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1
Pryor, Wanda G. "Tissue renin: extrarenal sources of renin and their probable functions in relation to the renin-angiotensin system." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 1987. http://digitalcommons.auctr.edu/dissertations/2770.
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During the past thirty years, investigators of the renin-angiotensin system have found renin-like substances in a number of non-traditional locations throughout mammalian systems. These renin-like substances have been found in virtually every component of the brain, as well as the salivary glands, adrenal glands, blood vessels, genital tracts of both males and females, tumor cell lines, and even the eyeball and retina. This thesis is a literary review which will focus on extrarenal renin sources located in the uterus and the testis. These two locations are of particular interest because of the probable function in the regulation of the reproductive cycle. In addition, information on submaxillary gland renin and brain renin will also be discussed but to a lesser extent than uterine and Leydig Cell renin.
Extrarenal renin sources have been tagged as renin-like enzymes, or more popularly as isorenins, because immunologically they react as true renin does. The immunoreactivity of these isorenins has been detected by a number of methods which include immunohistochemistry, specific staining characteristics of immunolabelling, native gel electrophoresis, sodium dodecyl sulfate gel electrophoresis, isoelectric focusing, double immunodiffusion, and symmetric chromatographic elution patterns.
Extensive research in this area is still underway. Numerous modes of detection are being used to evaluate the specific sites of synthesis for these extrarenal renin sources, as well as their release mechanisms and physiological roles. Undoubtedly, the data resulting from these investigations will reveal significant information regarding these non-traditional renin sources and their clinical relevance in the treatment of hypertension.
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Esch, Joep Hendrikus Maria van. "Unraveling the complexities of the renin-angiotensin system: from ACE to renin inhibition." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/13132.
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Brameld, John M. "The ovarian renin angiotensin system." Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293049.
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Oldham, A. A. "Species selectivity of renin inhibitors." Thesis, Open University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383703.
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Skipworth, J. R. A. "Hepatic mitochondrial renin-angiotensin systems." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1462711/.
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Introduction: The circulating renin-angiotensin system (RAS) was originally described as a key endocrine regulator of intravascular homeostasis; however, the existence of a local (tissue) RAS has become increasingly reported in a variety of tissues including liver. RAS components have now also been detected in rat heart, brain and smooth muscle cell mitochondria as well as within intramitochondrial dense bodies of rat adrenal tissue. Further, reduced RAS levels have been associated with improved endurance performance and fatigue resistance in human skeletal muscle, suggesting that low RAS activity is associated with metabolic efficiency, potentially via RAS action upon, or within, mitochondria. However, such investigation has often relied heavily upon qualitative techniques (e.g. Western blotting, immunofluorescence and electron microscopy), which contain inherent limitations in that they completely rely upon the limited specificity of antibodies to demonstrate the existence of intra-mitochondrial RAS components. Methods: The presence of RAS components within the mitochondria of rat hepatic tissue and liver cell-lines was investigated via sub-fractionation of rat liver tissue and cell-lines, followed by Western blotting, as well as via immunofluorescence and confocal microscopy, and electron microscopy. The mitochondrial effects of stimulating or antagonizing hepatic RAS were assessed via functional fluorescence microscopy (for assessment of NADH, calcium and mitochondrial membrane potential) and measurement of oxygen consumption within live cells of a liver cell-line. Results: Western blotting, immunofluorescence and electron microscopy suggested the presence of RAS components within mitochondria; however, there was a lack of results consistency between techniques and the staining patterns were largely non-specific. Western blotting further demonstrated the presence of a prominent 55 kDa band, when immunostaining a mitochondrial fraction with (angiotensin-converting enzyme) ACE Cterminal antibody (usual size 180 kDa). This was further explored via isolation of the 55 kDa molecule and mass spectrometry to yield results consistent with non-specific staining only. Addition of RAS agonists or antagonists to live liver cell-lines demonstrated no consistent results, except at supra-physiological levels, where RAS antagonists improved oxygen consumption. Conclusions: Such data suggest that the previous descriptions of RAS components within mitochondria are likely to be secondary to methodological flaws, particularly the reliance upon single antibodies, which have subsequently been shown to have poor specificity. Thus, the effect of ang II on liver mitochondria is unlikely to be direct and any such action is likely to occur via one of several intracellular pathways, regulation of gene expression or mitochondrial biogenesis.
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Xiao, Fang. "The vascular renin-angiotensin-aldosterone system." Thesis, Queen Mary, University of London, 2001. http://qmro.qmul.ac.uk/xmlui/handle/123456789/1788.
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The renin-angiotensin-aldosterone system (RAAS) is one of the major regulators of blood pressure. The actions and generation of RAAS components at the tissue level are less well appreciated. This work was designed to investigate the vascular wall not only as a target of the RAAS, but also as one of its sources. Immunocytochemical and immunoblotting analysis revealed positive renin immunoreactivity in the cytoplasm of cultured bovine aortic endothelial cells. Two immunoreactive bands of molecular mass approximately 37,000 and 40,000 dalton were identified. In situ hybridization confirmed that renin mRNA was localized in the same cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) using primers specific for human renin gave a clear single band with the predicted size for (pro)renin. These findings suggest that these vascular endothelial cells are a source of local synthesised renin. Conditioned medium from cultured bovine aortic endothelial cells (BAECCM) and rat aortic smooth muscle cells (RASMCCM) were shown to contain immunoreactive angiotensin II (Ang II) equivalent to 15.05 ± 4.67 pg/106 cells and 1 1.16 ± 1.8 pg/ 106 cells, respectively. Tritiated thymidine incorporation into aortic smooth muscle cells (ASMC) was increased by Ang II and by BAECCM. In both cases, this stimulated proliferation was inhibited by the Ang II type I (AT, ) receptor selective antagonist, losartan. Although tritiated thymidine uptake by rat aortic smooth muscle cells (RASMC) was not significantly enhanced by RASMCCM, it was significantly decreased by losartan in the presence of RASMCCM or of serum-free medium. Assay of RASMC proliferation by cell counting showed that the number of I cells in the presence of Ang II (10'6M) were nearly twice that in control cultures after r 2 days. These findings suggest that Ang II produced by ASMC locally may regulate ASMC growth in an autocrine or/and paracrine fashion, via the AT, receptor. RASMC was also shown to produce immunoreactive aldosterone. Ang II significantly enhanced aldosterone formation by RASMC. but not in the presence of losartan. Ang II stimulated 3H-thymidine uptake into RASMC was further enhanced by aldosterone, but inhibited by the aldosterone antagonist. spironolactone. and the 3ß-hydroxysteroid-dehydogenase inhibitor trilostane. These results suggest that the presence of locally generated aldosterone is essential for the stimulatory effects of Ang II, acting via the AT, receptor. on RASMC proliferation. Amplified products corresponding to transcripts of the CYP 11 BI gene were obtained by RT-PCR on RNA extracted from RASMC, using primers chosen from homologous parts of the exon I and exon 2 regions of CYP IIBI and CYP II B2 genes. Sequencing showed the presence of CYP 11 B1 transcript, but gave no evidence for CYP 11 B2 gene transcription. RT-PCR also gave a band corresponding to the 770 bp fragment from bases - 486 (upstream) to + 284 (exon 2) bp of the CYP 1lB1 gene. Furthermore, the present experiments demonstrated the transcription of the sequences 183-480 bp upstream from the CYP 11 B1 gene, and the use of competitive RT-PCR showed this was regulated by Ang 11. Thus. cultured RASMC may be the site of Ang 11 regulated transcription of a longer fragment of the CYP 11 B1 gene than generally expected. Finally, use of immunofluorescence and immunoblotting demonstrated the presence of an apparent binding carrier for 18-OH-DOC in cultured RASMC similar to that found in the rat adrenal.
