Cardiac Inhibition of Angiotensin Converting Enzyme: Role of Kinins
Malcolm J. Lewis, Ajay M. Shah in Endothelial Modulation of Cardiac Function, 2020
Different lines of evidence have led to the concept that the renin-angiotensin system (RAS) is functionally divided into circulating and multiple tissue-localized systems (Dzau and Re, 1987; Griendling et al., 1993; Kifor and Dzau, 1987; Lindpaintner et al., 1988; Linz et al., 1989; Schunkert et al., 1990; Yamada et al., 1991). More recently it has become obvious that the same is true for the kallikrein-kinin system (KKS) (Nolly et al., 1992; 1993; 1994a). Thus, the traditional endocrine concept has evolved into a concept of autocrine-paracrine functions of the RAS and KKS (Unger et al., 1991). Since angiotensin-converting enzyme (ACE) is identical with kininase II, ACE-inhibitors may exert part of their pharmacological effects via both of these autocrine-paracrine mechanisms (Unger et al., 1990; Unger et al., 1994).
Inflammation
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
The sources of most inflammatory proteins and peptides are the several different types of leukocytes. These cells contain many potentially harmful substances within their cytoplasm clustered in granules which are released into the surrounding inflamed tissue and appear in the circulation as various plasma proteins. There are five groups: (1) proteases, antiproteases, and oxidizing enzymes; (2) blood coagulation system; (3) complement systems; (4) kallikreinkinin system; and (5) the fibrinolytic system. In this section only the role of proteases, antiproteases, and oxidants during inflammation in tissue injury will be discussed. The kallikrein-kinin system has protein components, but the active mediators are relatively small peptides derived from proteins of this system.
Antihypertensive Drug Classes
Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei in Manual of Hypertension of the European Society of Hypertension, 2019
The core of the RAS pathway involves the conversion of angiotensinogen to angiotensin I (Ang I) by renin followed by its conversion to angiotensin II (Ang II) by ACE. Ang II acts via activation of angiotensin II receptor type 1 to induce arterial vasoconstriction, aldosterone synthesis and secretion, thus increasing sodium and water reabsorption and increasing blood pressure (BP) (3). ACE is also capable of degrading bradykinin (a potent vasodepressor peptide) which contributes to the increase in BP. ACE inhibitors inhibit competitively the activity of ACE resulting in downstream reduction of Ang II in blood and tissues as well as reduction of aldosterone secretion and stimulation of kallikrein-kinin system (1).
Inhibition of plasma kallikrein–kinin system to alleviate renal injury and arthritis symptoms in rats with adjuvant-induced arthritis
Published in Immunopharmacology and Immunotoxicology, 2018
Jie Zhu, Hui Wang, Jingyu Chen, Wei Wei
The kallikrein–kinin system (KKS) is an important endogenous enzyme system. Physiologically, KKS modulates the function of cardiovascular, kidneys and nervous system4. The KKS consists of two major cascades: ‘plasma KKS’ and ‘tissue KKS’. Plasma kallikrein is different from tissue kallikrein in molecular weight, biological functions and immunological properties5,6. Plasma KKS was involved in thrombosis, fibrinolysis and played a critical role during inflammatory processes in many diseases, such as heart disease, kidney disease and cancer5,7–9. Plasma KKS consists of four plasma proteins: prekallikrein, factor XII, factor XI and high molecular weight kininogen (HK). Upon activation, pre-kallikrein (PK) is converted to the active form kallikrein, which cleaves HK to release bradykinin (BK)10. Plasm KKS was also associated with the adaptive immune responses11. BK is a potent peptide that participates in inflammation, edema and vascular dilation and could change the transformation of antigen-specific T lymphocytes to Th1 and Th2 cell12,13.
Kinin B1 receptors as a therapeutic target for inflammation
Published in Expert Opinion on Therapeutic Targets, 2018
Fatimunnisa Qadri, Michael Bader
One particularly important family of inflammatory mediators playing an integral role during inflammation is the kinins. Kinins are blood- and tissue-derived vasoactive hormones and consist mainly of the nonapeptide, bradykinin (BK, Arg–Pro–Pro–Gly–Phe–Ser–Pro–Phe–Arg), the decapeptide Lys-bradykinin or kallidin (KD), and their carboxy-terminal des-Arg metabolites, des-Arg9-BK (DABK) and des-Arg10-KD (DAKD), respectively. There are two classical pathways for the generation of kinins, the plasma and tissue kallikrein–kinin system (KKS) (Figure 1). Kinins originate from kininogens (high and low molecular weight), which are circulatory glycoproteins primarily synthetized by the liver. The cleavage of kininogens by the proteolytic enzymes, kallikreins, in either plasma or tissue produces the kinins, BK, and KD, respectively. Both BK and KD are highly instable peptides and can be degraded very fast by several kininases including angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP), carboxypeptidase N (CPN), and carboxypeptidase M (CPM). These kininases are divided into two main types on the basis of their enzymology; kininase-I (CPN and CPM), and kininase-II (ACE). Kininase-I enzymes cleave the carboxyterminal arginine from either BK or KD giving rise to the active metabolites, DABK and DAKD, while the kininases-II cleave off the C-terminal dipeptide Phe–Arg [2–6].
Myocardial angiogenesis induced by exercise training involves a regulatory mechanism mediated by kinin receptors
Published in Clinical and Experimental Hypertension, 2021
Mei Shen, Min Yu, Chengxiu Qiu, Ge Zhang, Jingya Li, Wei Fang, Qiwen Wang
The kallikrein-kinin system (KKS) is an important modulatory system that exists in tissues and organs and has been implicated in many physiological and pathological processes. The biological action of the KKS is mediated by two known G-protein-coupled receptors, the B1 receptor and B2 receptor. The KKS exerts most of its effects via the B2 receptor, which is constitutively expressed in the vasculature (6). The B1 receptor has a higher affinity for kinin metabolites and is primarily expressed during tissue injury or inflammation (7).