Kinin B2 and B1 receptor-mediated vasoactive effects in rabbit synovium

Blood flow in response to bradykinin (BK, B-2 receptor agonist) and desArg(9) BK (B-1 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-1 beta (10 pmol) plus TNF alpha (10 pmol) or saline was injected intra-articularly. BK increased blood flow irrespective of pretreatment, whereas desArg(9)BK increased blood flow only in the cytokine-pretreated joints. The B-2 antagonist HOE 140 reversed (p < 0.01) only the BK responses, and the B-1 antagonist desArg(9)Leu(8)BK only reversed desArg(9)BK responses (p < 0.001). A nitric oxide synthase inhibitor, (L-NAME, 10 mu mol kg(-1)), reversed the effects of the kinins (p < 0.05), but not sodium nitroprusside-stimulated responses. The results suggest that the B-2 receptor is constitutively expressed and that the B-1 receptor can mediate responses in inflamed tissues. The results, in addition, indicate that the responses, mediated via both receptors, are nitric oxide-dependent. (C) 1998 Elsevier Science Inc.