Metabolic effects of angiotensin-converting enzyme inhibition: the role of bradykinin

Angiotensin-converting enzyme (ACE) inhibitors exert several general systemic and tissue-specific actions attributable to partial elimination of angiotensin II and to potentiation of bradykinin. This article briefly reviews the metabolic effects of ACE inhibition on insulin-dependent glucose transport and utilization, which are believed to be kinin-mediated and are enhanced by activation of the B2 type receptor of bradykinin. Studies using selective B1 or B2 receptor antagonists or genetically engineered mice with deleted B2 receptor gene have elucidated to a large extent which effects of bradykinin are mediated by each type of receptor. The data suggest that with physiologic conditions, most hemodynamic and metabolic actions of bradykinin are attributable to the B2 receptor. However, the hemodynamic (vasodilatory) actions are indirect, as they are mediated via activation of various locally generated tissue autacoids, such as prostaglandins and NO; in the absence of the B2 receptor, there is marked compensatory upregulation of the B1 receptor, which is also capable of activating these downstream mediators and thus maintaining the hemodynamic effects. On the contrary, the metabolic properties of bradykinin, ie, enhancement of insulin-mediated glucose transport across cell membranes and utilization of glucose, seem to be direct actions of the B2 receptor on insulin receptor and glucose transporter; in the absence of an intact B2 receptor, those metabolic actions are not taken over by the overexpressed B1 receptor.