kallidin and Cardiovascular-Diseases

The kinin B(1) receptor plays an important role in mediating the inflammatory effects of the kallikrein-kinin pathway. The recent development of orally available non-peptidic antagonists and genetically modified mice deficient in B(1) receptor expression have demonstrated that the receptor plays a pivotal role in the cellular, particularly neutrophil, recruitment associated with an acute inflammatory response. These tools have also enabled elucidation of the pathways involved in mediating this effect and have highlighted a major role for chemokines, particularly CXCL5 and CCL2. Neutrophil recruitment is involved in the pathogenesis of renal disease and has very recently been implicated in the early stages of atherosclerosis. In this review we discuss the most recent evidence linking the B(1) receptor with the pathogenesis of these two inflammatory cardiovascular diseases and highlight the therapeutic potential of the kinin B(1) receptor in these disease states.

Topics: Animals; Anti-Inflammatory Agents; Atherosclerosis; Bradykinin; Bradykinin B1 Receptor Antagonists; Cardiovascular Diseases; Drug Delivery Systems; Humans; Inflammation; Inflammation Mediators; Kallidin; Kidney Diseases; Neutrophil Infiltration; Receptor, Bradykinin B1

Bradykinin and Lys-bradykinin are potent peptide mediators implicated in several physiopathological effects in mammals. They act through activation of G-protein-coupled constitutive B(2) or inducible kinin B(1) receptors linked to signaling pathways involving increased intracellular Ca(++) concentrations and/or release of mediators including arachidonic acid metabolites, NO and EDHF. In the cardiovascular system, the kallikrein-kinin system exerts a fine control of vascular smooth muscle tone and arterial blood pressure, and plays a significant cardioprotective effect. This has been lately confirmed in experimental studies employing transgenic mice overexpressing human tissue kallikrein and animals with knockout of kinin B(1) and B(2) receptor gene. Disturbances in this system are associated with arterial hypertension, myocardial ischaemia and other clinical complications. Inhibitors of kininase II (angiotensin-converting enzyme) have been prescribed successfully to patients with cardiovascular diseases, but there is still a great interest in developing drugs or pharmacological strategies that augment the activity of kininogen-kallikrein-kinin system in pathological conditions. Delivery of adenovirus vector containing the human tissue kallikrein gene (gene kallikrein therapy) has emerged as a great potential to satisfy these conditions. This review provides a summary of plasma and tissue kallikrein-kinin system, focusing on the pharmacological properties, kinin receptors and drugs reported to interfere with their actions. The modulatory effects of the kallikrein-kinin system on cardiovascular system, particularly in regulating smooth muscle tone and arterial blood pressure and in preventing myocardium ischaemia have also been explored in the review.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Cardiotonic Agents; Cardiovascular Diseases; Cardiovascular System; Genetic Therapy; Humans; Kallidin; Kallikrein-Kinin System; Kininogens; Kinins; Plasma Kallikrein; Protease Inhibitors; Tissue Kallikreins

Topics: Animals; Arteries; Arteriovenous Anastomosis; Blood Circulation; Blood Vessels; Bradykinin; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Coronary Disease; Dogs; Guinea Pigs; Heart; Hemodynamics; Humans; Hypertension; Kallidin; Kallikreins; Kidney; Kinins; Models, Chemical; Myocardial Infarction; Pancreas; Salivary Glands; Shock

Topics: Animals; Arthritis; Blood Pressure; Bradykinin; Cardiovascular Diseases; Dogs; Edema; Guinea Pigs; Humans; Hypersensitivity; Injections, Intravenous; Kallidin; Kallikreins; Pancreatitis; Shock