scholarly journals Genetic clues to the etiology of Balkan endemic nephropathy: Investigating the role of ACE and AT1R polymorphisms

2010 ◽  
Vol 62 (4) ◽  
pp. 957-965
Author(s):  
Zorica Krcunovic ◽  
Ivana Novakovic ◽  
Nela Maksimovic ◽  
Danica Bukvic ◽  
Sanja Simic-Ogrizovic ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Study Groups ◽  
Balkan Endemic Nephropathy ◽  
Endemic Region ◽  
Angiotensin System ◽  
Ras Genes ◽  
Endemic Nephropathy ◽  
The Difference

Balkan endemic nephropathy (BEN) was recognized as a distinct entity more than 50 years ago, but the exact environmental and genetic causes of the disease remain elusive. Considering the role of the renin-angiotensin system (RAS) in the emergence of various nephropathies, in the present study we evaluated the possible association with BEN of polymorphisms in two RAS genes: I/D ACE (an angiotensin-converting enzyme) and A1166C AT1R (an angiotensin type 1 receptor). The study groups consisted of 48 BEN patients from the endemic region in the district of Kolubara, Serbia, 33 patients with other nephropathies and 42 healthy individuals. The ACE DD genotype was significantly more represented in the NBEN group (OR=5.447; 95%CI=1.862-15.932, p<0.01). The frequency of the AT1R CC genotype was higher in BEN patients compared to controls (0.104 vs. 0.048), but the difference was not significant. Though the analyzed polymorphisms are associated with certain nephropathies, we found no support for their specific role in BEN susceptibility.

scholarly journals High Order Gene-Gene Interactions in Eight Single Nucleotide Polymorphisms of Renin-Angiotensin System Genes for Hypertension Association Study

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Cheng-Hong Yang ◽  
Yu-Da Lin ◽  
Shyh-Jong Wu ◽  
Li-Yeh Chuang ◽  
Hsueh-Wei Chang
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Renin Angiotensin System ◽  
High Order ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ras Genes ◽  
Snp Interaction

Several single nucleotide polymorphisms (SNPs) of renin-angiotensin system (RAS) genes are associated with hypertension (HT) but most of them are focusing on single locus effects. Here, we introduce an unbalanced function based on multifactor dimensionality reduction (MDR) for multiloci genotypes to detect high order gene-gene (SNP-SNP) interaction in unbalanced cases and controls of HT data. Eight SNPs of three RAS genes (angiotensinogen,AGT; angiotensin-converting enzyme,ACE; angiotensin II type 1 receptor,AT1R) in HT and non-HT subjects were included that showed no significant genotype differences. In 2- to 6-locus models of the SNP-SNP interaction, the SNPs ofAGTandACEgenes were associated with hypertension (bootstrapping odds ratio [Boot-OR] = 1.972~3.785; 95%, confidence interval (CI) 1.26~6.21;P<0.005). In 7- and 8-locus model, SNP A1166C ofAT1Rgene is joined to improve the maximum Boot-OR values of 4.050 to 4.483; CI = 2.49 to 7.29;P<1.63E−08. In conclusion, the epistasis networks are identified by eight SNP-SNP interaction models.AGT,ACE, andAT1Rgenes have overall effects with susceptibility to hypertension, where the SNPs ofACEhave a mainly hypertension-associated effect and show an interacting effect to SNPs ofAGTandAT1Rgenes.

scholarly journals The renin-angiotensin system and male reproduction: new functions for old hormones

2003 ◽  
Vol 30 (3) ◽  
pp. 263-270 ◽  
Author(s):  
PS Leung ◽  
C Sernia
Keyword(s):  
Reproductive System ◽  
Renin Angiotensin System ◽  
Fluid Secretion ◽  
Male Reproductive System ◽  
Male Reproduction ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Acrosomal Exocytosis

