title: Potentiation of the biological efficacy of bradykinin by ACE inhibitors: a shift in the affinity of the B2 receptor?
abstract: We have recently demonstrated that the angiotensin I-converting enzyme (ACE) inhibitor ramiprilat augments the endothelium-dependent dilator response to bradykinin in the isolated perfused rat heart by an interaction at the B2 receptor level. We have now investigated whether this is an effect of the ACE inhibitor class of compounds by studying the bradykinin-induced vasoconstriction in isolated segments of the rabbit jugular vein. Among five different ACE inhibitors, moexiprilat and ramiprilat proved to be the most effective in potentiating the constrictor response to bradykinin. This effect was not mimicked by other protease inhibitors or the synthetic ACE substrate hippuryl-L-histidyl-L-leucine. The ACE inhibitors, on the other hand, failed to affect the constrictor or dilator responses elicited by other receptor-dependent agonists in this vascular model. These findings demonstrate that ACE inhibitors selectively potentiate the B2 receptor-mediated constrictor response to bradykinin in the rabbit jugular vein, possibly by increasing the affinity of the B2 receptor.
authors.affiliation: Center of Physiology, J.W. Goethe University Clinic, Frankfurt am Main, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hecker
authors.forename: A T
authors.initials: AT
authors.lastname: Bara
authors.forename: R
authors.initials: R
authors.lastname: Busse
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage*; D004357:Drug Synergism; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000008:administration & dosage; D007601:Jugular Veins / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000008:administration & dosage; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011480:Protease Inhibitors / Q000008:administration & dosage; D011817:Rabbits; D017257:Ramipril / Q000008:administration & dosage / Q000031:analogs & derivatives; D051381:Rats; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000187:drug effects* / Q000378:metabolism*; D044005:Tetrahydroisoquinolines; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D009842:Oligopeptides; D011480:Protease Inhibitors; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D044005:Tetrahydroisoquinolines; C010980:hippuryl-histidyl-leucine; C052549:ramiprilat; D007703:Peptidyl-Dipeptidase A; C059506:moexiprilat; D017257:Ramipril; D001920:Bradykinin