title: Kallikrein-kinin system as the dominant mechanism to counteract hyperactive renin-angiotensin system.
abstract: The renin-angiotensin system (RAS) generates, maintains, and makes worse hypertension and cardiovascular diseases (CVDs) through its biologically active component angiotensin II (Ang II), that causes vasoconstriction, sodium retention, and structural alterations of the heart and the arteries. A few endogenous vasodilators, kinins, natriuretic peptides, and possibly angiotensin (1-7), exert opposite actions and may provide useful therapeutic agents. As endothelial autacoids, the kinins are potent vasodilators, active natriuretics, and protectors of the endothelium. Indeed, the kallikrein-kinin system (KKS) is considered the dominant mechanism for counteracting the detrimental effects of the hyperactive RAS. The 2 systems, RAS and KKS, are controlled by the angiotensin-converting enzyme (ACE) that generates Ang II and inactivates the kinins. Inhibitors of ACE can reduce the impact of Ang II and potentiate the kinins, thus contributing to restore the cardiovascular homeostasis. In the last 20 years, ACE-inhibitors (ACE-Is) have become the drugs of first choice for the treatments of the major CVDs. ACE-Is not only reduce blood pressure, as sartans also do, but by protecting and potentiating the kinins, they can reduce morbidity and mortality and improve the quality of life for patients with CVDs. This paper provides a brief review of the literature on this topic.
authors.affiliation: a Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Regoli
authors.affiliation: b Department of Pharmacology and Physiology, Université de Sherbrooke, Québec, QC J1H 5N4, Canada.
authors.forename: Fernand
authors.initials: F
authors.lastname: Gobeil
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D016234:Kallikrein-Kinin System / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)
keywords: angiotensin-converting enzyme inhibitors; angiotensines; angiotensins; cardiovascular diseases; inhibiteurs de l’enzyme de conversion de l’angiotensine; kinines; kinins; maladies cardiovasculaires; natriuretic peptides; peptides natriurétiques