinins (p < 0.05), but not sodium nitroprusside-stimulated responses. The results suggest that the B2 receptor is constitutively expressed and that the B1 receptor can mediate responses in inflamed tissues. The results, in addition, indicate that the responses, mediated via both receptors, are nitric oxide-dependent.
Cambridge
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Pharmacology Group and Vascular Biology Research Centre, King's College, London, England, United Kingdom.
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D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology; D008833:Microcirculation; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D013583:Synovial Membrane / Q000098:blood supply*
D016861:Cyclooxygenase Inhibitors; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D009599:Nitroprusside; D009569:Nitric Oxide; D001920:Bradykinin; D009638:Norepinephrine; D007213:Indomethacin