Related Experiment Videos
Kinins in the cardiovascular system
1Hoechst Marion Roussel, Frankfurt am Main, Germany.
Insights
The kallikrein-kinin-system (KKS) plays a vital role in cardiovascular regulation and protection. Modulating KKS pathways offers potential for innovative treatments for cardiovascular diseases.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- The kallikrein-kinin-system (KKS) components are present in cardiac and vascular tissues, forming local and systemic pathways.
- Kinins, key mediators of KKS, influence cardiovascular regulation in health and disease via autocrine-paracrine mechanisms.
Purpose of the Study:
- To explore the role of kinins and KKS modulation in endogenous cardio- and vasculoprotective mechanisms.
- To investigate the interdependence of KKS and the Renin-Angiotensin-System (RAS) in cardiovascular function.
Main Methods:
- Analysis of experimental models of hypertension, hypertrophy, ischemia, remodeling, and preconditioning.
- Utilizing pharmacological tools like ACE inhibitors and kinin receptor antagonists.
- Elucidation through molecular biology and clinical research.
Main Results:
- Local KKS pathway modulation is crucial for endogenous cardio- and vasculoprotection.
- Kinins exert beneficial cardiovascular effects, while receptor antagonism worsens outcomes.
- ACE inhibitors highlight the complex interplay between KKS and RAS.
Conclusions:
- Kinins are significant mediators of cardiovascular protective mechanisms.
- Modulation of KKS pathways holds promise for innovative cardiovascular therapies.
- Further research will clarify the molecular perception of kinins in cardiovascular health and disease.
Abstract:
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.