The blood-borne renin-angiotensin system (RAS) is known best for its role in the maintenance of blood pressure and electrolyte and fluid homeostasis. However, numerous tIssues show intrinsic angiotensin-generating systems that cater for specific local needs through actions that add to, or differ from, the circulating RAS. The male reproductive system has several sites of intrinsic RAS activity. Recent focus on the epididymis, by our laboratories and by others, has contributed important details about the local RAS in this tIssue. The RAS components have been localized morphologically and topographically; they have been shown to be responsive to androgens and to hypoxia; and angiotensin has been shown to influence tubular, and consequently, fluid secretion. Components of the RAS have also been found in the testis, vas deferens, prostate and semen. Angiotensin II receptors, type 1 and, to a lesser extent, type 2 are widespread, and angiotensin IV receptors have been localized in the prostate. The roles of the RAS in local processes at these sites are still uncertain and have yet to be fully elucidated, although there is evidence for involvement in tubular contractility, spermatogenesis, sperm maturation, capacitation, acrosomal exocytosis and fertilization. Notwithstanding this evidence for the involvement of the RAS in various important aspects of male reproduction, there has so far been a lack of clinical evidence, demonstrable by changes in fertility, for a crucial role of the RAS in male reproduction. However, it is clear that there are several potential targets for manipulating the activity of the male reproductive system by interfering with the locally generated angiotensin systems.

Severe hypoglycaemia during pregnancy in women with type 1 diabetes: Possible role of renin–angiotensin system activity?

2009 ◽  
Vol 84 (1) ◽  
pp. 61-67 ◽  
Author(s):  
L. Ringholm Nielsen ◽  
U. Pedersen-Bjergaard ◽  
B. Thorsteinsson ◽  
F. Boomsma ◽  
P. Damm ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Severe Hypoglycaemia ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
System Activity ◽  
Renin Angiotensin

scholarly journals The intrarenal renin-angiotensin system in hypertension: Insights from mathematical modelling

2021 ◽  
Author(s):  
Delaney Smith ◽  
Anita Layton
Keyword(s):  
Computational Modelling ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Clinical Hypertension ◽  
Induced Hypertension ◽  
Intrarenal Ras

The renin-angiotensin system (RAS) plays a pivotal role in the maintenance of volume homeostasis and blood pressure. In addition to the well-studied systemic RAS, local RAS have been documented in various tissues, including the kidney. Given the role of the intrarenal RAS in the pathogenesis of hypertension, a role established via various pharmacologic and genetic studies, substantial efforts have been made to unravel the processes that govern intrarenal RAS activity. In particular, several mechanisms have been proposed to explain the rise in intrarenal angiotensin II (Ang II) that accompanies Ang II infusion, including increased angiotensin type 1 receptor (AT1R)-mediated uptake of Ang II and enhanced intrarenal Ang II production. However, experimentally isolating their contribution to the intrarenal accumulation of Ang II in Ang II--induced hypertension is challenging, given that they are fundamentally connected. Computational modelling is advantageous because the feedback underlying each mechanism can removed and the effect on intrarenal Ang II can be studied. In this work, the mechanisms governing the intrarenal accumulation of Ang II during Ang II infusion experiments are delineated and the role of the intrarenal RAS in Ang II-induced hypertension is studied. To accomplish this, a compartmental ODE model of the systemic and intrarenal RAS is developed and Ang II infusion experiments are simulated. Simulations indicate that AT1R-mediated uptake of Ang II is the primary mechanism by which Ang II accumulates in the kidney during Ang II infusion. Enhanced local Ang II production is unnecessary. The results demonstrate the role of the intrarenal RAS in the pathogenesis of Ang II-induced hypertension and consequently, clinical hypertension associated with an overactive RAS.

scholarly journals Angiotensin-(1–7) and angiotensin-(1–9): function in cardiac and vascular remodelling

2014 ◽  
Vol 126 (12) ◽  
pp. 815-827 ◽  
Author(s):  
Clare A. McKinney ◽  
Caroline Fattah ◽  
Christopher M. Loughrey ◽  
Graeme Milligan ◽  
Stuart A. Nicklin
Keyword(s):  
Renin Angiotensin System ◽  
Protective Role ◽  
Biologically Active ◽  
Cardiovascular Physiology ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Biologically Active Peptide ◽  
And Oxidative Stress

The RAS (renin–angiotensin system) is integral to cardiovascular physiology; however, dysregulation of this system largely contributes to the pathophysiology of CVD (cardiovascular disease). It is well established that AngII (angiotensin II), the main effector of the RAS, engages the AT1R (angiotensin type 1 receptor) and promotes cell growth, proliferation, migration and oxidative stress, all processes which contribute to remodelling of the heart and vasculature, ultimately leading to the development and progression of various CVDs, including heart failure and atherosclerosis. The counter-regulatory axis of the RAS, which is centred on the actions of ACE2 (angiotensin-converting enzyme 2) and the resultant production of Ang-(1–7) [angiotensin-(1–7)] from AngII, antagonizes the actions of AngII via the receptor Mas, thereby providing a protective role in CVD. More recently, another ACE2 metabolite, Ang-(1–9) [angiotensin-(1–9)], has been reported to be a biologically active peptide within the counter-regulatory axis of the RAS. The present review will discuss the role of the counter-regulatory RAS peptides Ang-(1–7) and Ang-(1–9) in the cardiovascular system, with a focus on their effects in remodelling of the heart and vasculature.

scholarly journals Angiotensin II Receptor Type 1-Mediated Vascular Oxidative Stress and Proinflammatory Gene Expression in Aldosterone-Induced Hypertension: The Possible Role of Local Renin-Angiotensin System

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1688-1696 ◽  
Author(s):  
Yuki Hirono ◽  
Takanobu Yoshimoto ◽  
Noriko Suzuki ◽  
Toru Sugiyama ◽  
Maya Sakurada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Renin Angiotensin System ◽  
Aortic Tissue ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin

Recently, aldosterone has been shown to activate local renin-angiotensin system in vitro. To elucidate the potential role of local renin-angiotensin system in aldosterone-induced cardiovascular injury, we investigated the effects of selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL), angiotensin (Ang) II type 1 receptor antagonist candesartan (ARB), and superoxide dismutase mimetic tempol (TEM) on the development of hypertension, vascular injury, oxidative stress, and inflammatory-related gene expression in aldosterone-treated hypertensive rats. The increased systolic blood pressure and vascular inflammatory changes were attenuated by cotreatment either with EPL, ARB, or TEM. Aldosterone increased angiotensin-converting enzyme expression in the aortic tissue; its effects were blocked by EPL but not by ARB or TEM. Aldosterone also increased Ang II contents in the aortic tissue in the presence of low circulating Ang II concentrations. Aldosterone induced expression of various inflammatory-related genes, whose effects were abolished by EPL, whereas the inhibitory effects of ARB and TEM varied depending on the gene. Aldosterone caused greater accumulation of the oxidant stress marker 4-hydroxy-2-neonenal in the endothelium; its effect was abolished by EPL, ARB, or TEM. Aldosterone increased mRNA levels of reduced nicotinamide adenine dinucleotide phosphate oxidase components; their effect was abolished by EPL, whereas ARB and TEM decreased only the p47phox mRNA level but not that of p22phox or gp91phox. The present findings suggest that the Ang II-dependent pathway resulting from vascular angiotensin-converting enzyme up-regulation and Ang II-independent pathway are both involved in the underlying mechanisms resulting in the development of hypertension, vascular inflammation, and oxidative stress induced by aldosterone.

Role of genetic variability in the renin-angiotensin system in diabetic and nondiabetic renal disease

2001 ◽  
Vol 21 (6) ◽  
pp. 580-592 ◽  
Author(s):  
Arnold Boonstra ◽  
Dick de Zeeuw ◽  
Paul E. de Jong ◽  
Gerjan Navis
Keyword(s):  
Genetic Variability ◽  
Renal Disease ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

A Review of Angiotensin Receptor Blocker-based Therapies at all Levels of Cardiovascular Risk

2011 ◽  
Vol 7 (4) ◽  
pp. 254 ◽  
Author(s):  
Giuliano Tocci ◽  
Lorenzo Castello ◽  
Massimo Volpe ◽  
◽  
◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ventricular Hypertrophy ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Clinical Settings ◽  
Angiotensin Ii Receptor ◽  
Angiotensin System ◽  
Receptor Blockers ◽  
Artery Disease

The renin–angiotensin system (RAS) has a key role in the maintenance of cardiovascular homeostasis, and water and electrolyte metabolism in healthy subjects, as well as in several diseases including hypertension, left ventricular hypertrophy and dysfunction, coronary artery disease, renal disease and congestive heart failure. These conditions are all characterised by abnormal production and activity of angiotensin II, which represents the final effector of the RAS. Over the last few decades, accumulating evidence has demonstrated that antihypertensive therapy based on angiotensin II receptor blockers (ARBs) has a major role in the selective antagonism of the main pathological activities of angiotensin II. Significant efforts have been made to demonstrate that blocking the angiotensin II receptor type 1 (AT1) subtype receptors through ARB-based therapy results in proven benefits in different clinical settings. In this review, we discuss the main benefits of antihypertensive strategies based on ARBs in terms of their efficacy, safety and tolerability.

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