title: 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.
authors.affiliation: Institute of Anesthesiology and Operative Intensive Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Breil
authors.forename: T
authors.initials: T
authors.lastname: Koch
authors.forename: S
authors.initials: S
authors.lastname: Goldberg
authors.forename: H
authors.initials: H
authors.lastname: Neuhof
authors.forename: K
authors.initials: K
authors.lastname: van Ackern
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D004487:Edema / Q000139:chemically induced*; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D018002:Receptors, Bradykinin / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D065168:Bradykinin Receptor Antagonists; D010455:Peptides; D018002:Receptors, Bradykinin; C071326:deltibant; C065679:icatibant; D001920:Bradykinin