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Comprehensive Physiology Jul 2014The renin-angiotensin system has powerful effects in control of the blood pressure and sodium homeostasis. These actions are coordinated through integrated actions in... (Review)
Review
The renin-angiotensin system has powerful effects in control of the blood pressure and sodium homeostasis. These actions are coordinated through integrated actions in the kidney, cardiovascular system and the central nervous system. Along with its impact on blood pressure, the renin-angiotensin system also influences a range of processes from inflammation and immune responses to longevity. Here, we review the actions of the "classical" renin-angiotensin system, whereby the substrate protein angiotensinogen is processed in a two-step reaction by renin and angiotensin converting enzyme, resulting in the sequential generation of angiotensin I and angiotensin II, the major biologically active renin-angiotensin system peptide, which exerts its actions via type 1 and type 2 angiotensin receptors. In recent years, several new enzymes, peptides, and receptors related to the renin-angiotensin system have been identified, manifesting a complexity that was previously unappreciated. While the functions of these alternative pathways will be reviewed elsewhere in this journal, our focus here is on the physiological role of components of the "classical" renin-angiotensin system, with an emphasis on new developments and modern concepts.
Topics: Angiotensinogen; Animals; Humans; Kidney; Peptidyl-Dipeptidase A; Renin; Renin-Angiotensin System
PubMed: 24944035
DOI: 10.1002/cphy.c130040 -
Physiology (Bethesda, Md.) Oct 2007The aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in salt, volume, and blood pressure... (Review)
Review
The aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in salt, volume, and blood pressure homeostasis of the body. Renin is mainly produced and released into circulation by the so-called juxtaglomerular epithelioid cells, located in the walls of renal afferent arterioles at the entrance of the glomerular capillary network. It has been known for a long time that renin synthesis and secretion are stimulated by the sympathetic nerves and the prostaglandins and are inhibited in negative feedback loops by angiotensin II, high blood pressure, salt, and volume overload. In contrast, the events controlling the function of renin-secreting cells at the organ and cellular level are markedly less clear and remain mysterious in certain aspects. The unravelling of these mysteries has led to new and interesting insights into the process of renin release.
Topics: Animals; Cyclic AMP; Humans; Juxtaglomerular Apparatus; Kidney; Paracrine Communication; Protein Processing, Post-Translational; Renin; Secretory Vesicles; Signal Transduction
PubMed: 17928544
DOI: 10.1152/physiol.00024.2007 -
Lakartidningen Dec 2023Reninoma - rare juxtaglomerular tumor associated with hypertension We present a case study of two female patients, aged 20-30 years, who were diagnosed with reninoma, a...
Reninoma - rare juxtaglomerular tumor associated with hypertension We present a case study of two female patients, aged 20-30 years, who were diagnosed with reninoma, a rare juxtaglomerular tumor associated with hypertension, high plasma renin and hypokalemia. Both patients were referred to the Department of Internal Medicine at Sahlgrenska University Hospital, but their cases were ten years apart. In both instances, the renin-secreting tumor was surgically removed, resulting in the normalization of blood pressure without the need for antihypertensive medication. Based on our findings, we recommend physicians interested in hypertension to analyze plasma renin levels before starting antihypertensive treatment in young patients. Additionally, we suggest performing an MRI of the kidneys followed by renal vein catheterization, which can confirm but not exclude the presence of a reninoma. It is important to note that treatment with RAAS (renin-angiotensin-aldosterone system) blockers may mask the effects of reninoma on blood pressure and potassium levels. Since RAAS blockers are contraindicated during pregnancy, it is of particular importance to diagnose reninoma in young women of childbearing age.
Topics: Humans; Female; Renin; Antihypertensive Agents; Hypertension; Kidney Neoplasms; Renin-Angiotensin System; Adenoma
PubMed: 38054585
DOI: No ID Found -
Nephron 2023The (pro)renin receptor (PRR) was originally cloned as a specific single-transmembrane receptor for prorenin and renin and has now emerged as a multifunctional protein... (Review)
Review
The (pro)renin receptor (PRR) was originally cloned as a specific single-transmembrane receptor for prorenin and renin and has now emerged as a multifunctional protein implicated in a wide variety of developmental and physiopathological processes. Activation of PRR in the kidney causes Na+ and water retention, contributing to elevation of blood pressure in response to various hypertensive stimuli. Part of the renal action of PRR depends on activation of intrarenal renin-angiotensin system. In recent years, accumulating evidence suggests that the prohypertensive action of renal PRR was largely mediated by production of the 28-kDa soluble (pro)renin receptor through protease-mediated cleavage of the extracellular domain of PRR. The generation of multiple isoforms of PRR due to the protease-mediated cleavage partially explains diversified actions of PRR. The current review will summarize recent advances in understanding the roles of sPPR in animal models of hypertension.
