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Sample records for dual renin-angiotensin system

  1. Dual Blockade of the Renin-angiotensin-aldosterone System in Type 2 Diabetic Kidney Disease

    PubMed Central

    Feng, Yan-Huan; Fu, Ping

    2016-01-01

    Objective: To examine the efficacy and safety of dual blockade of the renin-angiotensin-aldosterone system (RAAS) among patients with type 2 diabetic kidney disease. Data Sources: We searched the major literature repositories, including the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE, for randomized clinical trials published between January 1990 and October 2015 that compared the efficacy and safety of the use of dual blockade of the RAAS versus the use of monotherapy, without applying any language restrictions. Keywords for the searches included “diabetic nephropathy,” “chronic kidney disease,” “chronic renal insufficiency,” “diabetes mellitus,” “dual therapy,” “combined therapy,” “dual blockade,” “renin-angiotensin system,” “angiotensin-converting enzyme inhibitor,” “angiotensin-receptor blocker,” “aldosterone blockade,” “selective aldosterone blockade,” “renin inhibitor,” “direct renin inhibitor,” “mineralocorticoid receptor blocker,” etc. Study Selection: The selected articles were carefully reviewed. We excluded randomized clinical trials in which the kidney damage of patients was related to diseases other than diabetes mellitus. Results: Combination treatment with an angiotensin-converting enzyme inhibitor supplemented by an angiotensin II receptor blocking agent is expected to provide a more complete blockade of the RAAS and a better control of hypertension. However, existing literature has presented mixed results, in particular, related to patient safety. In view of this, we conducted a comprehensive literature review in order to explain the rationale for dual blockade of the RAAS, and to discuss the pros and cons. Conclusions: Despite the negative results of some recent large-scale studies, it may be immature to declare that the dual blockade is a failure because of the complex nature of the RAAS surrounding its diversified functions and utility. Further trials are warranted

  2. Reproduction and the renin-angiotensin system

    NASA Technical Reports Server (NTRS)

    Ganong, W. F.

    1995-01-01

    A unique aspect of the circulating renin-angiotensin system and the many independent tissue renin-angiotensin systems is their interactions at multiple levels with reproduction. These interactions, which have received relatively little attention, include effects of estrogens and possibly androgens on hepatic and renal angiotensinogen mRNA; effects of androgens on the Ren-2 gene and salivary renin in mice; the prorenin surge that occurs with but outlasts the LH surge during the menstrual cycle; the inhibitory effects of estrogens on thirst and water intake; the tissue renin-angiotensin systems in the brain, the anterior pituitary, and the ovaries and testes, that is, in all the components of the hypothalamo-pituitary-gonadal axis; the presence of some components of the renin-angiotensin system in the uterus and the fetoplacental unit; and the possible relation of renin and angiotensin to ovulation and fetal well-being. These interactions are described and their significance considered in this short review.

  3. Optimal antagonism of the Renin-Angiotensin-aldosterone system: do we need dual or triple therapy?

    PubMed

    Werner, Christian; Pöss, Janine; Böhm, Michael

    2010-07-01

    The cardiovascular and cardiorenal disease continuum comprises the transition from cardiovascular risk factors to endothelial dysfunction and atherosclerosis, to clinical complications such as myocardial infarction (MI) and stroke, to the development of persistent target-organ damage and, ultimately, to chronic congestive heart failure (CHF), end-stage renal disease or premature death. The renin-angiotensin-aldosterone system (RAAS) is involved in all steps along this pathway, and RAAS blockade with ACE inhibitors or angiotensin AT(1)-receptor antagonists (angiotensin receptor blockers; ARBs) has turned out to be beneficial for patient outcomes throughout the disease continuum. Both ACE inhibitors and ARBs can prevent or reverse endothelial dysfunction and atherosclerosis, thereby reducing the risk of cardiovascular events. These drugs have further been shown to reduce end-organ damage in the heart, kidneys and brain. Aldosterone antagonists such as spironolactone and eplerenone are increasingly recognized as a third class of RAAS inhibitor with potent risk-reducing properties, especially but not solely with respect to the inhibition of cardiac remodelling and the possible prevention of heart failure. In secondary prevention, head-to-head comparisons of ACE inhibitors and ARBs, such as the recent ONTARGET study, provided evidence that, in addition to better tolerability, ARBs are non-inferior to ACE inhibitors in the prevention of clinical endpoints such as MI and stroke in cardiovascular high-risk patients. However, the combination of both ramipril and telmisartan at the maximally tolerated dosage achieved no further benefits and was associated with more adverse events such as symptomatic hypotension and renal dysfunction. In acute MI complicated by heart failure, the VALIANT trial has shown similar effects of ACE inhibition with captopril and ARB treatment with valsartan, but dual RAAS blockade did not further reduce events. In CHF, meta-analyses of RESOLVD, Val

  4. The Renal Renin-Angiotensin System

    ERIC Educational Resources Information Center

    Harrison-Bernard, Lisa M.

    2009-01-01

    The renin-angiotensin system (RAS) is a critical regulator of sodium balance, extracellular fluid volume, vascular resistance, and, ultimately, arterial blood pressure. In the kidney, angiotensin II exerts its effects to conserve salt and water through a combination of the hemodynamic control of renal blood flow and glomerular filtration rate and…

  5. Dual renin-angiotensin system inhibition for prevention of renal and cardiovascular events: do the latest trials challenge existing evidence?

    PubMed Central

    2013-01-01

    Circulatory and tissue renin-angiotensin systems (RAS) play a central role in cardiovascular (CV) and renal pathophysiology, making RAS inhibition a logical therapeutic approach in the prevention of CV and renal disease in patients with hypertension. The cardio- and renoprotective effects observed with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) monotherapy, together with the availability of a direct renin inhibitor (DRI), led to the investigation of the potential benefits of dual RAS inhibition. In small studies, ARB and ACE inhibitor combinations were shown to be beneficial in patients with CV or renal disease, with improvement in surrogate markers. However, in larger outcome trials, involving combinations of ACE inhibitors, ARBs or DRIs, dual RAS inhibition did not show reduction in mortality in patients with diabetes, heart failure, coronary heart disease or after myocardial infarction, and was in fact, associated with increased harm. A recent meta-analysis of all major trials conducted over the past 22 years involving dual RAS inhibition has clearly shown that the risk-benefit ratio argues against the use of dual RAS inhibition. Hence, the recent evidence clearly advocates against the use of dual RAS inhibition, and single RAS inhibition appears to be the most suitable approach to controlling blood pressure and improving patient outcomes. PMID:23866091

  6. Dual inhibition of renin-angiotensin-aldosterone system and endothelin-1 in treatment of chronic kidney disease.

    PubMed

    Komers, Radko; Plotkin, Horacio

    2016-05-15

    Inhibition of the renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in treatment of chronic kidney diseases (CKD). However, reversal of the course of CKD or at least long-term stabilization of renal function are often difficult to achieve, and many patients still progress to end-stage renal disease. New treatments are needed to enhance protective actions of RAAS inhibitors (RAASis), such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and improve prognosis in CKD patients. Inhibition of endothelin (ET) system in combination with established RAASis may represent such an approach. There are complex interactions between both systems and similarities in their renal physiological and pathophysiological actions that provide theoretical rationale for combined inhibition. This view is supported by some experimental studies in models of both diabetic and nondiabetic CKD showing that a combination of RAASis with ET receptor antagonists (ERAs) ameliorate proteinuria, renal structural changes, and molecular markers of glomerulosclerosis, renal fibrosis, or inflammation more effectively than RAASis or ERAs alone. Practically all clinical studies exploring the effects of RAASis and ERAs combination in nephroprotection have thus far applied add-on designs, in which an ERA is added to baseline treatment with ACEIs or ARBs. These studies, conducted mostly in patients with diabetic nephropathy, have shown that ERAs effectively reduce residual proteinuria in patients with baseline RAASis treatment. Long-term studies are currently being conducted to determine whether promising antiproteinuric effects of the dual blockade will be translated in long-term nephroprotection with acceptable safety profile. PMID:27009050

  7. Dual inhibition of renin-angiotensin-aldosterone system and endothelin-1 in treatment of chronic kidney disease

    PubMed Central

    Plotkin, Horacio

    2016-01-01

    Inhibition of the renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in treatment of chronic kidney diseases (CKD). However, reversal of the course of CKD or at least long-term stabilization of renal function are often difficult to achieve, and many patients still progress to end-stage renal disease. New treatments are needed to enhance protective actions of RAAS inhibitors (RAASis), such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and improve prognosis in CKD patients. Inhibition of endothelin (ET) system in combination with established RAASis may represent such an approach. There are complex interactions between both systems and similarities in their renal physiological and pathophysiological actions that provide theoretical rationale for combined inhibition. This view is supported by some experimental studies in models of both diabetic and nondiabetic CKD showing that a combination of RAASis with ET receptor antagonists (ERAs) ameliorate proteinuria, renal structural changes, and molecular markers of glomerulosclerosis, renal fibrosis, or inflammation more effectively than RAASis or ERAs alone. Practically all clinical studies exploring the effects of RAASis and ERAs combination in nephroprotection have thus far applied add-on designs, in which an ERA is added to baseline treatment with ACEIs or ARBs. These studies, conducted mostly in patients with diabetic nephropathy, have shown that ERAs effectively reduce residual proteinuria in patients with baseline RAASis treatment. Long-term studies are currently being conducted to determine whether promising antiproteinuric effects of the dual blockade will be translated in long-term nephroprotection with acceptable safety profile. PMID:27009050

  8. Classical Renin-Angiotensin System in Kidney Physiology

    PubMed Central

    Sparks, Matthew A.; Crowley, Steven D.; Gurley, Susan B.; Mirotsou, Maria; Coffman, Thomas M.

    2014-01-01

    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, cardio-vascular 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. PMID:24944035

  9. Some Comparative Aspects of the Renin-Angiotensin System.

    ERIC Educational Resources Information Center

    Malvin, Richard L.

    1984-01-01

    The renin-angiotensin system (RAS) maintains salt and water balance. Discusses functions of the RAS as defined in mammalian species, considering how the system arose and what its original function was. Also discusses where some of the changes occurred in the system (and why) as well as other topics. (JN)

  10. Effect of renin-angiotensin system on sodium intake.

    PubMed Central

    Chiaraviglio, E

    1976-01-01

    1. Water and saline intake was measured in rats depleted of Na by I.P. dialysis. Na intake was prevented 180 min but not 60-90 min after bilateral nephrectomy. Unilateral nephrectomy as well as ureteral ligature had no effect on Na intake. 2. Renin (3u.) injected I.P. re-established the Na appetite abolished by nephrectomy. 3. Angiotensin I (5 ng) or II (5-40 ng) injected into the 3rd ventricle, also restored the Na intake and this effect was dose-dependent. 4. The angiotensin converting-enzyme inhibitor Sq 20,881 (1 mg/kg) inhibited the effect of AI but not that of AII in restoring Na intake. 5. It is concluded that the kidneys might play a role in the regulation of Na intake through the renin-angiotensin system. PMID:1255521

  11. African Americans, hypertension and the renin angiotensin system

    PubMed Central

    Williams, Sandra F; Nicholas, Susanne B; Vaziri, Nosratola D; Norris, Keith C

    2014-01-01

    African Americans have exceptionally high rates of hypertension and hypertension related complications. It is commonly reported that the blood pressure lowering efficacy of renin angiotensin system (RAS) inhibitors is attenuated in African Americans due to a greater likelihood of having a low renin profile. Therefore these agents are often not recommended as initial therapy in African Americans with hypertension. However, the high prevalence of comorbid conditions, such as diabetes, cardiovascular and chronic kidney disease makes treatment with RAS inhibitors more compelling. Despite lower circulating renin levels and a less significant fall in blood pressure in response to RAS inhibitors in African Americans, numerous clinical trials support the efficacy of RAS inhibitors to improve clinical outcomes in this population, especially in those with hypertension and risk factors for cardiovascular and related diseases. Here, we discuss the rationale of RAS blockade as part of a comprehensive approach to attenuate the high rates of premature morbidity and mortality associated with hypertension among African Americans. PMID:25276290

  12. The importance of the renin-angiotensin system in normal cardiovascular homeostasis

    NASA Technical Reports Server (NTRS)

    Haber, E.

    1975-01-01

    Studies were carried out on adult mongrel dogs (20 to 30 kilograms) to investigate the importance of the renin-angiotensin system. Results indicate that the renin-angiotensin system plays a major role in the maintenance of circulatory homeostasis when extracellular fluid volume is depleted. It was also found that angiotensin II concentration, in addition to renal perfusion pressure, is a factor in the regulation of renin release.

  13. The Adipose Renin-Angiotensin System Modulates Systemic Markers of Insulin Sensitivity and Activates the Intrarenal Renin-Angiotensin System

    DOE PAGESBeta

    Kim, Suyeon; Soltani-Bejnood, Morvarid; Quignard-Boulange, Annie; Massiera, Florence; Teboul, Michele; Ailhaud, Gerard; Kim, Jung Han; Moustaid-Moussa, Naima; Voy, Brynn H.

    2006-01-01

    Background . The adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass and may also impact systemic functions such as blood pressure and metabolism. Methods and results . A panel of mouse models including mice lacking angiotensinogen, Agt ( Agt -KO), mice expressing Agt solely in adipose tissue (aP2- Agt/Agt -KO), and mice overexpressing Agt in adipose tissue (aP2- Agt ) was studied. Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin, and resistin were significantly decreased in Agt -KO mice, while plasma adiponectin levels were increased. aP2- Agt mice exhibited increased adipositymore » and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also elevated in kidney of aP2- Agt mice. Conclusion . These findings demonstrate that alterations in adipose RAS activity significantly impact both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.« less

  14. Activation of the Renin-Angiotensin System Promotes Colitis Development

    PubMed Central

    Shi, Yongyan; Liu, Tianjing; He, Lei; Dougherty, Urszula; Chen, Li; Adhikari, Sarbani; Alpert, Lindsay; Zhou, Guolin; Liu, Weicheng; Wang, Jiaolong; Deb, Dilip K.; Hart, John; Liu, Shu Q.; Kwon, John; Pekow, Joel; Rubin, David T.; Zhao, Qun; Bissonnette, Marc; Li, Yan Chun

    2016-01-01

    The renin-angiotensin system (RAS) plays pathogenic roles in renal and cardiovascular disorders, but whether it is involved in colitis is unclear. Here we show that RenTgMK mice that overexpress active renin from the liver developed more severe colitis than wild-type controls. More than 50% RenTgMK mice died whereas all wild-type mice recovered. RenTgMK mice exhibited more robust mucosal TH17 and TH1/TH17 responses and more profound colonic epithelial cell apoptosis compared to wild-type controls. Treatment with aliskiren (a renin inhibitor), but not hydralazine (a smooth muscle relaxant), ameliorated colitis in RenTgMK mice, although both drugs normalized blood pressure. Chronic infusion of angiotensin II into wild-type mice mimicked the severe colitic phenotype of RenTgMK mice, and treatment with losartan [an angiotensin type 1 receptor blocker (ARB)] ameliorated colitis in wild-type mice, confirming a colitogenic role for the endogenous RAS. In human biopsies, pro-inflammatory cytokines were suppressed in patients with inflammatory bowel disease who were on ARB therapy compared to patients not receiving ARB therapy. These observations demonstrate that activation of the RAS promotes colitis in a blood pressure independent manner. Angiotensin II appears to drive colonic mucosal inflammation by promoting intestinal epithelial cell apoptosis and mucosal TH17 responses in colitis development. PMID:27271344

  15. The adipose renin-angiotensin system modulates sysemic markers of insulin sensitivity activates the intrarenal renin-angiotensin system

    SciTech Connect

    Kim, Suyeon; Soltani-Bejnood, Morvarid; Quignard-Boulange, Annie; Massiera, Florence; Teboul, Michele; Ailhaud, Gerard; Kim, Jung; Moustaid-Moussa, Naima; Voy, Brynn H

    2006-07-01

    BACKGROUND: A growing body of data provides increasing evidence that the adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass. Beyond its paracrine actions within adipose tissue, adipocyte-derived angiotensin II (Ang II) may also impact systemic functions such as blood pressure and metabolism. METHODS AND RESULTS: We used a genetic approach to manipulate adipose RAS activity in mice and then study the consequences on metabolic parameters and on feedback regulation of the RAS. The models included deletion of the angiotensinogen (Agt) gene (Agt-KO), its expression solely in adipose tissue under the control of an adipocyte-specific promoter (aP2-Agt/ Agt-KO), and overexpression in adipose tissue of wild type mice (aP2-Agt). Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin and resistin were significantly decreased in Agt-KO mice, while plasma adiponectin levels were increased. Overexpression of Agt in adipose tissue resulted in increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also markedly elevated in kidney of aP2-Agt mice, suggesting that hypertension in these animals may be in part due to stimulation of the intrarenal RAS. CONCLUSIONS: Taken together, the results from this study demonstrate that alterations in adipose RAS activity significantly alter both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.

  16. Brain renin-angiotensin system and dopaminergic cell vulnerability

    PubMed Central

    Labandeira-García, Jose L.; Garrido-Gil, Pablo; Rodriguez-Pallares, Jannette; Valenzuela, Rita; Borrajo, Ana; Rodríguez-Perez, Ana I.

    2014-01-01

    Although the renin-angiotensin system (RAS) was classically considered as a circulating system that regulates blood pressure, many tissues are now known to have a local RAS. Angiotensin, via type 1 receptors, is a major activator of the NADPH-oxidase complex, which mediates several key events in oxidative stress (OS) and inflammatory processes involved in the pathogenesis of major aging-related diseases. Several studies have demonstrated the presence of RAS components in the basal ganglia, and particularly in the nigrostriatal system. In the nigrostriatal system, RAS hyperactivation, via NADPH-oxidase complex activation, exacerbates OS and the microglial inflammatory response and contributes to progression of dopaminergic degeneration, which is inhibited by angiotensin receptor blockers and angiotensin converting enzyme (ACE) inhibitors. Several factors may induce an increase in RAS activity in the dopaminergic system. A decrease in dopaminergic activity induces compensatory upregulation of local RAS function in both dopaminergic neurons and glia. In addition to its role as an essential neurotransmitter, dopamine may also modulate microglial inflammatory responses and neuronal OS via RAS. Important counterregulatory interactions between angiotensin and dopamine have also been observed in several peripheral tissues. Neurotoxins and proinflammatory factors may also act on astrocytes to induce an increase in RAS activity, either independently of or before the loss of dopamine. Consistent with a major role of RAS in dopaminergic vulnerability, increased RAS activity has been observed in the nigra of animal models of aging, menopause and chronic cerebral hypoperfusion, which also showed higher dopaminergic vulnerability. Manipulation of the brain RAS may constitute an effective neuroprotective strategy against dopaminergic vulnerability and progression of Parkinson’s disease. PMID:25071471

  17. Nonclassical renin-angiotensin system and renal function.

    PubMed

    Chappell, Mark C

    2012-10-01

    The renin-angiotensin system (RAS) constitutes one of the most important hormonal systems in the physiological regulation of blood pressure through renal and nonrenal mechanisms. Indeed, dysregulation of the RAS is considered a major factor in the development of cardiovascular pathologies, including kidney injury, and blockade of this system by the inhibition of angiotensin converting enzyme (ACE) or blockade of the angiotensin type 1 receptor (AT1R) by selective antagonists constitutes an effective therapeutic regimen. It is now apparent with the identification of multiple components of the RAS within the kidney and other tissues that the system is actually composed of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS can be defined as the ACE-Ang II-AT1R axis that promotes vasoconstriction, water intake, sodium retention, and other mechanisms to maintain blood pressure, as well as increase oxidative stress, fibrosis, cellular growth, and inflammation in pathological conditions. In contrast, the nonclassical RAS composed primarily of the AngII/Ang III-AT2R pathway and the ACE2-Ang-(1-7)-AT7R axis generally opposes the actions of a stimulated Ang II-AT1R axis through an increase in nitric oxide and prostaglandins and mediates vasodilation, natriuresis, diuresis, and reduced oxidative stress. Moreover, increasing evidence suggests that these non-classical RAS components contribute to the therapeutic blockade of the classical system to reduce blood pressure and attenuate various indices of renal injury, as well as contribute to normal renal function. PMID:23720263

  18. Inflammation, oxidative stress and renin angiotensin system in atherosclerosis

    PubMed Central

    Husain, Kazim; Hernandez, Wilfredo; Ansari, Rais A; Ferder, Leon

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin II (Ang II) and a decrease in nitric oxide. The renin-angiotensin system (RAS), and its primary mediator Ang II, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors (angiotensin-converting enzyme inhibitors)], Ang II receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in ApoE-deficient atherosclerotic mice. PMID:26322175

  19. Renin-angiotensin system gene polymorphisms and endometrial cancer.

    PubMed

    Pringle, Kirsty G; Delforce, Sarah J; Wang, Yu; Ashton, Katie A; Proietto, Anthony; Otton, Geoffrey; Blackwell, C Caroline; Scott, Rodney J; Lumbers, Eugenie R

    2016-05-01

    Endometrial cancer (EC) is the most common gynaecological malignancy and its incidence is increasing. Dysregulation of the endometrial renin-angiotensin system (RAS) could predispose to EC; therefore, we studied the prevalence of RAS single nucleotide polymorphisms (SNPs) in Australian women with EC. SNPs assessed were AGT M235T (rs699); AGTR1 A1166C (rs5186); ACE A240T and T93C (rs4291, rs4292) and ATP6AP2 (rs2968915). They were identified using TaqMan SNP Genotyping Assays. The C allele of the AGTR1 SNP (rs5186) was more prevalent in women with EC (odds ratio (OR) 1.7, 95% confidence interval (CI) (1.2-2.3), P=0.002). The CC genotype of this SNP is associated with upregulation of the angiotensin II type 1 receptor (AGTR1). The G allele of AGT rs699, which is associated with higher angiotensinogen (AGT) levels, was less prevalent in women with EC (OR 0.54, 95% CI (0.39-0.74), P<0.001) compared with controls. AGT and AGT formed by removal of angiotensin I (des(Ang I)AGT) are both anti-angiogenic. In women with EC who had had hormone replacement therapy (HRT), the prevalence of the AGTR1 SNP (rs5186) and the ACE SNPs (rs4291 and rs4292) was greater than in women who had no record of HRT; SNP rs4291 is associated with increased plasma ACE activity. These data suggest there is an interaction between genotype, oestrogen replacement therapy and EC. In conclusion, the prevalence of two SNPs that enhance RAS activity was different in women with EC compared with healthy controls. These genetic factors may interact with obesity and hyperoestrogenism, predisposing ageing, obese women to EC. PMID:27068935

  20. Vascular inflammation and the renin-angiotensin system.

    PubMed

    Brasier, Allan R; Recinos, Adrian; Eledrisi, Mohsen S

    2002-08-01

    It is now well established that vascular inflammation is an independent risk factor for the development of atherosclerosis. In otherwise healthy patients, chronic elevations of circulating interleukin-6 or its biomarkers are predictors for increased risk in the development and progression of ischemic heart disease. Although multifactorial in etiology, vascular inflammation produces atherosclerosis by the continuous recruitment of circulating monocytes into the vessel wall and by contributing to an oxidant-rich inflammatory milieu that induces phenotypic changes in resident (noninflammatory) cells. In addition, the renin-angiotensin system (RAS) has important modulatory activities in the atherogenic process. Recent work has shown that angiotensin II (Ang II) has significant proinflammatory actions in the vascular wall, inducing the production of reactive oxygen species, inflammatory cytokines, and adhesion molecules. These latter effects on gene expression are mediated, at least in part, through the cytoplasmic nuclear factor-kappaB transcription factor. Through these actions, Ang II augments vascular inflammation, induces endothelial dysfunction, and, in so doing, enhances the atherogenic process. Our recent studies have defined a molecular mechanism for a biological positive-feedback loop that explains how vascular inflammation can be self-sustaining through upregulation of the vessel wall Ang II tone. Ang II produced locally by the inflamed vessel induces the synthesis and secretion of interleukin-6, a cytokine that induces synthesis of angiotensinogen in the liver through a janus kinase (JAK)/signal transducer and activator of transcription (STAT)-3 pathway. Enhanced angiotensinogen production, in turn, supplies more substrate to the activated vascular RAS, where locally produced Ang II synergizes with oxidized lipid to perpetuate atherosclerotic vascular inflammation. These observations suggest that one mechanism by which RAS antagonists prevent atherosclerosis

  1. Role of the Collecting Duct Renin Angiotensin System in Regulation of Blood Pressure and Renal Function.

    PubMed

    Ramkumar, Nirupama; Kohan, Donald E

    2016-04-01

    Recent evidence suggests that the renal tubular renin angiotensin system regulates urinary Na(+) and water excretion and blood pressure. Three key components of the tubular renin angiotensin system, namely renin, prorenin receptor, and angiotensin-II type 1 receptor, are localized to the collecting duct. This system may modulate collecting duct Na(+) and water reabsorption via angiotensin-II-dependent and angiotensin-II-independent pathways. Further, the system may be of greatest relevance in hypertensive states and particularly those characterized by high circulating angiotensin-II. In this review, we summarize the current knowledge on the synthesis, regulation, and function of collecting duct-derived renin angiotensin system components and examine recent developments with regard to regulation of blood pressure and renal fluid and Na(+) excretion. PMID:26951246

  2. Inhibition of the renin-angiotensin system for lowering coronary artery disease risk.

    PubMed

    Sheppard, Richard J; Schiffrin, Ernesto L

    2013-04-01

    The renin-angiotensin system when activated exerts proliferative and pro-inflammatory actions and thereby contributes to progression of atherosclerosis, including that occurring in the coronary arteries. It thus contributes as well to coronary artery disease (CAD). Several clinical trials have examined effects of renin-angiotensin system inhibition for primary and secondary prevention of coronary heart disease. These include important trials such as HOPE, EUROPA and PEACE using angiotensin converting enzyme inhibitors, VALIANT, OPTIMAAL and TRANSCEND using angiotensin receptor blockers, and the ongoing TOPCAT study in patients with preserved ejection fraction heart failure, many of who also have coronary artery disease. Data are unavailable as yet of effects of either direct renin inhibitors or the new angiotensin receptor/neprilysin inhibitor agents. Today, inhibition of the renin-angiotensin system is standard-of-care therapy for lowering cardiovascular risk in secondary prevention in high cardiovascular risk subjects. PMID:23523606

  3. The Relevance of the Renin-Angiotensin System in the Development of Drugs to Combat Preeclampsia

    PubMed Central

    Takeda, Satoru; Koya, Daisuke; Kanasaki, Keizo

    2015-01-01

    Preeclampsia is a hypertensive disorder that occurs during pregnancy. It has an unknown etiology and affects approximately 5–8% of pregnancies worldwide. The pathophysiology of preeclampsia is not yet known, and preeclampsia has been called “a disease of theories.” The central symptom of preeclampsia is hypertension. However, the etiology of the hypertension is unknown. In this review, we analyze the molecular mechanisms of preeclampsia with a particular focus on the pathogenesis of the hypertension in preeclampsia and its association with the renin-angiotensin system. In addition, we propose potential alternative strategies to target the renin-angiotensin system, which is enhanced during pregnancy. PMID:26000015

  4. New drug therapies interfering with the renin-angiotensin-aldosterone system for resistant hypertension.

    PubMed

    Monge, Matthieu; Lorthioir, Aurélien; Bobrie, Guillaume; Azizi, Michel

    2013-12-01

    There is a persistent need for the development of new antihypertensive drugs, because the control of blood pressure is still not achievable in a significant proportion of hypertensive patients. Since the approval in 2007 of aliskiren, no other new antihypertensive based on new mechanism(s) of action have been approved. In fact, the development of promising novel drugs has been stopped for safety, efficacy or marketing reasons. Despite these difficulties, the pipeline is not dry and different new antihypertensive strategies targeting the renin-angiotensin-aldosterone pathway, are in clinical development stage. The dual angiotensin II receptor-neprilysin inhibitor LCZ696, a single molecule synthetized by cocrystallisation of valsartan and the neprilysin inhibitor prodrug AHU377 is in development for resistant hypertension and for heart failure. Daglutril is a dual neprylisin-endothelin converting enzyme inhibitor which was shown to decrease BP in patients with type 2 diabetic nephropathy. Aldosterone synthase inhibitors and the third and fourth generation non-steroidal dihydropyridine based mineralocorticoid receptors blockers are new ways to target the multiple noxious effects of aldosterone in the kidney, vessels and heart. Centrally acting aminopeptidase A inhibitors block brain angiotensin III formation, one of the main effector peptides of the brain renin angiotensin system. However, a long time will be still necessary to evaluate extensively the efficacy and safety of these new approaches. In the mean time, using appropriate and personalized daily doses of available drugs, decreasing physician inertia, improving treatment adherence, improving access to healthcare and reducing treatment costs remain major objectives to reduce the incidence of resistant hypertension. PMID:24222656

  5. Azilsartan, aliskiren, and combination antihypertensives utilizing renin-angiotensin-aldosterone system antagonists.

    PubMed

    Lanier, Gregg; Sankholkar, Kedar; Aronow, Wilbert S

    2014-01-01

    Health care providers managing hypertension (HTN) have a large selection of pharmacologic agents to choose from, including several different classes of drugs and many similar drugs within each class. Antagonism of the renin-angiotensin-aldosterone system has been shown to be very effective for HTN, especially in patients with cardiovascular disease, diabetes, and heart failure. Within this group, there have been 2 new agents recently introduced to the US market and approved by the Food and Drug Administration. It is important for the HTN specialist to be familiar with the merits of these 2 drugs: the angiotensin receptor blocker Edarbi (azilsartan) and the renin inhibitor Tekturna (aliskiren). Additionally, there have been several new, fixed-dose combination antihypertensives introduced to the market since 2006 that use a renin-angiotensin-aldosterone antagonist. Seven of these combine 2 drugs together in a single pill: Edarbyclor (azilsartan/chlorthalidone), Exforge (amlodipine/valsartan), Azor (olmesartan/amlodipine), Twynsta (amlodipine/telmisartan), Tekturna HCT [aliskiren/hydrochlorothiazide (HCTZ)], Valturna (aliskiren/valsartan), Tekamlo (aliskiren/amlodipine). Three triple-drug combination medications have also been introduced recently: Exforge HCT (amlodipine/valsartan/HCTZ), Tribenzor (olmesartan/amlodipine/HCTZ), and Amturnide (aliskiren/amlodipine/hydrocholorothiazide). This review will summarize the trial data and important pharmacologic merits of these 2 new renin-angiotensin-aldosterone antagonists and the advantages of initiating treatment with one of the new fixed-dose, combination drugs approved over the last 5 years. PMID:22975662

  6. Renin-Angiotensin-Aldosterone System Blockade in Diabetic Nephropathy. Present Evidences

    PubMed Central

    Lozano-Maneiro, Luz; Puente-García, Adriana

    2015-01-01

    Diabetic Kidney Disease (DKD) is the leading cause of chronic kidney disease in developed countries and its prevalence has increased dramatically in the past few decades. These patients are at an increased risk for premature death, cardiovascular disease, and other severe illnesses that result in frequent hospitalizations and increased health-care utilization. Although much progress has been made in slowing the progression of diabetic nephropathy, renal dysfunction and the development of end-stage renal disease remain major concerns in diabetes. Dysregulation of the renin-angiotensin-aldosterone system (RAAS) results in progressive renal damage. RAAS blockade is the cornerstone of treatment of DKD, with proven efficacy in many arenas. The theoretically-attractive option of combining these medications that target different points in the pathway, potentially offering a more complete RAAS blockade, has also been tested in clinical trials, but long-term outcomes were disappointing. This review examines the “state of play” for RAAS blockade in DKD, dual blockade of various combinations, and a perspective on its benefits and potential risks. PMID:26569322

  7. The Renin-Angiotensin System Modulates Inflammatory Processes in Atherosclerosis: Evidence from Basic Research and Clinical Studies

    PubMed Central

    Montecucco, Fabrizio; Pende, Aldo; Mach, François

    2009-01-01

    Recent evidence shows that the renin-angiotensin system is a crucial player in atherosclerotic processes. The regulation of arterial blood pressure was considered from its first description of the main mechanism involved. Vasoconstriction (mediated by angiotensin II) and salt and water retention (mainly due to aldosterone) were classically considered as pivotal proatherosclerotic activities. However, basic research and animal studies strongly support angiotensin II as a proinflammatory mediator, which directly induces atherosclerotic plaque development and heart remodeling. Furthermore, angiotensin II induces proatherosclerotic cytokine and chemokine secretion and increases endothelial dysfunction. Accordingly, the pharmacological inhibition of the renin-angiotensin system improves prognosis of patients with cardiovascular disease even in settings of normal baseline blood pressure. In the present review, we focused on angiotensin-convertingenzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and renin inhibitors to update the direct activities of the renin-angiotensin system in inflammatory processes governing atherosclerosis. PMID:19390623

  8. Renin-angiotensin-aldosterone-kinin system influences on diabetic vascular disease and cardiomyopathy.

    PubMed

    Flack, J M; Hamaty, M; Staffileno, B A

    1998-01-01

    Diabetes mellitus is associated with an inordinately high risk of virtually all manifestations of cardiovascular-renal disease including atherosclerotic coronary and peripheral vascular disease, congestive heart failure, stroke, nephropathy, and cardiomyopathy unassociated with coronary heart disease. Abnormalities in the renin-angiotensin-aldosterone-kinin (RAAK) cascade have been implicated in the pathogenesis and clinical expression of these cardiovascular-renal sequelae. Thus, pharmacological modulation of the RAAK system is an attractive therapeutic target in diabetes mellitus. Indeed, emerging data from human clinical studies appear to confirm this thesis. PMID:9930381

  9. Transdermal contraception and the renin-angiotensin-aldosterone system in premenopausal women.

    PubMed

    Odutayo, Ayodele; Cherney, David; Miller, Judith; Ahmed, Sofia B; Lai, Vesta; Dunn, Sheila; Pun, Nicole; Moineddin, Rahim; Hladunewich, Michelle A

    2015-03-15

    The oral contraceptive pill (OCP) activates the renin-angiotensin-aldosterone system (RAAS) through first-pass hepatic metabolism. Although usually benign, RAAS activation may have detrimental effects on renal and hemodynamic function in some women. Since combined hormonal contraception with the transdermal patch (EVRA) does not undergo first-pass hepatic metabolism, we hypothesized that the RAAS response would be different from that of OCP subjects. Thirty-five nonsmoking, premenopausal women (15 control subjects, 10 OCP subjects, and 10 contraceptive patch subjects) without evidence of cardiovascular disease, renal disease, or diabetes were studied. Baseline angiotensinogen, renin, angiotensin II, aldosterone, and plasma renin activity were assessed along with hormonal and hemodynamic responses to simulated orthostatic stress using incremental lower body negative pressure (LBNP; -15, -25, and -40 mmHg). Baseline levels of angiotensinogen, angiotensin II, and plasma renin activity were significantly higher in OCP subjects compared with normotensive control and contraceptive patch subjects (P < 0.05), whereas aldosterone was significantly higher in OCP versus control subjects only (P < 0.05). Plasma renin levels were significantly lower at baseline in contraceptive patch subjects compared with normotensive control and OCP subjects (P < 0.05). In response to LBNP, increases in renin, angiotensin II, and aldosterone were attenuated in contraceptive patch subjects in conjunction with an exaggerated decline in mean arterial pressure (P < 0.05 vs. control and OCP subjects). The contraceptive patch in healthy premenopausal women is associated with an impaired ability to maintain blood pressure in response to LBNP, possibly due to insensitivity of the endogenous RAAS. Further evaluation may be beneficial in women with kidney disease. PMID:25587124

  10. Renin-angiotensin system in ventilator-induced diaphragmatic dysfunction: Potential protective role of Angiotensin (1-7).

    PubMed

    Sigurta', Anna; Zambelli, Vanessa; Bellani, Giacomo

    2016-09-01

    Ventilator-induced diaphragmatic dysfunction is a feared complication of mechanical ventilation that adversely affects the outcome of intensive care patients. Human and animal studies demonstrate atrophy and ultrastructural alteration of diaphragmatic muscular fibers attributable to increased oxidative stress, depression of the anabolic pathway regulated by Insulin-like growing factor 1 and increased proteolysis. The renin-angiotensin system, through its main peptide Angiotensin II, plays a major role in skeletal muscle diseases, mainly increasing oxidative stress and inducing insulin resistance, atrophy and fibrosis. Conversely, its counter-regulatory peptide Angiotensin (1-7) has a protective role in these processes. Recent data on rodent models show that renin-angiotensin system is activated after mechanical ventilation and that infusion of Angiotensin II induces diaphragmatic skeletal muscle atrophy. Given: (A) common pathways shared by ventilator-induced diaphragmatic dysfunction and skeletal muscle pathology induced by renin-angiotensin system, (B) evidences of an involvement of renin-angiotensin system in diaphragm atrophy and dysfunction, we hypothesize that renin-angiotensin system plays an important role in ventilator-induced diaphragmatic dysfunction, while Angiotensin (1-7) can have a protective effect on this pathological process. The activation of renin-angiotensin system in ventilator-induced diaphragmatic dysfunction can be demonstrated by quantification of its main components in the diaphragm of ventilated humans or animals. The infusion of Angiotensin (1-7) in an established rodent model of ventilator-induced diaphragmatic dysfunction can be used to test its potential protective role, that can be further confirmed with the infusion of Angiotensin (1-7) antagonists like A-779. Verifying this hypothesis can help in understanding the processes involved in ventilator-induced diaphragmatic dysfunction pathophysiology and open new possibilities for its

  11. Cholinergic signal activated renin angiotensin system associated with cardiovascular changes in the ovine fetus

    PubMed Central

    Geng, Chunsong; Mao, Caiping; Wu, Lei; Cheng, Yu; Liu, Rulu; Chen, Bingxin; Chen, Ling; Zhang, Lubo; Xu, Zhice

    2010-01-01

    Aim Cholinergic regulation is important in the control of cardiovascular and endocrine responses. The mechanisms behind cardiovascular responses induced by cholinergic activation are explored by studying hormonal systems, including renin-angiotensin and vasopressin (VP). Results In chronically prepared fetal sheep, intravenous infusion of the cholinergic agonist carbachol increased fetal systolic, diastolic, and mean arterial pressure accompanied with bradycardia at near-term. Although intravenous administration of carbachol had no effect on plasma VP concentrations, this agonist increased angiotensin I and angiotensin II levels in fetal plasma. Fetal blood values, including sodium, osmolality, nitric oxide, hemoglobin, and hematocrit were unchanged by intravenous carbachol. Conclusion Cholinergic activation by carbachol controls fetal blood pressure and heart rate in utero. An over-activated fetal renin-angiotensin-system (RAS) is associated with changes in vascular pressure following intravenous administration of carbachol, indicating that the cholinergic stimulation-mediated hormonal mechanism in the fetus might play a critical role in the regulation of cardiovascular homeostasis. PMID:19921993

  12. Angiotensin III: a physiological relevant peptide of the renin angiotensin system.

    PubMed

    Yugandhar, Vudhya G; Clark, Michelle A

    2013-08-01

    The renin angiotensin system (RAS) is a peptide hormone system that plays an important role in the pathophysiology of various diseases, including congestive heart failure, hypertension, myocardial infarction, and diabetic nephropathy. This has led researchers to focus extensively on this system, leading to the discovery of various peptides, peptidases, receptors and signal transduction mechanisms intrinsic to the RAS. Angiotensinogen (AGT), angiotensin (Ang) II, Ang III, Ang IV, and Ang-(1-7) are the main biologically active peptides of RAS. However, most of the available studies have focused on Ang II as the likely key peptide from the RAS that directly and indirectly regulates physiological functions leading to pathological conditions. However, data from recent studies suggest that Ang III may produce physiologically relevant effects that are similar to those produced by Ang II. Hence, this review focuses on Ang III and the myriad of physiological effects that it produces in the body. PMID:23692861

  13. Biomarkers of activation of renin-angiotensin-aldosterone system in heart failure: how useful, how feasible?

    PubMed

    Emdin, Michele; Fatini, Cinzia; Mirizzi, Gianluca; Poletti, Roberta; Borrelli, Chiara; Prontera, Concetta; Latini, Roberto; Passino, Claudio; Clerico, Aldo; Vergaro, Giuseppe

    2015-03-30

    Renin-angiotensin-aldosterone system (RAAS), participated by kidney, liver, vascular endothelium, and adrenal cortex, and counter-regulated by cardiac endocrine function, is a complex endocrine system regulating systemic functions, such as body salt and water homeostasis and vasomotion, in order to allow the accomplishment of physiological tasks, such as orthostasis, physical and emotional stimuli, and to react towards the hemorrhagic insult, in tight conjunction with other neurohormonal axes, namely the sympathetic nervous system, the endothelin and vasopressin systems. The systemic as well as the tissue RAAS are also dedicated to promote tissue remodeling, particularly relevant after damage, when chronic activation may configure as a maladaptive response, leading to fibrosis, hypertrophy and apoptosis, and organ dysfunction. RAAS activation is a fingerprint of systemic arterial hypertension, kidney dysfunction, vascular atherosclerotic disease, and is definitely an hallmark of heart failure, which rapidly shifts from organ disease to a disorder of neurohormonal regulatory systems. Chronic RAAS activation is an indirect or direct target of most effective pharmacological treatments in heart failure, such as beta-blockers, inhibitors of angiotensin converting enzyme, angiotensin receptor blockers, direct renin inhibitors, and mineralocorticoid receptor blockers. Biomarkers of RAAS activation are available, with different feasibility and accuracy, such as plasma renin activity, renin, angiotensin II, and aldosterone, which all accompany the increasing clinical severity of heart failure disease, and are well recognized prognostic factors, even in patients with optimal therapy. Polymorphisms influencing the expression and activity of RAAS pathways have been recognized as clinically relevant biomarkers, likely influencing either the individual clinical phenotype, or the response to drugs. This solid, growing evidence strongly suggests the rationale for the use of

  14. Effects of Renin-Angiotensin-Aldosterone System Blockade in Patients with End-Stage Renal Disease.

    PubMed

    Slomka, Teresa; Lennon, Emily S; Akbar, Hina; Gosmanova, Elvira O; Bhattacharya, Syamal K; Oliphant, Carrie S; Khouzam, Rami N

    2016-03-01

    Blockers of the renin-angiotensin-aldosterone system (RAAS), such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are routinely used in patients with chronic kidney disease because of their cardiovascular (CV) and renoprotective effects. However, there are no uniform recommendations about RAAS blockers for CV protection in the end-stage renal disease (ESRD) population other than the preferred drug class for blood pressure control. This uncertainty stems from the fact that patients with ESRD were generally excluded from randomized controlled trials evaluating the cardioprotective benefits of RAAS blockers. It is important to weigh the potential harms associated with the use of RAAS blockers, such as electrolyte disturbances and worsening anemia, with their role in protection of residual kidney function, alleviation of thirst and potential CV benefits. The objective of this review is to summarize the current knowledge about the use of RAAS blockers in patients with ESRD. PMID:26992264

  15. Nonalcoholic fatty liver disease and the renin-angiotensin system: Implications for treatment

    PubMed Central

    Paschos, Paschalis; Tziomalos, Konstantinos

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disease in Western countries. Treatment of NAFLD is currently based on lifestyle measures and no effective pharmacologic treatment is available so far. Emerging evidence, mainly from animal studies, suggests that the renin-angiotensin-aldosterone system may be of major importance in the pathogenesis of NAFLD and indicates that angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) as a potentially useful therapeutic approach. However, data from human studies are limited and contradictory. In addition, there are few randomized controlled trials (RCTs) on the effects of ACE-I or ARB in patients with NAFLD and most data are from retrospective studies, pilot prospective studies and post hoc analyses of clinical trials. Accordingly, more and larger RCTs are needed to directly assess the effectiveness of ACE-I and ARBs in NAFLD. PMID:23355909

  16. Renin-angiotensin system in thyroidectomized rats at different periods of development.

    PubMed

    Jiménez, E; Ruiz, M; Montiel, M; Narvaez, J A; Dieguez, J L; Morell, M

    1991-12-01

    The relationship between the renal function and some components of the renin-angiotensin system has been studied in hypothyroid rats thyroidectomized surgically at different periods of their life. Changes in plasma renin concentration (PRC) depending on the period hypothyroidism were induced. Results showed that the renin release control could result from an equilibrium between the reduced beta-adrenergic activity and the marked natriuresis observed in hypothyroidism. A reduction in plasma angiotensinogen concentration (PAC), due to a decrease in its hepatic production, was observed in thyroidectomized animals. PAC reduction was independent of the hypothyroidism induction period. Alterations in plasma renin activity (PRA) were a consequence of PRC and PAC changes in thyroidectomized animals, as an increase in fractional sodium excretion (FENa) time course dependent, was found in these rats. PMID:1725739

  17. Role of the Renin-Angiotensin System and Aldosterone on Cardiometabolic Syndrome

    PubMed Central

    Stiefel, P.; Vallejo-Vaz, A. J.; García Morillo, S.; Villar, J.