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Xu, Di. "Expression and functions of renin isoforms." Diss., University of Iowa, 2010. https://ir.uiowa.edu/etd/3015.
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Renin is an enzyme that catalyzes the rate-limiting step in the production of angiotensin peptides, and is thus a key regulator of processes controlled by angiotensin such as blood pressure, hydromineral balance, and metabolism. Our laboratory and others have previously identified a novel isoform of renin (icRen) which, as a result of the utilization of an alternate first exon, lacks the signal peptide and first third of the pro-segment of classical secreted renin (sRen). This alternate icRen isoform thus remains within the cytoplasm of the cell, but is constitutively active. Here, we report that while sRen is the predominant form of renin expressed in most tissues during development, icRen is the predominant form of renin within the adult brain. Thus, we hypothesized that sRen and icRen play distinct physiological roles in adult mice. To examine this hypothesis, we have utilized the Cre-LoxP system to selectively delete either isoform globally or within selected cell types such as neurons and glia. We have successfully developed a "sRen-flox" model, in which endogenous mouse sRen isoform can be selectively deleted, while not affecting endogenous icRen production. Breeding these mice against the E2A-Cre, Nestin-Cre, and GFAP-Cre mouse lines resulted in global-, neuronal-, and glial-specific knockouts of sRen, respectively. Physiological characterization of resulting mice has uncovered postnatal lethality, hypotension, renal atrophy, vascular dysfunction and decreased body weight and white adipose in the global knockouts. Depletion of sRen from only neuronal or glial cells does not appear to alter any of these phenotypes at baseline. From these data, we conclude that while peripheral sRen is of primary importance to blood pressure regulation, hydromineral balance, and metabolism, central expression of this isoform is unimportant. Further, comparison of our results to published findings from global total renin knockout models indirectly supports a role for icRen in the brain. We are currently in the process of generating icRen-flox and subsequent knockout mice, which will be useful models to directly analyze the physiological role(s) of icRen.
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Weatherford, Eric Thomas. "Regulation of renin gene expression by CTCF, Nr2f2, Nr2f6, Nr4a1 and maintenance of the renin expressing cell." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/1104.
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The renin angiotensin system (RAS) is critical for the regulation of blood pressure, electrolyte/fluid, and metabolic homeostasis. Regulation of the RAS is important in the development and treatment of hypertension. As part of the rate-limiting step in a cascade of events ending in the production of angiotensin II, renin is a major regulator of the RAS. Its expression is localized to the juxtaglomerular (JG) cells of the JG apparatus where it is exquisitely located to respond to various physiological cues. Understanding the regulation of renin expression and development of the juxtaglomerular cells is critical. Two regulatory elements, the enhancer and proximal promoter, have been found to be important in controlling cell- and tissue- specific baseline expression of the renin gene. Within the enhancer is a hormone response element (HRE) which confers a high level of activity to the enhancer. Nuclear receptors that bind this element have been found to bind the HRE and regulate renin promoter transcriptional activity. We have previously characterized the role of the orphan nuclear receptor Nr2f6 as a negative regulator of renin expression that mediates its effects through the HRE. However, gel shift assays indicate that there are other transcription factors binding this element. We have identified other orphan nuclear receptors that regulate renin expression. The first, Nr2f2 acts as a negative regulator of renin promoter activity but does not appear to affect baseline expression of the endogenous renin gene. The other, Nr4a1, is a positive regulator of renin expression, but it does not appear to mediate its effects through the HRE.
The transcriptional regulation of gene expression is controlled by regulatory elements separated by large distances from promoters. We and others have found that short transgenes of the human renin (hREN) locus are not sufficient to protect them from positional effects that can be exerted upon them by neighboring regulatory elements. We discovered a random truncation in a large genomic construct of the hREN gene that resulted in ubiquitous expression of renin not seen with the intact form. By locating the genomic insertion site of that transgene in the Zbtb20 gene, we found that the hREN promoter had come under control of that gene's regulatory elements. The gene downstream of renin however maintained its tissue-specific expression. We found that CCCTC-binding factor (CTCF) bound to chromatin in and around the renin locus. The presence of CTCF suggests that insulator elements are present in the renin locus, and their loss likely explains the results above.
Finally, we assessed the role of microRNAs in the development of renin expressing cells in the mouse kidneys by cell-specific deletion of the processing enzyme Dicer. This resulted in reduction of renin expression and a decrease in the number of renin expressing cells in the kidney. Mice were hypotensive and had several kidney abnormalities including a hypertrophied vasculature and striped fibrosis. These results indicate that Dicer and the miRNAs it processes are critical for the development and maintenance of renin expressing cells that contribute to normal kidney development.
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Benson, Victoria Louise St Vincent's Clinical School UNSW. "The role of calcineurin in high-renin and low-renin animal models of pressure overload left ventricular hypertrophy." Awarded by:University of New South Wales. St Vincent's Clinical School, 2005. http://handle.unsw.edu.au/1959.4/20843.
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Left ventricular hypertrophy (LVH) in response to pressure overload is associated with increased cardiovascular morbidity and mortality, making its prevention an important therapeutic goal. The role of a calcineurin-dependent molecular pathway in the induction of pressure-overload LVH is controversial. The present study tested the hypothesis that, in the setting of LV pressure overload, activation of the systemic renin-angiotensin system was necessary for activation of this calcineurin pathway. Mild LV pressure overload was induced in male Wistar rats by abdominal aortic constriction (AAC) or transverse aortic arch constriction (TAC), producing well-matched pressure gradients of 37 ?? 8 and 35 ?? 15 mmHg, respectively. Tight transverse aortic arch constriction (TTAC) in additional animals produced a pressure gradient of 75 ?? 15 mmHg. Only AAC increased plasma renin concentration and activated the calcineurin pathway, indicated by increased nuclear NFAT3 content. Plasma renin concentration and nuclear NFAT3 content were unchanged in TAC and TTAC animals. AAC animals developed more LVH 21 days post-banding than TAC and TTAC animals: the slope of the relationship between LV/body weight ratio and systolic blood pressure was much steeper in AAC animals than the combined TAC and TTAC animals (20x10-6 versus 5x10-6, p<0.001). Treatment with the calcineurin inhibitor FK506 did not significantly alter the slope of this relationship in the combined TAC and TTAC animals (8x10-6), but FK506 abolished this relationship in AAC animals (-5x10-6, R =0.0003). These data indicate that activation of the calcineurin pathway occurs only in high-renin hypertension, providing an additional stimulus to LVH induction. Calcineurin plays no role in the induction of LVH in low-renin hypertension, which is much more common clinically.
