Kinins in the cardiovascular system.
Growing evidence points to the existence of the components of the kallikrein-kinin-system (KKS) in cardiac and vascular tissue forming systemic and local KKS pathways involving different cell types like endothelial cells, cardiomyocytes and vascular smooth muscle cells. Kinins may contribute to the regulation of the cardiovascular system in health and disease and to the pharmacological effects of cardiovascular agents via autocrine-paracrine mechanisms. Based on observations from experimental models of hypertension, hypertrophy, ischemia, remodelling and preconditioning one can assume that modulation of local KKS pathways is instrumental for endogenous cardio- and vasculoprotective mechanisms. The role of kinins as possible mediators of such protective mechanisms is not only based on the existence of their generating pathways and their release, but also on observations that kinins, when given locally or being increased by inhibition of their breakdown, exert beneficial cardiovascular effects, whereas antagonism of their receptors worsens these effects. Indispensable pharmacological tools like ACE inhibitors and kinin receptor antagonists have helped to clarify these assumptions, which are now further elucidated by molecular biology and by clinical research. Especially the wealth of experimental and clinical findings with ACE inhibitors present a continuous challenge to investigate the role of kinins in the cardiovascular system and to have a closer look at the interdependence of KKS and the Renin-Angiotensin-System (RAS). Within our decade one might not only reach a clearer molecular perception of kinins in the cardiovascular system, and their role in human health and disease, but might also come to improved innovative treatment by modulation of the KKS pathways.
Schölkens
B A
BA
Hoechst Marion Roussel, Frankfurt am Main, Germany.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D016234:Kallikrein-Kinin System / Q000502:physiology; D007705:Kinins / Q000502:physiology*; D017202:Myocardial Ischemia / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D018002:Receptors, Bradykinin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D018002:Receptors, Bradykinin; D009569:Nitric Oxide; D001920:Bradykinin