    2011-01-01

    Aldosterone facilitates cardiovascular damage by increasing blood pressure and through different mechanisms that are independent of its effects on blood pressure. In this respect, recent evidence involves aldosterone in the pathogenesis of metabolic syndrome. Although this relationship is complex, there is some evidence suggesting that different factors may play an important role, such as insulin resistance, renin-angiotensin-aldosterone system, oxidative stress, sodium retention, increased sympathetic activity, levels of free fatty acids, or inflammatory cytokines and adipokines. In addition to the classical pathway by which aldosterone acts through the mineralocorticoid receptors leading to sodium retention, aldosterone also has other mechanisms that influence cardiovascular tissue remodelling. Finally, overweight and obesity promote the adrenal secretion of aldosterone, increasing the predisposition to type 2 diabetes mellitus. Further studies are needed to better establish therapeutic strategies that act on the blockade of mineralocorticoid receptor in the treatment and prevention of cardiovascular diseases related to the excess of aldosterone and the metabolic syndrome. PMID:21785705

  18. The role of renin-angiotensin aldosterone system related micro-ribonucleic acids in hypertension

    PubMed Central

    Wang, Hui-Bo; Yang, Jun

    2015-01-01

    Micro-ribonucleic acids (miRNAs) are small (21-25 nucleotide) single-stranded, evolutionarily conserved non-protein-coding RNAs, which control diverse cellular functions by interacting with the 3’ untranslated region of specific target messenger RNAs at the post-transcriptional level. Research shows that an aberrant expression profile of miRNAs has been linked to a series of diseases, including hypertension. In the past few decades, it has been demonstrated that excessive activation of the renin-angiotensin aldosterone system (RAAS) involves in the pathogenesis of hypertension. This article reviews the latest insights in the identification of RAAS-correlative miRNAs and the potential mechanisms for their roles in hypertension. PMID:26446323

  19. Renin-angiotensin system and its role in hyperoxic acute lung injury.

    PubMed

    Zhang, P X; Han, C H; Zhou, F J; Li, L; Zhang, H M; Liu, W W

    2016-01-01

    Oxygen is essential to sustain life, but at a high partial pressure oxygen may cause toxicity to the human body. These injuries to the lung are known as hyperoxic acute lung injury [HALI]). To date, numerous studies have been conducted to investigate the pathogenesis of HALI, for which some hypotheses have been proposed. Accumulating evidence indicates that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of some lung diseases, including acute lung injury (ALI), chronic obstructive pulmonary disease (COPD) and HALI. In this review, we briefly introduce the classic RAS, local (tissue) RAS and intracellular RAS, and we summarize findings on the relationship between local/classic RAS and HALI. The importance--and ambiguity--of the results of these studies indicate a need for further investigations of the RAS and its role in the patho- genesis of HALI. PMID:27416692

  20. Sex differences in hypertension: contribution of the renin-angiotensin system.

    PubMed

    Maric-Bilkan, Christine; Manigrasso, Michaele B

    2012-08-01

    Numerous studies have shown that female human beings exhibit lower blood pressure levels over much of their life span compared with their age-matched counterparts. This sexual dimorphism is apparent in human beings as well as most, if not all, mammals. However, after the onset of menopause blood pressure levels in women increase and become similar to those in men, suggesting an important role of sex hormones in the regulation of blood pressure. The lower blood pressure levels in premenopausal women are associated with a lower risk of development and progression of cardiovascular disease and hypertension compared with age-matched men. This clear female advantage with respect to lower incidence of cardiovascular disease no longer exists after menopause, again highlighting the importance of sex hormones in the pathophysiology of cardiovascular disease in both men and women. In fact, both estrogens and androgens have been implicated in the development of cardiovascular disease and hypertension, with estrogens, in general, being protective and androgens being detrimental. Although the exact mechanisms by which sex hormones contribute to the regulation of cardiovascular function and blood pressure are still being investigated, there is increasing evidence that modulating the activity of locally active hormonal systems is one of the major mechanisms of sex hormone actions in target organs, including the vasculature and kidneys. Indeed, several studies have demonstrated the importance of the interaction between sex hormones and the renin-angiotensin system in regulating cardiovascular function and blood pressure. Furthermore, the differential effects of estrogens and androgens on the expression and activity of the components of the renin-angiotensin system could possibly explain the sex differences in blood pressure levels and the development and progression of cardiovascular disease and hypertension. PMID:22795464

  1. Renin-Angiotensin System Blockade Associated with Statin Improves Endothelial Function in Diabetics

    PubMed Central

    Gismondi, Ronaldo Altenburg; Bedirian, Ricardo; Pozzobon, Cesar Romaro; Ladeira, Márcia Cristina; Oigman, Wille; Neves, Mário Fritsch

    2015-01-01

    Background Studies suggest that statins have pleiotropic effects, such as reduction in blood pressure, and improvement in endothelial function and vascular stiffness. Objective To analyze if prior statin use influences the effect of renin-angiotensin-aldosterone system inhibitors on blood pressure, endothelial function, and vascular stiffness. Methods Patients with diabetes and hypertension with office systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 80 mmHg had their antihypertensive medications replaced by amlodipine during 6 weeks. They were then randomized to either benazepril or losartan for 12 additional weeks while continuing on amlodipine. Blood pressure (assessed with ambulatory blood pressure monitoring), endothelial function (brachial artery flow-mediated dilation), and vascular stiffness (pulse wave velocity) were evaluated before and after the combined treatment. In this study, a post hoc analysis was performed to compare patients who were or were not on statins (SU and NSU groups, respectively). Results The SU group presented a greater reduction in the 24-hour systolic blood pressure (from 134 to 122 mmHg, p = 0.007), and in the brachial artery flow-mediated dilation (from 6.5 to 10.9%, p = 0.003) when compared with the NSU group (from 137 to 128 mmHg, p = 0.362, and from 7.5 to 8.3%, p = 0.820). There was no statistically significant difference in pulse wave velocity (SU group: from 9.95 to 9.90 m/s, p = 0.650; NSU group: from 10.65 to 11.05 m/s, p = 0.586). Conclusion Combined use of statins, amlodipine, and renin-angiotensin-aldosterone system inhibitors improves the antihypertensive response and endothelial function in patients with hypertension and diabetes. PMID:26465872

  2. Low LBNP Tolerance in Men is Associated With Attenuated Activation of The Renin-Angiotensin System

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Petersen, T. W.; Gabrielsen, A.; Pump, B.; Bie, P.; Christensen, N.-J.; Warberg, J.; Videbaeck, R.; Simonson, S. R.; Norsk, P.

    1999-01-01

    Vasoactive hormone concentrations [epinephrine (pE), norepinephrine (pNE), angiotensin II (pATII), vasopressin (pVP), endothelin 1 (pET1)] and plasma renin activity (pRA) were measured during lower body negative pressure (LBNP) to test the hypothesis that responsiveness of the renin-angiotensin system is related to LBNP tolerance. Healthy men (2,822 cal/day(exp -1), 2 mmol*kg(exp -1)*day(exp -1)) Na(+)) were exposed to 30 minutes of progressive LBNP to -50 mmHg. LBNP was uneventful for seven men (25 +/- 2 years, HiTol group), but eight men (26 +/- 3 years) reached pre-syncope after 11 +/- 1 minutes (P < 0.001, LoTol group). Mean arterial pressure was unchanged. Central venous pressure and left atrial diameter decreased in both groups (5-6 mmHg by approx. 30%, P < 0.05). Control [hormone] were similar but, pRA differed between groups (LoTol 0.6 +/- 0.1, HiTol 1.2 +/- 0.1 ng Ang1/(ml(exp -1)*h(exp -1)), P < 0.05). LBNP increased (P < 0.05) pRA and pATII more in HiTol (9.9 +/- 2.2 ng Ang1/(ml(exp -1)*h(exp -1)) and 58 +/- 12 pg/ml(exp -1)) than LoTol (4.3 +/- 0.9 ng Ang1/(ml*h) and 28 +/- 6 pg/ml(exp -1)). In contrast, pVP was higher (P < 0.05) in LoTol than in HiTol. The response of the renin-angiotensin system seems linked to the occurrence of pre-syncope, and measurement of resting pRA may be predictive.

  3. Low Response of Renin-Angiotensin System to Sodium Intake Intervention in Chinese Hypertensive Patients.

    PubMed

    Feng, Weijing; Cai, Qingqing; Yuan, Woliang; Liu, Yu; Bardeesi, Adham Sameer A; Wang, Jingfeng; Chen, Jie; Huang, Hui

    2016-02-01

    The interactions of sodium balance and response of renin-angiotensin-aldosterone system are important for maintaining the hemodynamic stability in physiological conditions. However, the influence of short-term sodium intake intervention in the response of renin-angiotensin system (RAS) on hypertensive patients is still unclear. Thus, we conducted a clinical trial to investigate the effects of short-term sodium intake intervention on the response of RAS in hypertensive patients.One hundred twenty-five primary Chinese hypertensive patients were divided into high, moderate, and low sodium groups by 24-hour urinary sodium excretion (UNa). All the patients received a 10-day dietary sodium intake intervention with standardized sodium (173.91mmol/day) and potassium (61.53mmol/day). Blood pressure, urinary sodium, urinary potassium, plasma sodium, potassium, creatinine, the levels of plasma renin activity, plasma angiotensin II concentrations (AT-II), and plasma aldosterone concentrations were detected before and after the intervention.Before the intervention, no differences were found in blood pressure and RAS among 3 groups. After standardized dietary sodium intake intervention, both UNa excretion and systolic pressure decreased in high-sodium group, while they increased in moderate and low-sodium groups. Intriguingly, there were no changes in the levels of plasma renin activity, AT-II, and plasma aldosterone concentrations among 3 groups during the intervention.The present study demonstrated that the influenced sodium excretion and blood pressure by short-term sodium intake intervention were independent of RAS quick response in Chinese hypertensive patients. PMID:26871780

  4. Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats.

    PubMed

    Dhar, Indu; Dhar, Arti; Wu, Lingyun; Desai, Kaushik M

    2013-01-01

    The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs). Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories) for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs). HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH), proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE) and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats. PMID:24040205

  5. Activation of the intrarenal renin-angiotensin-system in murine polycystic kidney disease

    PubMed Central

    Saigusa, Takamitsu; Dang, Yujing; Bunni, Marlene A; Amria, May Y; Steele, Stacy L; Fitzgibbon, Wayne R; Bell, P Darwin

    2015-01-01

    The mechanism for early hypertension in polycystic kidney disease (PKD) has not been elucidated. One potential pathway that may contribute to the elevation in blood pressure in PKD is the activation of the intrarenal renin-angiotensin-system (RAS). For example, it has been shown that kidney cyst and cystic fluid contains renin, angiotensin II (AngII), and angiotensinogen (Agt). Numerous studies suggest that ciliary dysfunction plays an important role in PKD pathogenesis. However, it is unknown whether the primary cilium affects the intrarenal RAS in PKD. The purpose of this study was to determine whether loss of cilia or polycystin 1 (PC1) increases intrarenal RAS in mouse model of PKD. Adult Ift88 and Pkd1 conditional floxed allele mice with or without cre were administered tamoxifen to induce global knockout of the gene. Three months after tamoxifen injection, kidney tissues were examined by histology, immunofluorescence, western blot, and mRNA to assess intrarenal RAS components. SV40 immortalized collecting duct cell lines from hypomorphic Ift88 mouse were used to assess intrarenal RAS components in collecting duct cells. Mice without cilia and PC1 demonstrated increased kidney cyst formation, systolic blood pressure, prorenin, and kidney and urinary angiotensinogen levels. Interestingly immunofluorescence study of the kidney revealed that the prorenin receptor was localized to the basolateral membrane of principal cells in cilia (−) but not in cilia (+) kidneys. Collecting duct cAMP responses to AngII administration was greater in cilia (−) vs. cilia (+) cells indicating enhanced intrarenal RAS activity in the absence of cilia. These data suggest that in the absence of cilia or PC1, there is an upregulation of intrarenal RAS components and activity, which may contribute to elevated blood pressure in PKD. PMID:25999403

  6. Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia

    PubMed Central

    Nogueira-Silva, Cristina; Carvalho-Dias, Emanuel; Piairo, Paulina; Nunes, Susana; Baptista, Maria J; Moura, Rute S; Correia-Pinto, Jorge

    2012-01-01

    Antenatal stimulation of lung growth is a reasonable approach to treat congenital diaphragmatic hernia (CDH), a disease characterized by pulmonary hypoplasia and hypertension. Several evidences from the literature demonstrated a possible involvement of renin-angiotensin system (RAS) during fetal lung development. Thus, the expression pattern of renin, angiotensin-converting enzyme, angiotensinogen, type 1 (AT1) and type 2 (AT2) receptors of angiotensin II (ANGII) was assessed by immunohisto-chemistry throughout gestation, whereas the function of RAS in the fetal lung was evaluated using fetal rat lung explants. These were morphometrically analyzed and intracellular pathway alterations assessed by Western blot. In nitrofen-induced CDH model, pregnant rats were treated with saline or PD-123319. In pups, lung growth, protein/DNA ratio, radial saccular count, epithelial differentiation and lung maturation, vascular morphometry, right ventricular hypertrophy and overload molecular markers, gasometry and survival time were evaluated. Results demonstrated that all RAS components were constitutively expressed in the lung during gestation and that ANGII had a stimulatory effect on lung branching, mediated by AT1 receptor, through p44/42 and Akt phosphorylation. This stimulatory effect on lung growth was mimicked by AT2-antagonist (PD-123319) treatment. In vivo antenatal PD-123319 treatment increased lung growth, ameliorated indirect parameters of pulmonary hypertension, improved lung function and survival time in nonventilated CDH pups, without maternal or fetal deleterious effects. Therefore, this study demonstrated a local and physiologically active RAS during lung morphogenesis. Moreover, selective inhibition of AT2 receptor is presented as a putative antenatal therapy for CDH. PMID:22113494

  7. Severe hypoglycaemia in type 1 diabetes: impact of the renin-angiotensin system and other risk factors.

    PubMed

    Pedersen-Bjergaard, Ulrik

    2009-11-01

    Hypoglycaemia is an unavoidable side effect to insulin therapy of diabetes. In daily life some hypoglycaemic episodes are recognised by the patients and corrected by ingestion of glucose, but occasionally unrecognised episodes progress into severe hypoglycaemia with cognitive impairment and the need for assistance from other persons in order to manage the situation. Such episodes represent the most feared side effect to insulin treatment and are regarded as the major limiting factor for achievement of recommended glycaemic targets in type 1 diabetes. The series of studies that constitute this thesis was conducted to assess the significance of severe hypoglycaemia as a clinical problem in the type 1 diabetic population, to evaluate the impact of known risk factors on occurrence of severe hypoglycaemia, and to identify new markers that could contribute to improved prediction of, and inspire to novel preventive measures of, severe hypoglycaemia. Our studies confirm that severe hypoglycaemia is still a major clinical problem in type 1 diabetes. The individual susceptibility to severe hypoglycaemia is highly varying and conventional risk factors - with major contribution from hypoglycaemia unawareness - only account for a limited part of this variation. Results from a case-series suggest that the use of psychoactive substances may be as significant as alcohol for promotion of risk of severe hypoglycaemia - a finding which needs to be confirmed by case-control studies. We identified elevated renin-angiotensin system activity as a novel predictor of risk of severe hypoglycaemia in type 1 diabetes with potential clinical significance. Thus, three sequential renin-angiotensin system-related risk factors were associated with severe hypoglycaemia, and by including these factors in a common model both subjects at low and at high risk within a one-year period were identified. Preliminary data suggest that this is explained by impaired capability of subjects with high renin-angiotensin

  8. A Salt-Induced Reno-Cerebral Reflex Activates Renin-Angiotensin Systems and Promotes CKD Progression.

    PubMed

    Cao, Wei; Li, Aiqing; Wang, Liangliang; Zhou, Zhanmei; Su, Zhengxiu; Bin, Wei; Wilcox, Christopher S; Hou, Fan Fan

    2015-07-01

    Salt intake promotes progression of CKD by uncertain mechanisms. We hypothesized that a salt-induced reno-cerebral reflex activates a renin-angiotensin axis to promote CKD. Sham-operated and 5/6-nephrectomized rats received a normal-salt (0.4%), low-salt (0.02%), or high-salt (4%) diet for 2 weeks. High salt in 5/6-nephrectomized rats increased renal NADPH oxidase, inflammation, BP, and albuminuria. Furthermore, high salt activated the intrarenal and cerebral, but not the systemic, renin-angiotensin axes and increased the activity of renal sympathetic nerves and neurons in the forebrain of these rats. Renal fibrosis was increased 2.2-fold by high versus low salt, but intracerebroventricular tempol, losartan, or clonidine reduced this fibrosis by 65%, 69%, or 59%, respectively, and renal denervation or deafferentation reduced this fibrosis by 43% or 38%, respectively (all P<0.05). Salt-induced fibrosis persisted after normalization of BP with hydralazine. These data suggest that the renal and cerebral renin-angiotensin axes are interlinked by a reno-cerebral reflex that is activated by salt and promotes oxidative stress, fibrosis, and progression of CKD independent of BP. PMID:25635129

  9. The renin-angiotensin-aldosterone system and calcium-regulatory hormones.

    PubMed

    Vaidya, A; Brown, J M; Williams, J S

    2015-09-01

    There is increasing evidence of a clinically relevant interplay between the renin-angiotensin-aldosterone system and calcium-regulatory systems. Classically, the former is considered a key regulator of sodium and volume homeostasis, while the latter is most often associated with skeletal health. However, emerging evidence suggests an overlap in regulatory control. Hyperaldosteronism and hyperparathyroidism represent pathophysiologic conditions that may contribute to or perpetuate each other; aldosterone regulates parathyroid hormone and associates with adverse skeletal complications, and parathyroid hormone regulates aldosterone and associates with adverse cardiovascular complications. As dysregulation in both systems is linked to poor cardiovascular and skeletal health, it is increasingly important to fully characterize how they interact to more precisely understand their impact on human health and potential therapies to modulate these interactions. This review describes the known clinical interactions between these two systems including observational and interventional studies. Specifically, we review studies describing the inhibition of renin activity by calcium and vitamin D, and a potentially bidirectional and stimulatory relationship between aldosterone and parathyroid hormone. Deciphering these relationships might clarify variability in outcomes research, inform the design of future intervention studies and provide insight into the results of prior and ongoing intervention studies. However, before these opportunities can be addressed, more effort must be placed on shifting observational data to the proof of concept phase. This will require reallocation of resources to conduct interventional studies and secure the necessary talent. PMID:25631218

  10. The role of the renin-angiotensin and natriuretic peptide systems in the pulmonary vasculature.

    PubMed Central

    Cargill, R I; Lipworth, B J

    1995-01-01

    1. The role of vasoactive peptide systems in the pulmonary vasculature has been studied much less extensively than systemic vascular and endocrine effects. The current understanding of the role of the renin-angiotensin (RAS) and natriuretic peptide systems (NPS) in the pulmonary circulation is therefore reviewed. 2. Plasma concentrations of angiotensin II, the main vasoactive component of the RAS, are elevated in pulmonary hypertension and may interact with hypoxaemia to cause further pulmonary vasoconstriction. Pharmacological manipulation of angiotensin II can attenuate hypoxic pulmonary vasoconstriction but larger studies are needed to establish the efficacy of this therapeutic strategy in established pulmonary hypertension. 3. Although all the known natriuretic peptides, ANP, BNP and CNP are elevated in cor pulmonale, only ANP and BNP appear to have pulmonary vasorelaxant activity in humans. ANP and BNP can also attenuate hypoxic pulmonary vasoconstriction, suggesting a possible counter-regulatory role for these peptides. Inhibition of ANP/BNP metabolism by neutral endopeptidase has been shown to attenuate development of hypoxic pulmonary hypertension but this property has not been tested in humans. 4. It is also well established that there are potentially important endocrine and systemic circulatory interactions between the RAS and NPS. This also occurs in the pulmonary circulation and in humans, where at least BNP acts to attenuate angiotensin II induced pulmonary vasoconstriction. This interaction may be particularly relevant as a mechanism to counter-regulate overactivity of the RAS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8527262

  11. Drug discovery in renin-angiotensin system intervention: past and future.

    PubMed

    Williams, Bryan

    2016-06-01

    The renin-angiotensin system (RAS) plays a central role in the control of blood pressure in the body and the way this interacts with other systems is widely recognized. This has not always been the case and this review summarizes how our knowledge has evolved from the initial discovery of renin by Tigerstedt and Berman in 1898. This includes the identification of angiotensin in the 1950s to the proposed relationship between this system, hypertension and ultimately cardiovascular disease. While the RAS is far more complex than originally thought, much is now known about this system and the wide ranging effects of angiotensin in the body. This has enabled the development of therapies that target the various proteins in this pathway and hence are implicated in disease. The first of these treatments was the angiotensin converting enzyme inhibitors (ACE-Is), followed by the angiotensin receptor blockers (ARBs), and more recently the direct renin inhibitors (DRIs). Clinical outcome trials have shown these drugs to be effective, but as they act at contrasting points in the RAS, there are differences in their efficacy and safety profiles. RAS blockade is the foundation of modern combination therapy with a calcium channel blocker and/or a diuretic given to reduce blood pressure and limit the impact of RAS activation. Other options that complement these treatments may be available in the future and will offer more choice to clinicians. PMID:27126389

  12. Autonomic, locomotor and cardiac abnormalities in a mouse model of muscular dystrophy: targeting the renin-angiotensin system.

    PubMed

    Sabharwal, Rasna; Chapleau, Mark W

    2014-04-01

    New Findings What is the topic of this review? This symposium report summarizes autonomic, cardiac and skeletal muscle abnormalities in sarcoglycan-δ-deficient mice (Sgcd-/-), a mouse model of limb girdle muscular dystrophy, with emphasis on the roles of autonomic dysregulation and activation of the renin-angiotensin system at a young age. What advances does it highlight? The contributions of the autonomic nervous system and the renin-angiotensin system to the pathogenesis of muscular dystrophy are highlighted. Results demonstrate that autonomic dysregulation precedes and predicts later development of cardiac dysfunction in Sgcd-/- mice and that treatment of young Sgcd-/- mice with the angiotensin type 1 receptor antagonist losartan or with angiotensin-(1-7) abrogates the autonomic dysregulation, attenuates skeletal muscle pathology and increases spontaneous locomotor activity. Muscular dystrophies are a heterogeneous group of genetic muscle diseases characterized by muscle weakness and atrophy. Mutations in sarcoglycans and other subunits of the dystrophin-glycoprotein complex cause muscular dystrophy and dilated cardiomyopathy in animals and humans. Aberrant autonomic signalling is recognized in a variety of neuromuscular disorders. We hypothesized that activation of the renin-angiotensin system contributes to skeletal muscle and autonomic dysfunction in mice deficient in the sarcoglycan-δ (Sgcd) gene at a young age and that this early autonomic dysfunction contributes to the later development of left ventricular (LV) dysfunction and increased mortality. We demonstrated that young Sgcd-/- mice exhibit histopathological features of skeletal muscle dystrophy, decreased locomotor activity and severe autonomic dysregulation, but normal LV function. Autonomic regulation continued to deteriorate in Sgcd-/- mice with age and was accompanied by LV dysfunction and dilated cardiomyopathy at older ages. Autonomic dysregulation at a young age predicted later development of

  13. Effects of Local Pancreatic Renin-Angiotensin System on the Microcirculation of Rat with Severe Acute Pancreatitis

    PubMed Central

    Feng, Ling; Long, Haocheng; Wang, Hui; Feng, Jiarui; Chen, Feixiang

    2015-01-01

    Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis. PMID:26170733

  14. Effects of Local Pancreatic Renin-Angiotensin System on the Microcirculation of Rat with Severe Acute Pancreatitis.

    PubMed

    Pan, Zhijian; Feng, Ling; Long, Haocheng; Wang, Hui; Feng, Jiarui; Chen, Feixiang

    2015-07-01

    Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis. PMID:26170733

  15. Nuclear Expression of Renin-Angiotensin System Components in NRK-52E Renal Epithelial Cells

    PubMed Central

    Alzayadneh, Ebaa M.; Chappell, Mark C.

    2014-01-01

    Introduction Isolated nuclei of sheep proximal tubules express angiotensin receptors as well as angiotensinogen (AGT) and renin. The present study characterized the NRK-52E tubular epithelial cell line for the intracellular expression of renin-angiotensin system (RAS) components. Methods RAS components were visualized by immunofluorescent staining in intact cells and protein expression in isolate nuclei. Results An antibody to the Ang I sequence of AGT (AI-AGT) revealed only cytosolic staining, while an antibody to an internal epitope of AGT (Int-AGT) revealed primarily nuclear staining. Immunoblots of nuclear and cytosolic fractions confirmed the differential cell staining of AGT. Immunostaining for renin was present on nuclei of intact cells. Nuclear renin activity averaged 0.77 ± 0.05 nmol/mg protein/hr that was reduced by aliskiren (0.13 ± 0.01 nmol/mg/hr, n=3, p<0.01); trypsin activation increased activity 3-fold. Peptide staining localized Ang II and Ang-(1–7) to the nucleus and peptide content averaged 59 ± 2 and 57 ± 22 fmol/mg (n=4), respectively. Peptide metabolism in isolated nuclei revealed the processing of Ang I to Ang-(1–7) by thimet oligopeptidase. Conclusion We conclude that the NRK-52E cells express an intracellular RAS localized to the nucleus and may be an appropriate cell model to elucidate the functional relevance of this system. PMID:24961503

  16. Pharmacological, immunological, and gene targeting of the renin-angiotensin system for treatment of cardiovascular disease.

    PubMed

    Igic, Rajko; Behnia, Rahim

    2007-01-01

    Effective blood pressure control with a large arsenal of conventional antihypertensive drugs, such as diuretics, beta-adrenergic blockers, and calcium channel blockers, significantly reduce the morbidity and mortality associated with cardiovascular disease. However, blood pressure control with these drugs does not reduce cardiovascular disease risks to the levels in normotensive persons. Only two drug classes that inhibit or antagonize portions of the renin-angiotensin system (RAS), angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor type-1 (AT(1) receptor) blockers, have protective and beneficial effects unrelated to the degree of blood pressure reduction. These drugs may prevent the blood pressure related functional and structural abnormalities of the cardiovascular system and reduce the end organ-damage. The first part of this review presents the components of the RAS, biological actions of angiotensin peptides, and the functions of the enzymes that generate and metabolize angiotensins, including the likely effect of manipulating them. Special attention is devoted to renin, ACE, ACE2, chymase, and neprilysin. The second part of this review presents the rationale for targeting the RAS, based on clinical studies of the ACE inhibitors and AT(1) receptor blockers. Finally, we present the investigational agents acting on the RAS that have a potential for clinical usage, and give the perspective of pharmacological, immunological and gene targeting of the RAS for treatment of cardiovascular disease. PMID:17504230

  17. Epochs in the depressor/pressor balance of the renin-angiotensin system.

    PubMed

    Colafella, Katrina M Mirabito; Hilliard, Lucinda M; Denton, Kate M

    2016-05-01

    The renin-angiotensin system (RAS) plays a commanding role in the regulation of extracellular fluid homoeostasis. Tigerstadt and Bergman first identified the RAS more than two centuries ago. By the 1980s a voyage of research and discovery into the mechanisms and actions of this system led to the development of drugs that block the RAS, which have become the mainstay for the treatment of cardiovascular and renal disease. In the last 25 years new components of the RAS have come to light, including the angiotensin type 2 receptor (AT2R) and the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang(1-7)]/Mas receptor (MasR) axis. These have been shown to counter the classical actions of angiotensin II (AngII) at the predominant angiotensin type 1 receptor (AT1R). Our studies, and those of others, have demonstrated that targeting these depressor RAS pathways may be therapeutically beneficial. It is apparent that the evolution of both the pressor and depressor RAS pathways is distinct throughout life and that the depressor/pressor balance of the RAS vary between the sexes. These temporal patterns of expression suggest that therapies targeting the RAS could be optimized for discrete epochs in life. PMID:27128801

  18. Atlas of tissue renin-angiotensin-aldosterone system in human: A transcriptomic meta-analysis.

    PubMed

    Nehme, Ali; Cerutti, Catherine; Dhaouadi, Nedra; Gustin, Marie Paule; Courand, Pierre-Yves; Zibara, Kazem; Bricca, Giampiero

    2015-01-01

    Tissue renin-angiotensin-aldosterone system (RAAS) has attracted much attention because of its physiological and pharmacological implications; however, a clear definition of tissue RAAS is still missing. We aimed to establish a preliminary atlas for the organization of RAAS across 23 different normal human tissues. A set of 37 genes encoding classical and novel RAAS participants including gluco- and mineralo-corticoids were defined as extended RAAS (extRAAS) system. Microarray data sets containing more than 10 normal tissues were downloaded from the GEO database. R software was used to extract expression levels and construct dendrograms of extRAAS genes within each data set. Tissue co-expression modules were then extracted from reproducible gene clusters across data sets. An atlas of the maps of tissue-specific organization of extRAAS was constructed from gene expression and coordination data. Our analysis included 143 data sets containing 4933 samples representing 23 different tissues. Expression data provided an insight on the favored pathways in a given tissue. Gene coordination indicated the existence of tissue-specific modules organized or not around conserved core groups of transcripts. The atlas of tissue-specific organization of extRAAS will help better understand tissue-specific effects of RAAS. This will provide a frame for developing more effective and selective pharmaceuticals targeting extRAAS. PMID:25992767

  19. Renin-angiotensin system: an old player with novel functions in skeletal muscle.

    PubMed

    Cabello-Verrugio, Claudio; Morales, María Gabriela; Rivera, Juan Carlos; Cabrera, Daniel; Simon, Felipe

    2015-05-01

    Skeletal muscle is a tissue that shows the most plasticity in the body; it can change in response to physiological and pathological stimuli. Among the diseases that affect skeletal muscle are myopathy-associated fibrosis, insulin resistance, and muscle atrophy. A common factor in these pathologies is the participation of the renin-angiotensin system (RAS). This system can be functionally separated into the classical and nonclassical RAS axis. The main components of the classical RAS pathway are angiotensin-converting enzyme (ACE), angiotensin II (Ang-II), and Ang-II receptors (AT receptors), whereas the nonclassical axis is composed of ACE2, angiotensin 1-7 [Ang (1-7)], and the Mas receptor. Hyperactivity of the classical axis in skeletal muscle has been associated with insulin resistance, atrophy, and fibrosis. In contrast, current evidence supports the action of the nonclassical RAS as a counter-regulator axis of the classical RAS pathway in skeletal muscle. In this review, we describe the mechanisms involved in the pathological effects of the classical RAS, advances in the use of pharmacological molecules to inhibit this axis, and the beneficial effects of stimulation of the nonclassical RAS pathway on insulin resistance, atrophy, and fibrosis in skeletal muscle. PMID:25764065

  20. Atlas of tissue renin-angiotensin-aldosterone system in human: A transcriptomic meta-analysis

    PubMed Central

    Nehme, Ali; Cerutti, Catherine; Dhaouadi, Nedra; Gustin, Marie Paule; Courand, Pierre-Yves; Zibara, Kazem; Bricca, Giampiero

    2015-01-01

    Tissue renin-angiotensin-aldosterone system (RAAS) has attracted much attention because of its physiological and pharmacological implications; however, a clear definition of tissue RAAS is still missing. We aimed to establish a preliminary atlas for the organization of RAAS across 23 different normal human tissues. A set of 37 genes encoding classical and novel RAAS participants including gluco- and mineralo-corticoids were defined as extended RAAS (extRAAS) system. Microarray data sets containing more than 10 normal tissues were downloaded from the GEO database. R software was used to extract expression levels and construct dendrograms of extRAAS genes within each data set. Tissue co-expression modules were then extracted from reproducible gene clusters across data sets. An atlas of the maps of tissue-specific organization of extRAAS was constructed from gene expression and coordination data. Our analysis included 143 data sets containing 4933 samples representing 23 different tissues. Expression data provided an insight on the favored pathways in a given tissue. Gene coordination indicated the existence of tissue-specific modules organized or not around conserved core groups of transcripts. The atlas of tissue-specific organization of extRAAS will help better understand tissue-specific effects of RAAS. This will provide a frame for developing more effective and selective pharmaceuticals targeting extRAAS. PMID:25992767

  1. Aliskiren inhibits the renin-angiotensin system in retinal pigment epithelium cells.

    PubMed

    Simão, Sónia; Santos, Daniela F; Silva, Gabriela A

    2016-09-20

    Observations of increased angiotensin II levels and activation of the (pro)renin receptor in retinopathies support the role of ocular renin-angiotensin system (RAS) in the development of retinal diseases. While targeting RAS presents significant therapeutic potential, current RAS-based therapies are ineffective halting the progression of these diseases. A new class of drugs, the direct renin inhibitors such as aliskiren, is a potential therapeutic alternative. However, it is unclear how aliskiren acts in the retina, in particular in the retinal pigment epithelium (RPE), the structure responsible for the maintenance of retinal homeostasis whose role is deeply compromised in retinal diseases. We firstly analyzed the expression and activity of the main RAS components in RPE cells. Time- and concentration-dependent treatments with aliskiren were performed to modulate different pathways of the RAS in RPE cells. Our data demonstrate that RPE cells express the main RAS constituents. Exposure of RPE cells to aliskiren inhibited the activity of renin and consequently decreased the levels of angiotensin II. Additionally, aliskiren reduced the translocation of the (pro)renin receptor to the cellular membrane of RPE cells preventing the activation of ERK1/2. Our findings of the RPE well-defined RAS, together with the demonstration that aliskiren effectively blocks this system at different steps of the cascade, suggest that aliskiren might be an alternative and successful drug in preventing the deleterious effects derived from the overactivation of the RAS, known to contribute to the pathogenesis of different retinal diseases. PMID:27343695

  2. Interaction of the renin angiotensin and cox systems in the kidney.

    PubMed

    Quadri, Syed S; Culver, Silas A; Li, Caixia; Siragy, Helmy M

    2016-01-01

    Cyclooxygenase-2 (COX-2) plays an important role in mediating actions of the renin-angiotensin system (RAS). This review sheds light on the recent developments regarding the complex interactions between components of RAS and COX-2; and their implications on renal function and disease. COX-2 is believed to counter regulate the effects of RAS activation and therefore counter balance the vasoconstriction effect of Ang II. In kidney, under normal conditions, these systems are essential for maintaining a balance between vasodilation and vasoconstriction. However, recent studies suggested a pivotal role for this interplay in pathology. COX-2 increases the renin release and Ang II formation leading to increase in blood pressure. COX-2 is also associated with diabetic nephropathy, where its upregulation in the kidney contributes to glomerular injury and albuminuria. Selective inhibition of COX-2 retards the progression of renal injury. COX-2 also mediates the pathologic effects of the (Pro)renin receptor (PRR) in the kidney. In summary, this review discusses the interaction between the RAS and COX-2 in health and disease. PMID:27100703

  3. The role of local renin-angiotensin system in arterial chemoreceptors in sleep-breathing disorders

    PubMed Central

    Fung, Man Lung

    2014-01-01

    The renin-angiotensin system (RAS) plays pivotal roles in the regulation of cardiovascular and renal functions to maintain the fluid and electrolyte homeostasis. Experimental studies have demonstrated a locally expressed RAS in the carotid body, which is functional significant in the effect of angiotensin peptides on the regulation of the activity of peripheral chemoreceptors and the chemoreflex. The physiological and pathophysiological implications of the RAS in the carotid body have been proposed upon recent studies showing a significant upregulation of the RAS expression under hypoxic conditions relevant to altitude acclimation and sleep apnea and also in animal model of heart failure. Specifically, the increased expression of angiotensinogen, angiotensin-converting enzyme and angiotensin AT1 receptors plays significant roles in the augmented carotid chemoreceptor activity and inflammation of the carotid body. This review aims to summarize these results with highlights on the pathophysiological function of the RAS under hypoxic conditions. It is concluded that the maladaptive changes of the RAS in the carotid body plays a pathogenic role in sleep apnea and heart failure, which could potentially be a therapeutic target for the treatment of the pathophysiological consequence of sleep apnea. PMID:25249981

  4. Soya protein attenuates abnormalities of the renin-angiotensin system in adipose tissue from obese rats.

    PubMed

    Frigolet, María E; Torres, Nimbe; Tovar, Armando R

    2012-01-01

    Several metabolic disturbances during obesity are associated with adipose tissue-altered functions. Adipocytes contain the renin-angiotensin system (RAS), which regulates signalling pathways that control angiogenesis via Akt in an autocrine fashion. Soya protein (Soy) consumption modifies the gene expression pattern in adipose tissue, resulting in an improved adipocyte function. Therefore, the aim of the present work is to study whether dietary Soy regulates the expression of RAS and angiogenesis-related genes and its association with the phosphorylated state of Akt in the adipose tissue of obese rats. Animals were fed a 30 % Soy or casein (Cas) diet containing 5 or 25 % fat for 160 d. mRNA abundance was studied in the adipose tissue, and Akt phosphorylation and hormone release were measured in the primary adipocyte culture. The present results show that Soy treatment in comparison with Cas consumption induces lower angiotensin release and increased insulin-stimulated Akt activation in adipocytes. Furthermore, Soy consumption varies the expression of RAS and angiogenesis-related genes, which maintain cell size and vascularity in the adipose tissue of rats fed a high-fat diet. Thus, adipocyte hypertrophy and impaired angiogenesis, which are frequently observed in dysfunctional adipose tissue, were avoided by consuming dietary Soy. Taken together, these findings suggest that Soy can be used as a dietary strategy to preserve adipocyte functionality and to prevent obesity abnormalities. PMID:21736766

  5. Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System.