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Broderson, Claudius [Verfasser]. "Laborbeurteilung des Renin-Angiotensin-Aldosteron-Systems : Evaluation im Praxisalltag und Vergleich verschiedener Methoden zur Renin-Bestimmung / Claudius Broderson." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2021. http://d-nb.info/1234984261/34.
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Wollschläger, Tanja. "Das Renin-Angiotensin-System in menschlicher Haut." [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=980109159.
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Tronvik, Erling. "Migraine, blood pressure andthe renin- angiotensin system." Doctoral thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for nevromedisin, 2009. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-5398.
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Nelissen-Vrancken, Henrica Johanna Maria Gerardine. "Local renin angiotensin systems and peripheral ischemia." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 1992. http://arno.unimaas.nl/show.cgi?fid=5719.
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Wystrach, Laura [Verfasser], and Gernot Michael [Akademischer Betreuer] Lang. "Das Renin-Angiotensin-System der humanen Bandscheibe." Freiburg : Universität, 2020. http://d-nb.info/1219851353/34.
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Palmer, Laura Elyse. "The renin angiotensin system and Alzheimer's disease." Thesis, University of Bristol, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.665486.
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Uchendu, Chukwuka Nwocha. "Renin-angiotensin system in the rat epididymis." Thesis, [Hong Kong] : University of Hong Kong, 1990. http://sunzi.lib.hku.hk/hkuto/record.jsp?B12923102.
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Rosenlöf, Katarina. "Erythropoietin receptor and comparison with renin substrate /." Hki : Societas scientiarum Fennica : Academic Bookstore [distr.], 1987. http://catalog.hathitrust.org/api/volumes/oclc/57854069.html.
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Diss. -- Helsingin yliopisto.Tiivistelmä ja 5 erip. - Tiivistelmä ilm. myös erillisenä. - Nimiösivulla myös: From the Minerva Foundation Institute for Medical Research, Unit of Clinical Physiology, and the Fourth Department of Medicine, University of Helsinki.
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Wollschläger, Tanja. "Das Renin-Angiotensin-System in menschlicher Haut." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2006. http://dx.doi.org/10.18452/15468.
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In der vorliegenden Arbeit wurde die Expression von Angiotensinogen, Renin, Angiotensin-Converting-Enzym (ACE) und von den Agiotensin-Rezeptoren AT1 und AT2 in humaner Haut untersucht, um zu sehen, ob humane Haut ein lokales Gewebe Renin-Angiotensin-System (RAS) besitzt und fähig ist, Angiotensin II (Ang II) zu synthetisieren sowie welche physiologische Rolle Ang II in humaner Haut haben könnte. Außerdem wurde das Expressionsmuster von Angiotensinogen, Renin und ACE in gesunder humaner Haut mit dem in Psoriasis, Basaliom und Spinaliom (SCC) verglichen, um einen Einblick in pathophysiologische Funktionen des RAS zu gewinnen. Mit Hilfe von RT-PCR konnten alle Komponenten des RAS in vitro auf mRNA Ebene in kultivierten primären Keratinozyten, Melanozyten, dermalen Fibroblasten und dermalen mikrovaskulären Endothelzellen (MVEC´s) nachgewiesen werden, mit einer Ausnahme: Melanozyten scheinen keine AT2-Rezeptoren zu exprimieren. Immunhistochemische Untersuchungen zeigten die Expression aller Komponenten auf Proteinebene in Epidermis und dermalen Gefäßwänden in Gewebeschnitten humaner Haut. Zusätzlich erfolgte der Nachweis von Ang II in kultivierten Keratinozyten mittels enzymatischen immunometrischen Assays. Während Angiotensinogen, Renin und ACE bei immunhistochemischen Untersuchungen an Gewebeschnitten gesunder menschlicher Haut in allen Epidermalschichten gleichmäßig verteilt waren, zeigte sich bei der Psoriasis eine deutliche Betonung der unteren Epidermalschichten. Immunhistochemische Untersuchungen von Basaliomen erbrachten eine verminderte Expression von Angiotensinogen und Renin innerhalb der Tumornester. ACE wurde in den Tumorzellen noch weniger exprimiert. In immunhistochemischen Untersuchungen von Spinaliomen färbten sich die Tumorzellen deutlich homogen an. Die Experimente haben gezeigt, dass alle Komponenten des RAS in enger Lokalisation in menschlicher Haut vorkommen und dass folglich ein lokales Gewebe RAS in humaner Haut existiert sowie dass humane Haut fähig ist, Ang II ohne Zufuhr weiterer Komponenten und ohne regulatorische Einflüsse aus der Zirkulation zu synthetisieren. Eine mögliche physiologische Rolle von Ang II könnte die Regulation von Keratinozyten-Proliferation und –Differenzierung über seine Rezeptoren sein. Bezüglich der pathophysiologischen Rolle haben die Untersuchungen eine Fehlregulation des kutanen RAS in Epidermis psoriatisch veränderter Haut gezeigt, welches ein Hinweis auf eine pathogenetische Rolle des RAS bei der gestörten Keratinozyten-Proliferation und –Differenzierung sein könnte. Das Expressionsmuster in den untersuchten Tumoren war uneinheitlich, weshalb eine Interpretation der Rolle des RAS in kutanen Tumoren ohne weitere Untersuchungen kaum möglich erscheint. 1The present study was designed to elucidate whether a local tissue renin-angiotensin system (RAS) is expressed in human skin, whether cutaneous cells are able to autonomously synthesise angiotensin II (Ang II), and to get a first insight into a putative physiological role of Ang II in this location. For this purpose, the expression of angiotensinogen, renin, angiotensin-converting enzyme (ACE) and of the angiotensin receptors AT1 and AT2 was examined in human skin samples and in diverse cutaneous cells in primary culture on mRNA- and protein-level. Furthermore, the study compared the expression pattern of angiotensinogen, renin and ACE in healthy human skin with that in psoriasis, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) to look for possible differences between healthy and diseased skin. Using mRNA derived from cultured primary keratinocytes, melanocytes, dermal fibroblasts and dermal microvascular endothelial cells (MVECs), all components of the RAS could be demonstrated by RT-PCR except for AT2 receptors in melanocytes. Immunohistochemical stainings of cryostat sections of human skin revealed the expression of all components at protein level within the epidermis and in dermal vessel walls. In addition, the presence of Ang II in cultured keratinocytes and their supernatants could be proven by enzyme immunometric assay giving strong evidence for the ability of keratinocytes to autonomously synthesise Ang II. Regarding the comparison of RAS expression in healthy versus diseased skin, expression of angiotensinogen, renin and ACE was altered in all dermatoses examined. While in normal skin, RAS components were distributed equally and homogenously throughout all layers of the epidermis, in psoriatic skin their expression was more intense in the basal epidermal layers and less intense in the upper layers. In BCC sections, expression of angiotensinogen and renin was down-regulated, and tumour cells stained negatively for ACE. In SCC cryostat sections, tumour cells stained positively for all RAS components with an intensity comparable to normal skin. Taken together, the experiments revealed that a local tissue RAS exists in human skin, and that human skin is able to autonomously synthesise Ang II without any supply of components from the circulation. The physiological role of Ang II in normal skin may comprise the regulation of keratinocyte proliferation and differentiation. Concerning a putative pathophysiological role of Ang II in skin, this study provides evidence for a deregulation of the RAS in psoriatic skin and in BCC pointing to an involvement of the RAS in the pathomechanisms of these dermatoses. 1
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Tunny, Terence John. "Renin in the diagnosis of renovascular hypertension." Thesis, Queensland University of Technology, 1988. https://eprints.qut.edu.au/36804/1/36804_Tunny_1993.pdf.
