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.

Implication of the Kallikrein-Kinin system in neurological disorders: Quest for potential biomarkers and mechanisms

“…Oxidative stress characterized by an excessive production of RAS byproducts, ROS and NADPH oxidase (Nox) along with matrix metalloproteinase-9 (MMP-9), cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), iNOS induced by proinflammatory factors such as cytokines, interleukins (IL) and peroxidants is usually thought to be responsible for tissue injury associated with a range of brain injury, inflammation, and degenerative diseases (Theodoropoulos and Loumos 1991, Abbott 2000, Stegbauer, Lee et al 2009, Uttara, Singh et al 2009, Labandeira-Garcia, Rodriguez-Perez et al 2017, Regoli and Gobeil 2017). A recent work by Yang et al highlighted the contribution of BK in enhancing the production and release of different molecules mediating apoptotic cell death from astrocytes (Yang, Hsieh et al 2013).…”

Study on molecular mechanisms of nattokinase in pharmacological action based on label‐free liquid chromatography–tandem mass spectrometry

“…In addition, the kallikrein–kinin system (KKS) could lower blood pressure and negatively regulate RAS. In the KKS, kininogen is degraded into kinin, which is helpful for controlling the blood pressure (Regoli & Gobeil, ). It was reported that nattokinase could lower the blood pressure and had impact on the renin activity (Kim et al, ).…”

Role of Matricellular CCN Proteins in Skeletal Muscle: Focus on CCN2/CTGF and Its Regulation by Vasoactive Peptides

“…B2Rs are constitutively expressed in several tissues, including skeletal muscle, while B1Rs are upregulated upon damage or inflammation. Frequently, the effects mediated by BK via B2 receptors are opposite to those of the classical axis of the RAS, being a potent vasorelaxant and antihypertensive agent [ 152 ]. RAS and KKS have different crosstalk points, where ACE is pivotal because it produces Ang-II and degrades BK.…”