    PubMed

    Weidemann, Benjamin J; Voong, Susan; Morales-Santiago, Fabiola I; Kahn, Michael Z; Ni, Jonathan; Littlejohn, Nicole K; Claflin, Kristin E; Burnett, Colin M L; Pearson, Nicole A; Lutter, Michael L; Grobe, Justin L

    2015-01-01

    Dietary fats and sodium are both palatable and are hypothesized to synergistically contribute to ingestive behavior and thereby obesity. Contrary to this hypothesis, C57BL/6J mice fed a 45% high fat diet exhibited weight gain that was inhibited by increased dietary sodium content. This suppressive effect of dietary sodium upon weight gain was mediated specifically through a reduction in digestive efficiency, with no effects on food intake behavior, physical activity, or resting metabolism. Replacement of circulating angiotensin II levels reversed the effects of high dietary sodium to suppress digestive efficiency. While the AT1 receptor antagonist losartan had no effect in mice fed low sodium, the AT2 receptor antagonist PD-123,319 suppressed digestive efficiency. Correspondingly, genetic deletion of the AT2 receptor in FVB/NCrl mice resulted in suppressed digestive efficiency even on a standard chow diet. Together these data underscore the importance of digestive efficiency in the pathogenesis of obesity, and implicate dietary sodium, the renin-angiotensin system, and the AT2 receptor in the control of digestive efficiency regardless of mouse strain or macronutrient composition of the diet. These findings highlight the need for greater understanding of nutrient absorption control physiology, and prompt more uniform assessment of digestive efficiency in animal studies of energy balance. PMID:26068176

  6. Renin-angiotensin system genes polymorphism in Egyptians with premature coronary artery disease.

    PubMed

    Abd El-Aziz, Tarek A; Hussein, Yousri M; Mohamed, Randa H; Shalaby, Sally M

    2012-05-01

    Genetics polymorphism of the renin-angiotensin system (RAS) affects the pathogenesis of atherosclerosis and associated with coronary artery disease (CAD). We aimed to investigate the association between the RAS genes and premature CAD (PCAD) in Egyptians. 116 patients with PCAD, 114 patients with late onset CAD and 119 controls were included in the study. Angiotensin converting enzyme (ACE), angiotensin II receptor type 1 (ATR1) and angiotensinogen (AGT) genes polymorphisms were analyzed by polymerase chain reaction (PCR). We found that ACE DD, AGT TT and ATR1 CC increased the risk of PCAD by 2.7, 2.8 and 2.86 respectively). Smoking, hypertension, diabetes, total cholesterol, triglycerides and LDL cholesterol were independent risk factors for the development of PCAD. We conclude that the ACE DD, AGT TT and ATR1 CC genotypes may increase the susceptibility of an individual to have PCAD. The coexistence of CAD risk factors with these risky RAS genotypes may lead to the development of PCAD in Egyptian patients. PMID:22387727

  7. Characterization of the renin-angiotensin system in the turtle Pseudemys scripta.

    PubMed

    Cipolle, M D; Zehr, J E

    1984-07-01

    Studies were conducted in freshwater turtles Pseudemys scripta to define some characteristics of the renin-angiotensin system in this reptile. Dialyzed acid-treated kidney extract (1 g tissue per ml water) produced a prolonged pressor response in unanesthetized turtles, which was eliminated by boiling the extract or by pretreating the turtle with [Sar1, Ile8]angiotensin II. A rat pressor assay was employed because turtle angiotensin (ANG) was bound poorly by the anti-[Asp1, Ile5, His9]ANG I used in our radioimmunoassay. Kidney extract incubated with homologous plasma (pH 5.5 and 25 degrees C) produced a time-dependent pressor response in rats. The pressor activity of the product was eliminated by dialysis or by pretreating the rats with [Sar1, Ile8]ANG II. The pressor response in anesthetized turtles to ANG I was significantly reduced by captopril, whereas the ANG II response remained unchanged, thus demonstrating the presence of ANG-converting enzyme activity in these animals. We determined the velocity of turtle ANG formation at various dilutions of enzyme (kidney extract) or substrate (plasma). Turtle kidney extract incubated with homologous plasma displayed typical Michaelis-Menten kinetics. Finally we conducted experiments to determine whether a portion of turtle plasma renin exists in an inactive form. Trypsinization caused a slight increase in plasma renin activity (PRA), whereas acidification to pH 3.3 yielded a fourfold increase in PRA. PMID:6377928

  8. Activation of calpain by renin-angiotensin system in pleural mesothelial cells mediates tuberculous pleural fibrosis

    PubMed Central

    Yang, Jie; Xiang, Fei; Cai, Peng-Cheng; Lu, Yu-Zhi; Xu, Xiao-Xiao; Yu, Fan; Li, Feng-Zhi; Greer, Peter A.; Shi, Huan-Zhong; Zhou, Qiong; Xin, Jian-Bao; Ye, Hong; Su, Yunchao

    2016-01-01

    Pleural fibrosis is defined as an excessive deposition of extracellular matrix (ECM) components that results in destruction of the normal pleural tissue architecture. It can result from diverse inflammatory conditions, especially tuberculous pleurisy. Pleural mesothelial cells (PMCs) play a pivotal role in pleural fibrosis. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodeling. However, the role of calpain in pleural fibrosis remains unknown. In the present study, we found that tuberculous pleural effusion (TPE) induced calpain activation in PMCs and that inhibition of calpain prevented TPE-induced collagen-I synthesis and cell proliferation of PMCs. Moreover, our data revealed that the levels of angiotensin (ANG)-converting enzyme (ACE) were significantly higher in pleural fluid of patients with TPE than those with malignant pleural effusion, and ACE-ANG II in TPE resulted in activation of calpain and subsequent triggering of the phosphatidylinositol 3-kinase (PI3K)/Akt/NF-κB signaling pathway in PMCs. Finally, calpain activation in PMCs and collagen depositions were confirmed in pleural biopsy specimens from patients with tuberculous pleurisy. Together, these studies demonstrated that calpain is activated by renin-angiotensin system in pleural fibrosis and mediates TPE-induced collagen-I synthesis and proliferation of PMCs via the PI3K/Akt/NF-κB signaling pathway. Calpain in PMCs might be a novel target for intervention in tuberculous pleural fibrosis. PMID:27261452

  9. Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen

    PubMed Central

    Joyce-Tan, Siew Mei; Zain, Shamsul Mohd; Abdul Sattar, Munavvar Zubaid; Abdullah, Nor Azizan

    2016-01-01

    Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls for AGT variants (P = 0.05) but not for ACE and AGTR1. Haplotype TCG of the AGT was associated with increased risk of T2DM (OR 1.92, 95% CI 1.15–3.20, permuted P = 0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of the AGT variants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk. PMID:26682227

  10. Renin-angiotensin-aldosterone system blockade in chronic kidney disease: current strategies and a look ahead.

    PubMed

    Viazzi, Francesca; Bonino, Barbara; Cappadona, Francesca; Pontremoli, Roberto

    2016-08-01

    The Renin-Angiotensin-Aldosterone System (RAAS) is profoundly involved in the pathogenesis of renal and cardiovascular organ damage, and has been the preferred therapeutic target for renal protection for over 30 years. Monotherapy with either an Angiotensin Converting Enzime Inhibitor (ACE-I) or an Angiotensin Receptor Blocker (ARB), together with optimal blood pressure control, remains the mainstay treatment for retarding the progression toward end-stage renal disease. Combining ACE-Is and ARBs, or either one with an Aldosterone Receptor Antagonist (ARA), has been shown to provide greater albuminuria reduction, and to possibly improve renal outcome, but at an increased risk of potentially severe side effects. Moreover, combination therapy has failed to provide additional cardiovascular protection, and large prospective trials on hard renal endpoints are lacking. Therefore this treatment should, at present, be limited to selected patients with residual proteinuria and high renal risk. Future studies with novel agents, which directly act on the RAAS at multiple levels or have a more favourable side effect profile, are greatly needed to further explore and define the potential for and the limitations of profound pharmacologic RAAS inhibition. PMID:26984204

  11. Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure.

    PubMed

    Vardeny, Orly; Miller, Ryan; Solomon, Scott D

    2014-12-01

    Neprilysin is an enzyme that contributes to the breakdown of the biologically active natriuretic peptides and several other vasoactive compounds. Inhibiting neprilysin has been a therapeutic target for several compounds that have been tested in cardiovascular disease, including ecadotril, candoxatril, omapatrilat, and LCZ696. Although ecadotril, candoxatril, and omapatrilat were initially tested in hypertension and/or heart failure, lack of efficacy and side effects led to discontinuation of their development. LCZ696 (sacubitril valsartan) is a first-in-class angiotensin receptor neprilysin inhibitor that has been developed for use in heart failure. This compound is composed of 2 molecular moieties in a single crystalline complex-the angiotensin receptor blocker valsartan and a neprilysin inhibitor prodrug-and has now been tested in hypertension, in a phase 2 trial in heart failure with preserved ejection fraction, and has demonstrated greater efficacy than enalapril in a phase 3 trial in heart failure with reduced ejection fraction. Its ability to inhibit the renin-angiotensin-aldosterone axis and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease. PMID:25306450

  12. Antenatal maternal protein deprivation: sexually dimorphic programming of the pancreatic renin-angiotensin system.

    PubMed

    Goyal, Ravi; Wong, Christine; Van Wickle, Jonathan; Longo, Lawrence D

    2013-06-01

    As an underlying mechanism of antenatal maternal malnutrition-induced type 2 diabetes mellitus (T2DM), alterations in the local pancreatic renin-angiotensin system (RAS) may play a significant role. We tested the hypothesis that antenatal maternal protein deprivation (AMPD) leads to increased activity of the local pancreatic RAS, with associated hyperglycemia in the adult progeny. Mice dams were fed either control or 50% protein restricted diet (AMPD) starting one week before conception and maintained during complete gestation. Our results demonstrate low birth weight (control 1.5 ± 0.03 and AMPD 1.3 ± 0.03) and sexually dimorphic programming of the pancreatic RAS, with development of hyperglycemia only in the female mice offspring as a consequence of AMPD. No significant difference in serum insulin concentration was observed; however, AMPD was associated with increased mRNA and protein expression of angiotensinogen, renin and angiotensin-converting enzyme (ACE)-1 in male and female offspring. Of importance, mRNA and protein expression of ACE 2 and angiotensin II receptors was up-regulated only in the male offspring, as a consequence of AMPD. We conclude that sexually dimorphic programming of the pancreatic RAS expression is associated with AMPD diet-mediated development of hyperglycemia. PMID:22898440

  13. [Protective effect and mechanism of β-CM7 on renin angiotensin system & diabetic cardiomyopathy].

    PubMed

    Wang, Kun; Han, Dongning; Zhang, Yujuan; Rong, Chao; Zhang, Yuanshu

    2016-02-01

    This article aimed at exploring the effects and protective mechanism of β-CM7 on renin angiotensin system (RAS) in diabetic rats myocardial tissue. We divided 32 male SD rats into 4 groups: control group, diabetic model control group, insulin (3.7x10(-8) mol/d) treatment group and β-CM7 (7.5x10(-8) mol/d) treatment group. After 30 days, all rats were decapitated and myocardical tissues were collected immediately. After injection, β-CM7 could decrease the content of Ang II, increase the content of Angl-7. And β-CM7 could improve the mRNA of AT1 receptor and Mas receptor. β-CM7 also could improve the mRNA of ACE and ACE2, enhance the activity of ACE and ACE2. These data confirmed tli β-CM7 could activate ACE2-Angl-7-Mas axis, negative passage in RAS, to inhibit the expression ACE mnRiJA and protein in rat myocardium, alleviate the myocardial tissue damage induced by Ang II. The effect of β-CM7 on inhibiting myocardium damage might be related to ACE/ACE2 passageway. PMID:27382769

  14. Stimulation of the renin-angiotensin system in cats with hypertrophic cardiomyopathy.

    PubMed

    Taugner, F M

    2001-01-01

    Feline hypertrophic cardiomyopathy (HCM) is a disease of the ventricular myocardium, which may cause sudden death in cats, but neither the aetiology nor the effect on the circulation are well understood. Fourteen cats of either sex with naturally occurring HCM were studied post mortem. Their ages ranged from 9 months to 10 years with an average age of 4.9 years. Heart weights and heart weight expressed as a percentage of body weight were elevated (27.9 g and 0.65%, respectively) as compared with normal values obtained in previous studies. Myocardial disarray was evident in nine of the 14 cats and moderate to severe fibrosis was present in six animals. To evaluate the renal renin-angiotensin system, semiquantitative morphometric data were obtained by means of renin immunohistochemistry and compared with results from an earlier study of 10 healthy cats by the author. The juxtaglomerular index was 36.8% in the cats with HCM as compared with 30.6% in healthy cats. The renin-positive portion of the afferent arteriole was increased in cats affected by HCM to 86.0 microm as compared with 49.9 microm in normal cats. The increase in kidney renin values in cats with HCM may have been due to decreased blood pressure and reduced renal perfusion resulting from impaired cardiac output. PMID:11578127

  15. Polymorphisms of the renin-angiotensin system genes predict progression of subclinical coronary atherosclerosis.

    PubMed

    Kretowski, Adam; McFann, Kim; Hokanson, John E; Maahs, David; Kinney, Gregory; Snell-Bergeon, Janet K; Wadwa, R Paul; Eckel, Robert H; Ogden, Lorraine; Garg, Satish; Li, Jia; Cheng, Suzanne; Erlich, Henry A; Rewers, Marian

    2007-03-01

    Premature coronary artery disease (CAD) in subjects with type 1 diabetes dramatically affects quality of life and morbidity and leads to premature death, but there is still little known about the mechanisms and predictors of this complication. In the present study, we explored the role of genetic variants of angiotensinogen (AGT, M235T), ACE (I/D), and angiotensin type 1 receptor (ATR1, A1166C) as predictors of rapid progression of subclinical coronary atherosclerosis. Five-hundred eighty-five type 1 diabetic patients and 592 similar age and sex control subjects were evaluated for progression of coronary artery calcification (CAC), a marker of subclinical CAD, before and after a 2.5-year follow-up. In logistic regression analysis, CAC progression was dramatically more likely in type 1 diabetic subjects not treated with ACE inhibitor/angiotensin receptor blocker who had the TT-ID-AA/AC genotype combination than in those with other genotypes (odds ratio 11.6 [95%CI 4.5-29.6], P < 0.0001) and was even stronger when adjusted for cardiovascular disease risk factors and the mean A1C (37.5 [3.6-388], P = 0.002). In conclusion, a combination of genotype variants of the renin-angiotensin system genes is a powerful determinant of subclinical progression of coronary artery atherosclerosis in type 1 diabetic patients and may partially explain accelerated CAD in type 1 diabetes. PMID:17327458

  16. [INTERACTION OF BETA-BLOCKER PROPRANOLOL WITH RENIN-ANGIOTENSIN SYSTEM INHIBITORS IN RAT KIDNEY].

    PubMed

    Kuzmin, O B; Buchneva, N V; Landar, L N

    2016-01-01

    Propranolol injection (0.5 mg/kg, s.c.) in anesthetized rats increases diuresis 1.60 times (p < 0.05) with simultaneous 1.54- and 1.62-fold increase (p < 0.05) in sodium and potassium excretion, respectively. Preliminary inhibition of renin-angiotensin system (RAS) activity using ACE inhibitor enalapril (1 mg/kg, orally, 7 days) increases the sensitivity of rat kidney to drug, increasing its diuretic effect 2.33 times, natriuresis 2.49 times, and urine potassium excretion 1.80 times (p < 0.05). After the preliminary insertion of AT1 angiotensin receptor antagonist losartan (1 mg/kg, orally, 7 days), propranolol causes 1.8-fold increase in diuresis, 2.48-fold decrease in urine sodium, and 1.71-fold decrease in kaliuresis (p < 0.05). Preliminary administration of direct renin inhibitor aliskiren (4 mg/kg, orally, 7 days) is accompanied by 2.30-fold increase in the diuretic effect of propranolol, 2.56-fold increase in natriuresis, and 2.27-fold increase in urine potassium excretion (p < 0.05). It is concluded that the renal tissue RAS is involved in the mechanism of propranolol action in the kidney, acting as modulator preventing excessive loss of water and electrolytes with urine. PMID:27455575

  17. Activation of calpain by renin-angiotensin system in pleural mesothelial cells mediates tuberculous pleural fibrosis.

    PubMed

    Yang, Jie; Xiang, Fei; Cai, Peng-Cheng; Lu, Yu-Zhi; Xu, Xiao-Xiao; Yu, Fan; Li, Feng-Zhi; Greer, Peter A; Shi, Huan-Zhong; Zhou, Qiong; Xin, Jian-Bao; Ye, Hong; Su, Yunchao; Ma, Wan-Li

    2016-07-01

    Pleural fibrosis is defined as an excessive deposition of extracellular matrix (ECM) components that results in destruction of the normal pleural tissue architecture. It can result from diverse inflammatory conditions, especially tuberculous pleurisy. Pleural mesothelial cells (PMCs) play a pivotal role in pleural fibrosis. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodeling. However, the role of calpain in pleural fibrosis remains unknown. In the present study, we found that tuberculous pleural effusion (TPE) induced calpain activation in PMCs and that inhibition of calpain prevented TPE-induced collagen-I synthesis and cell proliferation of PMCs. Moreover, our data revealed that the levels of angiotensin (ANG)-converting enzyme (ACE) were significantly higher in pleural fluid of patients with TPE than those with malignant pleural effusion, and ACE-ANG II in TPE resulted in activation of calpain and subsequent triggering of the phosphatidylinositol 3-kinase (PI3K)/Akt/NF-κB signaling pathway in PMCs. Finally, calpain activation in PMCs and collagen depositions were confirmed in pleural biopsy specimens from patients with tuberculous pleurisy. Together, these studies demonstrated that calpain is activated by renin-angiotensin system in pleural fibrosis and mediates TPE-induced collagen-I synthesis and proliferation of PMCs via the PI3K/Akt/NF-κB signaling pathway. Calpain in PMCs might be a novel target for intervention in tuberculous pleural fibrosis. PMID:27261452

  18. Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System

    PubMed Central

    Weidemann, Benjamin J.; Voong, Susan; Morales-Santiago, Fabiola I.; Kahn, Michael Z.; Ni, Jonathan; Littlejohn, Nicole K.; Claflin, Kristin E.; Burnett, Colin M.L.; Pearson, Nicole A.; Lutter, Michael L.; Grobe, Justin L.

    2015-01-01

    Dietary fats and sodium are both palatable and are hypothesized to synergistically contribute to ingestive behavior and thereby obesity. Contrary to this hypothesis, C57BL/6J mice fed a 45% high fat diet exhibited weight gain that was inhibited by increased dietary sodium content. This suppressive effect of dietary sodium upon weight gain was mediated specifically through a reduction in digestive efficiency, with no effects on food intake behavior, physical activity, or resting metabolism. Replacement of circulating angiotensin II levels reversed the effects of high dietary sodium to suppress digestive efficiency. While the AT1 receptor antagonist losartan had no effect in mice fed low sodium, the AT2 receptor antagonist PD-123,319 suppressed digestive efficiency. Correspondingly, genetic deletion of the AT2 receptor in FVB/NCrl mice resulted in suppressed digestive efficiency even on a standard chow diet. Together these data underscore the importance of digestive efficiency in the pathogenesis of obesity, and implicate dietary sodium, the renin-angiotensin system, and the AT2 receptor in the control of digestive efficiency regardless of mouse strain or macronutrient composition of the diet. These findings highlight the need for greater understanding of nutrient absorption control physiology, and prompt more uniform assessment of digestive efficiency in animal studies of energy balance. PMID:26068176

  19. Involvement of the renin-angiotensin system in abdominal and thoracic aortic aneurysms.

    PubMed

    Lu, Hong; Rateri, Debra L; Bruemmer, Dennis; Cassis, Lisa A; Daugherty, Alan

    2012-11-01

    Aortic aneurysms are relatively common maladies that may lead to the devastating consequence of aortic rupture. AAAs (abdominal aortic aneurysms) and TAAs (thoracic aortic aneurysms) are two common forms of aneurysmal diseases in humans that appear to have distinct pathologies and mechanisms. Despite this divergence, there are numerous and consistent demonstrations that overactivation of the RAS (renin-angiotensin system) promotes both AAAs and TAAs in animal models. For example, in mice, both AAAs and TAAs are formed during infusion of AngII (angiotensin II), the major bioactive peptide in the RAS. There are many proposed mechanisms by which the RAS initiates and perpetuates aortic aneurysms, including effects of AngII on a diverse array of cell types and mediators. These experimental findings are complemented in humans by genetic association studies and retrospective analyses of clinical data that generally support a role of the RAS in both AAAs and TAAs. Given the lack of a validated pharmacological therapy for any form of aortic aneurysm, there is a pressing need to determine whether the consistent findings on the role of the RAS in animal models are translatable to humans afflicted with these diseases. The present review compiles the recent literature that has shown the RAS as a critical component in the pathogenesis of aortic aneurysms. PMID:22788237

  20. Role of mineralocorticoid receptor and renin-angiotensin-aldosterone system in adipocyte dysfunction and obesity.

    PubMed

    Feraco, Alessandra; Armani, Andrea; Mammi, Caterina; Fabbri, Andrea; Rosano, Giuseppe M C; Caprio, Massimiliano

    2013-09-01

    The mineralocorticoid receptor (MR) classically mediates aldosterone effects on salt homeostasis and blood pressure regulation in epithelial target tissues. In recent years, functional MRs have been identified in non classical targets of aldosterone actions, in particular in adipose tissue, where they mediate the effects of aldosterone and glucocorticoids in the control of adipogenesis, adipose expansion and its pro-inflammatory capacity. In this context, inappropriate MR activation has been demonstrated to be a causal factor in several pathologic conditions such as vascular inflammation, endothelial dysfunction, insulin resistance and obesity. The aim of this review is to summarize the latest developments in this rapidly developing field, and will focus on the role of MR and renin-angiotensin-aldosterone system (RAAS) as potential leading characters in the early steps of adipocyte dysfunction and obesity. Indeed modulation of MR activity in adipose tissue has promise as a novel therapeutic approach to treat obesity and its related metabolic complications. This article is part of a Special Issue entitled 'CSR 2013'. PMID:23454117

  1. Renin-angiotensin system blockers regulate the metabolism of isolated fat cells in vitro.

    PubMed

    Caminhotto, R de O; Sertié, R A L; Andreotti, S; Campaãa, A B; Lima, F B

    2016-07-28

    Due to the presence of the renin-angiotensin system (RAS) in tissues and its specific influence on white adipose tissue, fat cells are possible targets of pharmacological RAS blockers commonly used as anti-hypertensive drugs. In the present study, we investigated the effects of different RAS blockers on fat cell metabolism, more specifically on lipolysis, lipogenesis and oxidation of energy substrates. Isolated primary adipocytes were incubated with different RAS blockers (aliskiren, captopril and losartan) in vitro for 24 h and lipolysis, lipogenesis and glucose oxidation capacities were determined in dose-response assays to a β-adrenergic agonist and to insulin. Although no change was found in lipolytic capacity, the RAS blockers modulated lipogenesis and glucose oxidation in a different way. While captopril decreased insulin-stimulated lipogenesis (-19% of maximal response and -60% of insulin responsiveness) due to reduced glucose derived glycerol synthesis (-19% of maximal response and 64% of insulin responsiveness), aliskiren increased insulin-stimulated glucose oxidation (+49% of maximal response and +292% of insulin responsiveness) in fat cells. Our experiments demonstrate that RAS blockers can differentially induce metabolic alterations in adipocyte metabolism, characterized by a reduction in lipogenic responsiveness or an increase in glucose oxidation. The impact of RAS blockers on adipocyte metabolism may have beneficial implications on metabolic disorders during their therapeutic use in hypertensive patients. PMID:27487419

  2. Renin-angiotensin system blockers regulate the metabolism of isolated fat cells in vitro

    PubMed Central

    Caminhotto, R de O.; Sertié, R.A.L.; Andreotti, S.; Campaãa, A.B.; Lima, F.B.

    2016-01-01

    Due to the presence of the renin-angiotensin system (RAS) in tissues and its specific influence on white adipose tissue, fat cells are possible targets of pharmacological RAS blockers commonly used as anti-hypertensive drugs. In the present study, we investigated the effects of different RAS blockers on fat cell metabolism, more specifically on lipolysis, lipogenesis and oxidation of energy substrates. Isolated primary adipocytes were incubated with different RAS blockers (aliskiren, captopril and losartan) in vitro for 24 h and lipolysis, lipogenesis and glucose oxidation capacities were determined in dose-response assays to a β-adrenergic agonist and to insulin. Although no change was found in lipolytic capacity, the RAS blockers modulated lipogenesis and glucose oxidation in a different way. While captopril decreased insulin-stimulated lipogenesis (−19% of maximal response and −60% of insulin responsiveness) due to reduced glucose derived glycerol synthesis (−19% of maximal response and 64% of insulin responsiveness), aliskiren increased insulin-stimulated glucose oxidation (+49% of maximal response and +292% of insulin responsiveness) in fat cells. Our experiments demonstrate that RAS blockers can differentially induce metabolic alterations in adipocyte metabolism, characterized by a reduction in lipogenic responsiveness or an increase in glucose oxidation. The impact of RAS blockers on adipocyte metabolism may have beneficial implications on metabolic disorders during their therapeutic use in hypertensive patients. PMID:27487419

  3. Use of renin angiotensin system inhibitors in patients with chronic kidney disease.

    PubMed

    Adam, W R; Wright, J R

    2016-05-01

    Current guidelines recommend renin angiotensin system inhibitors (RASI) as key components of treatment of hypertension in patients with chronic kidney disease (CKD), because of their effect on reducing the future rate of loss of glomerular filtration rate (GFR). A common risk of RASI in CKD is a haemodynamically mediated, and reversible, fall in GFR of varying severity and duration, any time after commencement of the Inhibitors. A benefit of the acute reduction in filtration rate with RASI may be a reduction in the future rate of loss in GFR: the greatest benefit likely to be in those patients with a greater rate of loss of GFR prior to, and a lesser acute loss of GFR after, introduction of RASI; and in those patients with significant proteinuria. An acute loss of GFR of >25% following the introduction of RASI is an indication to cease the RASI. An acute loss of GFR < 25% requires consideration of the likely risks of the lower GFR and benefits of any future reduced rate of loss of GFR. A fall in GFR in patients while on RASI is usually associated with a remediable cause. When the cause for the fall in GFR is not revealed, and the fall is less than 25%, hopeful expectancy is recommended. Hyperkalaemia in patients with CKD on RASI is more common with more severe disease, potassium retaining diuretics and hypoaldosteronism. Treatment should be modified to maintain a plasma potassium <6 mmol/L. PMID:27170242

  4. The renin-angiotensin system in the pathophysiology of type 2 diabetes.

    PubMed

    Goossens, Gijs H

    2012-01-01

    Increased activation of the renin-angiotensin system (RAS) has been related to cardiovascular disease and type 2 diabetes mellitus. Most randomized clinical trials have demonstrated that RAS blockade reduces the incidence of type 2 diabetes, which has been explained by improved insulin secretion and insulin sensitivity. In this review, an overview of the mechanisms that may underlie the association between the RAS and type 2 diabetes will be provided, with focus on skeletal muscle and adipose tissue function. This will include discussion of several human studies performed in our laboratory to investigate the metabolic and hemodynamic effects of the RAS, combining in vivo measurements of whole-body and tissue metabolism with molecular and immunohistochemical approaches. Available data suggest that the detrimental effects of the RAS on insulin secretion are mediated by a reduction in pancreatic blood flow and induction of islet fibrosis, oxidative stress as well as inflammation, whereas both impaired skeletal muscle function and adipose tissue dysfunction may underlie RAS-induced insulin resistance. Thus, although future studies in humans are warranted, current evidence supports that targeting the RAS in intervention studies may improve metabolic and cardiovascular function in conditions of insulin resistance like obesity and type 2 diabetes. PMID:22986649

  5. Associations between circulating components of the renin-angiotensin-aldosterone system and left ventricular mass.

    PubMed Central

    Schunkert, H.; Hense, H. W.; Muscholl, M.; Luchner, A.; Kürzinger, S.; Danser, A. H.; Riegger, G. A.

    1997-01-01

    OBJECTIVE: Cardiac growth may be modulated in part by the trophic effects of neurohormones. The aim of the present study was to investigate the relation between the basal activity of the renin-angiotensin-aldosterone system and left ventricular mass. DESIGN: A population based sample of 615 middle-age subjects was studied by standardised echocardiography; anthropometric measurements; and biochemical quantification of renin, pro-renin, angiotensinogen, angiotensin converting enzyme (ACE), and aldosterone. RESULTS: Echocardiographic left ventricular mass index correlated significantly with arterial blood pressure, age, and body mass index. In addition, in men ACE activity was significantly related to left ventricular mass index in univariate (P = 0.0007) and multivariate analyses (P = 0.008). Men with left ventricular hypertrophy presented with significantly higher serum ACE concentrations than those with normal left ventricular mass index (P = 0.002). In both men and women serum aldosterone was strongly related to septal and posterior wall thickness. Furthermore, in women serum aldosterone was positively and independently associated with left ventricular mass index (P = 0.0001). This effect was most prominent in hypertensive women. Finally, women with left ventricular hypertrophy presented with significantly higher serum aldosterone (P = 0.01). No significant associations with left ventricular mass index were observed for angiotensinogen, renin, or pro-renin. CONCLUSIONS: The data suggest that the variability of serum ACE or aldosterone, as occurred in this large population based sample, may contribute to the modulation of left ventricular mass. Images PMID:9038690

  6. The brain renin-angiotensin system: a diversity of functions and implications for CNS diseases.

    PubMed

    Wright, John W; Harding, Joseph W

    2013-01-01

    The classic renin-angiotensin system (RAS) was initially described as a hormone system designed to mediate cardiovascular and body water regulation, with angiotensin II as its major effector. The discovery of an independent local brain RAS composed of the necessary functional components (angiotensinogen, peptidases, angiotensins, and specific receptor proteins) significantly expanded the possible physiological and pharmacological functions of this system. This review first describes the enzymatic pathways resulting in active angiotensin ligands and their interaction with AT(1), AT(2), and AT(4) receptor subtypes. Next, we discuss the classic physiologies and behaviors controlled by the RAS including cardiovascular, thirst, and sodium appetite. A final section summarizes non-classic functions and clinical conditions mediated by the brain RAS with focus on memory and Alzheimer's disease. There is no doubt that the brain RAS is an important component in the development of dementia. It also appears to play a role in normal memory consolidation and retrieval. The presently available anti-dementia drugs are proving to be reasonably ineffective, thus alternative treatment approaches must be developed. At the same time, presently available drugs must be tested for their efficacy to treat newly identified syndromes and diseases connected with the RAS. The list of non-classic physiologies and behaviors is ever increasing in both number and scope, attesting to the multidimensional influences of the RAS. Such diversity in function presents a dilemma for both researchers and clinicians. Namely, the blunting of RAS subsystems in the hopes of combating one constellation of underlying causes and disease symptoms may be counter-balanced by unanticipated and unwanted consequences to another RAS subsystem. For example, the use of angiotensin-converting enzyme inhibitors and AT(1) and/or AT(2) receptor blockers have shown great promise in the treatment of cardiovascular related

  7. Renin-angiotensin system gene polymorphisms as risk factors for multiple sclerosis.

    PubMed

    Živković, Maja; Kolaković, Ana; Stojković, Ljiljana; Dinčić, Evica; Kostić, Smiljana; Alavantić, Dragan; Stanković, Aleksandra

    2016-04-15

    The components of renin-angiotensin system, such as angiotensin-converting enzyme (ACE), angiotensin II and angiotensin II receptor type 1 and 2 (AT1R and AT2R), are expressed in the central nervous system and leukocytes and proposed to be involved in the inflammation and pathogenesis of multiple sclerosis (MS). ACE I/D, AT1R 1166A/C and AT2R -1332A/G are functional polymorphisms associated with phenotypes of diverse chronic inflammatory diseases. The aim of this study was to investigate the association between ACE I/D, AT1R 1166A/C and AT2R -1332A/G gene polymorphisms and MS in Serbian population. A total of 470 MS patients and 478 controls participated in the study. Allele-specific polymerase chain reaction (PCR) was performed for genotyping of the ACE polymorphism. The AT1R and AT2R genotyping was done by duplex PCR and restriction fragment length polymorphism analysis. Both ACE homozygotes, II and DD, were significantly overrepresented in MS patients, compared to controls (χ(2) test p=0.03). Neither genotype nor allele frequencies of AT1R 1166A/C polymorphism were significantly different between patients and controls. Significant overrepresentation of AT2R -1332 AA genotype in female patients, compared to female controls, was detected (OR=1.67, 95%CI=1.13-2.49, χ(2) test p=0.01), suggesting that this genotype could be a gender-specific genetic risk factor for MS. PMID:27000216

  8. Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue

    PubMed Central

    Santos, Carlos F.; Morandini, Ana C.; Dionísio, Thiago J.; Faria, Flávio A.; Lima, Marta C.; Figueiredo, Caio M.; Colombini-Ishikiriama, Bella L.; Sipert, Carla R.; Maciel, Rubens P.; Akashi, Ana P.; Souza, Gabriela P.; Garlet, Gustavo P.; Rodini, Camila O.; Amaral, Sandra L.; Becari, Christiane; Salgado, Maria C.; Oliveira, Eduardo B.; Matus, Isaac; Didier, Daniela N.; Greene, Andrew S.

    2015-01-01

    The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression were found between healthy and diseased gingiva. However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts. When compared to healthy tissue, ACE activity was increased in human gingiva from volunteers with gingivitis. Human-gingiva homogenates generated Ang II, Ang 1-9 and Ang 1-7 when incubated with precursors. In gingiva homogenates, Ang II formation from Ang I was nearly abolished only when captopril and chymostatin were combined. Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin. In rat gingiva, RAS components were also found; their expression was not different between healthy and experimentally induced periodontitis (EP) groups. However, renin inhibition (aliskiren) and an AT1R antagonist (losartan) significantly blocked EP-alveolar-bone loss in rats. Collectively, these data are consistent with the hypothesis that a local RAS system is not only present but is also functional in both human and rat periodontal tissue. Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats. PMID:26244896

  9. Effect of propranolol on the splanchnic and peripheral renin angiotensin system in cirrhotic patients

    PubMed Central

    Vilas-Boas, Walkíria Wingester; Jr, Antônio Ribeiro-Oliveira; da Cunha Ribeiro, Renata; Vieira, Renata Lúcia Pereira; Almeida, Jerusa; Nadu, Ana Paula; Silva, Ana Cristina Simões e; Santos, Robson Augusto Souza

    2008-01-01

    AIM: To evaluate the effect of β-blockade on angiotensins in the splanchnic and peripheral circulation of cirrhotic patients and also to compare hemodynamic parameters during liver transplantation according to propranolol pre-treatment or not. METHODS: Patients were allocated into two groups: outpatients with advanced liver disease(LD) and during liver transplantation(LT). Both groups were subdivided according to treatment with propranolol or not. Plasma was collected through peripheral venipuncture to determine plasma renin activity(PRA), Angiotensin(Ang) I, Ang II, and Ang-(1-7) levels by radioimmunoassay in LD group. During liver transplantation, hemodynamic parameters were determined and blood samples were obtained from the portal vein to measure renin angiotensin system(RAS) components. RESULTS: PRA, Ang I, Ang II and Ang-(1-7) were significantly lower in the portal vein and periphery in all subgroups treated with propranolol as compared to non-treated. The relationships between Ang-(1-7) and Ang I levels and between Ang II and Ang I were significantly increased in LD group receiving propranolol. The ratio between Ang-(1-7) and Ang II remained unchanged in splanchnic and peripheral circulation in patients under β-blockade, whereas the relationship between Ang II and Ang I was significantly increased in splanchnic circulation of LT patients treated with propranolol. During liver transplantation, cardiac output and index as well systemic vascular resistance and index were reduced in propranolol-treated subgroup. CONCLUSION: In LD group, propranolol treatment reduced RAS mediators, but did not change the ratio between Ang-(1-7) and Ang II in splanchnic and peripheral circulation. Furthermore, the modification of hemodynamic parameters in propranolol treated patients was not associated with changes in the angiotensin ratio. PMID:19058308

  10. Recent Updates on the Proximal Tubule Renin-Angiotensin System in Angiotensin II-Dependent Hypertension.

    PubMed

    Li, Xiao C; Zhuo, Jia L

    2016-08-01

    It is well recognized that the renin-angiotensin system (RAS) exists not only as circulating, paracrine (cell to cell), but also intracrine (intracellular) system. In the kidney, however, it is difficult to dissect the respective contributions of circulating RAS versus intrarenal RAS to the physiological regulation of proximal tubular Na(+) reabsorption and hypertension. Here, we review recent studies to provide an update in this research field with a focus on the proximal tubular RAS in angiotensin II (ANG II)-induced hypertension. Careful analysis of available evidence supports the hypothesis that both local synthesis or formation and AT1 (AT1a) receptor- and/or megalin-mediated uptake of angiotensinogen (AGT), ANG I and ANG II contribute to high levels of ANG II in the proximal tubules of the kidney. Under physiological conditions, nearly all major components of the RAS including AGT, prorenin, renin, ANG I, and ANG II would be filtered by the glomerulus and taken up by the proximal tubules. In ANG II-dependent hypertension, the expression of AGT, prorenin, and (pro)renin receptors, and angiotensin-converting enzyme (ACE) is upregulated rather than downregulated in the kidney. Furthermore, hypertension damages the glomerular filtration barrier, which augments the filtration of circulating AGT, prorenin, renin, ANG I, and ANG II and their uptake in the proximal tubules. Together, increased local ANG II formation and augmented uptake of circulating ANG II in the proximal tubules, via activation of AT1 (AT1a) receptors and Na(+)/H(+) exchanger 3, may provide a powerful feedforward mechanism for promoting Na(+) retention and the development of ANG II-induced hypertension. PMID:27372447

  11. Low LBNP Tolerance in Men is Associated With Attenuated Activation of Renin-Angiotensin System

    NASA Technical Reports Server (NTRS)

    Greenleaf, John E.; Petersen, T. W.; Gabrielsen, A.; Pump, B.; Bie, P.; Christensen, N.-J.; Warberg, J.; Videbaeck, R.; Simonson, S. R.; Norsk, P.; Dalton, Bonnie P. (Technical Monitor)

    1999-01-01

    Vasoactive hormone concentrations (epinephrine (pE), norepinephrine (pNE), angiotensin II (pATII), vasopressin (pVP), endothelin 1 (pET1)] and plasma renin activity (pRA) were measured during lower body negative pressure (LBNP) to test the hypothesis that responsiveness of the reninangiotensin system is related to LBNP tolerance. Healthy men (2,822 cal per day, 2 mmol per kilogram per day Na (+)) were exposed to 30 min of progressive LBNP to -50mmHg. LBNP was uneventful for 7 men (2512 yr, HiTol group), but 8 men (26 plus or minus 3 yr) reached pre-syncope after 11 plus or minus 1 min (P less than 0.001, LoTol group). Mean arterial pressure was unchanged. Central venous pressure and left atrial diameter decreased in both groups (5-6 mmHg by 30%, P less than 0.05). Control [hormone] were similar but, pRA differed between groups (LoTol 0.6 plus or minus 0.1, HiTol 1.2 plus or minus 0.1 ng Ang1 per milliliter per hour, per hour, P less than 0.05). LBNP increased (P less than 0.05) pRA and pATII more in HiTol (9.9 plus or minus 2.2 ng Ang1 per milliliter per hour and 58 plus or minus 12 pg per milliliter) than LoTol (4.3 plus or minus 0.9 ng Angl per milliliter per hour and 28 plus or minus 6 pg per milliliter). In contrast, pVP was higher (P less than 0.05) in LoTol than in HiTol. The response of the renin-angiotensin system seems linked to the occurrence of pre-syncope, and measurement of resting pRA may be predictive.

