Cardioprotective properties of bradykinin: role of the B(2) receptor.
Following the introduction of angiotensin-converting enzyme (ACE) inhibitors in the treatment of hypertension and ischemic heart disease, there has been increasing interest in the bradykinin-mediated aspects of ACE inhibition. Several preclinical and clinical studies have been conducted using genetically engineered animals or pharmacological agonists and antagonists of the two receptors of bradykinin, B(1)R and B(2)R. The results have mostly indicated that the B(1)R, whose expression is induced by tissue damage, seem to have mostly noxious effects, whereas the constitutively expressed B(2)R, when activated, exert mostly beneficial actions. Accumulating evidence in the recent literature suggests that the B(2)R have an important role in the process of ischemic post-conditioning that limits the ischemia/reperfusion injury of the myocardium. In this article, we describe a series of experiments conducted on mice submitted to acute myocardial infarct and treated either with ACE inhibition (which produces potentiation of bradykinin resulting in non-selective B(1)R and B(2)R activation) or with a potent and highly selective B(2)R agonist. These data suggest that this latter pharmacological approach offers functional and structural benefits and is therefore a promising cardioprotective therapeutic modality against acute ischemic events.
Manolis
Athanasios J
AJ
Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Marketou
Maria E
ME
Gavras
Irene
I
Gavras
Haralambos
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D043782:Receptor, Bradykinin B2 / Q000819:agonists* / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D043782:Receptor, Bradykinin B2