title: Airway vasodilation by bradykinin is mediated via B2 receptors and modulated by peptidase inhibitors.
abstract: We studied the effect of exogenous bradykinin on blood flow in the airway microcirculation of anesthetized F344 rats in vivo. We made three successive determinations of airway blood flow and cardiac output using a modification of the reference sample microsphere technique. Injection of bradykinin into the left ventricle increased airway blood flow in a dose-related manner. Pretreatment with the bradykinin B2 receptor antagonist, Hoe 140, completely abolished bradykinin-, but not histamine-induced vasodilation. A bradykinin B1 receptor agonist, [des-Arg9]bradykinin, did not affect airway blood flow. We also studied the effect of inhibitors of angiotensin-converting enzyme (captopril) and neutral endopeptidase (phosphoramidon) on bradykinin-induced vasodilation. Pretreatment with captopril, but not phosphoramidon, potentiated the bradykinin-induced vasodilation. However, the addition of phosphoramidon further potentiated the effect of captopril. We conclude that injection of bradykinin into the left ventricle produces a dose-related vasodilation in the airway microcirculation mediated via B2 receptors, an effect that is modulated primarily by angiotensin-converting enzyme and, to a lesser extent, by neutral endopeptidase.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
authors.forename: I
authors.initials: I
authors.lastname: Yamawaki
authors.forename: P
authors.initials: P
authors.lastname: Geppetti
authors.forename: C
authors.initials: C
authors.lastname: Bertrand
authors.forename: B
authors.initials: B
authors.lastname: Chan
authors.forename: J A
authors.initials: JA
authors.lastname: Nadel
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D018002:Receptors, Bradykinin / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012137:Respiratory System / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D011480:Protease Inhibitors; D018002:Receptors, Bradykinin; D001920:Bradykinin