  12. Decongestion Strategies and Renin-Angiotensin-Aldosterone System Activation in Acute Heart Failure

    PubMed Central

    Mentz, Robert J.; Stevens, Susanna R.; DeVore, Adam D.; Lala, Anuradha; Vader, Justin M.; AbouEzzeddine, Omar F.; Khazanie, Prateeti; Redfield, Margaret M.; Stevenson, Lynne W.; O'Connor, Christopher M.; Goldsmith, Steven R.; Bart, Bradley A.; Anstrom, Kevin J.; Hernandez, Adrian F.; Braunwald, Eugene; Felker, G. Michael

    2014-01-01

    Background High dose diuretics in patients with acute heart failure (AHF) are thought to activate the renin-angiotensin-aldosterone system (RAAS), and alternative decongestion strategies, such as ultrafiltration (UF), have been proposed to mitigate this RAAS activation. Methods We analyzed 427 AHF patients enrolled in the DOSE-AHF and CARRESS-HF trials. We assessed the relationship between two markers of RAAS activation (plasma renin activity [PRA] and aldosterone) from baseline to 72-96h and decongestion strategy; high vs. low-dose and continuous infusion vs. bolus furosemide for DOSE-AHF and UF vs. stepped pharmacologic care for CARRESS-HF. We determined the relationship between RAAS biomarkers and 60-day outcomes. Results Patients with greater RAAS activation at baseline had lower blood pressures, lower serum sodium, and higher BUN. Continuous infusion furosemide and UF were associated with greater PRA increases (median +1.66 vs. +0.66 ng/mL/h with continuous vs. bolus, P=0.021; +4.05 vs. +0.56 ng/mL/h with UF vs. stepped care, P=0.014). There was no significant difference in RAAS biomarker change with high vs. low-dose diuretics (both P>0.5). Neither baseline log PRA nor log aldosterone was associated with increased death/HF hospitalization (HR for a doubling 1.05; 95% CI: 0.98-1.13, P=0.18 and HR 1.13; 95% CI: 0.99-1.28, P=0.069, respectively). The change in RAAS biomarkers from baseline to 72-96 h was not associated with outcomes (both P>0.5). Conclusions High-dose loop diuretics did not result in greater RAAS activation than low-dose diuretics. UF resulted in greater PRA increase than stepped pharmacologic care. Neither PRA nor aldosterone was significantly associated with short-term outcomes in this cohort. PMID:25543972

  13. The renin angiotensin system regulates Kupffer cells in colorectal liver metastases.

    PubMed

    Wen, Shu Wen; Ager, Eleanor I; Neo, Jaclyn; Christophi, Christopher

    2013-08-01

    Blockade of the renin angiotensin system (RAS) can inhibit tumor growth and this may be mediated via undefined immunomodulatory actions. This study investigated the effects of RAS blockade on liver macrophages (Kupffer cells; KCs) in an orthotopic murine model of colorectal cancer (CRC) liver metastases. Here we showed that pharmacological targeting of the RAS [ANG II (31.25 µg/kg/h i.p.), ANG-(1-7) (24 µg/kg/h i.p.) or the ACE inhibitor; captopril (750 mg/kg/d i.p.)] altered endogenous KC numbers in the tumor-bearing liver throughout metastatic growth. Captopril, and to a lesser extent ANG-(1-7), increased KC numbers in the liver but not tumor. KCs were found to express the key RAS components: ACE and AT1R. Treatment with captopril and ANG II increased the number of AT1R-expressing KCs, although total KC numbers were not affected by ANG II. Captopril (0.1 µM) also increased macrophage invasion in vitro. Additionally, captopril was administered with KC depletion before tumor induction (day 0) or at established metastatic growth (day 18) using gadolinium chloride (GdCl 3; 20 mg/kg). Livers were collected at day 21 and quantitative stereology used as a measure of tumor burden. Captopril reduced growth of CRC liver metastases. However, when captopril was combined with early KC depletion (day 0) tumor growth was significantly increased compared with captopril alone. In contrast, late KC depletion (day 18) failed to influence the anti-tumor effects of captopril. The result of these studies suggests that manipulation of the RAS can alter KC numbers and may subsequently influence progression of CRC liver metastases. PMID:23792575

  14. Fetal sex affects expression of renin-angiotensin system components in term human decidua.

    PubMed

    Wang, Yu; Pringle, Kirsty G; Sykes, Shane D; Marques, Francine Z; Morris, Brian J; Zakar, Tamas; Lumbers, Eugenie R

    2012-01-01

    The maternal decidua expresses the genes of the renin-angiotensin system (RAS). Human decidua was collected at term either before labor (i.e. cesarean delivery) or after spontaneous labor. The mRNA for prorenin (REN), prorenin receptor (ATP6AP2), angiotensinogen (AGT), angiotensin-converting enzymes 1 and 2 (ACE1 and ACE2), angiotensin II type 1 receptor (AGTR1), and angiotensin 1-7 receptor (MAS1) were measured by quantitative real-time RT-PCR. Decidual explants were cultured in duplicate for 24 and 48 h, and all RAS mRNA, and the secretion of prorenin, angiotensin II, and angiotensin 1-7 was measured using quantitative real-time RT-PCR, ELISA, and radioimmunoassay, respectively. In the decidua collected before labor, REN mRNA levels were higher if the fetus was female. In addition, REN, ATP6AP2, AGT, and MAS1 mRNA abundance was greater in decidual explants collected from women carrying a female fetus, as was prorenin protein. After 24 h, ACE1 mRNA was higher in the decidual explants from women with a male fetus, whereas after 48 h, both ACE1 and ACE2 mRNA was higher in decidual explants from women with a female fetus. Angiotensin II was present in all explants, but angiotensin 1-7 levels often registered below the lower limits of sensitivity for the assay. After labor, decidua, when compared with nonlaboring decidua, demonstrated lower REN expression when the fetus was female. Therefore, the maternal decidual RAS is regulated in a sex-specific manner, suggesting that it may function differently when the fetus is male than when it is female. PMID:22045662

  15. Blockade of the renin-angiotensin system improves cerebral microcirculatory perfusion in diabetic hypertensive rats.

    PubMed

    Estato, Vanessa; Obadia, Nathalie; Carvalho-Tavares, Juliana; Freitas, Felipe Santos; Reis, Patrícia; Castro-Faria Neto, Hugo; Lessa, Marcos Adriano; Tibiriçá, Eduardo

    2013-05-01

    We examined the functional and structural microcirculatory alterations in the brain, skeletal muscle and myocardium of non-diabetic spontaneously hypertensive rats (SHR) and diabetic SHR (D-SHR), as well as the effects of long-term treatment with the angiotensin AT1-receptor antagonist olmesartan and the angiotensin-converting enzyme inhibitor enalapril. Diabetes was experimentally induced by a combination of a high-fat diet with a single low dose of streptozotocin (35 mg/kg, intraperitoneal injection). D-SHR were orally administered with olmesartan (5 mg/kg/day), enalapril (10 mg/kg/day) or vehicle for 28 days, and compared with vehicle-treated non-diabetic SHR or normotensive non-diabetic Wistar-Kyoto rats. The cerebral and skeletal muscle functional capillary density of pentobarbital-anesthetized rats was assessed using intravital fluorescence videomicroscopy. Chronic treatment with olmesartan or enalapril significantly lowered blood pressure and reversed brain functional capillary rarefaction. Brain oxidative stress was reduced to non-diabetic control levels in animals treated with olmesartan or enalapril. Histochemical analysis of the structural capillary density showed that both olmesartan and enalapril increased the capillary-to-fiber ratio in skeletal muscle and the capillary-to-fiber volume density in the left ventricle. Olmesartan and enalapril also prevented collagen deposition and the increase in cardiomyocyte diameter in the left ventricle. Our results suggest that the association between hypertension and diabetes results in microvascular alterations in the brain, skeletal muscle and myocardium that can be prevented by chronic blockade of the renin-angiotensin system. PMID:23466285

  16. Intrarenal renin-angiotensin system mediates fatty acid-induced ER stress in the kidney.

    PubMed

    Li, Chunling; Lin, Yu; Luo, Renfei; Chen, Shaoming; Wang, Feifei; Zheng, Peili; Levi, Moshe; Yang, Tianxin; Wang, Weidong

    2016-03-01

    Obesity-related kidney disease is related to caloric excess promoting deleterious cellular responses. Accumulation of saturated free fatty acids in tubular cells produces lipotoxicity involving significant cellular dysfunction and injury. The objectives of this study were to elucidate the role of renin-angiotensin system (RAS) activation in saturated fatty acid-induced endoplasmic reticulum (ER) stress in cultured human proximal tubule epithelial cells (HK2) and in mice fed with a high-fat diet. Treatment with saturated fatty acid palmitic acid (PA; 0.8 mM) for 24 h induced ER stress in HK2, leading to an unfolded protein response as reflected by increased expressions of the ER chaperone binding immunoglobulin protein (BiP) and proapoptotic transcription factor C/EBP homologous protein (CHOP) protein as evaluated by immunoblotting. PA treatment also induced increased protein expression of inositol requiring protein 1α (IRE1α), phosphorylated eukaryotic initiation factor-α (eIF2α), and activating transcription factor 4 (ATF4) as well as activation of caspase-3. PA treatment was associated with increased angiotensin II levels in cultured medium. The angiotensin II type 1 receptor (AT1R) blocker valsartan or renin inhibitor aliskiren dramatically suppressed PA-induced upregulation of BiP, CHOP, IRE1α, p-eIF2α, and ATF4 in HK2 cells. In contrast, valsartan or aliskiren did not prevent ER stress induced by tunicamycin. C57BL/6 mice fed with a high-fat diet for 14 wk exhibited increased protein expressions of BiP and CHOP compared with control mice, which were significantly attenuated by the valsartan treatment. Increased angiotensin II levels in serum and urine were observed in mice fed with a high-fat diet when compared with controls. It is suggested that the intrarenal RAS activation may play an important role in diabetic kidney injury via mediating ER stress induced by saturated fatty acid. PMID:26672616

  17. The association of renin-angiotensin system genes with the progression of hepatocellular carcinoma.

    PubMed

    Ye, Guanxiong; Qin, Yong; Lu, Xianghong; Xu, Xiangdong; Xu, Shengqian; Wu, Chengjun; Wang, Xinmei; Wang, Shi; Pan, Debiao

    2015-03-27

    Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Angiogenesis is reported to play a pivotal role in the occurrence, development and metastasis of HCC. The renin-angiotensin system (RAS) is involved in the regulation of angiogenesis. Here, based on the analysis of HCC datasets from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA), we found that there was a negative correlation between the mRNA levels of angiotensin converting enzyme 2 (ACE2) and CD34. To explore the association of RAS with the progression from fibrosis to cirrhosis to HCC, liver specimens and serum samples were collected from patients with hepatic fibrosis, cirrhosis and HCC. Relative hepatic mRNA levels of CD34 and ACE2 were determined by real-time PCR, and the serum concentrations of Angiotensin II (Ang II), Ang (1-7) and vascular endothelial growth factor (VEGF) were detected by ELISA. We found that ACE2 mRNA was gradually decreased, while CD34 mRNA was progressively increased with the increasing grade of disease severity. Concentrations of Ang II, Ang (1-7) and VEGF were higher in the sera of patients than in that of healthy volunteers. These proteins' concentrations were also progressively increased with the increasing grade of disease severity. Moreover, a positive correlation was found between VEGF and Ang II or Ang (1-7), while negative correlation was observed between mRNA levels of CD34 and ACE2. More importantly, patients with higher level of ACE2 expression had longer survival time than those with lower level of ACE2 expression. Taken together, our data suggests that the low expression of ACE2 may be a useful indicator of poor prognosis in HCC. The RAS may have a role in the progression of HCC. PMID:25701390

  18. Chronic Renin-Angiotensin System (RAS) Blockade May Not Induce Hypotension During Anaesthesia for Bariatric Surgery.

    PubMed

    Salvetti, Guido; Di Salvo, Claudio; Ceccarini, Giovanni; Abramo, Antonio; Fierabracci, Paola; Magno, Silvia; Piaggi, Paolo; Vitti, Paolo; Santini, Ferruccio

    2016-06-01

    The use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) for the treatment of hypertensive obese patients is steadily increasing. Some studies have reported that the use of these drugs was associated with an increased risk of hypotensive episodes, during general anaesthesia. The number of bariatric procedures is also increasing worldwide, but there is a lack of studies investigating the hypotensive effect of renin-angiotensin system (RAS) blockers in severely obese patients during general anaesthesia for bariatric surgery. The aim of this pilot study was to evaluate hemodynamic changes induced by general anaesthesia in obese patients chronically treated with ACE-I or ARB compared to a control group not treated with antihypertensive therapy. Fourteen obese subjects (mean body mass index (BMI) 47.5 kg/m(2)) treated with ACE-I or ARB and twelve obese (mean BMI 45.7 kg/m2) controls not treated with antihypertensive therapy underwent general anaesthesia to perform laparoscopic bariatric surgery. Systolic blood pressure, diastolic blood pressure, and heart rate were monitored continuously and registered at different time points: T0 before induction, then at 2, 5, 7, 10, 15, 20, 30, 60, 90, 120, and 150 min after induction, and the last time point taken following recovery from anaesthesia. A progressive reduction of both systolic and diastolic blood pressure values was observed without significant differences between the two groups. A similar trend of heart rate values was observed. In conclusion, our pilot study suggests that RAS blockers may be continued during the perioperative period in patients undergoing bariatric surgery, without increasing the risk of hypotensive episodes. PMID:26328531

  19. Effects of dapagliflozin on blood pressure in hypertensive diabetic patients on renin-angiotensin system blockade.

    PubMed

    Weber, Michael A; Mansfield, Traci A; Alessi, Federica; Iqbal, Nayyar; Parikh, Shamik; Ptaszynska, Agata

    2016-04-01

    Hypertension and type 2 diabetes mellitus (T2DM) are risk factors for cardiovascular disease. Dapagliflozin improves glycemic control and systolic blood pressure (SBP) in T2DM patients. This double-blind phase III study evaluated the effects of dapagliflozin on glycemic control and blood pressure in patients with inadequately controlled T2DM and hypertension, despite ongoing therapy with a renin-angiotensin system blocker. Patients were randomized to receive dapagliflozin 10 mg (n = 302) or placebo (n = 311) once daily for 12 weeks. Endpoints were change from baseline to week 12 in seated SBP and glycosylated hemoglobin (HbA1c); longitudinal repeated-measures analysis was performed. Additional endpoints included other hemodynamic measures, serum uric acid, fasting plasma glucose, body weight, blood lipids and heart rate. After 12 weeks, dapagliflozin-treated versus placebo-treated patients showed significant reductions in HbA1c (-0.6% vs -0.1%, p < 0.0001), mean seated SBP (-10.4 vs -7.3 mmHg, p = 0.0010) and mean 24 h ambulatory SBP (-9.6 vs -6.7 mmHg, p = 0.0043). Dapagliflozin also reduced body weight compared with placebo (-1.0 vs -0.3 kg). Dapagliflozin was well tolerated, with adverse events consistent with previous studies. Dapagliflozin improved glycemic control, and reduced SBP as well as body weight in patients with poorly controlled T2DM and hypertension. PMID:26623980

  20. Age-Associated Changes in the Vascular Renin-Angiotensin System in Mice

    PubMed Central

    Yoon, Hye Eun; Kim, Eun Nim; Kim, Min Young; Lim, Ji Hee; Jang, In-Ae; Ban, Tae Hyun; Shin, Seok Joon; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2016-01-01

    Background. This study evaluated whether the change in the renin-angiotensin system (RAS) is associated with arterial aging in mice. Methods. Histologic changes and expressions of transforming growth factor-β (TGF-β), collagen IV, fibronectin, angiotensin II (Ang II), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), prorenin receptor (PRR), Mas receptor (MasR), endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and oxidase 4 (Nox2 and Nox4), 8-hydroxy-2′-deoxyguanosine (8-OHdG), 3-nitrotyrosine, and superoxide dismutase 1 and dismutase 2 (SOD1 and SOD2) were measured in the thoracic aortas from 2-month-old, 12-month-old, and 24-month-old C57/BL6 mice. Results. Twenty-four-month-old mice showed significantly increased aortic media thickness and expressions of TGF-β, collagen IV, and fibronectin, compared to 2-month-old and 12-month-old mice. The expressions of PRR, ACE, and Ang II, and AT1R-positive area significantly increased, whereas expressions of ACE2 and MasR and AT2R-positive area decreased with age. The expressions of phosphorylated serine1177-eNOS, SOD1, and SOD2 decreased, and the 8-OHdG-positive area and the 3-nitrotyrosine-positive area increased with age. The expression of Nox2 significantly increased with age, but that of Nox4 did not change. Conclusions. The enhanced PRR-ACE-Ang II-AT1R axis and reduced ACE2-MasR axis were associated with arterial aging in mice. PMID:27200147

  1. Saga of renin-angiotensin system and calcium channels in hypertensive diabetics: does it have a therapeutic edge?

    PubMed

    Kumar, Arun H S; Ramarao, P

    2005-01-01

    Current understanding of the genesis of diabetic vascular disease suggests that vascular complications, such as atherosclerosis and hypertension, are associated with changes in structural and functional parameters. Experimental and epidemiological data suggest that activation of the renin-angiotensin-aldosterone system plays an important role in the development of micro- and macro-vascular complications. Most of the negative cardiovascular actions of angiotensin II are mediated through AT1 receptors, whereas the AT2 receptors mediate largely beneficial effects. Hence, compared to angiotensin converting enzyme inhibitors (ACEIs), selective AT1 receptor blockers (ARBs) should provide additional end organ protection via AT2 receptors activation. Although ACEIs are useful therapeutically, they are being currently displaced by ARBs. Enhanced calcium ion channel activity is reported in vascular smooth muscles from diabetic animal models. Clinical benefits of calcium channel blockers (CCBs) in diabetic hypertensive patients are controversial, but there is increasing experimental evidence for the beneficial effects of dihydropyridine-type CCBs. Although the treatment of hypertension in diabetics reduces cardiovascular and microvascular complications, the ideal strategy for treating hypertension in diabetics has not been well defined and warrants a combination approach. Only limited clinical data regarding the use of ARBs in combination with CCBs in diabetics are available. The experimental data suggest that combination of a CCB and an AT1 receptor blocker, or a hypothetical dual blocker of AT1 receptors as well as of calcium channels would be an ideal regimen. There is, however, no conclusive clinical evidence to support the combined use of these drugs. This review highlights the available experimental data that support the therapeutic benefits of this combination. PMID:16007228

  2. Time to retrieve the best benefits from renin angiotensin aldosterone system (RAAS) inhibition in heart failure patients with reduced ejection fraction: lessons from randomized controlled trials and registries.

    PubMed

    Rossignol, Patrick; Zannad, Faiez; Pitt, Bertram

    2014-12-20

    Numerous registries, including the most recent ESC Euro-observational registry, have reported a large and persistent gap between real-life practice in the use of life-saving evidence-based therapies (such as renin angiotensin antagonists, beta-blockers, mineralocorticoid receptor antagonists) and recommended practices in international guidelines. Although the use of multiple renin angiotensin aldosterone system-inhibitors is associated with the development of worsening renal function and hyperkalemia in patients with heart failure and reduced ejection fraction, increased efforts should be expended to initiate and maintain target doses of these agents so as to provide their benefits on mortality and hospitalizations for heart failure. PMID:25465821

  3. Characterization of a local renin-angiotensin system in rat gingival tissue

    PubMed Central

    Santos, C.F.; Akashi, A.E.; Dionísio, T.J.; Sipert, C.R.; Didier, D.N.; Greene, A.S.; Oliveira, S.H.P.; Pereira, H.J.; Becari, C.; Oliveira, E.B.; Salgado, M.C.O.

    2009-01-01

    Background Systemic renin-angiotensin system (RAS) promotes plasmatic production of angiotensin (Ang) II, which acts through interaction with specific receptors. There is growing evidence that local systems in various tissues and organs are capable of generating angiotensins independently of circulating RAS. The aims of this work were to: 1) study the expression and localization of RAS components in rat gingival tissue and 2) evaluate the in vitro production of Ang II and other peptides catalyzed by rat gingival tissue homogenates incubated with different Ang II precursors. Methods Reverse transcription-polymerase chain reaction (RT-PCR) assessed mRNA expression. Immunohistochemical (IHC) analysis aimed to detect and localize renin. Standardized fluorimetric method with tripeptide Hippuryl-Histidyl-Leucine (Hip-His-Leu) was used to measure tissue ACE activity, while high performance liquid chromatography (HLPC) showed products formed after incubation of tissue homogenates with Ang I or tetradecapeptide renin substrate (TDP). Results mRNA for renin, angiotensinogen, ACE and Ang II receptors (AT1a, AT1b and AT2) was detected in gingival tissue; cultured gingival fibroblasts expressed renin, angiotensinogen and AT1a receptor. Renin was present in the vascular endothelium and intensely expressed in the epithelial basal layer of periodontally affected gingival tissue. ACE activity was detected (4.95±0.89 nmol His-Leu/g.min). When Ang I was used as substrate, Ang 1-9 (0.576±0.128 nmol/mg.min), Ang II (0.066±0.008 nmol/mg.min) and Ang 1-7 (0.111±0.017 nmol/mg.min) were formed, whereas these same peptides (0.139±0.031; 0.206±0.046 and 0.039±0.007 nmol/mg.min, respectively) and Ang I (0.973±0.139 nmol/mg.min) were formed when TDP was the substrate. Conclusion Results presented here clearly show existence of a local RAS in rat gingival tissue, which is capable of generating Ang II and other vasoactive peptides in vitro. PMID:19228099

  4. 1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system

    PubMed Central

    Li, Yan Chun; Kong, Juan; Wei, Minjie; Chen, Zhou-Feng; Liu, Shu Q.; Cao, Li-Ping

    2002-01-01

    Inappropriate activation of the renin-angiotensin system, which plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis, may represent a major risk factor for hypertension, heart attack, and stroke. Mounting evidence from clinical studies has demonstrated an inverse relationship between circulating vitamin D levels and the blood pressure and/or plasma renin activity, but the mechanism is not understood. We show here that renin expression and plasma angiotensin II production were increased severalfold in vitamin D receptor–null (VDR-null) mice, leading to hypertension, cardiac hypertrophy, and increased water intake. However, the salt- and volume-sensing mechanisms that control renin synthesis are still intact in the mutant mice. In wild-type mice, inhibition of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] synthesis also led to an increase in renin expression, whereas 1,25(OH)2D3 injection led to renin suppression. We found that vitamin D regulation of renin expression was independent of calcium metabolism and that 1,25(OH)2D3 markedly suppressed renin transcription by a VDR-mediated mechanism in cell cultures. Hence, 1,25(OH)2D3 is a novel negative endocrine regulator of the renin-angiotensin system. Its apparent critical role in electrolytes, volume, and blood pressure homeostasis suggests that vitamin D analogues could help prevent or ameliorate hypertension. PMID:12122115

  5. Association between the intrarenal renin-angiotensin system and renal injury in chronic kidney disease of dogs and cats.

    PubMed

    Mitani, Sawane; Yabuki, Akira; Taniguchi, Kazuyuki; Yamato, Osamu

    2013-02-01

    The association of renin and angiotensin II, which are potent components of the renin-angiotensin system, with the severity of chronic renal disease was investigated immunohistochemically in dogs and cats. Immunoreactivities of renin and angiotensin II were evaluated quantitatively, and their correlations with the degrees of glomerulosclerosis, glomerular hypertrophy, interstitial cell infiltration and interstitial fibrosis were statistically analyzed. Immunoreactivities for renin were detected in afferent arteries in both dogs and cats. The score of renin-positive signals showed no correlation with plasma creatinine concentration or any of the histopathological parameters, except for the diameter of glomeruli in dogs. Immunoreactivities for angiotensin II were detected in tubules (primarily proximal tubules) and interstitial mononuclear cells in both dogs and cats. The score of tubular angiotensin II correlated with glomerulosclerosis and cell infiltration in cats but not in dogs. The score of interstitial angiotensin II correlated with plasma creatinine concentration, glomerulosclerosis, cell infiltration and fibrosis in dogs and with glomerulosclerosis and cell infiltration in cats. In conclusion, the results of the study suggest that intrarenal renin-angiotensin system is correlated with the severity of kidney disease, with the underlying mechanism differing between dogs and cats. PMID:22986274

  6. Retarding the progression of chronic kidney disease with renin angiotensin system blockade.

    PubMed

    Limesh, M; Annigeri, R A; Mani, M K; Kowdle, P C; Rao, B Subba; Balasubramanian, S; Seshadri, R

    2012-03-01

    We assessed the effect of renin angiotensin system blockade (RASB) in chronic kidney disease (CKD) of diverse etiology. Two hundred and sixty-five consecutive CKD patients attending our renal clinic, with estimated glomerular filtration rate (eGFR) of 20-70 ml/min/1.73m(2) at baseline and a minimal follow-up of 1 year, were studied retrospectively. We devised a scoring system to quantify RASB, wherein the maximum dose of an agent recommended for control of hypertension was scored as 1. The renal endpoints studied were the rate of change in eGFR (ΔeGFR) and decline of eGFR>50%. The mean age was 48 ± 11.2 years and 69% were male. The mean duration of follow-up was 4 ± 2.7 years. The rate of ΔeGFR was -1.5 ± 5.0 ml/min/1.73 m(2) per year in patients who received RASB (N=168) and -6.0 ± 5.4 in those who did not (N=97) (P<0.001). The incidence of decline of eGFR >50% was 11.3% with RASB and 24.7% without (P=0.003). In a subgroup of patients who received RASB, the incidence of decline of eGFR >50% was 17.8% in the low-dose RASB group (N=84, RASB score 0.63 ± 0.38) and 4.8% in the high-dose group (N=84, RASB score 2.5 ± 0.7) (P=0.001). RASB was associated with significantly better renoprotection in CKD of diverse etiology, even in nonproteinuric diseases. This effect appeared to be dose-dependent, with higher supramaximal doses exhibiting better renoprotection than the lower conventional doses. Our results make a strong case for use of aggressive RASB in all CKD patients to postpone end-stage renal disease. PMID:22787312

  7. Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and ACE inhibition.

    PubMed

    Gonzalez-Villalobos, Romer A; Satou, Ryousuke; Ohashi, Naro; Semprun-Prieto, Laura C; Katsurada, Akemi; Kim, Catherine; Upchurch, G M; Prieto, Minolfa C; Kobori, Hiroyuki; Navar, L Gabriel

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibition (ACEi) ameliorates the development of hypertension and the intrarenal ANG II augmentation in ANG II-infused mice. To determine if these effects are associated with changes in the mouse intrarenal renin-angiotensin system, the expression of angiotensinogen (AGT), renin, ACE, angiotensin type 1 receptor (AT(1)R) mRNA (by quanitative RT-PCR) and protein [by Western blot (WB) and/or immunohistochemistry (IHC)] were analyzed. C57BL/6J male mice (9-12 wk old) were distributed as controls (n = 10), ANG II infused (ANG II = 8, 400 ng x kg(-1) x min(-1) for 12 days), ACEi only (ACEi = 10, lisinopril, 100 mg/l), and ANG II infused + ACEi (ANG II + ACEi = 11). When compared with controls (1.00), AGT protein (by WB) was increased by ANG II (1.29 +/- 0.13, P < 0.05), and this was not prevented by ACEi (ACEi + ANG II, 1.31 +/- 0.14, P < 0.05). ACE protein (by WB) was increased by ANG II (1.21 +/- 0.08, P < 0.05), and it was reduced by ACEi alone (0.88 +/- 0.07, P < 0.05) or in combination with ANG II (0.80 +/- 0.07, P < 0.05). AT(1)R protein (by WB) was increased by ANG II (1.27 +/- 0.06, P < 0.05) and ACEi (1.17 +/- 0.06, P < 0.05) but not ANG II + ACEi [1.15 +/- 0.06, not significant (NS)]. Tubular renin protein (semiquantified by IHC) was increased by ANG II (1.49 +/- 0.23, P < 0.05) and ACEi (1.57 +/- 0.15, P < 0.05), but not ANG II + ACEi (1.10 +/- 0.15, NS). No significant changes were observed in AGT, ACE, or AT(1)R mRNA. In summary, reduced responses of intrarenal tubular renin, ACE, and the AT(1)R protein to the stimulatory effects of chronic ANG II infusions, in the presence of ACEi, are associated with the effects of this treatment to ameliorate augmentations in blood pressure and intrarenal ANG II content during ANG II-induced hypertension. PMID:19846570

  8. Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and ACE inhibition

    PubMed Central

    Satou, Ryousuke; Ohashi, Naro; Semprun-Prieto, Laura C.; Katsurada, Akemi; Kim, Catherine; Upchurch, G. M.; Prieto, Minolfa C.; Kobori, Hiroyuki; Navar, L. Gabriel

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibition (ACEi) ameliorates the development of hypertension and the intrarenal ANG II augmentation in ANG II-infused mice. To determine if these effects are associated with changes in the mouse intrarenal renin-angiotensin system, the expression of angiotensinogen (AGT), renin, ACE, angiotensin type 1 receptor (AT1R) mRNA (by quanitative RT-PCR) and protein [by Western blot (WB) and/or immunohistochemistry (IHC)] were analyzed. C57BL/6J male mice (9–12 wk old) were distributed as controls (n = 10), ANG II infused (ANG II = 8, 400 ng·kg−1·min−1 for 12 days), ACEi only (ACEi = 10, lisinopril, 100 mg/l), and ANG II infused + ACEi (ANG II + ACEi = 11). When compared with controls (1.00), AGT protein (by WB) was increased by ANG II (1.29 ± 0.13, P < 0.05), and this was not prevented by ACEi (ACEi + ANG II, 1.31 ± 0.14, P < 0.05). ACE protein (by WB) was increased by ANG II (1.21 ± 0.08, P < 0.05), and it was reduced by ACEi alone (0.88 ± 0.07, P < 0.05) or in combination with ANG II (0.80 ± 0.07, P < 0.05). AT1R protein (by WB) was increased by ANG II (1.27 ± 0.06, P < 0.05) and ACEi (1.17 ± 0.06, P < 0.05) but not ANG II + ACEi [1.15 ± 0.06, not significant (NS)]. Tubular renin protein (semiquantified by IHC) was increased by ANG II (1.49 ± 0.23, P < 0.05) and ACEi (1.57 ± 0.15, P < 0.05), but not ANG II + ACEi (1.10 ± 0.15, NS). No significant changes were observed in AGT, ACE, or AT1R mRNA. In summary, reduced responses of intrarenal tubular renin, ACE, and the AT1R protein to the stimulatory effects of chronic ANG II infusions, in the presence of ACEi, are associated with the effects of this treatment to ameliorate augmentations in blood pressure and intrarenal ANG II content during ANG II-induced hypertension. PMID:19846570

  9. Hypertrophic response to hemodynamic overload: role of load vs. renin-angiotensin system activation

    NASA Technical Reports Server (NTRS)

    Koide, M.; Carabello, B. A.; Conrad, C. C.; Buckley, J. M.; DeFreyte, G.; Barnes, M.; Tomanek, R. J.; Wei, C. C.; Dell'Italia, L. J.; Cooper, G. 4th; Zile, M. R.

    1999-01-01

    Myocardial hypertrophy is one of the basic mechanisms by which the heart compensates for hemodynamic overload. The mechanisms by which hemodynamic overload is transduced by the cardiac muscle cell and translated into cardiac hypertrophy are not completely understood. Candidates include activation of the renin-angiotensin system (RAS) and angiotensin II receptor (AT1) stimulation. In this study, we tested the hypothesis that load, independent of the RAS, is sufficient to stimulate cardiac growth. Four groups of cats were studied: 14 normal controls, 20 pulmonary artery-banded (PAB) cats, 7 PAB cats in whom the AT1 was concomitantly and continuously blocked with losartan, and 8 PAB cats in whom the angiotensin-converting enzyme (ACE) was concomitantly and continuously blocked with captopril. Losartan cats had at least a one-log order increase in the ED50 of the blood pressure response to angiotensin II infusion. Right ventricular (RV) hypertrophy was assessed using the RV mass-to-body weight ratio and ventricular cardiocyte size. RV hemodynamic overload was assessed by measuring RV systolic and diastolic pressures. Neither the extent of RV pressure overload nor RV hypertrophy that resulted from PAB was affected by AT1 blockade with losartan or ACE inhibition with captopril. RV systolic pressure was increased from 21 +/- 3 mmHg in normals to 68 +/- 4 mmHg in PAB, 65 +/- 5 mmHg in PAB plus losartan and 62 +/- 3 mmHg in PAB plus captopril. RV-to-body weight ratio increased from 0.52 +/- 0.04 g/kg in normals to 1.11 +/- 0.06 g/kg in PAB, 1.06 +/- 0.06 g/kg in PAB plus losartan and 1.06 +/- 0.06 g/kg in PAB plus captopril. Thus 1) pharmacological modulation of the RAS with losartan and captopril did not change the extent of the hemodynamic overload or the hypertrophic response induced by PAB; 2) neither RAS activation nor angiotensin II receptor stimulation is an obligatory and necessary component of the signaling pathway that acts as an intermediary coupling load to the

  10. Polymorphisms of Renin-Angiotensin-Aldosterone System Gene in Chinese Han Patients with Nonfamilial Atrial Fibrillation

    PubMed Central

    Zhao, Li-qun; Wen, Zu-jia; Wei, Yong; Xu, Juan; Chen, Zheng; Qi, Bao-zhen; Wang, Zhi-ming; Shi, Yong-yong; Liu, Shao-wen

    2015-01-01

    Background Atrial fibrillation(AF) is the most common arrhythmia in the adult population. The activated renin-angiotensin-aldosterone system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation. The aim of this study was to investigate the association between nonfamilial AF and polymorphisms in RAS gene. Methods A total of 931 patients with nonfamilial AF, 663 non-AF heart disease patients and 727 healthy subjects were selected. 10 tagSNPs (tSNPs) (ACE gene rs8066114, AGT gene rs7539020, rs3789678, rs2478544, rs11568023, rs2478523, rs4762, rs699 and CYP11B2 rs3802230, rs3097) were chosen and genotyped in our study. Single-locus analysis and haplotype analysis were used in this study. Results In single-locus analysis, we found rs11568023 and rs3789678 in AGT gene were associated with nonfamilial AF in Chinese Han population. AF risk was associated with rs3789678 between the AF group and control groups. Under dominant model, the significant AF risk was observed in rs3789678 between the AF group and non AF heart control group; And the protective effect was found in rs11568023, compared with the non-AF heart disease control group. In multilocus haplotype analysis, the association between frequencies of the haplotypes and AF risk was showed in AGT gene (rs7539020-rs3789678), compared ‘TT’ haplotype with the common ‘TC’ haplotype, adjusted for age, gender, LVEF, LVEDD, LAD and frequency of hypertension and diabetes. The diplotype with ‘TC’, carrying rs3789678-C-allele, was associated with reduced risk of AF between the AF group and the healthy control group. The diplotype with ‘TT’ haplotype in the same block, carrying rs3789678-T-allele, was associated with increased risk of AF. Conclusions Via a large-scale case-control study, we found that rs3789678 site was potential susceptible locus of AF whereas rs11568023 was protective factor. PMID:25723521

  11. Low LBNP tolerance in men is associated with attenuated activation of the renin-angiotensin system

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Petersen, T. W.; Gabrielsen, A.; Pump, B.; Bie, P.; Christensen, N. J.; Warberg, J.; Videbaek, R.; Simonson, S. R.; Norsk, P.

    2000-01-01

    Plasma vasoactive hormone concentrations [epinephrine (p(Epi)), norepinephrine (p(NE)), ANG II (p(ANG II)), vasopressin (p(VP)), endothelin-1 (p(ET-1))] and plasma renin activity (p(RA)) were measured periodically and compared during lower body negative pressure (LBNP) to test the hypothesis that responsiveness of the renin-angiotensin system, the latter being one of the most powerful vasoconstrictors in the body, is of major importance for LBNP tolerance. Healthy men on a controlled diet (2,822 cal/day, 2 mmol. kg(-1). day(-1) Na(+)) were exposed to 30 min of LBNP from -15 to -50 mmHg. LBNP was uneventful for seven men [25 +/- 2 yr, high-tolerance (HiTol) group], but eight men (26 +/- 3 yr) reached presyncope after 11 +/- 1 min [P < 0.001, low-tolerance (LoTol) group]. Mean arterial pressure (MAP) did not change measurably, but central venous pressure and left atrial diameter decreased similarly in both groups (5-6 mmHg, by approximately 30%, P < 0.05). Control (0 mmHg LBNP) hormone concentrations were similar between groups, however, p(RA) differed between them (LoTol 0.6 +/- 0.1, HiTol 1.2 +/- 0.1 ng ANG I. ml(-1). h(-1), P < 0.05). LBNP increased (P < 0. 05) p(RA) and p(ANG II), respectively, more in the HiTol group (9.9 +/- 2.2 ng ANG I. ml(-1). h(-1) and 58 +/- 12 pg/ml) than in LoTol subjects (4.3 +/- 0.9 ng ANG I. ml(-1). h(-1) and 28 +/- 6 pg/ml). In contrast, the increase in p(VP) was higher (P < 0.05) in the LoTol than in the HiTol group. The increases (P < 0.05) for p(NE) were nonsignificant between groups, and p(ET-1) remained unchanged. Thus there may be a causal relationship between attenuated activation of p(RA) and p(ANG II) and presyncope, with p(VP) being a possible cofactor. Measurement of resting p(RA) may be of predictive value for those with lower hypotensive tolerance.

  12. Which patients should be on renin-angiotensin system blockers after coronary surgery?

    PubMed

    Alassar, Aiman; Bazerbashi, Samer; Easto, Rachel; Unsworth-White, Jonathan

    2014-10-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'which patients should be on renin-angiotensin system blockers after coronary surgery?' Using the reported search, 12 papers represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The 12 studies included 5 prospective randomized controlled trials (RCTs) and 1 meta-analysis. One RCT of 2553 stable patients post-coronary artery bypass surgery (CABG) with left ventricular (LV) ejection fraction ≤40% showed that angiotensin-converting enzyme inhibition (ACEI) therapy can and probably should be delayed beyond 7 days due to increased cardiovascular morbidity and mortality associated with immediate postoperative initiation of ACEI treatment. Another study showed that the cardioprotective benefits of ACEI following CABG are persistent with respect to an LV ejection fraction below or above 40% and whether percutaneous coronary intervention (PCI) or CABG was performed. A large multicentre international study of 4224 patients undergoing CABG looking at a composite outcome of rates of cardiac, cerebral and renal events and in-hospital mortality showed that continuous treatment with ACEI compared with no ACEI was associated with reductions of risks of non-fatal events (P = 0.009, odds ratio 0.69, 95% confidence interval 0.52-0.91). Addition of ACEI de novo following surgery was also associated with significant reduction in the risk of the composite outcome (P = 0.004) and of a cardiovascular event (P = 0.04). We conclude that angiotensin-converting enzyme inhibitor treatment plays an important role in minimizing ischaemic events after CABG even in low-risk patients. The cardioprotective benefits of these drugs are persistent at mid- and long-term follow-up, with respect to LV ejection fraction below or

  13. Klotho Ameliorates Kidney Injury and Fibrosis and Normalizes Blood Pressure by Targeting the Renin-Angiotensin System.

    PubMed

    Zhou, Lili; Mo, Hongyan; Miao, Jinhua; Zhou, Dong; Tan, Roderick J; Hou, Fan Fan; Liu, Youhua

    2015-12-01

    Loss of Klotho and activation of the renin-angiotensin system (RAS) are common pathological findings in chronic kidney diseases. However, whether these two events are intricately connected is poorly understood. We hypothesized that Klotho might protect kidneys by targeted inhibition of RAS activation in diseased kidneys. To test this hypothesis, mouse models of remnant kidney, as well as adriamycin nephropathy and unilateral ureteral obstruction, were utilized. At 6 weeks after 5/6 nephrectomy, kidney injury was evident, characterized by elevated albuminuria and serum creatinine levels, and excessive deposition of interstitial matrix proteins. These lesions were accompanied by loss of renal Klotho expression, up-regulation of RAS components, and development of hypertension. In vivo expression of exogenous Klotho through hydrodynamic-based gene delivery abolished the induction of multiple RAS proteins, including angiotensinogen, renin, angiotensin-converting enzyme, and angiotensin II type 1 receptor, and normalized blood pressure. Klotho also inhibited β-catenin activation and ameliorated renal fibrotic lesions. Similar results were obtained in mouse models of adriamycin and obstructive nephropathy. In cultured kidney tubular epithelial cells, Klotho dose-dependently blocked Wnt1-triggered RAS activation. Taken together, these results demonstrate that Klotho exerts its renal protection by targeted inhibition of RAS, a pathogenic pathway known to play a key role in the evolution and progression of hypertension and chronic kidney disorders. PMID:26475416

  14. Chronobiology and Pharmacologic Modulation of the Renin-Angiotensin-Aldosterone System in Dogs: What Have We Learned?

    PubMed

    Mochel, Jonathan P; Danhof, Meindert

    2015-01-01

    Congestive heart failure (CHF) is a primary cause of morbidity and mortality with an increasing prevalence in human and canine populations. Recognition of the role of renin-angiotensin-aldosterone system (RAAS) overactivation in the pathophysiology of CHF has led to significant medical advances. By decreasing systemic vascular resistance and angiotensin II (AII) production, angiotensin-converting enzyme (ACE) inhibitors such as benazepril improve cardiac hemodynamics and reduce mortality in human and dog CHF patients. Although several experiments have pointed out that efficacy of ACE inhibitors depends on the time of administration, little attention is paid to the optimum time of dosing of these medications. A thorough characterization of the chronobiology of the renin cascade has the potential to streamline the therapeutic management of RAAS-related diseases and to help determining the optimal time of drug administration that maximizes efficacy of ACE inhibitors, while minimizing the occurrence of adverse effects. We have developed an integrated pharmacokinetic-pharmacodynamic model that adequately captures the disposition kinetics of the paradigm drug benazeprilat, as well as the time-varying changes of systemic renin-angiotensin-aldosterone biomarkers, without and with ACE inhibition therapy. Based on these chronobiological investigations, the optimal efficacy of ACE inhibitors is expected with bedtime dosing. The data further show that benazepril influences the dynamics of the renin-angiotensin-aldosterone cascade, resulting in a profound decrease in AII and aldosterone (ALD), while increasing renin activity for about 24 h. From the results of recent investigations in human, it is hypothesized that reduction of AII and ALD is one of the drivers of increased survival and improved quality of life in dogs receiving ACE inhibitors. To support and consolidate this hypothesis, additional efforts should be directed toward the collection of circulating RAAS peptides

  15. Role of Renin-Angiotensin-Aldosterone System in Metabolic Syndrome and Obesity-related Hypertension.

    PubMed

    Kamide, K

    2014-08-12

    Several recent clinical trials show that blocking agents of the renin-angiotensin-aldosterone system (RAAS) reduce cardiovascular events in patients with metabolic syndrome based on insulin resistance and obesity, especially accumulated visceral fat. Our laboratory has focused on the relationship between the vascular RAAS and the action of insulin on the vasculature. We first revealed that the addition of insulin to cultured vascular smooth muscle cells (VSMC) markedly increases angiotensinogen and angiotensin II (Ang II) expression and production. Insulin addition also induces VSMC growth that is inhibited by the blockade of the RAAS by either ACEI or ARB which suggests a role for the RAAS in insulin-mediated growth. Insulin has a quite different effect on cultured vascular endothelial cells (EC) as it reduces angiotensinogen and renin expression. However, insulin added to EC induces a marked activation of ACE and the activated ACE promotes the conversion of Ang I to Ang II and cell growth under conditions of high insulin concentration. Ang II induces the progression of atherosclerosis through the production of oxidative stress that blocks insulin signaling and accelerates atherosclerosis. In this paper, we attempt to clarify the relationship between insulin resistance, the RAAS, and oxidative stress in vascular tissues to mimic in vivo conditions found in patients with metabolic syndrome and obesity-related hypertension as previously I reviewed in "Current Hypertension Reviews" in 2010 [1]. In addition, I update the relationships between vascular RAAS and insulin resistance for the last 4 years. JSH-2014 [2] states that the target goals of blood pressure (BP) for diabetes patients is lower than 130/80 mmHg, whereas updated JNC 8 [3] and ESH-ESC 2013 [4] recommends the target BP was changed to <140/90 mmHg for hypertensive patients with diabetes. Patients with diabetes and hypertension have reduced mortality as well as improved cardiovascular and cerebrovascular

  16. Renin-angiotensin system as a potential therapeutic target in stroke and retinopathy: experimental and clinical evidence.