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The aim of this thesis was to help define the pattern of renin secretion in unilateral renovascular hypertension and to assist in the improvement of an effective and reliable protocol for the use of renal venous renin ratio, in the diagnosis of renovascular hypertension.
A renin diurnal rhythm pattern difference was demonstrated between patients with essential hypertension and those with renovascular hypertension. Patients with renovascular hypertension lacked the described diurnal renin rhythm pattern of normal subjects and patients with essential hypertension. Thus, renin secretion in renovascular hypertension may be largely autonomous and independent of sympathetic nervous system activity variations. Renin secretion may more likely be dependent on the degree of renal ischemia in the affected kidney, which is directly correlated to the severity of the renal artery stenosis. Because of this lack of renin rhythm, the hypertension in patients with unilateral renovascular hypertension may respond more favorably to antihypertensive medications which have a direct lowering effect on the renin-angiotensin system, such as beta adrenoceptor blocking drugs or angiotensin converting enzyme inhibitors. Certainly this abnormal renin pattern, with renin hypersecretion on a continuing basis, may help understand why many patients with renovascular hypertension have moderate to severe hypertension, that is difficult to control on many conventional drug regimes. From a population screening viewpoint, suspected hypertensive patients with an abnormal renin pattern should be investigated further with dynamic testing such as renal venous renin ratios, to gauge if an active intervention to cure or improve the blood pressure levels is warranted. An abnormal renin pattern can be readily investigated with only two or three peripheral upright venous samples at 10am , 12md and 4pm and a comparision of the plasma renin activity levels as described in this thesis, searching for an abnormal renin rhythm. This test is not meant to be the sole screening test employed, but could prove to be a benifical adjunct to the presently available tests.
The angiotensin converting enzyme inhibitors, enalaprilat and captopril have been shown as most effective stimulators of the renin-angiotensin system, when administered during renal venous renin ratio procedures.
They enhance the lateralising power of the test, while preserving the contralateral suppression of renin in the unaffected kidney, an important diagnostic marker of unilateral renovascular hypertension. Enalaprilat and captopril proved to be more effective than the often used renin stimulus of head-up tilt, with none of the adverse syncopal reactions seen with tilting in approximately one third of patients. Since the completion of this study, head-up tilting has been avoided in patients undergoing renal venous renin ratio studies, unless they were already taking chronic angiotensin converting enzyme inhibitor drugs as antihypertensive medication. In these patients, tilting is still used as an effective stimulus to active renin secretion. Enalaprilat and captopril reduced mean arterial pressure levels significantly by 5 and 20 minutes respectively and levels continued to fall gradually during the 120 minute period of observation. Plasma aldosterone levels fell in response to the blockade of angiotensin II production and peripheral renin levels rose markedly. The use of enalaprilat and captopril eliminated the false negative renal venous renin ratios seen with the recumbent unstimulated samples. Intravenous enalaprilat may be the drug of choice, because the clinician can be certain of an effective plasma level in the shortest possible time, thus bypassing any potential problems with malabsorbtion of the drug through the gut, which could occur with oral captopril.
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Clasen, Ronald. "Regulation von Adiponektin durch das Renin-Angiotensin-System." [S.l.] : [s.n.], 2005. http://www.diss.fu-berlin.de/2005/185/index.html.
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L'Huillier, Nathalie. "Prorenin, its maturation and the (pro)renin receptor." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/29224.
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Expression of the mouse putative (pro)renin receptor (RR) was detected in all tissues and cell lines examined including human mesangial cells previously reported to be negative for RR. Mouse RR was also present during development from E9.5. Phylogenic studies revealed RR is highly conserved between species and likely to be important physiologically. The role of RR was investigated in a rat model in which (pro)renin triggers malignant hypertension (MH). TGR(Cyp1al-Ren2) animals carry a mouse renin gene under the control of the Cyp1a1 promoter inducible by dietary indole-3-carbinol. A rapid rise in blood pressure was accompanied by weight loss and polyuria. The animals exhibited microinfarctions, inflammatory cell infiltration and fibrinoid necrosis in the heart and distal tubule hyperplasia and thickening of intra-renal arterial wall without glomerulosclerosis, in the kidney. To investigate the possible role of RR, a prorenin decoy peptide was used to attempt to ameliorate the MH phenotype in TGR(Cyp1a1-Ren2) animals. This peptide which competes with prorenin for binding to RR, has been shown to improve vascular injuries in diabetic nephropathy. In TGR(Cyp1a1-Ren2), however, no changes in the MH phenotype could be observed, except in the mesentery in which less severe fibrinoid necrosis developed. To complement work on RR, prorenin maturation and renin storage were studied during development. The data showed the complete absence of renin granules in mouse kidneys before birth. Low sodium diet and ACE inhibition triggered (pro)renin granules to be produced in the foetal kidney. Two ACE inhibitors differing in their ability to cross the placenta were used. The data suggest that fetal renin granule formation is under the control of both foetal and maternal RAS. The lack of evidence for regulation of RR in a model of high prorenin and malignant hypertension suggests that the function of this protein may need to be re-assessed.
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Myhill, Deborah J. "The renin angiotensin system and the menstrual cycle." Thesis, University of Nottingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275233.
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Perrott, M. N. "The Renin-Angiotensin System and osmoregulation in fish." Thesis, University of Manchester, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233470.
