title: Beneficial effects of bradykinin on myocardial energy metabolism and infarct size.
abstract: There is growing evidence for a local kallikrein-kinin system in the heart. In the ischemic heart the enhanced generation and release of kinins seem to have cardioprotective actions. In isolated rat hearts with ischemia-reperfusion injuries, perfusion with bradykinin reduces the duration and incidence of ventricular fibrillations, improves cardiodynamics, reduces release of cytosolic enzymes, and preserves energy-rich phosphates and glycogen stores. In anesthetized animals, intracoronary infusion of bradykinin is followed by comparable beneficial changes and limits infarct size. Inhibition of breakdown of bradykinin and related peptides induces similar beneficial cardiac effects. Treatment with angiotensin-converting enzyme (ACE) inhibitors such as ramipril increases cardiac kinins and reduces postischemic reperfusion injuries in isolated rat hearts as well as infarct size and remodeling in postinfarcted animals, respectively. Blockade of B2 kinin receptors increases ischemia-induced effects. In isolated hearts, ischemia-reperfusion injuries intensify with the B2 kinin receptor antagonist icatibant, which also abolishes the cardioprotective effects of ACE inhibitors and of exogenous bradykinin. Infarct size reduction by ACE inhibitors and bradykinin in anesthetized animals is reversed by icatibant. Kinins contribute to the cardioprotective effects associated with ischemic preconditioning. Preconditioning or bradykinin-induced antiarrhythmic and infarct size-limiting effects are attenuated by icatibant.
authors.affiliation: Hoechst Marion Roussel, Disease Group Cardiovascular, Frankfurt/Main, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Linz
authors.forename: G
authors.initials: G
authors.lastname: Wiemer
authors.forename: B A
authors.initials: BA
authors.lastname: Schölkens
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000187:drug effects / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D006801:Humans; D007333:Insulin Resistance; D016234:Kallikrein-Kinin System / Q000187:drug effects; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D065168:Bradykinin Receptor Antagonists; C065679:icatibant; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin