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      Dysregulation of the Renin-Angiotensin System and the Vasopressinergic System Interactions in Cardiovascular Disorders

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          Abstract

          Purpose of Review

          In many instances, the renin-angiotensin system (RAS) and the vasopressinergic system (VPS) are jointly activated by the same stimuli and engaged in the regulation of the same processes.

          Recent Findings

          Angiotensin II (Ang II) and arginine vasopressin (AVP), which are the main active compounds of the RAS and the VPS, interact at several levels. Firstly, Ang II, acting on AT1 receptors (AT1R), plays a significant role in the release of AVP from vasopressinergic neurons and AVP, stimulating V1a receptors (V1aR), regulates the release of renin in the kidney. Secondly, Ang II and AVP, acting on AT1R and V1aR, respectively, exert vasoconstriction, increase cardiac contractility, stimulate the sympathoadrenal system, and elevate blood pressure. At the same time, they act antagonistically in the regulation of blood pressure by baroreflex. Thirdly, the cooperative action of Ang II acting on AT1R and AVP stimulating both V1aR and V2 receptors in the kidney is necessary for the appropriate regulation of renal blood flow and the efficient resorption of sodium and water. Furthermore, both peptides enhance the release of aldosterone and potentiate its action in the renal tubules.

          Summary

          In this review, we (1) point attention to the role of the cooperative action of Ang II and AVP for the regulation of blood pressure and the water-electrolyte balance under physiological conditions, (2) present the subcellular mechanisms underlying interactions of these two peptides, and (3) provide evidence that dysregulation of the cooperative action of Ang II and AVP significantly contributes to the development of disturbances in the regulation of blood pressure and the water-electrolyte balance in cardiovascular diseases.

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          Most cited references316

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          EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF.

          Cross-communication between different signalling systems allows the integration of the great diversity of stimuli that a cell receives under varying physiological situations. The transactivation of epidermal growth factor receptor (EGFR)-dependent signalling pathways upon stimulation of G-protein-coupled receptors (GPCRs), which are critical for the mitogenic activity of ligands such as lysophosphatidic acid, endothelin, thrombin, bombesin and carbachol, provides evidence for such an interconnected communication network. Here we show that EGFR transactivation upon GPCR stimulation involves proHB-EGF and a metalloproteinase activity that is rapidly induced upon GPCR-ligand interaction. We show that inhibition of proHB-EGF processing blocks GPCR-induced EGFR transactivation and downstream signals. The pathophysiological significance of this mechanism is demonstrated by inhibition of constitutive EGFR activity upon treatment of PC3 prostate carcinoma cells with the metalloproteinase inhibitor batimastat. Together, our results establish a new mechanistic concept for cross-communication among different signalling systems.
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            Angiotensin-converting enzyme 2, angiotensin-(1-7) and Mas: new players of the renin-angiotensin system.

            Angiotensin (Ang)-(1-7) is now recognized as a biologically active component of the renin-angiotensin system (RAS). Ang-(1-7) appears to play a central role in the RAS because it exerts a vast array of actions, many of them opposite to those attributed to the main effector peptide of the RAS, Ang II. The discovery of the Ang-converting enzyme (ACE) homolog ACE2 brought to light an important metabolic pathway responsible for Ang-(1-7) synthesis. This enzyme can form Ang-(1-7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1-9) with subsequent Ang-(1-7) formation by ACE. In addition, it is now well established that the G protein-coupled receptor Mas is a functional binding site for Ang-(1-7). Thus, the axis formed by ACE2/Ang-(1-7)/Mas appears to represent an endogenous counterregulatory pathway within the RAS, the actions of which are in opposition to the vasoconstrictor/proliferative arm of the RAS consisting of ACE, Ang II, and AT(1) receptor. In this brief review, we will discuss recent findings related to the biological role of the ACE2/Ang-(1-7)/Mas arm in the cardiovascular and renal systems, as well as in metabolism. In addition, we will highlight the potential interactions of Ang-(1-7) and Mas with AT(1) and AT(2) receptors.
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              Aquaporins in the kidney: from molecules to medicine.

              The discovery of aquaporin-1 (AQP1) answered the long-standing biophysical question of how water specifically crosses biological membranes. In the kidney, at least seven aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have demonstrated that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells, and AQP8 is present intracellularly at low abundance in proximal tubules and collecting duct principal cells, but the physiological function of these two channels remains undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. Body water balance is tightly regulated by vasopressin, and multiple studies now have underscored the essential roles of AQP2 in this. Vasopressin regulates acutely the water permeability of the kidney collecting duct by trafficking of AQP2 from intracellular vesicles to the apical plasma membrane. The long-term adaptational changes in body water balance are controlled in part by regulated changes in AQP2 and AQP3 expression levels. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting are seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy, and syndrome of inappropriate antidiuretic hormone secretion, both AQP2 expression levels and apical plasma membrane targetting are increased, suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.
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                Author and article information

                Contributors
                (+4822) 116 6107) , eszczepanska@wum.edu.pl
                Journal
                Curr Hypertens Rep
                Curr. Hypertens. Rep
                Current Hypertension Reports
                Springer US (New York )
                1522-6417
                1534-3111
                19 March 2018
                19 March 2018
                2018
                : 20
                : 3
                : 19
                Affiliations
                ISNI 0000000113287408, GRID grid.13339.3b, Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, , Medical University of Warsaw, ; Banacha 1b, 02-097 Warsaw, Poland
                Article
                823
                10.1007/s11906-018-0823-9
                5859051
                29556787
                f40dbda0-7623-4b19-925a-433a7e62a0c9
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Funding
                Funded by: Medical University of Warsaw
                Award ID: Project 1MA/2017
                Categories
                Mechanisms of Hypertension (M Weir, Section Editor)
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2018

                Cardiovascular Medicine
                aldosterone,angiotensin receptors,cardiovascular reflexes,heart failure,hypertension,hypoxia,renal failure,vasopressin receptors

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