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Baboolal, Keshwar. "The renin angiotensin system in experimental renal disease." Thesis, King's College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336469.
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Geyer, Florian Ferdinand [Verfasser]. "Rolle des Renin-Angiotensin-Aldosteron-Systems (bzw. von Renin, Aldosteron und deren Ratio) für die vaskuläre Funktion der Widerstandsgefäße / Florian Ferdinand Geyer." Mainz : Universitätsbibliothek der Johannes Gutenberg-Universität Mainz, 2020. http://d-nb.info/1224810228/34.
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Shuttleworth, Gail. "Porcine ovarian follicle development and the renin-angiotensin system." Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324699.
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Aust, Jonathan Gavin. "Molecular and physiological investigations of fish renin-angiotensin systems." Thesis, University of Exeter, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248168.
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Thompson, S. J. "The renin-angiotensin system in the fetal guinea pig." Thesis, University of Southampton, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.380343.
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Lister, P. M. "The synthesis of potential inhibitors of renin and pepsin." Thesis, University of Southampton, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373201.
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Abu-Kishk, Rabee Awni. "Vasodilator mechanisms and the intracellular control of renin secretion." Thesis, University of Southampton, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292931.
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Lu, Ko-Ting. "Identification of nuclear receptors that regulate renin gene expression." Thesis, University of Iowa, 2014. https://ir.uiowa.edu/etd/1877.
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Renin (REN) expression is required to maintain blood pressure and electrolyte homeostasis. However, the mechanisms by which REN is transcriptionally regulated remain elusive. We reported a functional role for several nuclear receptors (NRs) on REN gene transcription. To identify other candidate NRs that regulate REN, we analyzed a publicly available microarray dataset (GUDMAP Developing Kidney ST1) to compare the expression pattern of REN and the 48 NRs across different kidney cell types. Our analysis revealed 14 NRs exhibiting a similar pattern as REN. We hypothesized that these NRs are co-regulated with REN and can regulate REN transcription. To test this hypothesis, we set up 2 cohorts of mice in which REN expression was either high or low compared to control mice and measured expression of REN and NRs in renal cortex by qPCR. The high-REN cohort was given the ACE inhibitor captopril (100g/kg/day) for 10 days, and the low-REN group was implanted subcutaneously with a deoxycorticosterone acetate pellet (50mg) and received 0.15 M NaCl in drinking water for 21 days (DOCA-salt) in addition to water. Captopril increased REN and reduced NR2F6 expression relative to vehicle treatment (REN: 16±1, p
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Soares, Douglas dos Santos. "Hipertrofia cardíaca em camundongos submetidos à natação em diferentes volumes e intensidades de treinamento : avaliação do sistema renina angiotensina." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/169701.
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O exercício físico modula o sistema renina angiotensina (SRA), que tem um importante papel na fisiologia cardíaca, especialmente na promoção da hipertrofia cardíaca. O SRA pode ser dividido em dois eixos principais: o eixo clássico – representado pelo receptor AT1 (AT1R) ativado pela angiotensina II (ANG II) – e o eixo alternativo – que é ativado pela interação da angiotensina 1- 7 (ANG 1-7) com o receptor MAS (MASR). O balanço entre os eixos do SRA pode determinar um remodelamento cardíaco fisiológico ou patológico. Estudos têm demonstrado que altos volumes de exercício físico podem desencadear possíveis efeitos deletérios ao sistema cardiovascular. Neste contexto, nosso objetivo foi avaliar a hipertrofia cardíaca, o eixo clássico e o eixo alternativo do SRA no miocárdio de camundongos submetidos a variados volumes e intensidades de treinamento em natação. Para tal, camundongos balb/c foram divididos em três grupos: (I) sedentário (SED), (II) treinados 2x ao dia (T2) sem sobrecarga e (III) treinado 3x ao dia com sobrecarga de 2% do peso corporal (T3), totalizando 6 semanas de treinamento efetivo. Ambos os grupos treinados desenvolveram hipertrofia cardíaca, sem diferença nos níveis de fibrose. Bioquimicamente, observamos um aumento nos níveis do receptor MASR somente no grupo T2, enquanto que os níveis de AT1R aumentaram somente no grupo T3. Contudo, não foi observada alteração na concentração dos peptídeos ANGI, ANGII e ANG 1-7 no tecido cardíaco entre os grupos. Além do mais, o grupo T3 demonstrou um aumento na expressão de miosina de cadeia pesada- β em comparação ao grupo SED e redução da expressão da isoforma- @ em relação ao grupo T2. Em conclusão, nossos resultados sugerem que ambos os protocolos de exercício promoveram uma hipertrofia cardíaca semelhante, mas o protocolo com maior volume e intensidade promoveu uma ativação diferencial dos receptores do SRA e reativação de genes fetais. Estudos que avaliem protocolos com maior duração são necessários para esclarecer se estas mudanças representam uma ativação precoce dos mecanismos relatados para o desenvolvimento de um fenótipo com características patológicas.Exercise promotes physiological cardiac hypertrophy and induces the activation of the renin angiotensin system (RAS), which plays an important role in cardiac physiology, both through the classical axis – represented by the angiotensin II receptor type 1 (AT1) activated by angiotensin II (ANG II) – and the alternative axis – which is activated by the angiotensin 1-7 interaction with the MAS receptor. However, very intense exercise protocols could have deleterious effects on the cardiovascular system. In this context, we aimed to analyze the cardiac hypertrophy phenotype, as well as the classical (ANGII/AT1) and alternative (ANG1-7/MAS) RAS axes, in the myocardium of mice submitted to varying volume and intensity swimming exercises for the development of cardiac hypertrophy. To this end, male balb/c mice were divided into three groups: (I) sedentary (SED), (II) swimming twice a day (T2) without overload, and (III) swimming three times a day with a 2% body weight overload (T3), totaling six weeks of training. Both training groups developed cardiac hypertrophy. Interestingly, we observed an increase in MAS receptor levels only in group T2, while AT1 levels increased only in group T3. However, no change was observed regarding the levels of angiotensin peptides ANG-I, ANG-II, and ANG1-7, in either group. In addition, group T3 displayed a higher expression of myosin heavy chain-β (MHC-β) and lower expression levels of the alpha isoform (MHC-@). Fibrosis was not observed in any of the groups. In conclusion, our results suggest that both exercise protocols promoted a similar cardiac hypertrophy phenotype, but the protocol applying increased volume and intensity resulted in differential activation of RAS receptors and fetal gene reactivation. Studies applying longer duration protocols could elucidate if these changes represent early activation of mechanisms related to hypertrophy development with phenotypic pathological characteristics.
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Grünberger, Christian. "Das Kalzium-Paradoxon der Reninsekretion : Rolle kalziumregulierter Adenylatzyklasen." kostenfrei, 2009. http://www.opus-bayern.de/uni-regensburg/volltexte/2009/1386/.