Topics: Animals; Prorenin Receptor; Receptors, Cell Surface; Hypertension; Kidney; Renin-Angiotensin System; Renin
PubMed: 35871512
DOI: 10.1159/000525635 -
International Journal of Molecular... Apr 2023It has been our pleasure to have been able to develop two special issues within the International Journal of Molecular Sciences: Renin-Angiotensin-Aldosterone System in...
It has been our pleasure to have been able to develop two special issues within the International Journal of Molecular Sciences: Renin-Angiotensin-Aldosterone System in Pathologies and Renin-Angiotensin-Aldosterone System in Metabolism & Disease [...].
Topics: Humans; Renin-Angiotensin System; Metabolic Diseases; Aldosterone; Renin; Angiotensin II
PubMed: 37108577
DOI: 10.3390/ijms24087413 -
Kidney International Feb 2024Renin, an aspartate protease, regulates the renin-angiotensin system by cleaving its only known substrate angiotensinogen to angiotensin. Recent studies have suggested...
Renin, an aspartate protease, regulates the renin-angiotensin system by cleaving its only known substrate angiotensinogen to angiotensin. Recent studies have suggested that renin may also cleave complement component C3 to activate complement or contribute to its dysregulation. Typically, C3 is cleaved by C3 convertase, a serine protease that uses the hydroxyl group of a serine residue as a nucleophile. Here, we provide seven lines of evidence to show that renin does not cleave C3. First, there is no association between renin plasma levels and C3 levels in patients with C3 Glomerulopathies (C3G) and atypical Hemolytic Uremic Syndrome (aHUS), implying that serum C3 consumption is not increased in the presence of high renin. Second, in vitro tests of C3 conversion to C3b do not detect differences when sera from patients with high renin levels are compared to sera from patients with normal/low renin levels. Third, aliskiren, a renin inhibitor, does not block abnormal complement activity introduced by nephritic factors in the fluid phase. Fourth, aliskiren does not block dysregulated complement activity on cell surfaces. Fifth, recombinant renin from different sources does not cleave C3 even after 24 hours of incubation at 37 °C. Sixth, direct spiking of recombinant renin into sera samples of patients with C3G and aHUS does not enhance complement activity in either the fluid phase or on cell surfaces. And seventh, molecular modeling and docking place C3 in the active site of renin in a position that is not consistent with a productive ground state complex for catalytic hydrolysis. Thus, our study does not support a role for renin in the activation of complement.
Topics: Humans; Amides; Atypical Hemolytic Uremic Syndrome; Complement Activation; Complement C3; Complement C3-C5 Convertases; Complement Pathway, Alternative; Fumarates; Kidney Diseases; Renin
PubMed: 38008161
DOI: 10.1016/j.kint.2023.11.005 -
Pediatric Nephrology (Berlin, Germany) Apr 2014Renin-expressing cells appear early in the embryo and are distributed broadly throughout the body as organogenesis ensues. Their appearance in the metanephric kidney is... (Review)
Review
Renin-expressing cells appear early in the embryo and are distributed broadly throughout the body as organogenesis ensues. Their appearance in the metanephric kidney is a relatively late event in comparison with other organs such as the fetal adrenal gland. The functions of renin cells in extra renal tissues remain to be investigated. In the kidney, they participate locally in the assembly and branching of the renal arterial tree and later in the endocrine control of blood pressure and fluid-electrolyte homeostasis. Interestingly, this endocrine function is accomplished by the remarkable plasticity of renin cell descendants along the kidney arterioles and glomeruli which are capable of reacquiring the renin phenotype in response to physiological demands, increasing circulating renin and maintaining homeostasis. Given that renin cells are sensors of the status of the extracellular fluid and perfusion pressure, several signaling mechanisms (β-adrenergic receptors, Notch pathway, gap junctions and the renal baroreceptor) must be coordinated to ensure the maintenance of renin phenotype--and ultimately the availability of renin--during basal conditions and in response to homeostatic threats. Notably, key transcriptional (Creb/CBP/p300, RBP-J) and posttranscriptional (miR-330, miR125b-5p) effectors of those signaling pathways are prominent in the regulation of renin cell identity. The next challenge, it seems, would be to understand how those factors coordinate their efforts to control the endocrine and contractile phenotypes of the myoepithelioid granulated renin-expressing cell.
