Cardioprotective properties of bradykinin: Role of the B 2 receptor

Abstract

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, B1 R and B2 R. The results have mostly indicated that the B1 R, whose expression is induced by tissue damage, seem to have mostly noxious effects, whereas the constitutively expressed B2 R, when activated, exert mostly beneficial actions. Accumulating evidence in the recent literature suggests that the B2 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 B2 R activation) or with a potent and highly selective B2 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. © 2010 The Japanese Society of Hypertension All rights reserved.