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Bouwer, Juanita. "The association between physical activity, blood pressure and renin in black African teachers : the SABPA study / Bouwer J." Thesis, North-West University, 2011. http://hdl.handle.net/10394/7319.
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Objectives: The aim of this study was to determine associations between physical activity (PA), blood pressure (BP) and renin in urban black Africans. Methods: The study sample included 137 urban African males (N=68) and females (N=69) (aged 41.53 ± 8.13 and 44.16 ± 7.37 years, respectively), from the North West Province, South Africa. Anthropometric measurements, ambulatory blood pressure and energy expenditure were determined. Actical® accelerometers were used to determine energy expenditure (METS) over a 24 hour period. Fasting blood samples were used to determine fasting blood glucose, serum cotinine (COT), gamma–glutamyl transferase (GGT) and plasma renin. Results: A greater percentage (64%) of African males were hypertensive compared to African females (33.33%). SBP (p<0.001) and DBP (p<0.001) were significantly higher in males than females. Female subjects were more obese (32.00±7.75 kg/m2) whereas males demonstrated an overweight status (27.28±5.86kg/m2). Male subjects displayed overall higher lifestyle risks (BP, smoking, alcohol consumption, HIV–status) than females. Multivariate regression analyses demonstrated an inverse relationship between BP and renin in both males and females, but no associations existed between renin and physical inactivity. Conclusion: PA appeared not to buffer elevated blood pressure in this specific African sample, as no significant associations supported this hypothesis. The results confirm that black Africans display lower renin levels associated with elevated blood pressure. Furthermore, low renin and physical inactivity was not related to indicate elevated BP through elevated SNS activity.Thesis (M.Sc. (Biokinetics))--North-West University, Potchefstroom Campus, 2012.
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Keßler, Nicole [Verfasser]. "Einfluss der Überexpression unterschiedlicher Renin-Transkripte auf Wachstum und Metabolismus von Herzzellen: Funktionelle Bedeutung einer neu entdeckten zytosolischen Variante des Renin-Gens / Nicole Keßler." Greifswald : Universitätsbibliothek Greifswald, 2011. http://d-nb.info/1013534891/34.
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Nelson, Robert John. "Complementation of the mouse Ren-1d knockout with human renin." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/26813.
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Renin is an aspartyl protease most commonly associated with its systemic role in regulation of arterial pressure and electrolyte balance through its participation in the renin-angiotensin system (RAS). Under normal physiological conditions, renin synthesis and secretion is restricted to the granulated juxtaglomerular (JG) cells of the kidney. Most mammals possess a single renin gene, however most strains of laboratory mice possess two renin genes, termed Ren-ld and Ren-2. Mice lacking a functional Ren-ld gene exhibit a complete lack of renal JG cell granulation and abnormal macula densa morphology. Transgenic mice carrying a 145 kb BAC clone encompassing the Ren-ld and Ren-2 loci show complete restoration of JG cell granulation and normal renal macula densa structure. The structural features required for formation of dense-core renin secretory granules have not yet been identified. Here we describe attempts to rescue the mouse Ren-ld knockout by complementation with a large human renin (hREN) transgene. Transgenic mice were generated using a 55 kb fragment of a PAC clone encompassing the hREN locus, with approximately 35 kb of 5'-flanking sequence. The hREN transgene was backcrossed onto the Ren-ld knockout background, and these M/TV-complemented animals demonstrated restoration of JG cell granulation in a transgene expression level-dependent manner, whilst the atypical macula densa morphology was not rescued. These experiments suggest that the human renin and mouse renin-ld proteins have conserved structural features necessary for the formation of dense-core renin secretory granules. The Ren-ld knockout mouse model provides an ideal tool for the in vivo dissection of structural features of the renin protein responsible for formation of dense-core secretory granules in JG cells. From the renal JG cells, prorenin is secreted either rapidly and intact by a constitutive pathway from the Golgi or protogranules, or is packaged into immature granules and processed into active renin, which is stored in dense-core secretory granules until its regulated release is stimulated. Evidence suggests that the product of the Ren-ld gene, renin-ld is released by the regulated pathway of secretion, whilst the product of the Ren-2 gene, renin-2, is released via the constitutive pathway. It is not known whether the renin-2 protein is able to enter the regulated pathway of secretion. To investigate the trafficking pathways of the two mouse renin proteins, fusion proteins of the renin- ld and renin-2 proteins with enhanced green fluorescent protein (EGFP) were generated. The chimaeras were expressed in vitro in the JG-like As4.1 mouse renal carcinoma cell line. Renin-ld-EGFP was localised to large granular compartments, the Golgi apparatus and also to some smaller vesicles. Renin-2-EGFP was most evident in the Golgi apparatus, with some weaker expression in the cytoplasm, with no evidence of the fusion protein in any large granular compartment. These results confirm that the mouse renin-ld and renin-2 proteins are not equivalent, and support evidence that the renin-ld and renin-2 proteins are secreted by regulated and constitutive pathways, respectively.
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Chiu, Sui Mei Linda. "Identification of a renin binding site in the human placenta." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0001/MQ29676.pdf.
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Funke-Kaiser, Heiko [Verfasser]. "Genregulation im Endothelin- und Renin-Angiotensin-System / Heiko Funke-Kaiser." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2008. http://d-nb.info/1023049791/34.
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Borland, Julie Anne Agnew. "The renin angiotensin system in human coronary artery bypass grafts." Thesis, Imperial College London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248196.
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Pijacka, Wioletta. "Studies of the renin-angiotensin system in early embryonic development." Thesis, University of Nottingham, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.546550.
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Brinkmeier, Thomas [Verfasser]. "Molekulare Mechanismen der transkriptionellen Regulation des Renin-Gens / Thomas Brinkmeier." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2013. http://d-nb.info/1032558717/34.
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Padmanabhan, Neal. "Studies of the renin angiotensin system in the human vasculature." Thesis, University of Glasgow, 2000. http://theses.gla.ac.uk/1288/.
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The work presented in this thesis concentrates on the local generation of AII. Preliminary experiments using wire myography were performed in human resistance arteries from normal subjects, obtained by subcutaneous gluteal at biopsy. In these vessels, AI stimulated a contractile repose that was dependent on activation of the AII type 1 receptor (ATIR). Thus, conversion of AI to AII can occur within the vasculature. This conversion was resistant to inhibition of ACE with enalaprilat in human tissue. In contrast, AI responses in rabbit arteries were almost completely inhibited by enalaprilat. Further investigation demonstrated that the combination of enalaprilat and the chymase inhibitor, chymostatin (but neither agent alone), inhibited the response to AI in human resistance arteries. Thus, a dual pathway for AII generation exists in human arteries, probably mediated by ACE and chymase. Since the significance of non-ACE AII generation may be greatest in patients taking ACE-inhibitors, further studies were conducted on resistance arteries from patients with chronic heart failure (CHF) who were receiving such medication, compared to patients with coronary heart disease (CHD). In patients with CHD a similar dual pathway to that observed in normal volunteers appeared to be present. However, in arteries from patients with CHF, the contribution of chymase to AII generation - as inferred from the effect of inhibiting ACE - appeared to be less. Thus, the activity of the enzymes responsible for AII generation may be modulated by either the syndrome, or its treatment.
