BRADYKININ B-1 RECEPTORS IN HUMAN UMBILICAL VEIN

The present study was undertaken to demonstrate the presence of bradyk inin B, receptors mediating contraction of human umbilical vein. The b radykinin B-1 receptor selective agonist, des-Arg(9)-bradykinin, produ ced a dose-dependent contractile response of human umbilical vein ring s. Furthermore, des-Arg(9)-bradykinin-mediated response increased in a time-dependent manner in vitro. The maximal response to des-Arg(9)-br adykinin, expressed as percentage of the maximum elicited by serotonin , was: 10 +/- 2 at 15 min, 55 +/- 5 at 120 min and 80 +/- 3 at 300 min . Des-Arg(9)-bradykinin-mediated contractions were inhibited by the sp ecific bradykinin B-1 receptor antagonist des-Arg(9)-[Leu(8)]bradykini n which produced parallel shifts in the dose-response curve to the sel ective bradykinin B-1 receptor agonist. Schild regression analysis of data established a pA(2) value of 6.16 +/- 0.06. Kinin-induced contrac tion was not modified by pre-treatment with indomethacin (10 mu M), a cyclo-oxygenase inhibitor. On the other hand, continuous exposure to t he anti-inflammatory steroid dexamethasone (100 mu M) or to the protei n synthesis inhibitor cycloheximide (70 mu M) largely prevented the se nsitization to des-Arg(9)-bradykinin in incubated human umbilical vein rings. These results confirm the presence of bradykinin B-1 receptors which mediate contraction in isolated human umbilical vein. These res ponses are up-regulated in a time- and protein synthesis-dependent pro cess.