    PubMed

    Fouda, Abdelrahman Y; Artham, Sandeep; El-Remessy, Azza B; Fagan, Susan C

    2016-02-01

    As our knowledge expands, it is now clear that the renin-angiotensin (Ang) system (RAS) mediates functions other than regulating blood pressure (BP). The RAS plays a central role in the pathophysiology of different neurovascular unit disorders including stroke and retinopathy. Moreover, the beneficial actions of RAS modulation in brain and retina have been documented in experimental research, but not yet exploited clinically. The RAS is a complex system with distinct yet interconnected components. Understanding the different RAS components and their functions under brain and retinal pathological conditions is crucial to reap their benefits. The aim of the present review is to provide an experimental and clinical update on the role of RAS in the pathophysiology and treatment of stroke and retinopathy. Combining the evidence from both these disorders allows a unique opportunity to move both fields forward. PMID:26769658

  17. [The renin-angiotensin-aldosterone system during the extraction, concentration and reinfusion of ascitic fluid in cirrhotic patients].

    PubMed

    Giorcelli, V; Fossale, P G

    1983-01-01

    The course of hepatic cirrhosis involves alterations to the sodium-water balance, the aetiopathogenetic causes of which are still not entirely known. At first major importance was assigned to the role of secondary hyperaldosteronism which develops during the ascitic phase. This was subsequently recognised to have only a permissive rather than determinant function. Changes in the renin-angiotensin-aldosterone (RAA) system and variations in hydrosaline balance as the extracellular volume (ECV) expands during the reinfusion of concentrated ascitic fluid have been studied. The data reported show that ECV expansion causes increased diuresis, natriuresis and osmolar clearance. The RAA system is suppressed and at the same time kaliuresis increases. The latter factor points up the role played by increased solute flow to the distal tube in the diuretico-metabolic response, where aldosterone plays a purely permissive part. PMID:6675585

  18. The renin-angiotensin system and advanced glycation end-products in diabetic retinopathy: impacts and synergies.

    PubMed

    Miller, Antonia G; Zhu, Tong; Wilkinson-Berka, Jennifer L

    2013-11-01

    Diabetic retinopathy is a major cause of vision impairment and blindness and represents a significant health burden throughout the world. There is considerable interest in developing new treatments that retard the progression of diabetic retinopathy from its early to proliferative stages. It could be argued that the absence of an ideal therapy for diabetic retinopathy comes from an incomplete understanding about the biochemical mechanisms that underlie this disease, and their precise impact on specific retinal cell populations. Findings from pre-clinical and clinical studies indicate that both the renin-angiotensin system (RAS) and advanced glycation end-products (AGEs) influence various aspects of diabetic retinopathy. Of interest is growing evidence of cross-talk between the RAS and AGEs pathways. This review will discuss the role of both the RAS and AGEs in diabetic retinopathy, and how the identification of interactions between the two pathways may have implications for the development of new treatment strategies. PMID:23173957

  19. Activation of the renin-angiotensin system, specifically in the subfornical organ is sufficient to induce fluid intake

    PubMed Central

    Coble, Jeffrey P.; Cassell, Martin D.; Davis, Deborah R.; Grobe, Justin L.

    2014-01-01

    Increased activity of the renin-angiotensin system within the brain elevates fluid intake, blood pressure, and resting metabolic rate. Renin and angiotensinogen are coexpressed within the same cells of the subfornical organ, and the production and action of ANG II through the ANG II type 1 receptor in the subfornical organ (SFO) are necessary for fluid intake due to increased activity of the brain renin-angiotensin system. We generated an inducible model of ANG II production by breeding transgenic mice expressing human renin in neurons controlled by the synapsin promoter with transgenic mice containing a Cre-recombinase-inducible human angiotensinogen construct. Adenoviral delivery of Cre-recombinase causes SFO-selective induction of human angiotensinogen expression. Selective production of ANG II in the SFO results in increased water intake but did not change blood pressure or resting metabolic rate. The increase in water intake was ANG II type 1 receptor-dependent. When given a choice between water and 0.15 M NaCl, these mice increased total fluid and sodium, but not water, because of an increased preference for NaCl. When provided a choice between water and 0.3 M NaCl, the mice exhibited increased fluid, water, and sodium intake, but no change in preference for NaCl. The increase in fluid intake was blocked by an inhibitor of PKC, but not ERK, and was correlated with increased phosphorylated cyclic AMP response element binding protein in the subfornical organ. Thus, increased production and action of ANG II specifically in the subfornical organ are sufficient on their own to mediate an increase in drinking through PKC. PMID:24965793

  20. KCNQ1 A340E impairs electrolyte homeostasis independently of the renin-angiotensin-aldosterone system in mice.

    PubMed

    Pan, Q; Sang, Y; Sun, C; Li, G; Wang, Y

    2016-01-01

    KCNQ1 (KvLQT1) is the pore-forming a-subunit of the potassium channel. To uncover its role in electrolyte metabolism, we investigated the effects of KCNQ1 A340E, a loss-of-function mutant, on J343 mice. Compared with the normal controls (C57BL/6J mice) bearing the wild-type KCNQ1 gene, J343 mice bearing KCNQ1 A340E demonstrated a much higher 24-h intake of electrolytes (potassium, sodium, and chloride). However, they suffered from significant electrolyte loss through both the feces and urine during a period of 24 h. Unbalance in electrolyte metabolism disrupted the electrolyte homeostasis in the J343 mice, which was characterized by the comparatively lower level of serum potassium (J343 vs C57BL/6J: 12.06 ± 1.47 vs 14.44 ± 3.58 mM, P = 0.01) and higher levels of serum sodium (J343 vs C57BL/6J: 148.05 ± 4.47 vs 115.15 ± 17.25 mM, P = 4.20 x 10(-4)) and chloride (J343 vs C57BL/6J: 118.0 ± 4.47 vs 85.21 ± 11.90 mM, P = 2.47 x 10(-5)). Between the J343 and C57BL/6J mice, there was no statistically significant difference in KCNQ1 expression in the gastrointestinal tract and kidney. Normal concentrations of plasma renin, angiotensin I, and aldosterone were also detected in both lines of mice. KCNQ1, therefore, is suggested to play a central role in electrolyte metabolism. KCNQ1 A340E, with the loss-of-function phenotype, may dysregulate electrolyte homeostasis in mice independently of the activity of the renin-angiotensin-aldosterone system. PMID:27525866

  1. A systematic review of the role of renin angiotensin aldosterone system genes in diabetes mellitus, diabetic retinopathy and diabetic neuropathy

    PubMed Central

    Rahimi, Zohreh; Moradi, Mahmoudreza; Nasri, Hamid

    2014-01-01

    Background: The renin angiotensin aldosterone system (RAAS) plays a vital role in regulating glucose metabolism and blood pressure, electrolyte and fluid homeostasis. The aim of this systematic review is to assess the association of the RAAS genes with diabetes mellitus (DM) and its complications of retinopathy, neuropathy and cardiovascular disease (CVD). Materials and Methods: The relevant English-language studies were identified using the key words of DM, type 1 diabetes mellitus (T1DM), T2DM, renin angiotensin aldosterone polymorphisms or genotypes and RAAS from the search engines of MEDLINE/PubMed, and Scopus from January 1, 1995 to July 30, 2014. Inclusion criteria for selecting relevant studies were reporting the role of RAAS gene variants in the pathogenesis of T1DM or T2DM, diabetic retinopathy (DR), diabetic neuropathy and cardiovascular complication of DM. Results: The reviewers identified 204 studies of which 73 were eligible for inclusion in the present systematic review. The review indicates the angiotensinogen (AGT) M235T polymorphism might not affect the risk of DM. The role of angiotensin converting enzyme insertion/deletion (ACE I/D) and angiotensin II type 1 receptor gene (AT1R) A1166C polymorphisms in the pathogenesis of DM could not be established. Studies indicate the absence of an association between three polymorphisms of AGT M235T, ACE I/D and AT1R A1166C and DR in DM patients. A protective role for ACE II genotype against diabetic peripheral neuropathy has been suggested. Also, the ACE I/D polymorphism might be associated with the risk of CVD in DM patients. Conclusion: More studies with adequate sample size that investigate the influence of all RAAS gene variants together on the risk of DM and its complications are necessary to provide a more clear picture of the RAAS genes polymorphisms involvement in the pathogenesis of DM and its complications. PMID:25657757

  2. Activation of the Cardiac Renin-Angiotensin System in High Oxygen-Exposed Newborn Rats: Angiotensin Receptor Blockade Prevents the Developmental Programming of Cardiac Dysfunction.

    PubMed

    Bertagnolli, Mariane; Dios, Anne; Béland-Bonenfant, Sarah; Gascon, Gabrielle; Sutherland, Megan; Lukaszewski, Marie-Amélie; Cloutier, Anik; Paradis, Pierre; Schiffrin, Ernesto L; Nuyt, Anne Monique

    2016-04-01

    Newborn rats exposed to high oxygen (O2), mimicking preterm birth-related neonatal stress, develop later in life cardiac hypertrophy, dysfunction, fibrosis, and activation of the renin-angiotensin system. Cardiac renin-angiotensin system activation in O2-exposed adult rats is characterized by an imbalance in angiotensin (Ang) receptors type 1/2 (AT1/2), with prevailing AT1 expression. To study the role of renin-angiotensin system in the developmental programming of cardiac dysfunction, we assessed Ang receptor expression during neonatal high O2 exposure and whether AT1 receptor blockade prevents cardiac alterations in early adulthood. Sprague-Dawley newborn rats were kept with their mother in 80% O2 or room air (control) from days 3 to 10 (P3-P10) of life. Losartan or water was administered by gavage from P8 to P10 (n=9/group). Rats were studied at P3 (before O2 exposure), P5, P10 (end of O2), and P28. Losartan treatment had no impact on growth or kidney development. AT1 and Ang type 2 receptors were upregulated in the left ventricle by high O2 exposure (P5 and P10), which was prevented by Losartan treatment at P10. Losartan prevented the cardiac AT1/2 imbalance at P28. Losartan decreased cardiac hypertrophy and fibrosis and improved left ventricle fraction of shortening in P28 O2-exposed rats, which was associated with decreased oxidation of calcium/calmodulin-dependent protein kinase II, inhibition of the transforming growth factor-β/SMAD3 pathway, and upregulation of cardiac angiotensin-converting enzyme 2. In conclusion, short-term Ang II blockade during neonatal high O2 prevents the development of cardiac alterations later in life in rats. These findings highlight the key role of neonatal renin-angiotensin system activation in the developmental programming of cardiac dysfunction induced by deleterious neonatal conditions. PMID:26857347

  3. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.

    PubMed

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A; Castillo, Andrés E; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E; Kalergis, Alexis M

    2016-01-01

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. PMID:27347925

  4. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension

    PubMed Central

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A.; Castillo, Andrés E.; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E.; Kalergis, Alexis M.

    2016-01-01

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. PMID:27347925

  5. Obstructive nephropathy in the rat: possible roles for the renin-angiotensin system, prostaglandins, and thromboxanes in postobstructive renal function.

    PubMed Central

    Yarger, W E; Schocken, D D; Harris, R H

    1980-01-01

    Relief of unilateral ureteral obstruction (UUO) of 24 h duration in rats is followed by severe renal vasoconstriction in the postobstructive kidney (POK). The present study examined possible roles of renal prostaglandins (PG) and thromboxanes (TX), as well as the renin-angiotensin system, in this vasoconstriction. Administration of the cyclooxygenase inhibitor indomethacin, which blocks both PG and TX production, failed to improve POK hemodynamics in UUO rats. To explore the possible role of the TX compounds, which include the potent vasoconstrictor thromboxane A2 (TXA2), UUO rats were infused with imidazole, an agent that blocks synthesis of TX, but not of PG. Imidiazole led to two- to threefold increases in the clearance of both inulin and rho-aminohippuric acid by the POK. This effect of imidazole was abolished by indomethacin, suggesting that the amelioration of POK vasoconstriction by imidazole was a result of inhibition of vasoconstrictor TX synthesis (e.g. TXA2), with PG vasodilators (e.g. PGE2 or PG12) still active. Urea, infused in a solution whose osmolality and volume were identical to the imidazole infusion, failed to improve hemodynamics in the POK, making it unlikely that nonspecific effects of volume expansion or osmotic diuresis mediated the beneficial effect of imidazole. Further studies examined the possible role of the renin-angiotensin systems in the vasoconstriction of the POK. UUO rats infused with the angiotensin II antagonist, Saralasin, exhibited no significant improvement in POK function, a finding that might be at least partly attributable to agonist/vasoconstrictor properties of Saralasin. In other experiments, treatment of UUO rats with the angiotensin-converting enzyme blocker SQ 14225 (Captopril), in order to inhibit angiotensin II formation, led to at least twofold increases in the clearance of both inulin and rho-aminohippuric acid in the POK. It is unlikely that Captopril exerted this beneficial effect by potentiating the

  6. Reversal of cardiac fibrosis in deoxycorticosterone acetate-salt hypertensive rats by inhibition of the renin-angiotensin system.

    PubMed

    Brown, L; Duce, B; Miric, G; Sernia, C

    1999-01-01

    Fibrosis impairs cardiac function. This project has determined the expression and deposition of collagens and fibronectin and cardiac function in the deoxycorticosterone acetate (DOCA)-salt hypertensive rat after inhibition of the renin-angiotensin system. DOCA-salt hypertension was induced in 8-wk-old male Wistar rats by uninephrectomy and administration of DOCA (25 mg every fourth day, subcutaneously) and 1% NaCl in the drinking water for 4 wk. Starting 2 wk after surgery, rats were given either oral captopril (100 mg/kg), oral candesartan cilexetil (2 mg/kg), or subcutaneous spironolactone (50 mg/kg) daily for 2 wk (reversal protocol). DOCA-salt rats failed to gain weight with markedly increased water intake and decreased food intake; drug treatment did not alter these parameters. Systolic BP increased from 116+/-5 mmHg in uninephrectomized rats to 179+/-7 mmHg in DOCA-salt rats and was not decreased by treatment (captopril 172+/-1 mmHg; candesartan 187+/-2 mmHg; spironolactone 178+/-3 mmHg). Captopril, candesartan, and spironolactone reversed the increased collagen I mRNA in DOCA-salt rats; only candesartan reversed the increased collagen III mRNA. Collagen IV mRNA was unchanged in DOCA-salt rats and following treatment. Total fibronectin mRNA increased without changing the proportion of fibronectin mRNA as the fetal isoforms EIIIA and EIIIB. Captopril, candesartan, and spironolactone reversed the increased deposition of perivascular and interstitial collagen in DOCA-salt rats; the increased cardiac fibronectin deposition was reversed by candesartan and spironolactone. Captopril, candesartan, and spironolactone also attenuated or reversed the increased diastolic stiffness and the increased dP/dt but not the increased rate-pressure products in DOCA-salt rat hearts. Thus, inhibition of the renin-angiotensin system reverses cardiac fibrosis in DOCA-salt rats and returns some indices of myocardial function to normal. PMID:9892155

  7. Acute Total and Chronic Partial Sleep Deprivation: Effects on Neurobehavioral Functions, Waking EEG and Renin-Angiotensin System

    NASA Technical Reports Server (NTRS)

    Dijk, Derk-Jan

    1999-01-01

    protocol of the Quantitative EEG and Waking Neurobehavioral Function project. This will allow us to investigate two additional specific aims: 1) Test the hypothesis that chronic partial sleep deprivation during a 17 day bed rest experiment results in deterioration of neurobehavioral function during waking and increases in EEG power density in the theta frequencies, especially in frontal areas of the brain, as well as the nonREM- REM cycle dependent modulation of heart-rate variability. 2) Test the hypothesis that acute total sleep deprivation modifies the circadian rhythm of the renin-angiotensin system, changes the acute responsiveness of this system to posture beyond what a microgravity environment alone does and affects the nonREM-REM cycle dependent modulation of heart-rate variability.

  8. Effect of post-myocardial infarction exercise training on the renin-angiotensin-aldosterone system and cardiac function.

    PubMed

    Wan, Wenhan; Powers, Anthony S; Li, Ji; Ji, Lisa; Erikson, John M; Zhang, John Q

    2007-10-01

    After a myocardial infarction (MI), the injured heart undergoes intensive remodeling characterized by activation of the circulating renin-angiotensin-aldosterone system (RAAS), left ventricular (LV) dilation, and contractile dysfunction. Exercise training may attenuate activation of the RAAS and improve myocardial remodeling. In this study, we investigated whether starting exercise training early or late after MI would have different effect on circulating RAAS and LV dilation and function. Male Sprague-Dawley rats (7 weeks old) underwent surgically induced MI. After surgery, rats were matched for similar infarct sizes and assigned into two major groups, based on the designated starting time of exercise training. Exercise groups started exercise at either 1 or 6 weeks after MI and exercised on a treadmill for 8 weeks. Groups starting exercise 1 week after MI included sham-operated control (1Wk-Sham), MI-ksedentary (1Wk-MI-Sed), and MI-exercise (1Wk-MI-Ex). Groups starting exercise 6 weeks after MI included sham-operated control (6Wk-Sham), MI-sedentary (6Wk-MI-Sed), and MI-exercise (6Wk-MI-Ex). An echocardiogram was performed before and after exercise training. Blood samples were obtained at the end of experiments. The results showed that compared with sedentary rats with MI, exercise training significantly attenuated circulating renin, angiotensin converting enzyme, angiotensin II, and aldosterone. Rats in exercise groups had similar LV end-diastolic diameters compared with their sedentary counterparts and tended to have smaller LV end-systolic diameters, and percent fractional shortening in exercise rats was significantly higher than in sedentary rats. These findings suggest that exercise training does not cause LV dilation and preserves LV function. Post-MI exercise training also normalizes the circulating RAAS, and this effect is independent of timing of post-MI exercise. Exercise starting early or late after MI affects myocardial remodeling and function

  9. Acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis in the dog.

    PubMed Central

    Anderson, W P; Johnston, C I; Korner, P I

    1979-01-01

    1. The acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. 2. Stenosis was induced over 30 sec by inflation of a cuff around the renal artery to lower distal pressure to 60, 40 or 20 mmHg, with stenosis maintained for 1 hr. This resulted in an immediate fall in renal vascular resistance, but over the next 5--30 min both resistance and renal artery pressure were restored back towards prestenosis values. Only transient increases in systemic arterial blood pressure and plasma renin and angiotensin levels were seen with the two milder stenoses. Despite restoration of renal artery pressure, renal blood flow remained reduced at all grades of stenosis. 3. Pre-treatment with angiotensin I converting enzyme inhibitor or sarosine1, isoleucone8 angiotensin II greatly attenuated or abolished the restoration of renal artery pressure and renal vascular resistance after stenosis, and plasma renin and angiotensin II levels remained high. Renal dilatation was indefinitely maintained, but the normal restoration of resistance and pressure could be simulated by infusing angiotensin II into the renal artery. 4. The effective resistance to blood flow by the stenosis did not remain constant but varied with changes in the renal vascular resistance. PMID:219182

  10. High fat diet exacerbates neuroinflammation in an animal model of multiple sclerosis by activation of the Renin Angiotensin system.

    PubMed

    Timmermans, Silke; Bogie, Jeroen F J; Vanmierlo, Tim; Lütjohann, Dieter; Stinissen, Piet; Hellings, Niels; Hendriks, Jerome J A

    2014-03-01

    Epidemiological studies suggest a positive correlation between the incidence and severity of multiple sclerosis (MS) and the intake of fatty acids. It remains to be clarified whether high fat diet (HFD) indeed can exacerbate the disease pathology associated with MS and what the underlying mechanisms are. In this study, we determined the influence of HFD on the severity and pathology of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Mice were fed either normal diet (ND) or HFD and subsequently induced with EAE. Immunohistochemical staining and real-time PCR were used to determine immune cell infiltration and inflammatory mediators in the central nervous system (CNS). Our data show that HFD increases immune cell infiltration and inflammatory mediator production in the CNS and thereby aggravates EAE. Moreover, our data demonstrate that activation of the renin angiotensin system (RAS) is associated with the HFD-mediated effects on EAE severity. These results show that HFD exacerbates an autoreactive immune response within the CNS. This indicates that diets containing excess fat have a significant influence on neuroinflammation in EAE, which may have important implications for the treatment and prevention of neuroinflammatory disorders. PMID:24068577

  11. Study of prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves

    PubMed Central

    Bhadoo, Divya; Bajpai, M.; Abid, Ali; Sukanya, Gayan; Agarwala, Sandeep; Srinivas, M.; Deka, Deepika; Agarwal, Nutan; Agarwal, Ramesh; Kumar, Rakesh

    2015-01-01

    Aims: Study on prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves. Materials and Methods: Antenatally diagnosed hydronephrosis patients were included. Postnatally, they were divided into two groups, posterior urethral valve (PUV) and non-PUV. The studied parameters were: Gestational age at detection, surgical intervention, ultrasound findings, cord blood and follow up plasma renin activity (PRA) values, vesico-ureteric reflux (VUR), renal scars, and glomerular filtration rate (GFR). Results: A total of 25 patients were included, 10 PUV and 15 non-PUV. All infants with PUV underwent primary valve incision. GFR was less than 60 ml/min/1.73 m2 body surface area in 4 patients at last follow-up. Keyhole sign, oligoamnios, absent bladder cycling, and cortical cysts were not consistent findings on antenatal ultrasound in PUV. Cord blood PRA was significantly higher (P < 0.0001) in PUV compared to non-PUV patients. Gestational age at detection of hydronephrosis, cortical cysts, bladder wall thickness, and amniotic fluid index were not significantly correlated with GFR while PRA could differentiate between poor and better prognosis cases with PUV. Conclusions: Ultrasound was neither uniformly useful in diagnosing PUV antenatally, nor differentiating it from cases with non-PUV hydronephrosis. In congenital hydronephrosis, cord blood PRA was significantly higher in cases with PUV compared to non-PUV cases and fell significantly after valve ablation. Cord blood PRA could distinguish between poor and better prognosis cases with PUV. PMID:25829668

  12. Prenatal dehydration alters renin-angiotensin system associated with angiotensin-increased blood pressure in young offspring.

    PubMed

    Guan, Junchang; Mao, Caiping; Xu, Feichao; Geng, Chunsong; Zhu, Liyan; Wang, Aiqing; Xu, Zhice

    2009-12-01

    The renin-angiotensin system (RAS) has an important role in cardiovascular homeostasis. This study determined the influence of water deprivation during pregnancy on the development of the RAS in rats, and examined blood pressure (BP) in the adolescent offspring. Pregnant rats were water deprived for 3 days at late gestation, and we examined fetal cardiac ultrastructure, as well as heart angiotensin (Ang) II receptor protein and mRNA, liver angiotensinogen and plasma Ang II concentrations. We also tested cardiovascular responses to i.v. Ang II in the young offspring. In utero exposure to maternal water deprivation significantly decreased fetal body and heart weight, and increased fetal plasma sodium and osmolality. Fetal liver angiotensinogen mRNA, plasma Ang I and Ang II concentrations were also increased. Although fetal AT(1a) and AT(1b) receptor mRNA and AT(1) protein were not changed, AT(2) receptor mRNA and protein levels in the heart were significantly increased following maternal dehydration. Prenatal exposure to maternal water deprivation had no effect on baseline BP; however, it significantly increased BP in response to i.v. Ang II infusion, and decreased baroreflex sensitivity in the offspring. In addition, the heart AT(2) receptor mRNA and protein were higher in the offspring exposed to prenatal dehydration. The results of this study demonstrate that prenatal dehydration affected the RAS development associated with an Ang II-increased BP in fetal origin. PMID:19779489

  13. The Beneficial Effect of Renin-Angiotensin-Aldosterone System Blockade in Marfan Syndrome Patients after Aortic Root Replacement

    PubMed Central

    Lee, Seung-Jun; Oh, Jaewon; Ko, Young-Guk; Lee, Sak; Chang, Byung-Chul; Lee, Do Yun; Kwak, Young-Ran

    2016-01-01

    Purpose In this study, we evaluated the long term beneficial effect of Renin-Angiotensin-Aldosterone System (RAAS) blockade therapy in treatment of Marfan aortopathy. Materials and Methods We reviewed Marfan syndrome (MFS) patients who underwent aortic root replacement (ARR) between January 1996 and January 2011. All patients were prescribed β-blockers indefinitely. We compared major aortic events including mortality, aortic dissection, and reoperation in patients without RAAS blockade (group 1, n=27) to those with (group 2, n=63). The aortic growth rate was calculated by dividing the diameter change on CT scans taken immediately post-operatively and the latest scan available. Results There were no differences in clinical parameters except for age which was higher in patients with RAAS blockade. In group 1, 2 (7%) deaths, 5 (19%) aortic dissections, and 7 (26%) reoperations occurred. In group 2, 3 (5%) deaths, 2 (3%) aortic dissections, and 3 (5%) reoperations occurred. A Kaplan-Meier plot demonstrated improved survival free from major aortic events in group 2. On multivariate Cox, RAAS blockade was an independent negative predictor of major aortic events (hazard ratio 0.38, 95% confidence interval 0.30-0.43, p=0.002). Mean diameter change in descending thoracic and supra-renal abdominal aorta was significantly higher in patients without RAAS blockade (p<0.05). Conclusion In MFS patients who underwent ARR, the addition of RAAS blockade to β-blocker was associated with reduction of aortic dilatation and clinical events. PMID:26632386

  14. Exercise Training Improves the Altered Renin-Angiotensin System in the Rostral Ventrolateral Medulla of Hypertensive Rats

    PubMed Central

    Ren, Chang-zhen; Yang, Ya-Hong; Sun, Jia-cen; Wu, Zhao-Tang; Zhang, Ru-Wen; Shen, Du; Wang, Yang-Kai

    2016-01-01

    The imbalance between angiotensin II (Ang II) and angiotensin 1–7 (Ang 1–7) in the brain has been reported to contribute to cardiovascular dysfunction in hypertension. Exercise training (ExT) is beneficial to hypertension and the mechanism is unclear. This study was aimed to determine if ExT improves hypertension via adjusting renin angiotensin system in cardiovascular centers including the rostral ventrolateral medulla (RVLM). Spontaneously hypertensive rats (SHR, 8 weeks old) were subjected to low-intensity ExT or kept sedentary (Sed) for 12 weeks. Blood pressure elevation coupled with increase in age was significantly decreased in SHR received ExT compared with Sed. The results in vivo showed that ExT significantly reduced or increased the cardiovascular responses to central application of sarthran (antagonist of Ang II) or A779 (antagonist of Ang 1–7), respectively. The protein expression of the Ang II acting receptor AT1R and the Ang 1–7 acting receptor Mas in the RVLM was significantly reduced and elevated in SHR following ExT, respectively. Moreover, production of reactive oxygen species in the RVLM was significantly decreased in SHR following ExT. The current data suggest that ExT improves hypertension via improving the balance of Ang II and Ang 1–7 and antioxidative stress at the level of RVLM. PMID:26881037

  15. The renin-angiotensin-aldosterone system and its blockade in diabetic nephropathy: main focus on the role of aldosterone.

    PubMed

    Schjoedt, Katrine Jordan

    2011-04-01

    Diabetic nephropathy is the most common cause of end-stage renal disease in the western world. Despite major improvements in both prevention and treatment of diabetic nephropathy, there is a continuous need to improve identification and treatment of "non-responders". In recent years, several experimental studies have shown that aldosterone plays a role in the development and progression of diabetic nephropathy, independent of angiotensin II and blood pressure levels. Blocking the renin-angiotensin-aldosterone system with an ACE-inhibitor (ACEI) and/or ambulatory blood pressure should theoretically inhibit the secretion of aldosterone. However, an increase in aldosterone during long-term treatment with ACEIs, so-called aldosterone escape or aldosterone breakthrough, has been described. In the present thesis, our studies evaluating the incidence and clinical impact (i.e. a faster rate of decline in kidney function) of aldosterone escape in type 1 diabetic patients with diabetic nephropathy, possible mechanisms of aldosterone escape, and finally the beneficial effect of blocking aldosterone on albuminuria, blood pressure and renal autoregulation is being reviewed, together with some aspects of the existing treatment recommendations. PMID:21466768

  16. Maternal Dexamethasone Treatment Alters Tissue and Circulating Components of the Renin-Angiotensin System in the Pregnant Ewe and Fetus.

    PubMed

    Forhead, Alison J; Jellyman, Juanita K; De Blasio, Miles J; Johnson, Emma; Giussani, Dino A; Broughton Pipkin, Fiona; Fowden, Abigail L

    2015-08-01

    Antenatal synthetic glucocorticoids promote fetal maturation in pregnant women at risk of preterm delivery and their mechanism of action may involve other endocrine systems. This study investigated the effect of maternal dexamethasone treatment, at clinically relevant doses, on components of the renin-angiotensin system (RAS) in the pregnant ewe and fetus. From 125 days of gestation (term, 145 ± 2 d), 10 ewes carrying single fetuses of mixed sex (3 female, 7 male) were injected twice im, at 10-11 pm, with dexamethasone (2 × 12 mg, n = 5) or saline (n = 5) at 24-hour intervals. At 10 hours after the second injection, maternal dexamethasone treatment increased angiotensin-converting enzyme (ACE) mRNA levels in the fetal lungs, kidneys, and heart and ACE concentration in the circulation and lungs, but not kidneys, of the fetuses. Fetal cardiac mRNA abundance of angiotensin II (AII) type 2 receptor decreased after maternal dexamethasone treatment. Between the two groups of fetuses, there were no significant differences in plasma angiotensinogen or renin concentrations; in transcript levels of renal renin, or AII type 1 or 2 receptors in the lungs and kidneys; or in pulmonary, renal or cardiac protein content of the AII receptors. In the pregnant ewes, dexamethasone administration increased pulmonary ACE and plasma angiotensinogen, and decreased plasma renin, concentrations. Some of the effects of dexamethasone treatment on the maternal and fetal RAS were associated with altered insulin and thyroid hormone activity. Changes in the local and circulating RAS induced by dexamethasone exposure in utero may contribute to the maturational and tissue-specific actions of antenatal glucocorticoid treatment. PMID:26039155

  17. The role of renin-angiotensin system in cellular differentiation: implications in pancreatic islet cell development and islet transplantation.

    PubMed

    Wang, Lin; Leung, Po Sing

    2013-12-01

    In addition to the well-characterized circulating renin-angiotensin system (RAS), local RAS has been identified recently in diverse tissues and organs. The presence of key components of the RAS in local tissues is important for our understanding of the patho-physiological mechanism(s) of several metabolic diseases, and may serve as a major therapeutic target for cardiometabolic syndromes. Locally generated and physiologically active RAS components have functions that are distinct from the classical vasoconstriction and fluid homeostasis actions of systemic RAS and cater specifically for local tissues. Local RAS can affect islet-cell function and structure in the adult pancreas as well as proliferation and differentiation of pancreatic stem/progenitor cells during development. Differentiation of stem/progenitor cells into insulin-expressing cells suitable for therapeutic transplantation offers a desperately needed new approach for replacement of glucose-responsive insulin producing cells in diabetic patients. Given that the generation of functional and transplantable islet cells has proven to be difficult, elucidation of RAS involvement in cellular regeneration and differentiation may propel pancreatic stem/progenitor cell development and thus β-cell regeneration forward. This review provides a critical appraisal of current research progress on the role of the RAS, including the newly characterized ACE2/Ang-(1-7)/Mas axis in the proliferation, differentiation, and maturation of pancreatic stem/progenitor cells. It is thus plausible to propose that the AT1 stimulation could be a repair mechanism involving the AT2R as well as the ACE2/Ang-(1-7)/Mas axis in directing β-cell development in diabetic patients using genetic and pharmaceutical manipulation of the RAS. PMID:23994025

  18. Maternal Dexamethasone Treatment Alters Tissue and Circulating Components of the Renin-Angiotensin System in the Pregnant Ewe and Fetus

    PubMed Central

    Jellyman, Juanita K.; De Blasio, Miles J.; Johnson, Emma; Giussani, Dino A.; Broughton Pipkin, Fiona; Fowden, Abigail L.

    2015-01-01

    Antenatal synthetic glucocorticoids promote fetal maturation in pregnant women at risk of preterm delivery and their mechanism of action may involve other endocrine systems. This study investigated the effect of maternal dexamethasone treatment, at clinically relevant doses, on components of the renin-angiotensin system (RAS) in the pregnant ewe and fetus. From 125 days of gestation (term, 145 ± 2 d), 10 ewes carrying single fetuses of mixed sex (3 female, 7 male) were injected twice im, at 10–11 pm, with dexamethasone (2 × 12 mg, n = 5) or saline (n = 5) at 24-hour intervals. At 10 hours after the second injection, maternal dexamethasone treatment increased angiotensin-converting enzyme (ACE) mRNA levels in the fetal lungs, kidneys, and heart and ACE concentration in the circulation and lungs, but not kidneys, of the fetuses. Fetal cardiac mRNA abundance of angiotensin II (AII) type 2 receptor decreased after maternal dexamethasone treatment. Between the two groups of fetuses, there were no significant differences in plasma angiotensinogen or renin concentrations; in transcript levels of renal renin, or AII type 1 or 2 receptors in the lungs and kidneys; or in pulmonary, renal or cardiac protein content of the AII receptors. In the pregnant ewes, dexamethasone administration increased pulmonary ACE and plasma angiotensinogen, and decreased plasma renin, concentrations. Some of the effects of dexamethasone treatment on the maternal and fetal RAS were associated with altered insulin and thyroid hormone activity. Changes in the local and circulating RAS induced by dexamethasone exposure in utero may contribute to the maturational and tissue-specific actions of antenatal glucocorticoid treatment. PMID:26039155

  19. Chronobiology of the renin-angiotensin-aldosterone system in dogs: relation to blood pressure and renal physiology.

    PubMed

    Mochel, Jonathan P; Fink, Martin; Peyrou, Mathieu; Desevaux, Cyril; Deurinck, Mark; Giraudel, Jérôme M; Danhof, Meindert

    2013-11-01

    The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the regulation of blood pressure and volume homeostasis. Its contribution to the development of cardiovascular diseases has long been recognized. Extensive literature has shown that peptides of the RAAS oscillate with a circadian periodicity in humans, under strong influence of posture, sleep, and age. Although observations of time-variant changes in the renin cascade are available in dogs, no detailed chronobiological investigation has been conducted so far. The present studies were designed to explore the circadian variations of plasma renin activity (RA) and urinary aldosterone-to-creatinine ratio (UA:C) in relation to blood pressure (BP), sodium (UNa, UNa,fe), and potassium (UK, UK,fe) renal handling. Data derived from intensive blood and urine sampling, as well as continuous BP monitoring, were collected throughout a 24-h time period, and analyzed by means of nonlinear mixed-effects models. Differences between the geometric means of day and night observations were compared by parametric statistics. Our results show that variables of the renin cascade, BP, and urinary electrolytes oscillate with significant day-night differences in dogs. An approximately 2-fold (1.6-3.2-fold) change between the average day and night measurements was found for RA (p < 0.001), UA:C (p = 0.01), UK,fe (p = 0.01), and UNa (p = 0.007). Circadian variations in BP, albeit small (less than 10 mm Hg), were statistically significant (p < 0.01) and supported by the model-based analysis. For all variables but UNa and UNa,fe, the levels were higher at night than during the day. The data also indicate that blood pressure oscillates in parallel to the RAAS, such that, as opposed to healthy humans, BP does not drop at night in dogs. The postprandial decrease in RA is assumed to be related to body fluid volume expansion secondary to water and sodium intake, whereas the reduction of UA:C reflects

  20. The Effect of Renin-angiotensin System Inhibitors on Kidney Allograft Survival: A Systematic Review and Meta-analysis

    PubMed Central

    Cheungpasitporn, Wisit; Thongprayoon, Charat; Mao, Michael A.; Kittanamongkolchai, Wonngarm; Sathick, Insara J. J.; Erickson, Stephen B.

    2016-01-01

    Background: The use of renin-angiotensin system (RAS) inhibitors in patients with chronic kidney disease, and especially in diabetic kidney disease, has been shown to provide renoprotective effects and slow progression to end-stage renal disease. However, this protective effect in kidney transplant patient populations is unclear. Aim: The objective of this systematic review and meta-analysis was to evaluate the effect of RAS inhibitors on kidney allograft survival. Materials and Methods: A literature search for randomized controlled trials (RCTs) was performed from inception through February 2016. Studies that reported relative risks or hazard ratios comparing the risks of renal graft loss in renal transplant recipients who received RAS inhibitors vs. controls were included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. Results: Five studies (3 RCTs and 2 cohort studies) with 20024 kidney transplant patients were included in the meta-analysis. Pooled RR of allograft failure in recipients who received RAS inhibitors was 0.73 (95% CI: 0.45–1.21). When meta-analysis was limited only to RCTs, the pooled RR of allograft failure in patients using RAS inhibitors was 0.59 (95%: CI 0.20–1.69). The risk for mortality (RR: 1.13 [95% CI: 0.62–2.07]) in patients using RAS inhibitors compared to controls was not significantly reduced. Conclusion: This meta-analysis demonstrated insignificant reduced risks of renal graft loss among renal transplant recipients who received RAS inhibitors. Future studies assessing the potential benefits of RAS inhibitors on allograft survival in specific kidney transplant patient populations are needed. PMID:27583237

  1. [Does a genetic predisposition for infarction expansion exist? Evaluation of genetic polymorphisms of the renin-angiotensin system].

    PubMed

    Zedda, N; Onnis, E; Angius, A; Balata, F; Cherchi, P A; Sole, G; Olla, N; Poddie, D; Cao, A; Cherchi, A; Pirastu, M

    1997-03-01

    Aim of this study is to carry out a genetic analysis of polymorphisms of the renin-angiotensin system in a genetically homogeneous population, in patients with and without myocardial infarction (AMI) expansion and to evaluate the influence of non genetic, mechanical factors. The study was conducted on 299 patients with first AMI. Ecocardiography studies were performed on all patients on day 1 and 3 from the onset of AMI and before discharge. Eighty-four patients were excluded because of inadequate quality of echocardiograms and 215 (163 males, 52 females) were admitted. Of these, 157 had no evidence of AMI expansion (EXP-) while 58 had expansion (EXP+). DNA was extracted by standard methods from blood samples. Age and gender had no influence on AMI expansion. Anterior infarction (p < 0.000001) and Q-wave infarction (p < 0.00002) were found more frequently in EXP+. Peak of creatine phosphokinase was higher in EXP+ than in EXP- (p < 0.00001). The percent of patients treated with thrombolysis or with hypertension and/or left ventricular hypertrophy was not significantly different in the two groups. AGT MT235 polymorphism of angiotensinogen gene, I/D polymorphism of ACE gene and AT1 A1166C of AT1 receptor of angiotensin II were not significantly different in two groups. Stratified analysis showed that in patients with anterior AMI (n = 87), with a higher risk of AMI expansion, there is a significant difference (p < 0.02) in ACE genotype between EXP- and EXP+. Odds ratio assuming the dominant effect of I allele (II+ ID < DD) was 3.35 (confidence interval 1.41-7.56) with increased risk of expansion. More extension studies are need to verify if these results can contribute to early identification of patients at higher risk and to optimize therapeutic approach. PMID:9172934

  2. Exacerbation of acute kidney injury by bone marrow stromal cells from rats with persistent renin-angiotensin system activation.

