Abstract
This review addresses the physiological role of the kallikrein–kinin system in arteries, heart and kidney and the consequences of kallikrein and kinin actions in diseases affecting these organs, especially ischemic and diabetic diseases. Emphasis is put on pharmacological and genetic studies targeting kallikrein; ACE/kininase II; and the two kinin receptors, B1 (B1R) and B2 (B2R), distinguished through the work of Domenico Regoli and his collaborators. Potential therapeutic interest and limitations of the pharmacological manipulation of B1R or B2R activity in cardiovascular and renal diseases are discussed. This discussion addresses either the activation or inhibition of these receptors, based on recent clinical and experimental studies.
Highlights
Cardiovascular and Renal Diseases.The plurality of structurally related but molecularly distinct membrane receptors triggering cellular signaling and physiological action is a feature of several vasomotor peptide systems, such as renin–angiotensin, kallikrein–kinin and vasopressin
This review addresses the physiological or pharmacological agonism and antagonism of kinin receptors, B1R or B2R, in clinical and experimental diseases
Attacks of angioedema are triggered by unopposed local plasmakallikrein activation and subsequent kinin release [91]
Summary
Activation of the B1 receptor depends on the availability of both kinins and carboxypeptidases hydrolyzing BK and releasing desArg9-BK Another interesting feature of the B1 receptor is its absence or low abundance in resting condition but its inducibility in pathological situations by several physicochemical and biological factors that include hypoxia, ischemia and hyperglycemia. The main receptor mediating the vasodilator action of bradykinin, called B2 (B2R), on the other hand, is constitutively synthesized and present in abundance in the vascular endothelium and other tissues. This receptor binds bradykinin and lysyl–bradykinin with favorable kinetic properties and has high signaling. This review addresses the physiological or pharmacological agonism and antagonism of kinin receptors, B1R or B2R, in clinical and experimental diseases
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call