Pharmacology and cardiovascular implications of the kinin-kallikrein system

Abstract

Kinins are peptide hormones that can exert a significant influence on the regulation of blood pressure and vascular tone due to their vasodilatatory, natriuretic and growth modulating activity. Their cardiovascular involvement in physiological and pathophysiological situations has been studied intensively since inhibitors for angiotensin I-converting enzyme and selective receptor antagonists have become available for pharmacologically potentiating or inhibiting kinin-mediated reactions. Molecular biological analysis and the establishment of genetically modified animal models have also allowed newer information to be acquired on this subject. In this review, the components and cardiovascularly relevant mechanisms of the kinin-kallikrein system shall be described. Organ-specific effects concerning the kidneys, the vascular system, the heart and nervous tissue shall also be illustrated. On this issue, the physiological functions and pathophysiological implications of the kinin-kallikrein system should be clearly distinguished from the many, mostly endothelium-mediated protective effects which occur during ACE inhibition due to the potentiation of kinin effects. Finally, a view shall also be cast upon newly discovered targets of action, which could be exploited for therapeutically altering the kinin-kallikrein system.