Pathophysiological activities of the kallikrein-kinin system with emphasis on the cardiovascular disorders

Abstract

Recent evidence suggests an important role for the kallikrein-kinin system in the pathophysiology of hyperalgesia, arthritis, inflammatory bowel disease, pancreatitis, asthma and endotoxemia. In fact, hyperactivity of kinins can be considered as pro-inflammatory because of their ability to cause all the cardinal signs of inflammation directly activating their B1 and B2 receptors. Kinins are also able to release other potent inflammatory mediators. In endotoxemia, excessive kinin release may account for inducing severe life threatening hypotension. Several specific kinin receptor antagonists are being developed with the major interest in treating these pathological conditions to block the activation of kinin receptors. Furthermore, kallikrein inhibitors may have a role in the treatment of arthritis and inflammatory gut diseases to block the excessive release of kallikrein. On the other side, all the components of the kallikrein-kinin system are located in the vascular smooth muscle as well as in the heart. From numerous observations obtained from clinical and experimental models of diabetes, hypertension, cardiac failure, ischemia, myocardial infarction and left ventricular hypertrophy, it can be assumed that the reduced activity of the local kallikrein-kinin system may be instrumental for the induction of cardiovascular related diseases. The ability of kallikrein gene delivery to produce a wide spectrum of beneficial effects makes it an excellent candidate in treating hypertension, cardiovascular and renal diseases. In addition, stable kinin agonists may also be available in the future as therapeutic agents for cardiovascular and renal disorders.