    PubMed

    Kankuri, Esko; Mervaala, Elina E; Storvik, Markus; Ahola, Aija M J; Levijoki, Jouko; Müller, Dominik N; Finckenberg, Piet; Mervaala, Eero M

    2015-06-01

    Hypertension and persistent activation of the renin-angiotensin system (RAS) are predisposing factors for the development of acute kidney injury (AKI). Although bone-marrow-derived stromal cells (BMSCs) have shown therapeutic promise in treatment of AKI, the impact of pathological RAS on BMSC functionality has remained unresolved. RAS and its local components in the bone marrow are involved in several key steps of cell maturation processes. This may also render the BMSC population vulnerable to alterations even in the early phases of RAS pathology. We isolated transgenic BMSCs (TG-BMSCs) from young end-organ-disease-free rats with increased RAS activation [human angiotensinogen/renin double transgenic rats (dTGRs)] that eventually develop hypertension and die of end-organ damage and kidney failure at 8 weeks of age. Control cells (SD-BMSCs) were isolated from wild-type Sprague-Dawley rats. Cell phenotype, mitochondrial reactive oxygen species (ROS) production and respiration were assessed, and gene expression profiling was carried out using microarrays. Cells' therapeutic efficacy was evaluated in a rat model of acute ischaemia/reperfusion-induced AKI. Serum urea and creatinine were measured at 24 h and 48 h. Acute tubular damage was scored and immunohistochemistry was used for evaluation for markers of inflammation [monocyte chemoattractant protein (MCP-1), ED-1], and kidney injury [kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL)]. TG-BMSCs showed distinct mitochondrial morphology, decreased cell respiration and increased production of ROS. Gene expression profiling revealed a pronounced pro-inflammatory phenotype. In contrast with the therapeutic effect of SD-BMSCs, administration of TG-BMSCs in the AKI model resulted in exacerbation of kidney injury and high mortality. Our results demonstrate that early persistent RAS activation can dramatically compromise therapeutic potential of BMSCs by causing a shift into a pro

  3. Concomitant inhibition of renin angiotensin system and Toll-like receptor 2 attenuates renal injury in unilateral ureteral obstructed mice

    PubMed Central

    Chung, Sarah; Jeong, Jin Young; Chang, Yoon Kyung; Choi, Dae Eun; Na, Ki Ryang; Lim, Beom Jin; Lee, Kang Wook

    2016-01-01

    Background/Aims: There has been controversy about the role of Toll-like receptor 2 (TLR2) in renal injury following ureteric obstruction. Although inhibition of the renin angiotensin system (RAS) reduces TLR2 expression in mice, the exact relationship between TLR2 and RAS is not known. The aim of this study was to determine whether the RAS modulates TLR2. Methods: We used 8-week-old male wild type (WT) and TLR2-knockout (KO) mice on a C57Bl/6 background. Unilateral ureteral obstruction (UUO) was induced by complete ligation of the left ureter. Angiotensin (Ang) II (1,000 ng/kg/min) and the direct renin inhibitor aliskiren (25 mg/kg/day) were administrated to mice using an osmotic minipump. Molecular and histologic evaluations were performed. Results: Ang II infusion increased mRNA expression of TLR2 in WT mouse kidneys (p < 0.05). The expression of renin mRNA in TLR2-KO UUO kidneys was significantly higher than that in WT UUO kidneys (p < 0.05). There were no differences in tissue injury score or mRNA expression of monocyte chemotactic protein 1 (MCP-1), osteopontin (OPN), or transforming growth factor β (TGF-β) between TLR2-KO UUO and WT UUO kidneys. However, aliskiren decreased the tissue injury score and mRNA expression of TLR2, MCP-1, OPN, and TGF-β in WT UUO kidneys (p < 0.05). Aliskiren-treated TLR2-KO UUO kidneys showed less kidney injury than aliskiren-treated WT UUO kidneys. Conclusions: TLR2 deletion induced activation of the RAS in UUO kidneys. Moreover, inhibition of both RAS and TLR2 had an additive ameliorative effect on UUO injury of the kidney. PMID:26932402

  4. Aldosterone, Parathyroid Hormone, and the Use of Renin-Angiotensin-Aldosterone System Inhibitors: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Brown, Jenifer; de Boer, Ian H.; Robinson-Cohen, Cassianne; Siscovick, David S.; Kestenbaum, Bryan; Allison, Matthew

    2015-01-01

    Context: Aldosterone and PTH are implicated in the pathogenesis of cardiovascular and skeletal diseases. An expanding body of evidence supports a bidirectional and positive physiologic relationship between aldosterone and PTH. Large population-based studies confirming this relationship, and whether it may be targeted as a potential method to mitigate the clinical consequences associated with excess aldosterone and PTH, are needed. Objective: We hypothesized that higher aldosterone levels would associate with higher PTH, and that the use of renin-angiotensin-aldosterone system (RAAS) inhibitors would predict lower PTH in a large, multi-ethnic, community-based cohort. Design, Setting, Participants: We conducted cross-sectional analyses of participants in the Multi-Ethnic Study of Atherosclerosis without apparent primary hyperparathyroidism or chronic kidney disease (n = 5668). We evaluated associations of RAAS inhibitor use with PTH concentration among 1888 treated hypertensive participants. We also tested associations of serum aldosterone concentration with PTH concentration among 1547 participants with these measurements. Outcome: Serum PTH concentration. Results: Higher aldosterone associated with higher PTH (β = 0.19 pg/ml per 1 ng/dl of aldosterone, P < .0001), and this finding was most pronounced among those with a primary hyperaldosteronism-like phenotype. There was a stepwise increment in PTH when comparing untreated normotensives, hypertensives using RAAS inhibitors, untreated hypertensives, and treated hypertensives using non-RAAS inhibitors (40.8, 45.0, 46.2, 47.1 pg/ml, respectively). The use of any RAAS inhibitor independently associated with lower PTH (β = −2.327 pg/ml per use of RAAS inhibitor, P = .006), when compared with the use of any non-RAAS inhibitor medication. Conclusions: Higher serum aldosterone concentration is associated with higher serum PTH concentration, and the use of RAAS inhibitors is associated with lower PTH concentration

  5. H2S Inhibits Hyperglycemia-Induced Intrarenal Renin-Angiotensin System Activation via Attenuation of Reactive Oxygen Species Generation

    PubMed Central

    Ni, Jun; Li, Chen; Shao, Decui; Liu, Jia; Shen, Yang; Wang, Zhen; Zhou, Li; Zhang, Wei; Huang, Yu; Yu, Chen; Wang, Rui; Lu, Limin

    2013-01-01

    Decrease in endogenous hydrogen sulfide (H2S) was reported to participate in the pathogenesis of diabetic nephropathy (DN). This study is aimed at exploring the relationship between the abnormalities in H2S metabolism, hyperglycemia-induced oxidative stress and the activation of intrarenal renin-angiotensin system (RAS). Cultured renal mesangial cells (MCs) and streptozotocin (STZ) induced diabetic rats were used for the studies. The expressions of angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin II (Ang II) type I receptor (AT1), transforming growth factor-β1 (TGF-β1) and collagen IV were measured by real time PCR and Western blot. Reactive oxygen species (ROS) production was assessed by fluorescent probe assays. Cell proliferation was analyzed by 5'-bromo-2'-deoxyuridine incorporation assay. Ang II concentration was measured by an enzyme immunoassay. AGT, ACE and AT1 receptor mRNA levels and Ang II concentration were increased in high glucose (HG) -treated MCs, the cell proliferation rate and the production of TGF-β1 and of collagen IV productions were also increased. The NADPH oxidase inhibitor diphenylenechloride iodonium (DPI) was able to reverse the HG-induced RAS activation and the changes in cell proliferation and collagen synthesis. Supplementation of H2S attenuated HG-induced elevations in ROS and RAS activation. Blockade on H2S biosynthesis from cystathione-γ-lyase (CSE) by DL-propargylglycine (PPG) resulted in effects similar to that of HG treatment. In STZ-induced diabetic rats, the changes in RAS were also reversed by H2S supplementation without affecting blood glucose concentration. These data suggested that the decrease in H2S under hyperglycemic condition leads to an imbalance between oxidative and reductive species. The increased oxidative species results in intrarenal RAS activation, which, in turn, contributes to the pathogenesis of renal dysfunction. PMID:24058553

  6. Sequential activation of the intrarenal renin-angiotensin system in the progression of hypertensive nephropathy in Goldblatt rats.

    PubMed

    Kim, Yang Gyun; Lee, Sang Ho; Kim, Se-Yun; Lee, Arah; Moon, Ju Young; Jeong, Kyung-Hwan; Lee, Tae Won; Lim, Sung Jig; Sohn, Il Suk; Ihm, Chun-Gyoo

    2016-07-01

    The intrarenal renin-angiotensin system (RAS) has an important role in generating and maintaining hypertension in two-kidney, one-clip (2K1C) rats. This study evaluated how various intrarenal RAS components contributed to hypertension not only in the maintenance period (5w; 5 wk after operation) but also earlier (2w; 2 wk after operation). We inserted a 2.5-mm clip into the left renal artery of Sprague-Dawley rats and euthanized them at 2w and 5w following the operation. Systolic blood pressure increased within 1 wk after the operation, and left ventricular hypertrophy occurred in 2K1C rats. At 2w, juxtaglomerular apparatus (JGA) and collecting duct (CD) renin increased in clipped kidney (CK) of 2K1C rats. The tubular angiotensin I-converting enzyme (ACE) was not changed, but peritubular ACE2 decreased in nonclipped kidney (NCK) and CK of 2K1C rats. At 5w, ACE and CD renin were enhanced, and ACE2 was still lessened in both kidneys of 2K1C rats. However, plasma renin activity (PRA) was not different from that in sham rats. In proximal tubules of CK, the ANG II type 1 receptor (AT1R) was not suppressed, but the Mas receptor (MasR) was reduced; thus the AT1R/MasR ratio was elevated. Although hypoxic change in CK could not be excluded, the JGA renin of CK and CD renin in both kidneys was highly expressed independent of time. Peritubular ACE2 changed in the earlier period, and uninhibited AT1R in proximal tubules of CK was presented in the maintenance period. In 2K1C rats, attenuated ACE2 seems to contribute to initiating hypertension while upregulated ACE in combination with unsuppressed AT1R may have a key role in maintaining hypertension. PMID:26823279

  7. Low birth weight activates the renin-angiotensin system, but limits cardiac angiogenesis in early postnatal life.

    PubMed

    Wang, Kimberley C W; Brooks, Doug A; Summers-Pearce, Brooke; Bobrovskaya, Larisa; Tosh, Darran N; Duffield, Jaime A; Botting, Kimberley J; Zhang, Song; Caroline McMillen, I; Morrison, Janna L

    2015-02-01

    Low birth weight (LBW) is associated with increased risk of adult cardiovascular disease and this association may be partly a consequence of early programming of the renin-angiotensin system (RAS). We investigated the effects of LBW on expression of molecules in the RAS and cardiac tissue remodeling. Left ventricular samples were collected from the hearts of 21 days old lambs that were born average birth weight (ABW) and LBW. Cardiac mRNA expression was quantified using real-time RT-PCR and protein expression was quantified using Western blotting. DNA methylation and histone acetylation were assessed by combined bisulfite restriction analysis and chromatin immunoprecipitation, respectively. There were increased plasma renin activity, angiotensin I (ANGI), and ANGII concentrations in LBW compared to ABW lambs at day 20. In LBW lambs, there was increased expression of cardiac ACE2 mRNA, decreased ANGII receptor type 1 (AT1R) protein, and acetylation of histone H3K9 of the AT1R promoter but no changes in AT1R mRNA expression and AT1R promoter DNA methylation. There was no difference in the abundance of proteins involved in autophagy or fibrosis. BIRC5 and VEGF mRNA expression was increased; however, the total length of the capillaries was decreased in the hearts of LBW lambs. Activation of the circulating and local cardiac RAS in neonatal LBW lambs may be expected to increase cardiac fibrosis, autophagy, and capillary length. However, we observed only a decrease in total capillary length, suggesting a dysregulation of the RAS in the heart of LBW lambs and this may have significant implications for heart health in later life. PMID:25649246

  8. The predictability of renin-angiotensin-aldosterone system factors for clinical outcome in patients with acute decompensated heart failure.

    PubMed

    Nakada, Yasuki; Takahama, Hiroyuki; Kanzaki, Hideaki; Sugano, Yasuo; Hasegawa, Takuya; Ohara, Takahiro; Amaki, Makoto; Funada, Akira; Yoshida, Akemi; Yasuda, Satoshi; Ogawa, Hisao; Anzai, Toshihisa

    2016-06-01

    Although counter-regulation between B-type natriuretic peptide (BNP) levels and renin-angiotensin-aldosterone system (RAAS) activation in heart failure (HF) has been suggested, whether the regulation is preserved in acute decompensated heart failure (ADHF) patients remains unclear. This study aimed to determine: (1) the relationship between RAAS activation and clinical outcomes in ADHF patients, and (2) the relationships between plasma BNP levels and degrees of activation in RAAS factors. This study included ADHF patients (n = 103, NYHA3-4, plasma BNP > 200 pg/ml). We studied the predictability of RAAS factors for cardiovascular events and the relationships between plasma BNP levels and the degrees of activation in RAAS factors, which were evaluated by plasma renin activity (PRA) and aldosterone concentration (PAC). PRA was a strong predictor of cardiovascular (CV) events over 1 year, even after accounting for plasma BNP levels (hazard ratio (HR): 1.04, CI [1.02-1.06], p < 0.01) and medication such as RAAS blockers (HR: 1.03, CI [1.01-1.05], p < 0.01), whereas PAC was borderline-significant (univariate analysis, p = 0.06). Cut-off value of PRA (5.3 ng/ml/h) was determined by AUC curve. Of the enrolled patients, higher PRA was found in 40 % of them. Although no correlation between the plasma BNP levels and PRA was found (p = 0.36), after adjusting for hemodynamic parameters, eGFR and medication, a correlation was found between them (p = 0.01). Elevated RAAS factors were found in a substantial number of ADHF patients with high plasma BNP levels in the association with hemodynamic state, which predicts poor clinical outcomes. The measurements of RAAS factors help to stratify ADHF patients at risk for further CV events. PMID:25964073

  9. Treatment with patiromer decreases aldosterone in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.

    PubMed

    Weir, Matthew R; Bakris, George L; Gross, Coleman; Mayo, Martha R; Garza, Dahlia; Stasiv, Yuri; Yuan, Jinwei; Berman, Lance; Williams, Gordon H

    2016-09-01

    Elevated serum aldosterone can be vasculotoxic and facilitate cardiorenal damage. Renin-angiotensin system inhibitors reduce serum aldosterone levels and/or block its effects but can cause hyperkalemia. Patiromer, a nonabsorbed potassium binder, decreases serum potassium in patients with chronic kidney disease on renin-angiotensin system inhibitors. Here we examined the effect of patiromer treatment on serum aldosterone, blood pressure, and albuminuria in patients with chronic kidney disease on renin-angiotensin system inhibitors with hyperkalemia (serum potassium 5.1-6.5 mEq/l). We analyzed data from the phase 3 OPAL-HK study (4-week initial treatment phase of 243 patients; 8-week randomized withdrawal phase of 107 patients). In the treatment phase, the (mean ± standard error) serum potassium was decreased concordantly with the serum aldosterone (-1.99 ± 0.51 ng/dl), systolic/diastolic blood pressure (-5.64 ± 1.04 mm Hg/-3.84 ± 0.69 mm Hg), and albumin-to-creatinine ratio (-203.7 ± 54.7 mg/g), all in a statistically significant manner. The change in the plasma renin activity (-0.44 ± 0.63 μg/l/hr) was not significant. In the withdrawal phase, mean aldosterone levels were sustained with patiromer (+0.23 ± 1.07 ng/dl) and significantly increased with placebo (+2.78 ± 1.25 ng/dl). Patients on patiromer had significant reductions in mean systolic/diastolic blood pressure (-6.70 ± 1.59/-2.15 ± 1.06 mm Hg), whereas those on placebo did not (-1.21 ± 1.89 mm Hg/+1.72 ± 1.26 mm Hg). Significant changes in plasma renin activity were found only in the placebo group (-3.90 ± 1.41 μg/l/hr). Thus, patiromer reduced serum potassium and aldosterone levels independent of plasma renin activity in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors. PMID:27350174

  10. Effects of Aerobic Exercise Training on Cardiac Renin-Angiotensin System in an Obese Zucker Rat Strain

    PubMed Central

    Barretti, Diego Lopes Mendes; Magalhães, Flávio de Castro; Fernandes, Tiago; do Carmo, Everton Crivoi; Rosa, Kaleizu Teodoro; Irigoyen, Maria Claudia; Negrão, Carlos Eduardo; Oliveira, Edilamar Menezes

    2012-01-01

    Objective Obesity and renin angiotensin system (RAS) hyperactivity are profoundly involved in cardiovascular diseases, however aerobic exercise training (EXT) can prevent obesity and cardiac RAS activation. The study hypothesis was to investigate whether obesity and its association with EXT alter the systemic and cardiac RAS components in an obese Zucker rat strain. Methods The rats were divided into the following groups: Lean Zucker rats (LZR); lean Zucker rats plus EXT (LZR+EXT); obese Zucker rats (OZR) and obese Zucker rats plus EXT (OZR+EXT). EXT consisted of 10 weeks of 60-min swimming sessions, 5 days/week. At the end of the training protocol heart rate (HR), systolic blood pressure (SBP), cardiac hypertrophy (CH) and function, local and systemic components of RAS were evaluated. Also, systemic glucose, triglycerides, total cholesterol and its LDL and HDL fractions were measured. Results The resting HR decreased (∼12%) for both LZR+EXT and OZR+EXT. However, only the LZR+EXT reached significance (p<0.05), while a tendency was found for OZR versus OZR+EXT (p = 0.07). In addition, exercise reduced (57%) triglycerides and (61%) LDL in the OZR+EXT. The systemic angiotensin I-converting enzyme (ACE) activity did not differ regardless of obesity and EXT, however, the OZR and OZR+EXT showed (66%) and (42%), respectively, less angiotensin II (Ang II) plasma concentration when compared with LZR. Furthermore, the results showed that EXT in the OZR prevented increase in CH, cardiac ACE activity, Ang II and AT2 receptor caused by obesity. In addition, exercise augmented cardiac ACE2 in both training groups. Conclusion Despite the unchanged ACE and lower systemic Ang II levels in obesity, the cardiac RAS was increased in OZR and EXT in obese Zucker rats reduced some of the cardiac RAS components and prevented obesity-related CH. These results show that EXT prevented the heart RAS hyperactivity and cardiac maladaptive morphological alterations in obese Zucker rats

  11. Renin-Angiotensin System Blockers May Prolong Survival of Metastatic Non-Small Cell Lung Cancer Patients Receiving Erlotinib

    PubMed Central

    Aydiner, Adnan; Ciftci, Rumeysa; Sen, Fatma

    2015-01-01

    Abstract The aim of this study is to determine whether renin-angiotensin system blockers (RASBs), which include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-2 receptor 1 blockers (ARBs), improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC). The medical charts of 117 patients with metastatic NSCLC were retrospectively assessed. Thirty-seven patients (RASB group) using RASBs during systemic treatment were compared with 80 controls (control group) who did not use RASBs following the diagnosis of NSCLC. The histological tumor subtype, performance status, age, sex, smoking status, comorbidities, other medications, chemotherapeutics (CT), and erlotinib that were received in any line of treatment were recorded. We compared the OS of the patients in the RASB and control groups. The median (±SD) age of the patients was 61 (±1) years and all patients were administered systemic treatment (CT or erlotinib). The patients in RASB group were more likely to be smokers, have hypertension and ischemic heart disease, and use erlotinib, thiazides, beta-blockers, and calcium-channel blockers (P < 0.05 for all) compared with the control group. The median follow-up time was 18.9 months (range 1–102 months) for the entire group. The median follow-up period was longer for RASB group than control group (17 vs 11 months, P = 0.033). The most commonly prescribed RASB agent was valsartan (n = 12/37). At the time of the analysis, 98 (83.7%) of all patients had died. In the univariate analysis, the median OS was longer in the RASB group compared with the control group (17 [±4.1] vs 12 [±1.4] months, P = 0.016). Interestingly, further analyses revealed that RASBs significantly improved OS only if used with erlotinib concurrently (34 [±13.8] vs 25 [±5] months, P = 0.002) and the OS benefit was more attributable to ARBs because only 4 patients received ACEI and erlotinib concurrently. However, the benefit of

  12. Renin-Angiotensin system blockers may prolong survival of metastatic non-small cell lung cancer patients receiving erlotinib.

    PubMed

    Aydiner, Adnan; Ciftci, Rumeysa; Sen, Fatma

    2015-06-01

    The aim of this study is to determine whether renin-angiotensin system blockers (RASBs), which include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-2 receptor 1 blockers (ARBs), improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC).The medical charts of 117 patients with metastatic NSCLC were retrospectively assessed. Thirty-seven patients (RASB group) using RASBs during systemic treatment were compared with 80 controls (control group) who did not use RASBs following the diagnosis of NSCLC. The histological tumor subtype, performance status, age, sex, smoking status, comorbidities, other medications, chemotherapeutics (CT), and erlotinib that were received in any line of treatment were recorded. We compared the OS of the patients in the RASB and control groups.The median (±SD) age of the patients was 61 (±1) years and all patients were administered systemic treatment (CT or erlotinib). The patients in RASB group were more likely to be smokers, have hypertension and ischemic heart disease, and use erlotinib, thiazides, beta-blockers, and calcium-channel blockers (P < 0.05 for all) compared with the control group. The median follow-up time was 18.9 months (range 1-102 months) for the entire group. The median follow-up period was longer for RASB group than control group (17 vs 11 months, P = 0.033). The most commonly prescribed RASB agent was valsartan (n = 12/37). At the time of the analysis, 98 (83.7%) of all patients had died. In the univariate analysis, the median OS was longer in the RASB group compared with the control group (17 [±4.1] vs 12 [±1.4] months, P = 0.016). Interestingly, further analyses revealed that RASBs significantly improved OS only if used with erlotinib concurrently (34 [±13.8] vs 25 [±5] months, P = 0.002) and the OS benefit was more attributable to ARBs because only 4 patients received ACEI and erlotinib concurrently. However, the benefit of ARBs on OS

  13. Plasma Molecular Signatures in Hypertensive Patients With Renin-Angiotensin System Suppression: New Predictors of Renal Damage and De Novo Albuminuria Indicators.

    PubMed

    Baldan-Martin, Montserrat; Mourino-Alvarez, Laura; Gonzalez-Calero, Laura; Moreno-Luna, Rafael; Sastre-Oliva, Tamara; Ruiz-Hurtado, Gema; Segura, Julian; Lopez, Juan Antonio; Vazquez, Jesus; Vivanco, Fernando; Alvarez-Llamas, Gloria; Ruilope, Luis M; de la Cuesta, Fernando; Barderas, Maria G

    2016-07-01

    Albuminuria is a risk factor strongly associated with cardiovascular disease, the first cause of death in the general population. It is well established that renin-angiotensin system suppressors prevent the development of new-onset albuminuria in naïf hypertensive patients and diminish its excretion, but we cannot forget the percentage of hypertensive patients who develop de novo albuminuria. Here, we applied multiple proteomic strategy with the purpose to elucidate specific molecular pathways involved in the pathogenesis and provide predictors and chronic organ damage indicators. Briefly, 1143 patients were followed up for a minimum period of 3 years. One hundred and twenty-nine hypertensive patients chronically renin-angiotensin system suppressed were recruited, classified in 3 different groups depending on their albuminuria levels (normoalbuminuria, de novo albuminuria, and sustained albuminuria), and investigated by multiple proteomic strategies. Our strategy allowed us to perform one of the deepest plasma proteomic analysis to date, which has shown 2 proteomic signatures: (1) with predictive value of de novo albuminuria and (2) sustained albuminuria indicator proteins. These proteins are involved in inflammation, immune as well as in the proteasome activation occurring in situations of endoplasmic reticulum stress. Furthermore, these results open the possibility of a future strategy based on anti-immune therapy to treat hypertension which could help to prevent the development of albuminuria and, hence, the progression of kidney damage. PMID:27217411

  14. Medullary Endocannabinoids Contribute to the Differential Resting Baroreflex Sensitivity in Rats with Altered Brain Renin-Angiotensin System Expression.

    PubMed

    Schaich, Chris L; Grabenauer, Megan; Thomas, Brian F; Shaltout, Hossam A; Gallagher, Patricia E; Howlett, Allyn C; Diz, Debra I

    2016-01-01

    CB1 cannabinoid receptors are expressed on vagal afferent fibers and neurons within the solitary tract nucleus (NTS), providing anatomical evidence for their role in arterial baroreflex modulation. To better understand the relationship between the brain renin-angiotensin system (RAS) and endocannabinoid expression within the NTS, we measured dorsal medullary endocannabinoid tissue content and the effects of CB1 receptor blockade at this brain site on cardiac baroreflex sensitivity (BRS) in ASrAOGEN rats with low glial angiotensinogen, normal Sprague-Dawley rats and (mRen2)27 rats with upregulated brain RAS expression. Mass spectrometry revealed higher levels of the endocannabinoid 2-arachidonoylglycerol in (mRen2)27 compared to ASrAOGEN rats (2.70 ± 0.28 vs. 1.17 ± 0.09 ng/mg tissue; P < 0.01), while Sprague-Dawley rats had intermediate content (1.85 ± 0.27 ng/mg tissue). Microinjection of the CB1receptor antagonist SR141716A (36 pmol) into the NTS did not change cardiac BRS in anesthetized Sprague-Dawley rats (1.04 ± 0.05 ms/mmHg baseline vs. 1.17 ± 0.11 ms/mmHg after 10 min). However, SR141716A in (mRen2)27 rats dose-dependently improved BRS in this strain: 0.36 pmol of SR141716A increased BRS from 0.43 ± 0.03 to 0.71 ± 0.04 ms/mmHg (P < 0.001), and 36 pmol of SR141716A increased BRS from 0.47 ± 0.02 to 0.94 ± 0.10 ms/mmHg (P < 0.01). In contrast, 0.36 pmol (1.50 ± 0.12 vs. 0.86 ± 0.08 ms/mmHg; P < 0.05) and 36 pmol (1.38 ± 0.16 vs. 0.46 ± 0.003 ms/mmHg; P < 0.01) of SR141716A significantly reduced BRS in ASrAOGEN rats. These observations reveal differential dose-related effects of the brain endocannabinoid system that influence cardiovagal BRS in animals with genetic alterations in the brain RAS. PMID:27375489

  15. Medullary Endocannabinoids Contribute to the Differential Resting Baroreflex Sensitivity in Rats with Altered Brain Renin-Angiotensin System Expression

    PubMed Central

    Schaich, Chris L.; Grabenauer, Megan; Thomas, Brian F.; Shaltout, Hossam A.; Gallagher, Patricia E.; Howlett, Allyn C.; Diz, Debra I.

    2016-01-01

    CB1 cannabinoid receptors are expressed on vagal afferent fibers and neurons within the solitary tract nucleus (NTS), providing anatomical evidence for their role in arterial baroreflex modulation. To better understand the relationship between the brain renin-angiotensin system (RAS) and endocannabinoid expression within the NTS, we measured dorsal medullary endocannabinoid tissue content and the effects of CB1 receptor blockade at this brain site on cardiac baroreflex sensitivity (BRS) in ASrAOGEN rats with low glial angiotensinogen, normal Sprague-Dawley rats and (mRen2)27 rats with upregulated brain RAS expression. Mass spectrometry revealed higher levels of the endocannabinoid 2-arachidonoylglycerol in (mRen2)27 compared to ASrAOGEN rats (2.70 ± 0.28 vs. 1.17 ± 0.09 ng/mg tissue; P < 0.01), while Sprague-Dawley rats had intermediate content (1.85 ± 0.27 ng/mg tissue). Microinjection of the CB1receptor antagonist SR141716A (36 pmol) into the NTS did not change cardiac BRS in anesthetized Sprague-Dawley rats (1.04 ± 0.05 ms/mmHg baseline vs. 1.17 ± 0.11 ms/mmHg after 10 min). However, SR141716A in (mRen2)27 rats dose-dependently improved BRS in this strain: 0.36 pmol of SR141716A increased BRS from 0.43 ± 0.03 to 0.71 ± 0.04 ms/mmHg (P < 0.001), and 36 pmol of SR141716A increased BRS from 0.47 ± 0.02 to 0.94 ± 0.10 ms/mmHg (P < 0.01). In contrast, 0.36 pmol (1.50 ± 0.12 vs. 0.86 ± 0.08 ms/mmHg; P < 0.05) and 36 pmol (1.38 ± 0.16 vs. 0.46 ± 0.003 ms/mmHg; P < 0.01) of SR141716A significantly reduced BRS in ASrAOGEN rats. These observations reveal differential dose-related effects of the brain endocannabinoid system that influence cardiovagal BRS in animals with genetic alterations in the brain RAS. PMID:27375489

  16. Inflammatory markers in paroxysmal atrial fibrillation and the protective role of renin-angiotensin-aldosterone system inhibitors

    PubMed Central

    ROŞIANU, ŞTEFAN HORIA; ROŞIANU, ADELA-NICOLETA; ALDICA, MIHAI; CĂPÂLNEANU, RADU; BUZOIANU, ANCA DANA

    2013-01-01

    Background Experimental and clinical studies have shown the importance of inflammation in the pathophysiology of atrial fibrillation (AF). The renin-angiotensin-aldosterone system (RAAS) may play an important role in the pathogenesis of AF in correlation with the inflammatory process. RAAS inhibition may have important therapeutic value in limiting AF. The aim of this study was the correlation between inflammatory markers and recurrent episodes of AF in patients with known paroxysmal atrial fibrillation, with and without treatment with RAAS inhibitors. Methods and results We studied 82 patients with paroxysmal AF recorded at “Niculae Stancioiu” Heart Institute Cluj-Napoca, divided into two groups: group A treated with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) and group B without this medication. All patients underwent clinical examination, ECG, echocardiography and determination of plasma levels of inflammatory markers represented by high sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6). In the group treated with ACE inhibitors/ARBs, AF burden was significantly lower than in patients without treatment. We obtained a strong positive correlation between blood levels of high-sensitivity CRP and those of IL-6 (r=0.64, p<0.001), the number of yearly AF episodes (r=0.570, p<0.001), LA diameter (r=0.5, p<0.001) and LA volume (r=0.5, p<0.001). We found moderate positive correlations between blood levels of IL-6 and LA diameter (r=0.305, p=0.01), LA volume (r=0.314, p=0.01), the number of yearly AF episodes (r=0.489, p<0.001), the total number of AF episodes (r=0.304, p<0.001), BMI (r=0.473, p<0.001), LA area (r=0.458, p<0.001), LA area index (r=0.334, p=0.007) and LA volume index (r=0.304, p=0.01). The number of yearly AF episodes and BMI values influenced IL-6 blood levels (t=3.46, p=0.001, respectively t=2.17, p=0.03). Conclusions Inflammation is present in patients with AF, with or without treatment with

  17. Correlation of renin angiotensin system (RAS) candidate gene polymorphisms with response to Ramipril in patients with essential hypertension

    PubMed Central

    Gupta, S; Chattopadhyaya, I; Agrawal, BK; Sehajpal, PK; Goel, RK

    2015-01-01

    Background: The renin-angiotensin system (RAS) is an important facet of blood pressure regulation physiology. Treatment of essential hypertension targets the RAS using Angiotensin Converting Enzyme Inhibitors (ACEIs). However, ACEIs are not uniformly effective and show inter-individual pharmacodynamic variations. Aim: To assess the correlation between genetic polymorphisms in the genes coding for RAS components (angiotensin converting enzyme (ACE I/D), α-adducin (ADD1) and β1-adrenoreceptor (β1-ADR)) and response to Ramipril. Materials and Methods: We recruited 120 patients with essential hypertension who were administered Ramipril monotherapy initially, followed by combination therapy, if needed, based on their responses. Relationship between genotypes of the three candidate genes and decrease in the blood pressure (BP) was analyzed. Results: One hundred and six patients were evaluable at the end of the study period and 21 different genotypes were observed among them. Seven of them were classified as responders after 8 weeks and at the end of 12 weeks, an additional 77 (72.64%) were deemed responders. 19/22 non-responders were treated with combination therapy and 7/19 (36.84%) showed a response to the same. There was a significant difference between the proportions of responders and non-responders among the genotypes of the ADD1 and β1-ADR genes (P = 0.005 and 0.003, respectively). The best predictors of response to Ramipril 5 mg daily were the II/GG/SS, II/TG/SS, II/GG/SG, ID/GG/SS, ID/GG/SG and ID/TT/SS and DD/GG/SS; II/GG/GG, II/TT/SG, ID/TG/SG, ID/TT/SG, DD/GG/SG and DD/GG/GG were moderately predictive and II/TT/SS, II/TG/GG, ID/TG/GG, DD/TG/SG and DD/TG/GG were poorly predictive of response. Discussion: Variable responses to Ramipril may be the result of genetic factors. Conclusion: Pre-prescription genotyping may help individualize treatment. PMID:25511213

  18. Impact of The Protective Renin-Angiotensin System (RAS) on The Vasoreparative Function of CD34+ CACs in Diabetic Retinopathy

    NASA Technical Reports Server (NTRS)

    Duan, Yaqian; Moldovan, Leni; Miller, Rehae C.; Beli, Eleni; Salazar, Tatiana; Hazra, Sugata; Al-Sabah, Jude; Chalam, KV; Raghunandan, Sneha; Vyas, Ruchi; Parsons-Wingerter, Patricia; Oudit, Gavin Y.; Grant, Maria B.

    2016-01-01

    Purpose: In diabetes, the impaired vasoreparative function of Circulating Angiogenic Cells (CACs) is believed to contribute to the progression of diabetic retinopathy (DR). Accumulating evidence suggests that the protective arm of renin-angiotensin system (RAS) ACE2 Angiotensin-(1-7) Mas plays an important role in restoring the function of diabetic CACs. We examined the protective RAS in CACs in diabetic individuals with different stages of retinopathy. Methods: Study subjects (n43) were recruited as controls or diabetics with either no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR or proliferative DR (PDR). Fundus photography and fluorescein angiograms were analyzed using Vessel Generation Analysis (VESGEN) software in a cohort of subjects. CD34+ CACs were isolated from peripheral blood of diabetics and control subjects. RAS gene expressions in CACs were measured by qPCR. The vasoreparative function of CACs was assessed by migration ability toward CXCL12 using the QCM 5M 96-well chemotaxis cell migration assay. Results: ACE2 gene is a key enzyme converting the deleterious Angiotensin II to the beneficial Angiotensin-(1-7). ACE2 expression in CACs from diabetic subjects without DR was increased compared to controls, suggestive of compensation (p0.0437). The expression of Mas (Angiotensin-(1-7) receptor) in CACs was also increased in diabetics without DR, while was reduced in NPDR compared to controls (p0.0002), indicating a possible loss of compensation of the protective RAS at this stage of DR. The presence of even mild NPDR was associated with CD34+ CAC migratory dysfunction. When pretreating CACs of DR subjects with Angiotensin-(1-7), migratory ability to a chemoattractant CXCL12 was restored (p0.0008). By VESGEN analysis, an increase in small vessel density was observed in NPDR subjects when compared with the controls. Conclusions: These data suggest the protective RAS axis within diabetic CACs may help maintain their vasoreparative potential

  19. Mesenchymal Stromal Cells Prevent Renal Fibrosis in a Rat Model of Unilateral Ureteral Obstruction by Suppressing the Renin-Angiotensin System via HuR

    PubMed Central

    Gregorini, Marilena; Corradetti, Valeria; Rocca, Chiara; Pattonieri, Eleonora Francesca; Valsania, Teresa; Milanesi, Samantha; Serpieri, Nicoletta; Bedino, Giulia; Esposito, Pasquale; Libetta, Carmelo; Avanzini, Maria Antonietta; Mantelli, Melissa; Ingo, Daniela; Peressini, Sabrina; Albertini, Riccardo; Dal Canton, Antonio; Rampino, Teresa

    2016-01-01

    We studied Mesenchymal Stromal Cells (MSC) effects in experimental Unilateral Ureteral Obstruction (UUO), a fibrogenic renal disease. Rats were divided in 5 groups: sham, UUO, MSC treated-UUO, ACEi treated-UUO, MSC+ACEi treated- UUO. Data were collected at 1, 7, 21 days. UUO induced monocyte renal infiltration, tubular cell apoptosis, tubular atrophy, interstitial fibrosis and overexpression of TGFβ, Renin mRNA (RENmRNA), increase of Renin, Angiotensin II (AII) and aldosterone serum levels. Both lisinopril (ACEi) and MSC treatment prevented monocyte infiltration, reduced tubular cell apoptosis, renal fibrosis and TGFβ expression. Combined therapy provided a further suppression of monocyte infiltration and tubular injury. Lisinopril alone caused a rebound activation of Renin-Angiotensin System (RAS), while MSC suppressed RENmRNA and Renin synthesis and induced a decrease of AII and aldosterone serum levels. Furthermore, in in-vitro and in-vivo experiments, MSC inhibit Human antigen R (HuR) trascription, an enhancer of RENmRNA stability by IL10 release. In conclusion, we demonstrate that in UUO MSC prevent fibrosis, by decreasing HuR-dependent RENmRNA stability. Our findings give a clue to understand the molecular mechanism through which MSC may prevent fibrosis in a wide and heterogeneous number of diseases that share RAS activation as common upstream pathogenic mechanism. PMID:26866372

  20. Uric acid induces oxidative stress via an activation of the renin-angiotensin system in 3T3-L1 adipocytes.

    PubMed

    Zhang, Jun-xia; Zhang, Yu-ping; Wu, Qi-nan; Chen, Bing

    2015-02-01

    Hyperuricemia is recently reported involving in various obesity-related cardiovascular disorders, especially hypertension. However, the underlying mechanisms are not completely understood. In the present study, we investigated whether uric acid upregulates renin-angiotensin system (RAS) expression in adipocytes. We also examined whether RAS activation plays a role in uric acid-induced oxidative stress in adipocytes. The adipocytes of different phenotypes were incubated with uric acid for 48 h, respectively. Losartan (10(-4) M) or captopril (10(-4) M) was used to block adipose tissue RAS activation. mRNA expressions of angiotensinogen (AGT), angiotensin-converting enzyme-1 (ACE-1), renin, angiotensin type 1 receptor (AT1R), and angiotensin type 2 receptor (AT2R) were evaluated with real-time PCR. Angiotensin II concentrations in supernatant were measured by ELISA. Intracellular reactive species (ROS) levels were measured by fluorescent probe DCFH-DA, DHR, or NBT assay. The uric acid upregulated both RAS (AGT, ACE1, renin, AT1R, and AT2R) mRNA expressions and angiotensin II protein secretion and caused a significant increase in ROS production in 3T3-L1 adipocytes. These effects could be prevented by RAS inhibitors, either losartan or captopril. RAS activation has been causally implicated in oxidative stress induced by uric acid in 3T3-L1 adipocytes, suggesting a plausible mechanism through which hyperuricemia contributes to the pathogenesis of obesity-related cardiovascular diseases. PMID:24671741

  1. Targeting Cardiac Mast Cells: Pharmacological Modulation of the Local Renin-Angiotensin System

    PubMed Central

    Reid, Alicia C.; Brazin, Jacqueline A.; Morrey, Christopher; Silver, Randi B.; Levi, Roberto

    2012-01-01

    Enhanced production of angiotensin II and excessive release of norepinephrine in the ischemic heart are major causes of arrhythmias and sudden cardiac death. Mast cell-dependent mechanisms are pivotal in the local formation of angiotensin II and modulation of norepinephrine release in cardiac pathophysiology. Cardiac mast cells increase in number in myocardial ischemia and are located in close proximity to sympathetic neurons expressing angiotensin AT1- and histamine H3-receptors. Once activated, cardiac mast cells release a host of potent pro-inflammatory and pro-fibrotic cytokines, chemokines, preformed mediators (e.g., histamine) and proteases (e.g., renin). In myocardial ischemia, angiotensin II (formed locally from mast cell-derived renin) and histamine (also released from local mast cells) respectively activate AT1- and H3-receptors on sympathetic nerve endings. Stimulation of angiotensin AT1-receptors is arrhythmogenic whereas H3-receptor activation is cardioprotective. It is likely that in ischemia/reperfusion the balance may be tipped toward the deleterious effects of mast cell renin, as demonstrated in mast cell-deficient mice, lacking mast cell renin and histamine in the heart. In these mice, no ventricular fibrillation occurs at reperfusion following ischemia, as opposed to wild-type hearts which all fibrillate. Preventing mast cell degranulation in the heart and inhibiting the activation of a local reninangiotensin system, hence abolishing its detrimental effects on cardiac rhythmicity, appears to be more significant than the loss of histamine-induced cardioprotection. This suggests that therapeutic targets in the treatment of myocardial ischemia, and potentially congestive heart failure and hypertension, should include prevention of mast cell degranulation, mast cell renin inhibition, local ACE inhibition, ANG II antagonism and H3-receptor activation. PMID:22103845

  2. Meta-analysis of effects of obstructive sleep apnea on the renin-angiotensin-aldosterone system

    PubMed Central

    Jin, Ze-Ning; Wei, Yong-Xiang

    2016-01-01

    Background Obstructive sleep apnea (OSA) is the most common cause of resistant hypertension, which has been proposed to result from activation of the renin–angiotensin–aldosterone system (RAAS). We meta-analyzed the effects of OSA on plasma levels of RAAS components. Methods Full-text studies published on MEDLINE and EMBASE analyzing fasting plasma levels of at least one RAAS component in adults with OSA with or without hypertension. OSA was diagnosed as an apnea-hypopnea index or respiratory disturbance index ≥ 5. Study quality was evaluated using the Newcastle-Ottawa Scale, and heterogeneity was assessed using the I2 statistic. Results from individual studies were synthesized using inverse variance and pooled using a random-effects model. Subgroup analysis, sensitivity analysis, and meta-regression were performed, and risk of publication bias was assessed. Results The meta-analysis included 13 studies, of which 10 reported results on renin (n = 470 cases and controls), 7 on angiotensin II (AngII, n = 384), and 9 on aldosterone (n = 439). AngII levels were significantly higher in OSA than in controls [mean differences = 3.39 ng/L, 95% CI: 2.00–4.79, P < 0.00001], while aldosterone levels were significantly higher in OSA with hypertension than OSA but not with hypertension (mean differences = 1.32 ng/dL, 95% CI: 0.58–2.07, P = 0.0005). Meta-analysis of all studies suggested no significant differences in aldosterone between OSA and controls, but a significant pooled mean difference of 1.35 ng/mL (95% CI: 0.88–1.82, P < 0.00001) emerged after excluding one small-sample study. No significant risk of publication bias was detected among all included studies. Conclusions OSA is associated with higher AngII and aldosterone levels, especially in hypertensive patients. OSA may cause hypertension, at least in part, by stimulating RAAS activity. PMID:27403143

  3. To RAS or not to RAS? The evidence for and cautions with renin-angiotensin system inhibition in patients with diabetic kidney disease.

