Metabolism of Bradykinin by Peptidases in Health and Disease

This chapter provides an overview of the metabolism of bradykinin (BK) by peptidases in health and disease. The enzymatic breakdown of kinins affects the duration of their biological actions as the plasma half-life of intravenously injected BK is in the range of seconds. Kinins are cleaved in vitro and in vivo by enzymes that belong to families, such as zinc-metallopeptidases, astacin-like metallopeptidases, and catheptic enzymes. Vane noted the importance of the pulmonary circulation in the metabolism of vasoactive substances, such as BK as well as angiotensin 1 and 5- hydroxytryptamine. It is clear after decades of research that angiotensin 1-converting enzyme (ACE) on the vascular endothelial cell surface is the most important inactivator of blood-borne BK. BK may act primarily in an autocrine and paracrine fashion, establishing the importance of local regulation of its activity by enzymes on cell surfaces. Thus, the assortment of other enzymes that can inactivate BK is important in a variety of physiological and pathological situations. Most physiological systems have redundant pathways of metabolism so that the abolishment of one pathway is compensated for by the presence of others. This is demonstrated by the pharmacological inhibition of ACE in hypertension.