Influence of B2 receptor antagonists on bradykinin-induced vasodilation and edema formation in isolated rabbit hindlimbs

In search of new possibilities to prevent acute inflammatory vascular reaction, we examined the effect of two selective B₂ receptor antagonists, CP 0127 ([Bissuccimidohexane (L-Cys⁶)^–1] and HOE 140 (D-Arg[Hyp³, Thi⁵, D-Tic⁷, Oic⁸]BK), on changes in perfusion pressure and on edema formation caused by bradykinin (BK) in the isolated perfused rabbit hindlimbs. CP 0127 and HOE 140 were added to the perfusion fluid 2 min prior to the first BK-administration (5 × 10^–9 mol/l). A second BK-stimulation was performed after 30 minutes. The antagonists were tested in groups of 6 experiments each at concentrations of 10^–6 mol/l, 5 × 10^–9 mol/l and 10^–10 mol/l. CP 0127 was also tested in a concentration of 10^–8 mol/l. The application of BK resulted in an acute decrease of the mean arterial pressure and in a continual edema formation, reflected by an increase of organ weight (controls,n=6). Pretreatment with CP 0127 as well as with HOE 140 attenuated dose-dependently the BK-induced vasodilation (p < 0.005) and edema formation. The current results indicate that CP 0127 and HOE 140 are able to reduce BK-induced effects on vascular tone and edema formation.