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Pountain, Sarah. "Studies on the renin-angiotensin system in the developing ovary." Thesis, University of Nottingham, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435497.
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Cooper, Andrea Claire. "The renin angiotensin system in the human placenta throughout gestation." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312204.
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Rajaram, Jessica. "The renin-angiotensin system enzymes in chronic obstructive pulmonary disease." Thesis, University of Southampton, 2016. https://eprints.soton.ac.uk/397328/.
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Dunn, Cherise. "Investigating the role of the Renin Angiotensin System in cancer." Doctoral thesis, University of Cape Town, 2017. http://hdl.handle.net/11427/26862.
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It has recently been discovered that cancer shares a link with metabolic diseases, including that of cardiovascular disease, diabetes, amongst others, where common sets of genes show similar gene expression. There is thus interest to investigate current therapies for metabolic diseases as possible anti-cancer agents. The renin-angiotensin system (RAS) regulates blood pressure and cardiovascular homeostasis through Angiotensin Converting Enzyme-1 (ACE-1) and its homolog ACE-2. RAS has also been implicated in the progression of various cancers due to the increased action of the vasoconstrictor, angiotensin II, which requires ACE-1 and specifically the Angiotensin Type 1 Receptor (AT1R) for its function. In this study, we investigated the potential association of the endogenous ACE-1 and ACE-2 enzymes in cervical cancer. Our results showed that ACE-1 and AT1R protein expression was elevated in cervical cancer cell lines compared to normal cells and that this correlated with elevated ACE-1 enzyme activity in cancer cells. Treatment with the ACE-1 inhibitors, Captopril and Lisinopril, reduced this activity. We showed that ACE-1 axis stimulation in cancer cells results in increased calcium signaling preferentially via the AT1R and this associates with cancer cell proliferation. Candesartan, an AT1R blocker significantly reduced these effects. ACE-2 expression and activity were decreased in cancer compared to normal cells. Our data shows that ACE2 activators, the natural peptide angiotensin 1-7 and small molecule Diminazene aceturate (DIZE) have anticancer effects with DIZE inducing a G2/M arrest in cancer cells. We also investigated associations between drugs targeting RAS and current chemotherapeutic agents, Cisplatin (CDDP) and Doxorubicin (DOX). Our data shows that ACE-1 axis inhibitors have an antagonistic effect on CDDP, while the ACE-2 activator DIZE associates synergistically with DOX. Taken together, these results suggest that elevated ACE- 1 expression associates with cervical cancer and that the inhibitors of ACE-1 function or activators of ACE-2 function have potential as anticancer therapies as single agents or in combination treatments with current chemotherapeutics.
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Hering, Lydia. "Die Bedeutung des Renin-Angiotensin-Systems im Tiermodell für Präeklampsie." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2012. http://dx.doi.org/10.18452/16550.
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Das Renin-Angiotensin-System ist nachweislich in die Entwicklung der schwangerschaftsspezifischen Erkrankung Präeklampsie involviert. Ziel der Arbeit ist die Charakterisierung der Effekte des zirkulierenden sowie uteroplazentaren Renin-Angiotensin-Systems im Rattenmodell. Wurden weibliche Ratten, transgen für humanes Angiotensinogen, mit männlichen Ratten, transgen für humanes Renin verpaart, so entwickelten sie während der Schwangerschaft Bluthochdruck und Proteinurie, während die umgekehrte Kreuzung diese Hauptsymptome der Präeklampsie nicht zeigte. Weiterhin wurde mit einer Kontrollgruppe sowie einer Angiotensin II behandelten Gruppe gearbeitet. Chronisch, systemische Angiotensin II Infusion (1000 ng/kg/min) erhöhte zirkulierendes Angiotensin II während in der umgekehrten, Präeklampsie-negativen Kreuzung uteroplazentares Angiotensin II erhöht war. In der Präeklampsie-positiven Gruppe war Angiotensin II zirkulär und uteroplazentar erhöht. Bluthochdruck und Albuminurie waren alleinig in den Tiermodellen mit erhöhtem zirkulierendem Angiotensin II nachweisbar. In der Kontrollgruppe kam es während der Schwangerschaft zu einer physiologischen Herzhypertrophie, während in der Präeklampsie-positiven Gruppe Anzeichen einer pathologischen Herzhypertrophie nachweisbar waren. Weiterhin unterstützte uteroplazentares Angiotensin II die tiefe Invasion von Trophoblasten in plazentafernen Spiralarterien, während zirkulierendes Angiotensin II die Trophoblasteninvasion im gesamten mesometrialen Dreieck diffus förderte. In Zellkulturexperimenten konnte gezeigt werden, dass Angiotensin II die Mobilität und die Invasion einer Trophoblastenzelllinie förderte. Ebenso erhöhte Angiotensin II die Migration von Trophoblasten in Plazentakulturen. Diese Ergebnisse verdeutlichen den unterschiedlichen Einfluss des zirkulierenden und uteroplazentaren Renin-Angiotensin-Systems auf die Schwangerschaft und tragen damit zum Verständnis pathologischer Prozesse bei, die zu Präeklampsie führen.Dysregulation of the renin-angiotensin-system is important in preeclampsia, a pregnancy specific disorder, characterized by high blood pressure and albuminuria. Aim of this study is to characterize the effects of circulation and uteroplacental renin-angiotensin-system during pregnancy in a rat model. Female rats transgenic for the human angiotensinogen gene crossed with males transgenic for the human renin gene develop preeclampsia, whereas those of the opposite cross do not. We used this model to study the role of angiotensin II in trophoblast invasion, which is shallow in human preeclampsia but deeper in this model. We investigated the following groups: preeclampsia rats, opposite-cross rats, angiotensin II–infused rats and control rats. Angiotensin II infusion increased only circulating angiotensin II levels, opposite cross influenced only uteroplacental angiotensin II and preeclampsia rats showed increased circulating and uteroplacental angiotensin II. Blood pressure and albuminuria occurred in the models with high circulating angiotensin II but not in other models. Control rats showed physiological heart hypertrophy during pregnancy whereas pathological heart hypertrophy occurred in preeclampsia rats. High uteroplacental angiotensin II influenced deep trophoblast invasion in distant spiral arteries whilst the effect of circulating angiotensin II was more diffuse. We then studied human trophoblast cell line and villous explants derived from first-trimester pregnancy. Local angiotensin II dose-dependently increased migration, invasion and motility. The data suggest that angiotensin II stimulates trophoblast invasion in vivo in the rat and in vitro in human cells, a hitherto fore unrecognized function.