    PubMed

    St Peter, Wendy L; Odum, Lauren E; Whaley-Connell, Adam T

    2013-05-01

    Substantial morbidity, mortality, and costs are associated with progressive diabetic kidney disease (DKD). A goal of Healthy People 2020 is to reduce kidney disease attributable to diabetes mellitus and increase the proportion of patients who receive agents that interrupt the renin-angiotensin system (RAS), such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). The mechanisms that contribute to progressive loss of kidney function in patients with diabetes are disrupted by inhibition of the RAS. ACEIs, ARBs and direct renin inhibitors (DRIs) all reduce the effect of angiotensin II, yet each works through a different mechanism and displays properties that may or may not be replicated by the others. As single agents, RAS inhibitors and blockers have been shown to slow the rate of progression of DKD and to reduce new cases of end-stage renal disease in various subsets of patients with diabetes and proteinuria (e.g., albuminuria). However, even with contemporary use of ACEIs, ARBs, and, more recently, DRIs, the burden of kidney disease remains high. Thus investigators sought to explore the utility of combining agents (e.g., dual RAS therapy) in various regimens for cardiovascular and kidney end points. Recent data from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) studies suggest that kidney-related outcomes (composite of dialysis initiation, doubling serum creatinine concentration, or death) were increased with ACEI plus ARB or DRI plus ARB combinations. Consequently, dual therapy should not be routinely prescribed in patients with diabetes until further data become available from other future studies. This review provides an introduction to DKD and a rationale for using RAS inhibition; discusses screening, detection, and monitoring of patients with DKD; and summarizes results from meta-analyses and

  4. The role of local renin-angiotensin system on high glucose-induced cell toxicity, apoptosis and reactive oxygen species production in PC12 cells

    PubMed Central

    Shahveisi, Kaveh; Mousavi, Seyed Hadi; Hosseini, Mahmoud; Rad, Abolfazl Khajavi; Jalali, Seyed Amir; Rajaei, Ziba; Sadeghnia, Hamid Reza; Hadjzadeh, Mousa-Al-Reza

    2014-01-01

    Objective(s): Hyperglycemia, oxidative stress and apoptosis have key roles in pathogenesis of diabetic neuropathy. There are local renin-angiotensin systems (RASs) in different tissues such as neural tissue. Local RASs are involved in physiological and pathophysiological processes such as inflammation, proliferation and apoptosis. This study aimed to investigate the role of local renin-angiotensin system on high glucose-induced cell toxicity, apoptosis and reactive oxygen species (ROS) production in PC12 cells, as a cell model of diabetic neuropathy. Materials and Methods: PC12 cells were exposed to a high glucose concentration (27 mg/ml), captopril (ACE inhibitor), telmisartan and losartan (AT1 antagonists), and also PD123319 (AT2 antagonist) were administered before and after induction of high glucose toxicity. Then cell viability was assessed by MTT assay and apoptotic cells and intracellular ROS production were detected by annexin V-propidium iodide and DCFDA, respectively, using flow cytometry. Results: High glucose concentration decreased cell viability, and increased apoptotic cells. Intracellular ROS production was also increased. In PC12 cells pretreatment and treatment by the drugs showed a significant improvement in cell viability and reduced apoptosis in captopril, telmisartan and PD123319 but only captopril and telmisartan were able to reduce ROS production. Losrtan significantly lowered ROS but didn't show any improvements in cell viability and apoptotic cells. Conclusion: The results of the present study showed that RAS inhibitors reduced cell toxicity and apoptosis and ROS production was induced by high glucose. It may be suggested that local RAS has a role in high glucose toxicity. PMID:25422756

  5. Living high training low induces physiological cardiac hypertrophy accompanied by down-regulation and redistribution of the renin-angiotensin system

    PubMed Central

    Shi, Wei; Meszaros, J Gary; Zeng, Shao-ju; Sun, Ying-yu; Zuo, Ming-xue

    2013-01-01

    Aim: Living high training low” (LHTL) is an exercise-training protocol that refers living in hypoxia stress and training at normal level of O2. In this study, we investigated whether LHTL caused physiological heart hypertrophy accompanied by changes of biomarkers in renin-angiotensin system in rats. Methods: Adult male SD rats were randomly assigned into 4 groups, and trained on living low-sedentary (LLS, control), living low-training low (LLTL), living high-sedentary (LHS) and living high-training low (LHTL) protocols, respectively, for 4 weeks. Hematological parameters, hemodynamic measurement, heart hypertrophy and plasma angiotensin II (Ang II) level of the rats were measured. The gene and protein expression of angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II receptor I (AT1) in heart tissue was assessed using RT-PCR and immunohistochemistry, respectively. Results: LLTL, LHS and LHTL significantly improved cardiac function, increased hemoglobin concentration and RBC. At the molecular level, LLTL, LHS and LHTL significantly decreased the expression of ACE, AGT and AT1 genes, but increased the expression of ACE and AT1 proteins in heart tissue. Moreover, ACE and AT1 protein expression was significantly increased in the endocardium, but unchanged in the epicardium. Conclusion: LHTL training protocol suppresses ACE, AGT and AT1 gene expression in heart tissue, but increases ACE and AT1 protein expression specifically in the endocardium, suggesting that the physiological heart hypertrophy induced by LHTL is regulated by region-specific expression of renin-angiotensin system components. PMID:23377552

  6. The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome.

    PubMed

    Putnam, Kelly; Shoemaker, Robin; Yiannikouris, Frederique; Cassis, Lisa A

    2012-03-15

    The renin-angiotensin system (RAS) is an important therapeutic target in the treatment of hypertension. Obesity has emerged as a primary contributor to essential hypertension in the United States and clusters with other metabolic disorders (hyperglycemia, hypertension, high triglycerides, low HDL cholesterol) defined within the metabolic syndrome. In addition to hypertension, RAS blockade may also serve as an effective treatment strategy to control impaired glucose and insulin tolerance and dyslipidemias in patients with the metabolic syndrome. Hyperglycemia, insulin resistance, and/or specific cholesterol metabolites have been demonstrated to activate components required for the synthesis [angiotensinogen, renin, angiotensin-converting enzyme (ACE)], degradation (ACE2), or responsiveness (angiotensin II type 1 receptors, Mas receptors) to angiotensin peptides in cell types (e.g., pancreatic islet cells, adipocytes, macrophages) that mediate specific disorders of the metabolic syndrome. An activated local RAS in these cell types may contribute to dysregulated function by promoting oxidative stress, apoptosis, and inflammation. This review will discuss data demonstrating the regulation of components of the RAS by cholesterol and its metabolites, glucose, and/or insulin in cell types implicated in disorders of the metabolic syndrome. In addition, we discuss data supporting a role for an activated local RAS in dyslipidemias and glucose intolerance/insulin resistance and the development of hypertension in the metabolic syndrome. Identification of an activated RAS as a common thread contributing to several disorders of the metabolic syndrome makes the use of angiotensin receptor blockers and ACE inhibitors an intriguing and novel option for multisymptom treatment. PMID:22227126

  7. The Renin-Angiotensin-Aldosterone System in Smokers and Non-Smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.

    PubMed

    Delgado, Graciela E; Siekmeier, Rüdiger; Krämer, Bernhard K; Grübler, Martin; Tomaschitz, Andreas; März, Winfried; Kleber, Marcus E

    2016-01-01

    High concentrations of renin and aldosterone are risk factors for cardiovascular diseases (CVD) which are the leading cause of morbidity and mortality worldwide. Enhanced activation of the renin-angiotensin-aldosterone system (RAAS) by cigarette smoking has been reported. The aim of our study was to analyze the effect of cigarette smoking on parameters of the RAAS in active smokers (AS) and life-time non-smokers (NS) of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study as well as the utility of RAAS parameter for risk prediction. We determined the concentration of aldosterone, renin, angiotensin-I and angiotensin-II in participants of the LURIC study. Smoking status was assessed by a questionnaire and the measurement of plasma cotinine concentration. Parameters were log transformed before entering analyses, where appropriate. We used a multivariate Cox regression analysis to assess the effect of parameters on mortality. From the 3316 LURIC participants 777 were AS and 1178 NS. Within a median observation period of 10 years 221 (28.4 %) AS and 302 (25.6 %) NS died. After adjustment for age, gender, and the use of anti-hypertensive medication, only angiotensin-I was significantly different in AS compared to NS with an estimated marginal mean (95 % CI) of 1607 (1541-1673) ng/L and 1719 (1667-1772) ng/L, respectively. For both NS and AS renin and angiotensin-II were directly associated with mortality in the multivariate Cox regression analysis. Angiotensin-I was only associated with increased risk for mortality in NS (HR (95 % CI) of 0.69 (0.53-0.89)). We conclude that increased renin and angiotensin-II are independent predictors of mortality in AS and NS, while angiotensin-I was associated with reduced risk of death in NS only. PMID:27334735

  8. Effect of ipsilateral ureteric obstruction on contralateral kidney and role of renin angiotensin system blockade on renal recovery in experimentally induced unilateral ureteric obstruction

    PubMed Central

    Panda, Shasanka S.; Bajpai, Minu; Sinha, Anand; Mallick, Saumyaranjan; Sharma, Mehar C.

    2013-01-01

    Aims: To study, the effects of ipsilateral ureteric obstruction on contralateral kidney and the role of renin angiotensin system (RAS) blockade on renal recovery in experimentally induced unilateral ureteric obstruction. Materials and Methods: Unilateral upper ureteric obstruction was created in 96 adult Wistar rats that were reversed after pre-determined intervals. Losartan and Enalapril were given to different subgroups of rats following relief of obstruction. Results: The severity of dilatation on the contralateral kidney varied with duration of ipsilateral obstruction longer the duration more severe the dilatation. There is direct correlation between renal parenchymal damage, pelvi-ureteric junction (PUJ) fibrosis, inflammation and severity of pelvi-calyceal system dilatation of contralateral kidney with duration of ipsilateral PUJ obstruction. Conclusions: Considerable injury is also inflicted to the contralateral normal kidney while ipsilateral kidney remains obstructed. Use of RAS blocking drugs has been found to significantly improve renal recovery on the contralateral kidney. It can, thus, be postulated that contralateral renal parenchymal injury was mediated through activation of RAS. PMID:23798807

  9. Pharmacological interventions into the renin-angiotensin system with ACE inhibitors and angiotensin II receptor antagonists: effects beyond blood pressure lowering.

    PubMed

    Düsing, Rainer

    2016-06-01

    Hypertension is recognized as an important risk factor for cardiovascular morbidity and mortality. Lowering of blood pressure has been shown to minimize the risk of cardiovascular events, with the majority of antihypertensives demonstrating a similar ability to reduce coronary events and stroke for a given reduction in blood pressure. Agents that modify the activity of the renin-angiotensin system (RAS) have been proposed to exhibit additional effects that might go beyond simple blood pressure lowering. The RAS is a crucial system that regulates extracellular fluid volume and blood pressure. Proposed potential benefits of RAS blockade that go beyond blood pressure lowering include a reduction in platelet aggregation and thrombosis, blunting of cardiac and vascular remodeling, favorable metabolic effects and reno- and cerebro-protection. However, factors such as treatment adherence, duration of action of antihypertensive agents and differences in effects on central versus brachial blood pressure may also result in apparent differences in efficacy of different antihypertensives. The aim of this review article is to examine the available data from clinical studies of antihypertensive drugs for evidence of effects that might legitimately be claimed to go beyond simple blood pressure lowering. PMID:27122491

  10. Role of renin-angiotensin-aldosterone system gene polymorphisms and hypertension-induced end-stage renal disease in autosomal dominant polycystic kidney disease.

    PubMed

    Ramanathan, Gnanasambandan; Elumalai, Ramprasad; Periyasamy, Soundararajan; Lakkakula, Bhaskar

    2014-07-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidneys and is marked by progressive cyst growth and decline in kidney function, resulting in end-stage renal disease (ESRD). Hypertension is thought to be a significant modifying factor in the progression of renal failure in ADPKD. A number of genetic variations involved in renin-angiotensin-aldosterone system (RAAS) pathway genes have clinical or physiological impacts on pathogenesis of hypertension-induced ESRD in ADPKD. Information on RAAS pathway gene polymorphisms and their association with ESRD and ADPKD, published till March 2013, was collected using MEDLINE search. The present review deals with RAAS gene polymorphisms focused on hypertension-induced ESRD in ADPKD in different populations. The results were inconclusive and limited by heterogeneity in the study designs and the population stratification. In lieu of applying next generation sequencing technologies to study complex diseases, it is also possible to apply the same to unravel the complexity of ESRD in ADPKD. PMID:25001132

  11. The effects of antidiuretic hormone and state of potassium balance on the renin-angiotensin system in rats with diabetes insipidus.

    PubMed Central

    Fernández-Repollet, E; Maldonado, M M; Opava-Stitzer, S

    1982-01-01

    1. The influence of ADH and the state of potassium balance on the renin-angiotensin system was studied in rats with hereditary diabetes insipidus (DI rats). 2. Plasma renin concentration in DI rats was higher than in control Long-Evans rats. 3. Spontaneous reversal of the hypokalaemia normally found in DI rats did not reduce plasma renin concentration (p.r.c.), suggesting that potassium deficiency does not contribute significantly to the elevation of p.r.c. in DI rats. Similarly, a low potassium diet failed to further increase p.r.c. in DI rats. 4. In contrast, the p.r.c. of DI rats was significantly diminished by a high potassium intake both in the presence and absence of ADH. A highly significant inverse correlation was found between p.r.c. and urinary potassium excretion in both ADH-treated and untreated DI rats on low, normal and high potassium diets. 5. Plasma renin concentration was significantly lower in ADH-treated than in untreated DI rats on a high potassium intake, suggesting that the inhibitory effects of ADH and potassium are additive. 6. ADH consistently reduced p.r.c. in DI rats independent of the state of potassium balance. 7. ADH and potassium may inhibit renin secretion via different mechanisms of action. PMID:7047719

  12. Effects of aqueous extract of Hibiscus sabdariffa on the renin-angiotensin-aldosterone system of Nigerians with mild to moderate essential hypertension: A comparative study with lisinopril

    PubMed Central

    Nwachukwu, Daniel Chukwu; Aneke, Eddy Ikemefuna; Obika, Leonard Fidelis; Nwachukwu, Nkiru Zuada

    2015-01-01

    Objectives: The present study investigated the effects of aqueous extract of Hibiscus sabdariffa (HS) on the three basic components of renin-angiotensin-aldosterone system: Plasma renin, serum angiotensin-converting enzyme (ACE), and plasma aldosterone (PA) in mild to moderate essential hypertensive Nigerians and compared with that of lisinopril, an ACE inhibitor. Materials and Methods: A double-blind controlled randomized clinical study was used. Seventy-eight newly diagnosed but untreated mild to moderate hypertensive subjects attending Medical Outpatients Clinic of Enugu State University Teaching Hospital, Enugu were recruited for the study. Those in Group A received placebo (150 mg/kg/day), Group B were given lisinopril (10 mg once daily) while those in Group C received aqueous extract of HS (150 mg/kg/day). After 4 weeks of treatment, the levels of plasma renin, serum ACE, and PA were determined. Results: HS and lisinopril significantly (P < 0.001) reduced PA compared to placebo by 32.06% and 30.01%, respectively. Their effects on serum ACE and plasma renin activity (PRA) were not significant compared to placebo; they reduced ACE by 6.63% and 5.67% but increased plasma PRA by 2.77% and 5.36%, respectively. Conclusion: HS reduced serum ACE and PA in mild to moderate hypertensive Nigerians with equal efficacy as lisinopril. These actions are possibly due to the presence of anthocyanins in the extract. PMID:26600645

  13. Prenatal inflammation-induced NF-κB dyshomeostasis contributes to renin-angiotensin system over-activity resulting in prenatally programmed hypertension in offspring

    PubMed Central

    Deng, Youcai; Deng, Yafei; He, Xiaoyan; Chu, Jianhong; Zhou, Jianzhi; Zhang, Qi; Guo, Wei; Huang, Pei; Guan, Xiao; Tang, Yuan; Wei, Yanling; Zhao, Shanyu; Zhang, Xingxing; Wei, Chiming; Namaka, Michael; Yi, Ping; Yu, Jianhua; Li, Xiaohui

    2016-01-01

    Studies involving the use of prenatally programmed hypertension have been shown to potentially contribute to prevention of essential hypertension (EH). Our previous research has demonstrated that prenatal inflammatory stimulation leads to offspring’s aortic dysfunction and hypertension in pregnant Sprague-Dawley rats challenged with lipopolysaccharide (LPS). The present study found that prenatal LPS exposure led to NF-κB dyshomeostasis from fetus to adult, which was characterized by PI3K-Akt activation mediated degradation of IκBα protein and impaired NF-κB self-negative feedback loop mediated less newly synthesis of IκBα mRNA in thoracic aortas (gestational day 20, postnatal week 7 and 16). Prenatal or postnatal exposure of the IκBα degradation inhibitor, pyrollidine dithiocarbamate, effectively blocked NF-κB activation, endothelium dysfunction, and renin-angiotensin system (RAS) over-activity in thoracic aortas, resulting in reduced blood pressure in offspring that received prenatal exposure to LPS. Surprisingly, NF-κB dyshomeostasis and RAS over-activity were only found in thoracic aortas but not in superior mesenteric arteries. Collectively, our data demonstrate that the early life NF-κB dyshomeostasis induced by prenatal inflammatory exposure plays an essential role in the development of EH through triggering RAS over-activity. We conclude that early life NF-κB dyshomeostasis is a key predictor of EH, and thus, NF-κB inhibition represents an effective interventional strategy for EH prevention. PMID:26877256

  14. Prolonged fasting increases the response of the renin-angiotensin-aldosterone system, but not vasopressin levels, in postweaned northern elephant seal pups

    NASA Technical Reports Server (NTRS)

    Ortiz, R. M.; Wade, C. E.; Ortiz, C. L.

    2000-01-01

    The 8- to 12-week postweaning fast exhibited by northern elephant seal pups (Mirounga angustirostris) occurs without any apparent deleterious effects on fluid and electrolyte homeostasis. However, during the fast the role of vasopressin (AVP) has been shown to be inconclusive and the involvement of the renin-angiotensin-aldosterone system (RAAS) has yet to be examined. To examine the effects of prolonged fasting on these osmoregulatory hormones, 15 postweaned pups were serially blood-sampled during the first 49 days of their fast. Fasting did not induce significant changes in ionic or osmotic concentrations, suggesting electrolyte homeostasis. Total proteins were reduced by day 21 of fasting and remained depressed, suggesting a lack of dehydration. Aldosterone and plasma renin activity exhibited a correlated, linear increase over the first 49 days of the fast, suggesting an active RAAS. Aldosterone exhibited a parabolic trend over the fast with a peak at day 35, suggesting a shift in the sensitivity of the kidney to aldosterone later in the fast. AVP was elevated at day 49 only, but concentrations were relatively low. RAAS was modified during the postweaning fast in pups and appears to play a significant role in the regulation of electrolyte and, most likely, water homeostasis during this period. Copyright 2000 Academic Press.

  15. Response Prediction and Influence of Tolvaptan in Chronic Heart Failure Patients Considering the Interaction of the Renin-Angiotensin-Aldosterone System and Arginine Vasopressin.

    PubMed

    Kadota, Muneyuki; Ise, Takayuki; Yagi, Shusuke; Iwase, Takashi; Akaike, Masashi; Ueno, Rie; Kawabata, Yutaka; Hara, Tomoya; Ogasawara, Kozue; Bando, Mika; Bando, Sachiko; Matsuura, Tomomi; Yamaguchi, Koji; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Sata, Masataka

    2016-07-27

    The renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP) regulate body fluids. Although conventional diuretics have been used for treating heart failure, they activate RAAS and exacerbate renal function. Tolvaptan, a newly developed vasopressin-2 receptor antagonist, elicits aquaresis and improves volume overload in heart failure patients, however, the predictors of tolvaptan effectiveness and the influence on the RAAS and renal function according to tolvaptan therapy are not established. We evaluated 26 chronic heart failure patients receiving therapy with 15 mg/day tolvaptan and examined their laboratory and urinary data before and after tolvaptan therapy. A response to tolvaptan was defined as a body weight decrease by more than 2 kg in a week and a urine volume increase by 500 mL/ day compared with that before tolvaptan administration. Body weight, urine volume, and brain natriuretic peptide levels significantly improved (P < 0.05), without any worsening of renal function represented by serum creatinine, sodium, and potassium. Moreover, no significant changes were observed in the plasma renin activity and plasma aldosterone concentration (PAC). In the responder group, urine osmolality before tolvaptan administration was significantly higher (P < 0.05) but declined significantly after tolvaptan administration (P < 0.05). The AVP/PAC ratio before administration was positively correlated with the efficacy of tolvaptan. Tolvaptan treatment could prevent RAAS activation in chronic heart failure patients. Moreover, monitoring the AVP/PAC ratio may be useful in predicting the tolvaptan response. PMID:27357439

  16. Expression of components of the renin-angiotensin system in proliferating infantile haemangioma may account for the propranolol-induced accelerated involution.

    PubMed

    Itinteang, Tinte; Brasch, Helen D; Tan, Swee T; Day, Darren J

    2011-06-01

    Infantile haemangioma is a benign tumour of the microvasculature characterised by excessive proliferation of immature endothelial cells. It typically undergoes rapid proliferation during infancy followed by spontaneous slow involution during childhood often leaving a fibro-fatty residuum. In 2008, propranolol, a non-selective β-blocker, was serendipitously discovered to induce accelerated involution of a proliferating infantile haemangioma. However, the mechanism by which propranolol causes this dramatic effect is unclear. Using immunohistochemical staining, we show that the CD34+ endothelial progenitor cells of the microvessels in proliferating infantile haemangioma express angiotensin-converting enzyme and angiotensin II receptor-2, but not angiotensin II receptor-1. We have also shown using our in vitro explant model that the cells emanating from proliferating haemangioma biopsies form blast-like structures that proliferate in the presence of angiotensin II. We present here a plausible model involving the renin-angiotensin system that may account for the propranolol-induced accelerated involution of proliferating infantile haemangioma. PMID:20870476

  17. Role of chymase in the local renin-angiotensin system in keloids: inhibition of chymase may be an effective therapeutic approach to treat keloids

    PubMed Central

    Wang, Ru; Chen, Junjie; Zhang, Zhenyu; Cen, Ying

    2015-01-01

    Background Histologically, keloids contain excess fibroblasts and an overabundance of dermal collagen. Recently, it was reported that chymase induced a profibrotic response via transforming growth factor-β1 (TGF-β1)/Smad activation in keloid fibroblasts (KFs). However, the role of chymase in the local renin-angiotensin system (RAS) in keloids has not been elucidated. This study aims to determine whether chymase plays an important role in the local RAS in keloids. Methods We compared the expression and activity of chymase in keloids and normal skin tissues using Western blotting and radioimmunoassay, and studied the expression of TGF-β1, interleukin-1β, collagen I, hydroxyproline, and angiotensin II in KFs after chymase and inhibitors’ treatment. Results The results revealed an increased activity of chymase in keloid tissues, and that chymase enhanced the expression of angiotensin II, collagen I, TGF-β1, and interleukin-1β in KFs. Blockade of the chymase pathway involved in the local RAS lowered the expression of these signaling factors. Conclusion This research suggests that inhibition of chymase might be an effective therapeutic approach to improve the clinical treatment of keloids. PMID:26357464

  18. Long-Term Regulation of the Local Renin-Angiotensin System in the Myocardium of Spontaneously Hypertensive Rats by Feeding Bioactive Peptides Derived from Spirulina platensis.

    PubMed

    Pan, Huanglei; She, Xingxing; Wu, Hongli; Ma, Jun; Ren, Difeng; Lu, Jun

    2015-09-01

    This study investigated the long-term (8 weeks) anti-hypertensive effects of 10 mg/kg tripeptides isolated from Spirulina platensis, Ile-Gln-Pro (IQP) and Val-Glu-Pro (VEP), and S. platensis hydrolysates (SH) on spontaneously hypertensive rats. The treatment period was 6 weeks, and observation continued for another 2 weeks. After treatment, weighted systolic blood pressure, weighted diastolic blood pressure, left ventricular mass index, and right ventricular mass index of groups treated with IQP, VEP, and SH were significantly lower than those of the group treated with distilled water, even when the treatments had been withdrawn for 2 weeks. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting showed the mRNA expression levels and protein/peptide concentrations of the main components of the renin angiotensin system in myocardium were significantly affected by treatment: angiotensin converting enzyme, angiotensin II, and angiotensin type 1 receptor were down-regulated, whereas angiotensin type 2 receptor, angiotensin converting enzyme 2, angiotensin-(1-7), and Mas receptor were up-regulated. PMID:26245714

  19. Activation of systemic, but not local, renin-angiotensin system is associated with upregulation of TNF-α during prolonged fasting in northern elephant seal pups.

    PubMed

    Suzuki, Miwa; Vázquez-Medina, José Pablo; Viscarra, Jose A; Soñanez-Organis, José G; Crocker, Daniel E; Ortiz, Rudy M

    2013-09-01

    Northern elephant seal pups naturally endure a 2-3 month post-weaning fast that is associated with activation of systemic renin-angiotensin system (RAS), a decrease in plasma adiponectin (Acrp30), and insulin resistance (IR)-like conditions. Angiotensin II (Ang II) and tumor necrosis factor-alpha (TNF-α) are potential causal factors of IR, while Acrp30 may improve insulin signaling. However, the effects of fasting-induced activation of RAS on IR-like conditions in seals are not well described. To assess the effects of prolonged food deprivation on systemic and local RAS, and their potential contribution to TNF-α as they relate to an IR condition, the mRNA expressions of adipose and muscle RAS components and immuno-relevant molecules were measured along with plasma RAS components. Mean plasma renin activity and Ang II concentrations increased by 89 and 1658%, respectively, while plasma angiotensinogen (AGT) decreased by 49% over the fast, indicative of systemic RAS activation. Prolonged fasting was associated with decreases in adipose and muscle AGT mRNA expressions of 69 and 68%, respectively, corresponding with decreases in tissue protein content, suggesting suppression of local AGT production. Muscle TNF-α mRNA and protein increased by 239 and 314%, whereas those of adipose Acrp30 decreased by 32 and 98%, respectively. Collectively, this study suggests that prolonged fasting activates a systemic RAS, which contributes to an increase in muscle TNF-α and suppression of adipose Acrp30. This targeted and tissue-specific regulation of TNF-α and Acrp30 is likely coordinated to synergistically contribute to the development of an IR-like condition, independent of local RAS activity. These data enhance our understanding of the adaptive mechanisms evolved by elephant seals to tolerate potentially detrimental conditions. PMID:23685967

  20. Mechanisms responsible for postmenopausal hypertension in a rat model: Roles of the renal sympathetic nervous system and the renin-angiotensin system.

    PubMed

    Maranon, Rodrigo O; Reckelhoff, Jane F

    2016-02-01

    Hypertension in postmenopausal women is less well controlled than in age-matched men. The aging female SHR is a model of postmenopausal hypertension that is mediated in part by activation of the renin-angiotensin system (RAS) and by the renal sympathetic nervous system. In this study, the hypothesis was tested that renal denervation would lower the blood pressure in old female SHR and would attenuate the antihypertensive effects of AT1 receptor antagonism. Retired breeder female SHR were subjected to right uninephrectomy (UNX) and left renal denervation (RD) or UNX and sham, and 2 weeks later, baseline mean arterial pressure (MAP; radiotelemetry) was measured for 4 days, and then rats were treated with angiotensin (AT1) receptor antagonist, losartan (40 mg/kg/day po) for 6 days. Renal denervation reduced MAP in old females compared to sham (172 ± 6 vs. 193 ± 6 mm Hg; P < 0.05). Losartan reduced MAP in both sham and RD rats similarly (numerically and by percentage) (142 ± 10 vs. 161 ± 6 mm Hg; P < 0.05 vs. RD, P < 0.05 vs. baseline). However, female SHR rats remained significantly hypertensive despite both pharmacological intervention and RD. The data suggest that both the renal sympathetic nervous system and the RAS have independent effects to control the blood pressure in old female SHR. Since the denervated rats treated with losartan remained hypertensive, the data also suggest that other mechanisms than the RAS and renal sympathetic nervous system contribute to the hypertension in old female SHR. The data also suggest that multiple mechanisms may mediate the elevated blood pressure in postmenopausal women. PMID:26811052

  1. [Inhibition of renin-angiotensin-aldosterone system in heart failure, or from CONSENSUS to PARADIGM-HF].

    PubMed

    Vítovec, Jiří; Špinar, Jindřich; Špinarová, Lenka

    2015-05-01

    An historical survey is presented of mortality trials on angiotensin-aldosteron system inhibition in patients with chronic heart failure. From the CONSENSUS trial up to the PARADIGM-HF trial, ACE inhibitors/angiotensin II receptor antagonists (AT1-blockers, ARBs, sartans), along with mineralocorticoid receptor blockers, have been the gold standard of treatment. Both direct renin blocker aliskiren and dual blocker enalapril + neprilysin proved ineffective; on the other hand, the new dual inhibitor valsartan + neprilysin LCZ 696 is a new and promising therapeutic agent for future treatment of chronic heart failure. PMID:26075858

  2. Comparative effects of pinacidil and prazosin on blood pressure, weight, plasma volume, the renin-angiotensin-aldosterone system, and the renal kallikrein-kinin system in patients with essential hypertension.

    PubMed

    Solomon, R J; Weinberg, M S

    1987-12-01

    Patients with essential hypertension were randomized to treatment with either prazosin or pinacidil, a new direct-acting vasodilator. Factors that might modulate the antihypertensive response and result in pseudotolerance to these drugs were measured before initiation of therapy and following 12 weeks of treatment. Despite significant reductions in blood pressure, pinacidil and prazosin did not produce an increase in plasma volume, did not activate the renin-angiotensin-aldosterone system, and did not interfere with the renal kallikrein-kinin system. The data fail to reveal evidence of physiologic compensatory changes that would lead to the development of pseudotolerance. PMID:3330989

  3. Angiotensin type 1a receptor-deficient mice develop diabetes-induced cardiac dysfunction, which is prevented by renin-angiotensin system inhibitors

    PubMed Central

    2013-01-01

    Background Diabetes-induced organ damage is significantly associated with the activation of the renin-angiotensin system (RAS). Recently, several studies have demonstrated a change in the RAS from an extracellular to an intracellular system, in several cell types, in response to high ambient glucose levels. In cardiac myocytes, intracellular angiotensin (ANG) II synthesis and actions are ACE and AT1 independent, respectively. However, a role of this system in diabetes-induced organ damage is not clear. Methods To determine a role of the intracellular ANG II in diabetic cardiomyopathy, we induced diabetes using streptozotocin in AT1a receptor deficient (AT1a-KO) mice to exclude any effects of extracellular ANG II. Further, diabetic animals were treated with a renin inhibitor aliskiren, an ACE inhibitor benazeprilat, and an AT1 receptor blocker valsartan. Results AT1a-KO mice developed significant diastolic and systolic dysfunction following 10 wks of diabetes, as determined by echocardiography. All three drugs prevented the development of cardiac dysfunction in these animals, without affecting blood pressure or glucose levels. A significant down regulation of components of the kallikrein-kinin system (KKS) was observed in diabetic animals, which was largely prevented by benazeprilat and valsartan, while aliskiren normalized kininogen expression. Conclusions These data indicated that the AT1a receptor, thus extracellular ANG II, are not required for the development of diabetic cardiomyopathy. The KKS might contribute to the beneficial effects of benazeprilat and valsartan in diabetic cardiomyopathy. A role of intracellular ANG II is suggested by the inhibitory effects of aliskiren, which needs confirmation in future studies. PMID:24215514

  4. The world pandemic of vitamin D deficiency could possibly be explained by cellular inflammatory response activity induced by the renin-angiotensin system

    PubMed Central

    Ferder, Marcelo; Inserra, Felipe; Manucha, Walter

    2013-01-01

    This review attempts to show that there may be a relationship between inflammatory processes induced by chronic overstimulation of the renin-angiotensin system (RAS) and the worldwide deficiency of vitamin D (VitD) and that both disorders are probably associated with environmental factors. Low VitD levels represent a risk factor for several apparently different diseases, such as infectious, autoimmune, neurodegenerative, and cardiovascular diseases, as well as diabetes, osteoporosis, and cancer. Moreover, VitD insufficiency seems to predispose to hypertension, metabolic syndrome, left ventricular hypertrophy, heart failure, and chronic vascular inflammation. On the other hand, inappropriate stimulation of the RAS has also been associated with the pathogenesis of hypertension, heart attack, stroke, and hypertrophy of the left ventricle and vascular smooth muscle cells. Because VitD receptors (VDRs) and RAS receptors are almost distributed in the same tissues, a possible link between VitD and the RAS is even more plausible. Furthermore, from an evolutionary point of view, both systems were developed simultaneously, actively participating in the regulation of inflammatory and immunological mechanisms. Changes in RAS activity and activation of the VDR seem to be inversely related; thus any changes in one of these systems would have a completely opposite effect on the other, making it possible to speculate that the two systems could have a feedback relationship. In fact, the pandemic of VitD deficiency could be the other face of increased RAS activity, which probably causes lower activity or lower levels of VitD. Finally, from a therapeutic point of view, the combination of RAS blockade and VDR stimulation appears to be more effective than either RAS blockade or VDR stimulation individually. PMID:23364265

  5. The PGE(2)-EP4 receptor is necessary for stimulation of the renin-angiotensin-aldosterone system in response to low dietary salt intake in vivo.

    PubMed

    Pöschke, Antje; Kern, Niklas; Maruyama, Takayuki; Pavenstädt, Hermann; Narumiya, Shuh; Jensen, Boye L; Nüsing, Rolf M

    2012-11-15

    Increased cyclooxygenase-2 (COX-2) expression and PGE(2) synthesis have been shown to be prerequisites for renal renin release after Na(+) deprivation. To answer the question of whether EP4 receptor type of PGE(2) mediates renin regulation under a low-salt diet, we examined renin regulation in EP4(+/+), EP4(-/-), and in wild-type mice treated with EP4 receptor antagonist. After 2 wk of a low-salt diet (0.02% wt/wt NaCl), EP4(+/+) mice showed diminished Na(+) excretion, unchanged K(+) excretion, and reduced Ca(2+) excretion. Diuresis and plasma electrolytes remained unchanged. EP4(-/-) exhibited a similar attenuation of Na(+) excretion; however, diuresis and K(+) excretion were enhanced, and plasma Na(+) concentration was higher, whereas plasma K(+) concentration was lower compared with control diet. There were no significant differences between EP4(+/+) and EP4(-/-) mice in blood pressure, creatinine clearance, and plasma antidiuretic hormone (ADH) concentration. Following salt restriction, plasma renin and aldosterone concentrations and kidney renin mRNA level rose significantly in EP4(+/+) but not in EP4(-/-) and in wild-type mice treated with EP4 antagonist ONO-AE3-208. In the latter two groups, the low-salt diet caused a significantly greater rise in PGE(2) excretion. Furthermore, mRNA expression for COX-2 and PGE(2) synthetic activity was significantly greater in EP4(-/-) than in EP4(+/+) mice. We conclude that low dietary salt intake induces expression of COX-2 followed by enhanced renal PGE(2) synthesis, which stimulates the renin-angiotensin-aldosterone system by activation of EP4 receptor. Most likely, defects at the step of EP4 receptor block negative feedback mechanisms on the renal COX system, leading to persistently high PGE(2) levels, diuresis, and K(+) loss. PMID:22993066

  6. Proopiomelanocortin but not vasopressin or renin-angiotensin system induces resuscitative effects of central 5-HT1A activation in haemorrhagic shock in rats.

    PubMed

    Sowa, P; Adamczyk-Sowa, M; Zwirska-Korczala, K; Pierzchala, K; Adamczyk, D; Paluch, Z; Misiolek, M

    2014-10-01

    The aim of this study was to determine the effectory mechanisms: vasopressin, renin-angiotensin system and proopiomelanocortin-derived peptides (POMC), partaking in the effects of serotonin through central serotonin 1A receptor (5-HT1A) receptors in haemorrhagic shock in rats. The study was conducted on male Wistar rats. All experimental procedures were carried out under full anaesthesia. The principal experiment included a 2 hour observation period in haemorrhagic shock. Drugs used - a selective 5-HT1A agonist 8-OH-DPAT (5 μg/5 μl); V1a receptor antagonist [β-mercapto-β, β-cyclo-pentamethylenepropionyl(1),O-me-Tyr(2),Arg(8)]AVP (10 μg/kg); angiotensin type I receptor antagonist (AT1) ZD7155 (0.5 mg/kg, i.v.); angiotensin-converting-enzyme inhibitor captopril (30 mg/kg, i.v.); melanocortin type 4 (MC4) receptor antagonist HS014 (5 μg, i.c.v.). There was no influence of ZD715, captopril or blocking of the V1a receptors on changes in the heart rate (HR), mean arterial pressure (MAP), peripheral blood flow or resistance caused by the central stimulation of 5-HT1A receptors (P≥0.05). However, selective blocking of central MC4 receptors caused a slight, but significant decrease in HR and MAP (P<0.05). POMC derivatives acting via the central MC4 receptor participate in the resuscitative effects of 8-OH-DPAT. The angiotensin and vasopressin systems do not participate in these actions. PMID:25371525

  7. Molecular characterization and transcriptional regulation of the renin-angiotensin system genes in Senegalese sole (Solea senegalensis Kaup, 1858): differential gene regulation by salinity.

    PubMed

    Armesto, Paula; Cousin, Xavier; Salas-Leiton, Emilio; Asensio, Esther; Manchado, Manuel; Infante, Carlos

    2015-06-01

    In this work, the complete cDNA sequence encoding angiotensinogen (agt) in the euryhaline flatfish Senegalese sole was obtained. Additionally, putative coding sequences belonging to other renin-angiotensin system (RAS) genes including renin (ren), angiotensin-converting enzyme (ace), angiotensin-converting enzyme 2 (ace2), as well as angiotensin II receptor type I (agtr1) and type II (agtr2), were also identified. In juvenile tissues, agt transcripts were mainly detected in liver, ren in kidney, ace and ace2 in intestine, agtr1 in kidney and brain, and agtr2 in liver and kidney. Expression analysis of the six RAS genes after a salinity shift revealed a clear increase of agt mRNA abundance in liver just after transferring soles to high salinity water (60 ppt) with a peak at 48 h. Moreover, gene expression analysis in gills showed transcriptional regulation of ace and agtr1 at 48 h and agtr2 at 96 h after transferring soles to 60 ppt. Incubation of larvae before mouth opening (until 3 days post hatch; dph) at low salinity (10 ppt) resulted in a coordinated transcriptional up-regulation of RAS genes. Nevertheless, no differences in mRNA abundance between salinities were observed when larvae were cultivated to low salinity after mouth opening. Whole-mount in situ hybridization (WISH) signal for agt and ace in 3 dph larvae incubated at 10 ppt and 35 ppt confirmed that the former gene was mainly expressed in liver whereas the later gene was mainly located in pharynx and posterior gut, without pronounced differences in intensity between salinities. Possible physiological significance of all these results is discussed. PMID:25645294

  8. Addition of hydrochlorothiazide to angiotensin receptor blocker therapy can achieve a lower sodium balance with no acceleration of intrarenal renin angiotensin system in patients with chronic kidney disease

    PubMed Central

    Fuwa, Daisuke; Fukuda, Michio; Ogiyama, Yoshiaki; Sato, Ryo; Mizuno, Masashi; Miura, Toshiyuki; Abe-Dohmae, Sumiko; Michikawa, Makoto; Kobori, Hiroyuki; Ohte, Nobuyuki

    2016-01-01

    Objective Angiotensin receptor blockers (ARBs) produce a lower sodium (Na) balance, and the natriuretic effect is enhanced under Na deprivation, despite falls in blood pressure (BP) and glomerular filtration rate (GFR). Methods The effect of additional hydrochlorothiazide (HCTZ; 12.5 mg/day) to ARB treatment (valsartan; 80 mg/day) on glomerulotubular Na balance was evaluated in 23 patients with chronic kidney disease. Results Add-on HCTZ decreased GFR, tubular Na load, and tubular Na reabsorption (tNa), although 24-hour urinary Na excretion (UNaV) remained constant. Daily urinary angiotensinogen excretion (UAGTV, 152±10→82±17 μg/g Cre) reduced (p=0.02). Changes in tubular Na load (r2=0.26) and tNa (r2=0.25) correlated with baseline 24-hour UAGTV. Changes in filtered Na load correlated with changes in nighttime systolic BP (r2=0.17), but not with changes in daytime systolic BP. The change in the tNa to filtered Na load ratio was influenced by the change in daytime UNaV (β=−0.67, F=16.8), rather than the change in nighttime UNaV. Conclusions Lower Na balance was produced by add-on HCTZ to ARB treatment without an increase of intra-renal renin-angiotensin system activity, leading to restoration of nocturnal hypertension. A further study is needed to demonstrate that the reduction of UAGTV by additional diuretics to ARBs prevents the progression of nephropathy or cardiovascular events. PMID:27283968

  9. Meta-analysis of the effects of preoperative renin-angiotensin system inhibitor therapy on major adverse cardiac events in patients undergoing cardiac surgery.

