The Kinin System: Present and Future Pharmacological Targets

Kallikrein kinin system (KKS) is a complex system produced in various organs. This system includes kininogen (precursor for kinin), kallikreins and the pharmacologically active bradykinin (BK) which is considered either proinflammatory or cardioprotective. It's a proinflammatory polypeptide that is involved in many pathological conditions and can cause pain, inflammation, increased vascular permeability, vasodilation, contraction of various smooth muscle as well as cell proliferation. On the other hand, it has been shown that BK has cardioprotective effects as all components of KKS are located in the cardiac muscles. Numerous observations obtained show that decreased activity of this system may lead to cardiovascular diseases such as hypertension, cardiac failure and myocardial infarction. BK acts on two receptors, B 1 and B 2 receptors which are linked physiologically through their natural stimuli and their common participation in a variety of inflammatory responses. Recently, numerous BK antagonists have been developed in order to treat several diseases which are due to excessive BK formation. Although BK has many beneficial effects, some undesirable effects have been recognized that can be reversed with BK antagonists. In addition, products of this system have multiple interactions with other important metabolic pathways such as the renin-angiotensin system.