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Claflin, Kristin Elizabeth. "The brain renin-angiotensin system in metabolic and cardiovascular regulation." Diss., University of Iowa, 2016. https://ir.uiowa.edu/etd/2196.
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Leptin acts within the brain to increase resting metabolic rate (RMR) and blood pressure (BP). The renin-angiotensin system (RAS) elicits similar effects in the brain, as reviewed in chapter 1, and it has previously been shown that central angiotensin II type 1 (AT1) receptors are required for leptin-mediated inductions in sympathetic nerve activity to the brown adipose tissue. Thus, we hypothesize that the brain RAS mediates the metabolic effects of leptin. To investigate the interaction between the RAS and leptin, we generated the AT1ALepR-KO mouse which lacks the AT1A receptor in leptin-sensitive cells. In chapter 2, we demonstrated that stimulation of RMR by DOCA-salt and high fat diet requires AT1A receptors in leptin receptor-expressing cells and that these cells expressing both AT1A and the leptin receptor appear to be agouti related-peptide (AgRP) neurons. In chapter 3, we investigated the role of AT1A specifically in AgRP neurons by utilizing AT1AAgRP-KO mice. Similar to AT1ALepR-KO mice, AT1AAgRP-KO mice exhibited deficits in BAT SNA responses to leptin and induction of RMR by alpha melanocyte stimulating hormone. In chapter 4, we utilized a novel transgenic mouse model to demonstrate that microglia do not express the AT1A receptor under chow or high fat diet fed conditions. Taken together, we conclude that a subset of AgRP neurons, which express both the leptin receptor and the AT1A receptor, are critical for the control of sympathetic nerve activity and ultimately RMR.
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Sahoo, G. "Synthetic studies toward prototype renin inhibitors, basiliskamides and decarestrictine C1." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2008. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/2684.
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Lima, Marta da Cunha. "O sistema renina-angiotensina na doença periodontal induzida experimentalmente em ratos." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/25/25132/tde-18012012-105831/.
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A doença periodontal (DP) compreende um grupo de lesões que afetam os tecidos periodontais de proteção (gengivite) e suporte (periodontite), envolvendo a participação de células residentes, células estruturais e mediadores inflamatórios. Pesquisa recente do nosso laboratório mostrou a existência de um Sistema Renina-Angiotensina (SRA) local no tecido gengival de ratos e sugeriu que o SRA possa ter participação na DP. Portanto, o objetivo deste trabalho foi avaliar a se o SRA está envolvido na iniciação e na progressão da DP induzida experimentalmente em ratos. Para tanto, foi utilizado modelo de indução da DP por colocação de ligadura, por 7 e 14 dias, ao redor do primeiro molar inferior de ratos e tratamento destes animais com drogas que afetam o SRA [losartan (50 mg/Kg/dia), alisquireno (30 mg/Kg/dia) ou enalapril (10 mg/Kg/dia)]. Foram realizadas técnicas de análise da perda óssea alveolar, reação em cadeia da polimerase (PCR) quantitativa e imunoistoquímica. Após a coleta, os dados foram devidamente analisados por meio de gráficos e tabelas, sendo utilizada ANOVA a 2 e 3 critérios e adotado nível de significância de 5%. Em nível protéico, houve aumento significativo da maioria dos componentes do SRA (p<0,05) na DP. A renina apresentou aumento nos tratamentos com losartan, alisquireno e enalapril tanto nos animais sham (cirurgia fictícia de indução da DP) quanto nos animais com DP, aos 7 e 14 dias, e não apresentou marcação no grupo controle (água), demonstrando efeito dependente dos tratamentos farmacológicos. Na DP houve aumento dos componentes AT1 (aos 7 e 14 dias), AT2 (aos 7 dias) e enzima conversora da angiotensina (ECA; aos 7 e 14 dias) nos grupos tratados com losartan, alisquireno e enalapril. Também houve aumento de imunomarcação nos animais com DP para AT2 (aos 14 dias) e ECA (aos 14 dias) em animais do grupo controle. Em relação à expressão gênica, houve aumento da expressão de RNAm nos animais com DP para o receptor AT2 no grupo controle (aos 7 e 14 dias), e nos animais tratados com losartan ou enalapril (aos 7 dias). Houve aumento da expressão de RNAm para a ECA nos animais com DP tratados com losartan e enalapril (aos 7 dias), e controle (aos 14 dias). O tratamento por 14 dias com as drogas losartan ou alisquireno, mas não com enalapril, foi capaz de diminuir significativamente a perda óssea alveolar (p<0,05). Portanto, pode-se concluir que o SRA está envolvido na iniciação e na progressão da DP induzida experimentalmente em ratos.Periodontal disease (PD) comprises a group of lesions that affect protection (gingivitis) and support periodontal tissues (periodontitis) involving the participation of resident and structural cells as well as inflammatory mediators. Recent research in our laboratory showed the existence of a local gingival renin-angiotensin system (RAS), and suggested that it might participate in PD. Therefore, the aim of this study was to evaluate whether the RAS is involved in the initiation and progression of the experimentally-induced PD in rats. For this purpose, a model of ligature placement, for 7 and 14 days, around the lower first molar in rats, and the treatment of such animals with drugs that affect the RAS [losartan (50 mg/Kg/day), aliskiren (30 mg/Kg/day) or enalapril (10 mg/Kg/day)] were employed. The following techniques were performed: alveolar bone loss analysis, quantitative real-time polymerase chain reaction and immunohistochemistry. Data were collected, organized in tables and graphs, and submitted to 2 and 3 way ANOVA with significance level established at 5%. In the protein level, there was a significant increase in the majority of the RAS components in PD. Immunolocalization for renin increased when animals were treated with losartan, aliskiren or enalapril, for 7 and 14 days, in both sham (fictitious surgery for PD induction) and PD animals, whereas the control group (water) had no staining, demonstrating a drug-related effect. In animals with PD treated with losartan, aliskiren or enalapril there was an increase in staining for AT1 (at 7 and 14 days), AT2 (at 7 days) and angiotensin-converting enzyme (ACE; at 7 and 14 days). There was also increased staining in PD animals for AT2 (at 14 days) and ACE (at 14 days) in the control group. As far as genic expression, there was an increase in mRNA expression for AT2 in control animals with PD (at 7 and 14 days), and in the animals treated with losartan or enalapril (at 7 days). There was an increase in mRNA for ACE in animals with PD treated with losartan or enalapril (at 7 days) as well as control rats (at 14 days). Treatment for 14 days with losartan or aliskiren, but not enalapril, significantly decreased alveolar bone loss (p<0.05). Therefore, one can conclude that the RAS is involved in the initiation and progression of the experimentally-induced PD in rats.