SYMPATHETIC-DEPENDENCE IN BRADYKININ-INDUCED SYNOVIAL PLASMA EXTRAVASATION IS DOSE-RELATED

While previous studies have implicated a role for sympathetic postgang lionic neuron-terminals in bradykinin-induced plasma extravasation, a recent report by Cambridge and Brain [Br. J. Pharmacol., 115 (1995) 64 1-647] has suggested that it is sympathetic-independent. However, the doses of bradykinin used in these two groups of studies were considera bly different. Therefore, in the present study, we characterized the s ympathetic-dependence of plasma extravasation at varying doses of brad ykinin. By measuring the concentration of Evans blue dye extravasation into the joint perfusate following its intravenous injection, bradyki nin-induced plasma extravasation in the knee joint cavity was determin ed spectrophotometrically. To examine the role of sympathetic postgang lionic neuron terminals in mediating bradykinin-induced plasma extrava sation, we used surgical ablation of the lumbar sympathetic chain. Int raarticular perfusion of BK dose-dependently increased synovial plasma extravasation. After surgical sympathectomy, the dose-response curve for bradykinin-induced plasma extravasation was significantly shifted to the right. We conclude that at concentrations observed in inflamed tissues (between 10(-8) and 10(-7) M), bradykinin-induced plasma extra vasation is largely mediated by sympathetic postganglionic neuron term inals.