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.