Topics: Animals; Humans; Kidney; Organogenesis; Renin; Stem Cells
PubMed: 24337407
DOI: 10.1007/s00467-013-2688-0 -
Frontiers in Bioscience (Scholar... Jan 2013Renin is known as a secretory glycoprotein produced, stored and released by the kidney. Renin cleaves angiotensin (ANG) I from angiotensinogen, which is further cleaved... (Review)
Review
Renin is known as a secretory glycoprotein produced, stored and released by the kidney. Renin cleaves angiotensin (ANG) I from angiotensinogen, which is further cleaved to ANG II by ANG-converting enzyme. ANG II acts via specific receptors located at the cell membrane. Recently renin transcripts have been discovered which encode a cytosolic protein that cannot be secreted. These transcripts are derived from the same renin gene but probably use another promoter located within intron A. Whereas the kidney exclusively expresses the transcript encoding secretory renin, other tissues additionally or exclusively express transcripts encoding cytosolic renin. The cytosolic renin protein exerts functions different and even opposite to those of secretory renin. Whereas secretory renin increases necrotic death rates of cardiac cells, the cytosolic renin isoform even protects cells from necrotic death. This review describes the properties of cytosolic renin and its cellular functions and discusses possible mechanisms of actions particularly in the light of the discovery of direct nuclear and mitochondrial effects of ANG' s.
Topics: Animals; Cytosol; Humans; Renin; Renin-Angiotensin System
PubMed: 23277045
DOI: 10.2741/s366 -
American Journal of Physiology.... Mar 2015The kidneys are important endocrine organs. They secrete humoral factors, such as calcitriol, erythropoietin, klotho, and renin into the circulation, and therefore, they... (Review)
Review
The kidneys are important endocrine organs. They secrete humoral factors, such as calcitriol, erythropoietin, klotho, and renin into the circulation, and therefore, they are essentially involved in the regulation of a variety of processes ranging from bone formation to erythropoiesis. The endocrine functions are established by cells, such as proximal or distal tubular cells, renocortical interstitial cells, or mural cells of afferent arterioles. These endocrine cells are either fixed in number, such as tubular cells, which individually and gradually upregulate or downregulate hormone production, or they belong to a pool of cells, which display a recruitment behavior, such as erythropoietin- and renin-producing cells. In the latter case, regulation of humoral function occurs via (de)recruitment of active endocrine cells. As a consequence renin- and erythropoietin-producing cells in the kidney show a high degree of plasticity by reversibly switching between distinct cell states. In this review, we will focus on the characteristics of renin- and of erythropoietin-producing cells, especially on their origin and localization, their reversible transformations, and the mediators, which are responsible for transformation. Finally, we will discuss a possible interconversion of renin and erythropoietin expression.
Topics: Animals; Calcitriol; Endocrine Cells; Erythropoietin; Gene Expression Regulation; Glucuronidase; Humans; Kidney; Klotho Proteins; Phenotype; Renin; Signal Transduction
PubMed: 25608752
DOI: 10.1152/ajpregu.00568.2013 -
Physiological Reviews Apr 2010The protease renin is the key enzyme of the renin-angiotensin-aldosterone cascade, which is relevant under both physiological and pathophysiological settings. The kidney... (Review)
Review
The protease renin is the key enzyme of the renin-angiotensin-aldosterone cascade, which is relevant under both physiological and pathophysiological settings. The kidney is the only organ capable of releasing enzymatically active renin. Although the characteristic juxtaglomerular position is the best known site of renin generation, renin-producing cells in the kidney can vary in number and localization. (Pro)renin gene transcription in these cells is controlled by a number of transcription factors, among which CREB is the best characterized. Pro-renin is stored in vesicles, activated to renin, and then released upon demand. The release of renin is under the control of the cAMP (stimulatory) and Ca(2+) (inhibitory) signaling pathways. Meanwhile, a great number of intrarenally generated or systemically acting factors have been identified that control the renin secretion directly at the level of renin-producing cells, by activating either of the signaling pathways mentioned above. The broad spectrum of biological actions of (pro)renin is mediated by receptors for (pro)renin, angiotensin II and angiotensin-(1-7).
Topics: Angiotensins; Animals; Gene Expression Regulation; Humans; Kidney; Renin; Signal Transduction
PubMed: 20393195
DOI: 10.1152/physrev.00011.2009