Kinins and Cardiovascular Diseases

Kinins are synthesized from their precursors by different enzymes and participate in the regulation of cardiovascular function through bradykinin (BK) B1 and B2 receptors. They modulate blood coagulation by exerting antithrombotic and profibrinolytic actions. By activating B2 receptors that results in the release of nitric oxide and prostacyclin, kinins inhibit vascular smooth muscle growth and neointima formation, which may play an inhibitory role on the atherosclerosis development, while through the activation of B1 receptors, they may play a deleterious role in this disease. Kinins are potent endogenous vasodilators that are involved in the regulation of coronary vascular tone. However, due to their metabolic characteristics, these peptides act mainly as an autocrine/paracrine factor to locally regulate blood perfusion of organs. By modulating cellular energy metabolism and myocardial oxygen consumption, they protect cardiac and vascular endothelial function in myocardial ischemia and heart failure. Finally, mounting evidence indicates that kinins are involved in the actions of some drugs actually used in the treatment of cardiovascular diseases such as angiotensin-converting enzyme inhibitors and angiotensin AT1 receptor antagonists. Taken together, the kinin system constitutes a potential therapeutic target for cardiovascular diseases. Experiments in animals attempted to explore the kinin system as a therapeutic means, including the mobilization of endogenous kinins using pharmacological agents, searching BK analogs with long-acting properties and gene therapies. However, the potential values of the kinin system have not been taken into consideration in clinical practice for cardiovascular indications.