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

Abstract

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 x 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 x 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.

LF 16.0335, a novel potent and selective nonpeptide antagonist of the human bradykinin B2 receptor

“…Any detrimental effects of acutely elevated bradykinin are mediated by the activation of B 2 receptors which are constitutively expressed in a number of tissues. In this regard, stimulation of bradykinin B 2 receptors increases vascular permeability and produces vasodilatation, both effects leading ultimately to tissue oedema (Kamiya et al , 1993; Breil et al , 1995; Schilling & Wahl, 1997). Bradykinin is also a potent algogenic agent which produces pain by stimulating nociceptive nerve terminals and sensitising them to other stimuli, including mechanical stimulation and heat (Rang et al , 1991; Walker et al , 1995; Cesare & McNaughton, 1996).…”

Effects of bradykinin, histamine and serotonin on pulmonary vascular resistance and permeability

“…Thus, the absence of an increase in pulmonary vascular permeability upon bradykinin challenge suggests the absence of bradykinin B # receptors in the microvascular pulmonary endothelium. In contrast to the effects in rabbit lungs, equimolar concentrations of bradykinin evoke a decrease in vascular resistance and an increase in vascular permeability in isolated perfused rabbit hindlimbs (Breil et al 1995). The different effect of bradykinin on vascular permeability in pulmonary and systemic circulations suggests that the distribution of bradykinin receptors in the lung differs from that in the systemic microvessels.…”