    PubMed

    Cheng, Xiaocheng; Tong, Jin; Hu, Qiongwen; Chen, Shaojie; Yin, Yuehui; Liu, Zengzhang

    2015-06-01

    The purpose of this meta-analysis was to assess the role of preoperative renin-angiotensin system inhibitor (RASI) therapy on major adverse cardiac events (MACE) in patients undergoing cardiac surgery. The Medline, Cochrane Library and Embase databases were searched for clinical studies published up to May 2014. Studies that evaluated the effects of preoperative RASI therapy in cardiac surgery were included. Odds ratio (OR) estimates were generated under a random-effects model. After a literature search in the major databases, 18 studies were identified [three randomized prospective clinical trials (RCTs) and 15 observational trials] that reported outcomes of 54 528 cardiac surgery patients with (n = 22 661; 42%) or without (n = 31 867; 58%) preoperative RASI therapy. Pool analysis indicated that preoperative RASI therapy was not associated with a significant reduction of early all-cause mortality [OR: 1.01; 95% confidence interval (CI) 0.88-1.15, P = 0.93; I(2) = 25%], myocardial infarction (OR: 1.04; 95% CI 0.91-1.19, P = 0.60; I(2) = 16%), or stroke (OR: 0.93; 95% CI 0.75-1.14, P = 0.46; I(2) = 38%). Meta-regression analysis confirmed that there was a strong negative correlation between the percentage of diabetics and early all-cause mortality (P = 0.03). Furthermore, preoperative RASI therapy significantly reduced mortality in studies containing a high proportion of diabetic patients (OR: 0.84; 95% CI 0.71-0.99, P = 0.04; I(2) = 0%). In conclusion, our meta-analysis indicated that although preoperative RASI therapy was not associated with a lower risk of MACE in cardiac surgery patients, it might provide benefits for diabetic patients. PMID:25301954

  10. Functional and molecular evidence for expression of the renin angiotensin system and ADAM17-mediated ACE2 shedding in COS7 cells

    PubMed Central

    Grobe, Nadja; Di Fulvio, Mauricio; Kashkari, Nada; Chodavarapu, Harshita; Somineni, Hari K.; Singh, Richa

    2015-01-01

    The renin angiotensin system (RAS) plays a vital role in the regulation of the cardiovascular and renal functions. COS7 is a robust and easily transfectable cell line derived from the kidney of the African green monkey, Cercopithecus aethiops. The aims of this study were to 1) demonstrate the presence of an endogenous and functional RAS in COS7, and 2) investigate the role of a disintegrin and metalloproteinase-17 (ADAM17) in the ectodomain shedding of angiotensin converting enzyme-2 (ACE2). Reverse transcription coupled to gene-specific polymerase chain reaction demonstrated expression of ACE, ACE2, angiotensin II type 1 receptor (AT1R), and renin at the transcript levels in total RNA cell extracts. Western blot and immunohistochemistry identified ACE (60 kDa), ACE2 (75 kDa), AT1R (43 kDa), renin (41 kDa), and ADAM17 (130 kDa) in COS7. At the functional level, a sensitive and selective mass spectrometric approach detected endogenous renin, ACE, and ACE2 activities. ANG-(1–7) formation (m/z 899) from the natural substrate ANG II (m/z 1,046) was detected in lysates and media. COS7 cells stably expressing shRNA constructs directed against endogenous ADAM17 showed reduced ACE2 shedding into the media. This is the first study demonstrating endogenous expression of the RAS and ADAM17 in the widely used COS7 cell line and its utility to study ectodomain shedding of ACE2 mediated by ADAM17 in vitro. The transfectable nature of this cell line makes it an attractive cell model for studying the molecular, functional, and pharmacological properties of the renal RAS. PMID:25740155

  11. Comparative Effects of Statin Therapy versus Renin-Angiotensin System Blocking Therapy in Patients with Ischemic Heart Failure Who Underwent Percutaneous Coronary Intervention

    PubMed Central

    Won, Jumin; Jeong, Myung Ho; Park, Hyuk Jin; Kim, Min Chul; Kim, Woo Jin; Kim, Hyun Kuk; Sim, Doo Sun; Kim, Ju Han; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun

    2016-01-01

    Statins and renin-angiotensin system (RAS) blockers are key drugs for treating patients with an acute myocardial infarction (AMI). This study was designed to show the association between treatment with statins or RAS blockers and clinical outcomes and the efficacy of two drug combination therapies in patients with ischemic heart failure (IHF) who underwent revascularization for an AMI. A total of 804 AMI patients with a left ventricular ejection fraction <40% who undertook percutaneous coronary interventions (PCI) were analyzed using the Korea Acute Myocardial Infarction Registry (KAMIR). They were divided into four groups according to the use of medications [Group I: combination of statin and RAS blocker (n=611), Group II: statin alone (n=112), Group III: RAS blocker alone (n=53), Group IV: neither treatment (n=28)]. The cumulative incidence of major adverse cardiac and cerebrovascular events (MACCEs) and independent predictors of MACCEs were investigated. Over a median follow-up study of nearly 1 year, MACCEs had occurred in 48 patients (7.9%) in Group I, 16 patients (14.3%) in Group II, 3 patients (5.7%) in Group III, 7 patients (21.4%) in Group IV (p=0.013). Groups using RAS blocker (Group I and III) showed better clinical outcomes compared with the other groups. By multivariate analysis, use of RAS blockers was the most powerful independent predictor of MACCEs in patients with IHF who underwent PCI (odds ratio 0.469, 95% confidence interval 0.285-0.772; p=0.003), but statin therapy was not found to be an independent predictor. The use of RAS blockers, but not statins, was associated with better clinical outcomes in patients with IHF who underwent PCI. PMID:27231678

  12. Effect of exercise training on the renin-angiotensin-aldosterone system in healthy individuals: a systematic review and meta-analysis.

    PubMed

    Goessler, Karla; Polito, Marcos; Cornelissen, Véronique Ann

    2016-03-01

    The aim of this systematic review and meta-analysis was to evaluate the effect of exercise training on parameters of the renin-angiotensin-aldosterone system (RAAS) in healthy adults, and to investigate the relation with training induced changes in blood pressure. A systematic search was conducted and we included randomized controlled trials lasting ⩾4 weeks investigating the effects of exercise on parameters of the RAAS in healthy adults (age ⩾18 years) and published in a peer-reviewed journal up to December 2013. Fixed effects models were used and data are reported as weighted means and 95% confidence limits (CL). Eleven randomized controlled trials with a total of 375 individuals were included. Plasma renin activity was reduced after exercise training (n= 7 trials, standardized mean difference -0.25 (95% CL -0.5 to -0.001), P=0.049), whereas no effect was observed on serum aldosterone ((n= 3 trials; standardized mean difference -0.79 (-1.97 to +0.39)) or angiotensin II (n=3 trials; standardized mean difference -0.16 (-0.61 to +0.30). Significant reductions in systolic blood pressure -5.65 mm Hg (-8.12 to -3.17) and diastolic blood pressure -3.64 mm Hg (-5.4 to -1.91) following exercise training were observed. No relation was found between net changes in plasma renin activity and net changes in blood pressure (P>0.05). To conclude, although we observed a significant reduction in plasma renin activity following exercise training this was not related to the observed blood pressure reduction. Given the small number of studies and small sample sizes, larger well-controlled randomized studies are required to confirm our results and to investigate the potential role of the RAAS in the observed improvements in blood pressure following exercise training. PMID:26399454

  13. Similarities and differences of X and Y chromosome homologous genes, SRY and SOX3, in regulating the renin-angiotensin system promoters

    PubMed Central

    Araujo, Fabiano C.; Milsted, Amy; Watanabe, Ingrid K. M.; Del Puerto, Helen L.; Santos, Robson A. S.; Lazar, Jozef; Reis, Fernando M.

    2015-01-01

    The renin-angiotensin system (RAS) is subject to sex-specific modulation by hormones and gene products. However, sex differences in the balance between the vasoconstrictor/proliferative ACE/ANG II/AT1 axis, and the vasodilator/antiproliferative ACE2/ANG-(1–7)/MAS axis are poorly known. Data in the rat have suggested the male-specific Y-chromosome gene Sry to contribute to balance between these two axes, but why the testis-determining gene has these functions remains unknown. A combination of in silico genetic/protein comparisons, functional luciferase assays for promoters of the human RAS, and RNA-Seq profiling in rat were used to address if regulation of Sry on the RAS is conserved in the homologous X-chromosome gene, Sox3. Both SRY and SOX3 upregulated the promoter of Angiotensinogen (AGT) and downregulated the promoters of ACE2, AT2, and MAS, likely through overlapping mechanisms. The regulation by both SRY and SOX3 on the MAS promoter indicates a cis regulation through multiple SOX binding sites. The Renin (REN) promoter is upregulated by SRY and downregulated by SOX3, likely through trans and cis mechanisms, respectively. Sry transcripts are found in all analyzed male rat tissues including the kidney, while Sox3 transcripts are found only in the brain and testis, suggesting that the primary tissue for renin production (kidney) can only be regulated by SRY and not SOX3. These results suggest that SRY regulation of the RAS is partially shared with its X-chromosome homolog SOX3, but SRY gained a sex-specific control in the kidney for the rate-limiting step of the RAS, potentially resulting in male-specific blood pressure regulation. PMID:25759379

  14. The effect of perinatal taurine on adult renal function does not appear to be mediated by taurine’s inhibition of the renin-angiotensin system

    PubMed Central

    Roysommuti, Sanya; Kritsongsakchai, Angkana; Wyss, J. Michael

    2016-01-01

    This study tests the hypothesis that perinatal taurine supplementation alters adult renal function by inhibition of the renin-angiotensin system. Female Sprague-Dawley rats were fed normal rat chow and given water alone (Control) or water containing an angiotensin converting enzyme inhibitor (captopril, 400 mg/ml) from conception until delivery (FD) or from delivery until weaning (LD). After weaning, the rats received normal rat chow and tap water. At 7–8 weeks of age, renal function at rest and after acute saline load was studied in conscious, restrained male rats. Body weight, mean arterial pressure, heart rate, effective renal blood flow, and renal vascular resistance were not significantly different among the three groups. Compared to Control, glomerular filtration rate, but not filtration fraction, significantly increased after saline load in both FD and LD groups. Water excretion significantly increased only in FD compared to Control, while fractional water excretion was significantly increased after saline load in both FD and LD groups. Sodium excretion significantly increased after saline load only in FD, while both captopril-treated groups significantly decreased fractional sodium excretion. Potassium excretion significantly increased in both FD and LD groups, while fractional potassium excretion significantly increased at rest in FD and decreased in LD groups after saline load. These effects of perinatal RAS inhibition on adult renal function contrast sharply, and are opposite in many cases to, the effects of perinatal taurine supplementation. Thus, these data suggest that perinatal taurine supplementation does not alter adult renal function through its ability to inhibit the perinatal RAS. PMID:25833535

  15. Early Training-Induced Reduction of Angiotensinogen in Autonomic Areas—The Main Effect of Exercise on Brain Renin-Angiotensin System in Hypertensive Rats

    PubMed Central

    Chaar, Laiali Jurdi; Alves, Tatiana Pereira; Batista Junior, Alvaro Martins; Michelini, Lisete Compagno

    2015-01-01

    Background Exercise training (T) blunts functional deficits and renin-angiotensin system (RAS) hyperactivity in hypertensive individuals. There is no information on T-induced temporal changes of brain RAS. We evaluate now the simultaneous effects of T on functional responses and time course changes in the expression/activity of brain RAS components in autonomic cardiovascular-controlling areas. Methods and Results Spontaneously hypertensive rats (SHR) and age-matched normotensive controls (WKY) were trained for 0, 1, 2, 4, 8 and 12 weeks. Sedentary (S) groups served as time-controls. After arterial pressure (AP) and heart rate (HR) recordings at rest, fresh and fixed brains were harvested for qPCR and immunofluorescence assays. SHR-S vs. WKY-S exhibited higher mean AP (MAP) and HR, increased pressure variability and sympathetic activity, elevated AT1 receptor (AT1) expression in nucleus tractus solitarii (NTS) and higher Mas receptor expression in the rostroventrolateral medulla (RVLM). In SHR, T promptly (T2 on) reduced sympathetic variability to heart/vessels and largely decreased angiotensinogen expression in the paraventricular hypothalamic nucleus (PVN) and NTS, with a late RVLM reduction (T4). AT1 expression was only reduced at T12 (PVN and NTS) with transient, not maintained Mas receptor changes in PVN and RVLM. These responses were accompanied by baseline MAP and HR reduction in the SHR-T (from T4 on). In the SHR group, PVN angiotensinogen expression correlated positively with sympathetic activity, resting MAP and HR. In WKY-T, a precocious (T2-T12) RVLM AT1 decrease preceded the appearance of resting bradycardia (from T8 on). Conclusions Early and maintained reduction of angiotensinogen content in autonomic areas of the SHR is the most prominent effect of training on brain RAS. Down-regulation of PVN RAS expression is an essential factor to drive cardiovascular benefits in SHR-T, while resting bradycardia in WKY-T is correlated to RVLM AT1 reduction. PMID

  16. The renin-angiotensin system mediates epidermal growth factor receptor-vitamin D receptor cross-talk in colitis-associated colon cancer

    PubMed Central

    Sadiq, Farhana; Almoghrabi, Anas; Mustafi, Devkumar; Kreisheh, Maggi; Sundaramurthy, Sumana; Liu, Weicheng; Konda, Vani J.; Pekow, Joel; Khare, Sharad; Hart, John; Joseph, Loren; Wyrwicz, Alice; Karczmar, Gregory S.; Li, Yan Chun; Bissonnette, Marc

    2014-01-01

    Purpose We previously showed that epidermal growth factor receptor (EGFR) promotes tumorigenesis in the azoxymethane/dextran sulfate sodium (AOM/DSS) model, whereas vitamin D (VD) suppresses tumorigenesis. EGFR-vitamin D receptor (VDR) interactions, however, are incompletely understood. VD inhibits the renin-angiotensin system (RAS), whereas RAS can activate EGFR. We aimed to elucidate EGFR-VDR cross-talk in colorectal carcinogenesis. Experimental Design To examine VDR-RAS interactions, we treated Vdr+/+ and Vdr/− mice with AOM/DSS. Effects of VDR on RAS and EGFR were examined by Westerns, immunostaining and real time PCR. We also examined the effect of vitamin D3 on colonic RAS in Vdr+/+ mice. EGFR regulation of VDR was examined in hypomorphic EgfrWaved2 (Wa2) and Egfrwildtype mice. Ang II-induced EGFR activation was studied in cell culture. Results Vdr deletion significantly increased tumorigenesis, activated EGFR and βcatenin signaling and increased colonic RAS components: including renin and angiotensin II. Dietary VD3 supplementation suppressed colonic renin. Renin was increased in human colon cancers. In studies in vitro, Ang II activated EGFR and stimulated colon cancer cell proliferation by an EGFR-mediated mechanism. Ang II also activated macrophages and colonic fibroblasts. Compared to tumors from EgfrWaved2 mice, tumors from Egfrwildtype mice showed up-regulated Snail1, a suppressor of VDR, and down-regulated VDR. Conclusions VDR suppresses the colonic RAS cascade, limits EGFR signals and inhibits colitis-associated tumorigenesis, whereas EGFR increases Snail1 and down-regulates VDR in colonic tumors. Taken together, these results uncover a RAS-dependent mechanism mediating EGFR and VDR cross-talk in colon cancer. PMID:25212605

  17. Effect of Beta Blockers and Renin-Angiotensin System Inhibitors on Survival in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

    PubMed

    Lee, Pil Hyung; Park, Gyung-Min; Kim, Young-Hak; Yun, Sung-Cheol; Chang, Mineok; Roh, Jae-Hyung; Yoon, Sung-Han; Ahn, Jung-Min; Park, Duk-Woo; Kang, Soo-Jin; Lee, Seung-Whan; Lee, Cheol Whan; Park, Seong-Wook; Park, Seung-Jung

    2016-03-01

    Because it remains uncertain whether β-blockers (BBs) and/or renin-angiotensin system inhibitors benefit a broad population of acute myocardial infarction (AMI) patients, we sought to evaluate the effectiveness of these drugs in improving survival for post-AMI patients who underwent a percutaneous coronary intervention (PCI).From the nationwide data of the South Korea National Health Insurance, 33,390 patients with a diagnosis of AMI who underwent a PCI between 2009 and 2013 and survived at least 30 days were included in this study. We evaluated the risk of all-cause death for patients treated with both BB and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor antagonist (ARB) (n = 16,280), only BB (n = 3683), and only ACEI/ARB (n = 9849), with the drug-untreated patients (n = 3578) as the reference.Over a median follow-up of 2.4 years, although treated patients displayed a trend toward improved survival, there were no significant differences in the adjusted risk of all-cause death when patients were treated with both drugs (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.70-1.06, P = 0.154), BB (HR 0.88, 95% CI 0.68-1.14, P = 0.325), or ACEI/ARB (HR 0.84, 95% CI 0.68-1.04, P = 0.111). No additional benefit was found for the combination therapy compared with either isolated BB (HR 0.98, 95% CI 0.80-1.21, P = 0.856) or ACEI/ARB (HR 1.03, 95% CI 0.89-1.19, P = 0.727) therapy.Treatment with BB and/or ACEI/ARB has limited effect on survival in unselected nonfatal AMI patients who undergo PCI. PMID:26962802

  18. Horizon 2020 in Diabetic Kidney Disease: The Clinical Trial Pipeline for Add-On Therapies on Top of Renin Angiotensin System Blockade

    PubMed Central

    Perez-Gomez, Maria Vanessa; Sanchez-Niño, Maria Dolores; Sanz, Ana Belen; Martín-Cleary, Catalina; Ruiz-Ortega, Marta; Egido, Jesus; Navarro-González, Juan F.; Ortiz, Alberto; Fernandez-Fernandez, Beatriz

    2015-01-01

    Diabetic kidney disease is the most frequent cause of end-stage renal disease. This implies failure of current therapeutic approaches based on renin-angiotensin system (RAS) blockade. Recent phase 3 clinical trials of paricalcitol in early diabetic kidney disease and bardoxolone methyl in advanced diabetic kidney disease failed to meet the primary endpoint or terminated on safety concerns, respectively. However, various novel strategies are undergoing phase 2 and 3 randomized controlled trials targeting inflammation, fibrosis and signaling pathways. Among agents currently undergoing trials that may modify the clinical practice on top of RAS blockade in a 5-year horizon, anti-inflammatory agents currently hold the most promise while anti-fibrotic agents have so far disappointed. Pentoxifylline, an anti-inflammatory agent already in clinical use, was recently reported to delay estimated glomerular filtration rate (eGFR) loss in chronic kidney disease (CKD) stage 3–4 diabetic kidney disease when associated with RAS blockade and promising phase 2 data are available for the pentoxifylline derivative CTP-499. Among agents targeting chemokines or chemokine receptors, the oral small molecule C-C chemokine receptor type 2 (CCR2) inhibitor CCX140 decreased albuminuria and eGFR loss in phase 2 trials. A dose-finding trial of the anti-IL-1β antibody gevokizumab in diabetic kidney disease will start in 2015. However, clinical development is most advanced for the endothelin receptor A blocker atrasentan, which is undergoing a phase 3 trial with a primary outcome of preserving eGFR. The potential for success of these approaches and other pipeline agents is discussed in detail. PMID:26239562

  19. Inhibition of angiotensin-converting enzyme stimulates fracture healing and periosteal callus formation – role of a local renin-angiotensin system

    PubMed Central

    Garcia, P; Schwenzer, S; Slotta, JE; Scheuer, C; Tami, AE; Holstein, JH; Histing, T; Burkhardt, M; Pohlemann, T; Menger, MD

    2010-01-01

    Background and purpose: The renin-angiotensin system (RAS) regulates blood pressure and electrolyte homeostasis. In addition, ‘local’ tissue-specific RAS have been identified, regulating regeneration, cell growth, apoptosis, inflammation and angiogenesis. Although components of the RAS are expressed in osteoblasts and osteoclasts, a local RAS in bone has not yet been described and there is no information on whether the RAS is involved in fracture healing. Therefore, we studied the expression and function of the key RAS component, angiotensin-converting enzyme (ACE), during fracture healing. Experimental approach: In a murine femur fracture model, animals were treated with the ACE inhibitor perindopril or vehicle only. Fracture healing was analysed after 2, 5 and 10 weeks using X-ray, micro-CT, histomorphometry, immunohistochemistry, Western blotting and biomechanical testing. Key results: ACE was expressed in osteoblasts and hypertrophic chondrocytes in the periosteal callus during fracture healing, accompanied by expression of the angiotensin type-1 and type-2 receptors. Perindopril treatment reduced blood pressure and bone mineral density in unfractured femora. However, it improved periosteal callus formation, bone bridging of the fracture gap and torsional stiffness. ACE inhibition did not affect cell proliferation, but reduced apoptotic cell death. After 10 week treatment, a smaller callus diameter and bone volume after perindopril treatment indicated an advanced stage of bone remodelling. Conclusions: Our study provides evidence for a local RAS in bone that influenced the process of fracture healing. We show for the first time that inhibition of ACE is capable of accelerating bone healing and remodelling. PMID:20233225

  20. Human placental renin-angiotensin system in normotensive and pre-eclamptic pregnancies at high altitude and after acute hypoxia-reoxygenation insult.

    PubMed

    Kurlak, Lesia O; Mistry, Hiten D; Cindrova-Davies, Tereza; Burton, Graham J; Broughton Pipkin, Fiona

    2016-03-01

    A functioning placental renin-angiotensin system (RAS) appears necessary for uncomplicated pregnancy and is present during placentation, which occurs under low oxygen tensions. Placental RAS is increased in pre-eclampsia (PE), characterised by placental dysfunction and elevated oxidative stress. We investigated the effect of high altitude hypoxia on the RAS and hypoxia-inducible factors (HIFs) by measuring mRNA and protein expression in term placentae from normotensive (NT) and PE women who delivered at sea level or above 3100 m, using an explant model of hypoxia-reoxygenation to assess the impact of acute oxidative stress on the RAS and HIFs. Protein levels of prorenin (P = 0.049), prorenin receptor (PRR; P = 0.0004), and angiotensin type 1 receptor (AT1R, P = 0.006) and type 2 receptor (AT2R, P = 0.002) were all significantly higher in placentae from NT women at altitude, despite mRNA expression being unaffected. However, mRNA expression of all RAS components was significantly lower in PE at altitude than at sea level, yet PRR, angiotensinogen (AGT) and AT1R proteins were all increased. The increase in transcript and protein expression of all the HIFs and NADPH oxidase 4 seen in PE compared to NT at sea level was blunted at high altitude. Experimentally induced oxidative stress stimulated AGT mRNA (P = 0.04) and protein (P = 0.025). AT1R (r = 0.77, P < 0.001) and AT2R (r = 0.81, P < 0.001) mRNA both significantly correlated with HIF-1β, whilst AT2R also correlated with HIF-1α (r = 0.512, P < 0.013). Our observations suggest that the placental RAS is responsive to changes in tissue oxygenation: this could be important in the interplay between reactive oxygen species as cell-signalling molecules for angiogenesis and hence placental development and function. PMID:26574162

  1. Novel concept in the mechanism of injury and protection of gastric mucosa: role of renin-angiotensin system and active metabolites of angiotensin.

    PubMed

    Brzozowski, T; Ptak-Belowska, A; Kwiecien, S; Krzysiek-Maczka, G; Strzalka, M; Drozdowicz, D; Pajdo, R; Olszanecki, R; Korbut, R; Konturek, S J; Pawlik, W W

    2012-01-01

    The term cytoprotection pioneered by Robert and colleagues has been introduced to describe the remarkable ability of endogenous and exogenous prostaglandins (PGs) to prevent acute gastric hemorrhagic lesions induced by noxious stimuli such as ethanol, bile acids, hiperosmolar solutions and nonsteroidal anti-inflammatory agents such as aspirin. Since that time many factors were implicated to possess gastroprotective properties such as growth factors including epidermal growth factor (EGF) and transforming factor alpha (TGFα), vasodilatory mediators such as nitric oxide (NO) and calcitonin gene related peptide (CGRP) as well as appetite gut hormones including gastrin and cholecystokinin (CCK), leptin and recently ghrelin. This protective action of gut peptides has been attributed to the release of PG but question remains whether another peptide angiotensin, the classic component of the systemic and local renin-angiotensin system (RAS) could be involved in the mechanism of gastric integrity and gastroprotection. After renin stimulation, the circulating angiotensin I is converted to angiotensin II (ANG II) by the activity of the Angiotensin Converting Enzyme (ACE). The ANG II acting via its binding to two major receptor subtypes the ANG type 1 (AT1) and type 2 (AT2) has been shown be activated during stress and to contribute to the pathogenesis of cold stress- and ischemia-reperfusion-induced gastric lesions. All bioactive angiotensin peptides can be generated not only in systemic circulation, but also locally in several tissues and organs. Recently the new functional components of RAS, such as Ang-(1-7), Ang IV, Ang-(1-12) and novel pathways ACE2 have been described suggesting the gastroprotective role for the novel ANG II metabolite, Ang-(1-7). The fact that Ang-(1-7) is produced in excessive amounts in the gastric mucosa of rodents and that pretreatment by Ang-(1-7) exhibits a potent gastroprotective activity against the gastric lesions induced by cold

  2. Association of Genetic Polymorphisms of Renin-Angiotensin-Aldosterone System-Related Genes with Arterio-Venous Fistula Malfunction in Hemodialysis Patients.

    PubMed

    Chen, Yu-Wei; Wu, Yu-Te; Lin, Jhin-Shyaun; Yang, Wu-Chang; Hsu, Yung-Ho; Lee, Kuo-Hua; Ou, Shou-Ming; Chen, Yung-Tai; Shih, Chia-Jen; Lee, Pui-Ching; Chan, Chia-Hao; Chung, Ming-Yi; Lin, Chih-Ching

    2016-01-01

    Hemodialysis (HD) is the most commonly-used renal replacement therapy for patients with end-stage renal disease worldwide. Arterio-venous fistula (AVF) is the vascular access of choice for HD patients with lowest risk of infection and thrombosis. In addition to environmental factors, genetic factors may also contribute to malfunction of AVF. Previous studies have demonstrated the effect of genotype polymorphisms of angiotensin converting enzyme on vascular access malfunction. We conducted a multicenter, cross-sectional study to evaluate the association between genetic polymorphisms of renin-angiotensin-aldosterone system and AVF malfunction. Totally, 577 patients were enrolled. Their mean age was 60 years old and 53% were male. HD patients with AVF malfunction had longer duration of HD (92.5 ± 68.1 vs. 61.2 ± 51.9 months, p < 0.001), lower prevalence of hypertension (44.8% vs. 55.3%, p = 0.025), right-sided (31.8% vs. 18.4%, p = 0.002) and upper arm AVF (26.6% vs. 9.7%, p < 0.001), and higher mean dynamic venous pressure (DVP) (147.8 ± 28.3 vs. 139.8 ± 30.0, p = 0.021). In subgroup analysis of different genders, location of AVF and DVP remained significant clinical risk factors of AVF malfunction in univariate and multivariate binary logistic regression in female HD patients. Among male HD patients, univariate binary logistic regression analysis revealed that right-side AVF and upper arm location are two important clinical risk factors. In addition, two single nucleotide polymorphisms (SNPs), rs275653 (Odds ratio 1.90, p = 0.038) and rs1492099 (Odds ratio 2.29, p = 0.017) of angiotensin II receptor 1 (AGTR1), were associated with increased risk of AVF malfunction. After adjustment for age and other clinical factors, minor allele-containing genotype polymorphisms (AA and CA) of rs1492099 still remained to be a significant risk factor of AVF malfunction (Odds ratio 3.63, p = 0.005). In conclusion, we demonstrated that rs1492099, a SNP of AGTR1 gene, could be a

  3. Effects of renin-angiotensin system blockade on the islet morphology and function in rats with long-term high-fat diet.

    PubMed

    Yuan, Li; Li, Xin; Li, Jin; Li, Hai-Ling; Cheng, Suo-Suo

    2013-08-01

    The renin-angiotensin system (RAS) has an important role in the endocrine pancreas. Multiple researches have shown that even in the insulin resistance phase, there are many abnormalities in islets morphology and function. This study aimed at investigating the effects of RAS blockade on the islets function in rats with long-term high-fat diet and its mechanisms. Wistar rats with 16-week high-fat diet were randomly divided into perindopril intervention group (FP, n = 15) and telmisartan intervention group (FT, n = 15). After 8-week intervention, insulin sensitivity and islets function were detected by hyperinsulinemic euglycemic clamp and intravenous glucose tolerance test (IVGTT), respectively. The pancreases were stained by immunohistochemistry technique to qualitatively and/or quantitatively analyze the relative content of insulin (IRC), NF-KB, uncoupling protein 2 (UCP2) and caspase-3 in islets. The apoptosis of islet cells was detected by TUNEL. The expression of angiotensin II receptor 1 (AT1R), interleukin-1β (IL-1β), hypoxia-inducing factor (HIF)-1α and CHOP mRNA in the islets was detected by reverse transcription polymerase chain reaction (RT-PCR). Compared with normal control group (NC, n = 15), the glucose infusion rate (GIR), area under the insulin curve (AUCI) of 0-10 min and IRC were decreased in high-fat control group (FC, n = 15). The relative content of NF-KB, UCP-2 and caspase-3 was increased significantly with the increased number of apoptotic cells in unit islets area. The relative expression of AT1R, IL-1β, HIF-1α and CHOP was also increased evidently (all P < 0.01). After intervention, the GIR, AUCI of 0-10 min and IRC were all increased obviously with the decreased relative concentration of NF-KB, UCP-2, caspase-3 and the number of apoptotic cell in unit islets area. The relative expression of AT1R, IL-1β, HIF-1α and CHOP mRNA was reduced significantly (all P < 0.01 or P < 0.05). There were no significant differences between groups FP

  4. Strong suppression of the renin-angiotensin system has a renal-protective effect in hypertensive patients: high-dose ARB with ACE inhibitor (Hawaii) study.

    PubMed

    Ohishi, Mitsuru; Takeya, Yasushi; Tatara, Yuji; Yamamoto, Koichi; Onishi, Miyuki; Maekawa, Yoshihiro; Kamide, Kei; Rakugi, Hiromi

    2010-11-01

    The principal means for reducing proteinuria in patients with chronic kidney disease are strong blockade of the renin-angiotensin system and strict regulation of blood pressure (BP). This study compared the efficacy of the maximum permissible doses of two common angiotensin receptor blockers (ARBs), namely valsartan (maximum dose=160 mg per day) and olmesartan (maximum dose=40 mg per day). We also investigated whether a high-dose ARB or the combination of an angiotensin-converting enzyme inhibitor with a high-dose ARB would be more renal protective. We recruited 87 poorly controlled hypertensive patients. In the first study, 50 patients without proteinuria were switched from valsartan (160 mg per day) to olmesartan (40 mg per day) for 4 months. In the second study, 37 patients with proteinuria were randomized to either switch from valsartan 160 mg per day to 40 mg per day olmesartan (n=19; Olm-G) or addition of 2.5-10 mg per day imidapril (stepped up by 2.5 mg per month) to valsartan at 160 mg per day (n=18; Imi-G). After 4 months, the BP level decreased (first study) from 157/88 mm Hg to 145/82 mm Hg (P<0.001) and (second study) from 149/86 mm Hg to 135/77 mm Hg and 145/82 mm Hg for Olm-G and Imi-G, respectively. Furthermore, in the second study, urinary protein/creatinine excretion was reduced from 2.0±1.8 g g⁻¹ to 0.8±0.8 g g⁻¹ (P=0.0242) in Olm-G and from 1.4±1.3 g g⁻¹ to 0.9±1.0 g g⁻¹ (P=0.0398) in Imi-G. The significance persisted after adjustment for BP or other risk factors. Our results suggested that the maximum dose of olmesartan was more effective than that of valsartan and comparable with the combination of valsartan and imidapril for reducing BP and proteinuria in poorly controlled hypertensive patients. PMID:20703230

  5. Renoprotective Effect of the Combination of Renin-angiotensin System Inhibitor and Calcium Channel Blocker in Patients with Hypertension and Chronic Kidney Disease

    PubMed Central

    Huang, Rong-Shuang; Cheng, Yi-Ming; Zeng, Xiao-Xi; Kim, Sehee; Fu, Ping

    2016-01-01

    Background: Renin-angiotensin system inhibitor and calcium channel blocker (CCB) are widely used in controlling blood pressure (BP) in patients with chronic kidney disease (CKD). We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and CCB (i.e., ACEI/ARB + CCB) with ACEI/ARB monotherapy in patients with hypertension and CKD. Methods: Publications were identified from PubMed, Embase, Medline, and Cochrane databases. Only randomized controlled trials (RCTs) of BP lowering treatment for patients with hypertension and CKD were considered. The outcomes of end-stage renal disease (ESRD), cardiovascular events, BP, urinary protein measures, estimated glomerular filtration rate (GFR), and adverse events were extracted. Results: Based on seven RCTs with 628 patients, ACEI/ARB + CCB did not show additional benefit for the incidence of ESRD (risk ratio [RR] = 0.84; 95% confidence interval [CI]: 0.52–1.33) and cardiovascular events (RR = 0.58; 95% CI: 0.21–1.63) significantly, compared with ACEI/ARB monotherapy. There were no significant differences in change from baseline to the end points in diastolic BP (weighted mean difference [WMD] = −1.28 mmHg; 95% CI: −3.18 to −0.62), proteinuria (standard mean difference = −0.55; 95% CI: −1.41 to −0.30), GFR (WMD = −0.32 ml/min; 95% CI: −1.53 to −0.89), and occurrence of adverse events (RR = 1.05; 95% CI: 0.72–1.53). However, ACEI/ARB + CCB showed a greater reduction in systolic BP (WMD = −4.46 mmHg; 95% CI: −6.95 to −1.97), compared with ACEI/ARB monotherapy. Conclusion: ACEI/ARB + CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy. PMID:26904991

  6. Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and meta-analysis of randomized trials

    PubMed Central

    Fakheri, Robert; Toklu, Bora; Messerli, Franz H

    2016-01-01

    Objective To evaluate the outcomes with use of renin angiotensin system (RAS) blockers compared with other antihypertensive agents in people with diabetes. Design Meta-analysis. Data sources and study selection PubMed, Embase, and the Cochrane central register of controlled trials databases for randomized trials of RAS blockers versus other antihypertensive agents in people with diabetes mellitus. Outcomes were death, cardiovascular death, myocardial infarction, angina, stroke, heart failure, revascularization, and end stage renal disease. Results The search yielded 19 randomized controlled trials that enrolled 25 414 participants with diabetes for a total of 95 910 patient years of follow-up. When compared with other antihypertensive agents, RAS blockers were associated with a similar risk of death (relative risk 0.99, 95% confidence interval 0.93 to 1.05), cardiovascular death (1.02, 0.83 to 1.24), myocardial infarction (0.87, 0.64 to 1.18), angina pectoris (0.80, 0.58 to 1.11), stroke (1.04, 0.92 to 1.17), heart failure (0.90, 0.76 to 1.07), and revascularization (0.97, 0.77 to 1.22). There was also no difference in the hard renal outcome of end stage renal disease (0.99, 0.78 to 1.28) (power of 94% to show a 23% reduction in end stage renal disease). Conclusions In people with diabetes, RAS blockers are not superior to other antihypertensive drug classes such as thiazides, calcium channel blockers, and β blockers at reducing the risk of hard cardiovascular and renal endpoints. These findings support the recommendations of the guidelines of the European Society of Cardiology/European Society of Hypertension and eighth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure to also use other antihypertensive agents in people with diabetes but without kidney disease. PMID:26868137

  7. New approaches to hyperkalemia in patients with indications for renin angiotensin aldosterone inhibitors: Considerations for trial design and regulatory approval.

    PubMed

    Zannad, Faiez; Rossignol, Patrick; Stough, Wendy Gattis; Epstein, Murray; Alonso Garcia, Maria de Los Angeles; Bakris, George L; Butler, Javed; Kosiborod, Mikhail; Berman, Lance; Mebazaa, Alexandre; Rasmussen, Henrik S; Ruilope, Luis M; Stockbridge, Norman; Thompson, Aliza; Wittes, Janet; Pitt, Bertram

    2016-08-01

    Hyperkalemia is a common clinical problem, especially in patients with chronic kidney disease, diabetes mellitus, or heart failure. Treatment with renin angiotensin aldosterone system inhibitors exacerbates the risk of hyperkalemia in these patients. Concern about hyperkalemia can result in the failure to initiate, suboptimal dosing, or discontinuation of renin angiotensin aldosterone system inhibitor therapy in patients; effective treatments for hyperkalemia might mitigate such undertreatment. New treatments for hyperkalemia in development may offer better efficacy, tolerability and safety profiles than do existing approved treatments. These compounds might enable more eligible patients to receive renin angiotensin aldosterone system inhibitor therapy or to receive renin angiotensin aldosterone system inhibitors at target doses. The evidence needed to support a treatment claim (reduction in serum potassium) differs from that needed to support a prevention claim (preventing hyperkalemia to allow renin angiotensin aldosterone system inhibitor treatment). Thus, several issues related to clinical trial design and drug development need to be considered. This paper summarizes and expands upon a discussion at the Global Cardiovascular Clinical Trialists 2014 Forum and examines methodologic considerations for trials of new potassium binders for the prevention and management of hyperkalemia in patients with renin angiotensin aldosterone system inhibitor indications. PMID:27140336

  8. Furosemide stimulation of parathormone in humans: role of the calcium-sensing receptor and the renin-angiotensin system.

    PubMed

    Muller, Marie-Eve; Forni Ogna, Valentina; Maillard, Marc; Stoudmann, Candice; Zweiacker, Carole; Anex, Christiane; Wuerzner, Grégoire; Burnier, Michel; Bonny, Olivier

    2015-12-01

    Interactions between sodium and calcium regulating systems are poorly characterized but clinically important. Parathyroid hormone (PTH) levels are increased shortly after furosemide treatment by an unknown mechanism, and this effect is blunted by the previous administration of a calcimimetic in animal studies. Here, we explored further the possible underlying mechanisms of this observation in a randomized crossover placebo-controlled study performed in 18 human males. Volunteers took either cinacalcet (60 mg) or placebo and received a 20 mg furosemide injection 3 h later. Plasma samples were collected at 15-min intervals and analyzed for intact PTH, calcium, sodium, potassium, magnesium, phosphate, plasma renin activity (PRA), and aldosterone up to 6 h after furosemide injection. Urinary electrolyte excretion was also monitored. Subjects under placebo presented a sharp increase in PTH levels after furosemide injection. In the presence of cinacalcet, PTH levels were suppressed and marginal increase of PTH was observed. No significant changes in electrolytes and urinary excretion were identified that could explain the furosemide-induced increase in PTH levels. PRA and aldosterone were stimulated by furosemide injection but were not affected by previous cinacalcet ingestion. Expression of NKCC1, but not NKCC2, was found in parathyroid tissue. In conclusion, our results indicate that furosemide acutely stimulates PTH secretion in the absence of any detectable electrolyte changes in healthy adults. A possible direct effect of furosemide on parathyroid gland needs further studies. PMID:26089029

  9. Intrarenal alterations of the angiotensin-converting enzyme type 2/angiotensin 1-7 complex of the renin-angiotensin system do not alter the course of malignant hypertension in Cyp1a1-Ren-2 transgenic rats.

    PubMed

    Husková, Zuzana; Kopkan, Libor; Červenková, Lenka; Doleželová, Šárka; Vaňourková, Zdeňka; Škaroupková, Petra; Nishiyama, Akira; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz; Kramer, Herbert J; Červenka, Luděk

    2016-04-01

    The role of the intrarenal renin-angiotensin system (RAS) in the pathophysiology of malignant hypertension is not fully understood. Accumulating evidence indicates that the recently discovered vasodilator axis of the RAS, angiotensin-converting enzyme (ACE) type 2 (ACE2)/angiotensin 1-7 (ANG 1-7), constitutes an endogenous system counterbalancing the hypertensiogenic axis, ACE/angiotensin II (ANG II)/AT1 receptor. This study aimed to evaluate the role of the intrarenal vasodilator RAS axis in the pathophysiology of ANG II-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. ANG II-dependent malignant hypertension was induced by 13 days' dietary administration of indole-3-carbinol (I3C), a natural xenobiotic that activates the mouse renin gene in Cyp1a1-Ren-2 transgenic rats. It was hypothesized that pharmacologically-induced inhibition of the ACE2/ANG 1-7 complex should aggravate, and activation of this axis should attenuate, the course of ANG II-dependent malignant hypertension. Blood pressure (BP) was monitored by radiotelemetry. ACE2 inhibitor (DX 600, 0.2 μg/day) and ACE2 activator (DIZE, 1 mg/day) were administrated via osmotic minipumps. Even though ACE2 inhibitor significantly decreased and ACE2 activator increased intrarenal ANG 1-7 concentrations, the course of BP, as well as of albuminuria, cardiac hypertrophy and renal glomerular damage, were not altered. It was shown that intrarenal alterations in the ACE2/ANG 1-7 complex did not significantly modify the course of malignant hypertension in I3C-induced Cyp1a1-Ren-2 transgenic rats. Thus, in our experimental setting alterations of this intrarenal vasodilator complex of the RAS do not significantly modify the form of malignant hypertension that clearly depends on the inappropriately increased activity of the ACE/ANG II/AT1 receptor axis. PMID:26833491

  10. Reduced Expression of the Extracellular Calcium-Sensing Receptor (CaSR) Is Associated with Activation of the Renin-Angiotensin System (RAS) to Promote Vascular Remodeling in the Pathogenesis of Essential Hypertension

    PubMed Central

    Wang, La-mei; Tang, Na; Zhong, Hua; Liu, Yong-min; Li, Zhen; Feng, Qian; He, Fang

    2016-01-01

    The proliferation of vascular smooth muscle cells (VSMCs), remodeling of the vasculature, and the renin-angiotensin system (RAS) play important roles in the development of essential hypertension (EH), which is defined as high blood pressure (BP) in which secondary causes, such as renovascular disease, are absent. The calcium-sensing receptor (CaSR) is involved in the regulation of BP. However, the underlying mechanisms by which the CaSR regulates BP are poorly understood. In the present study, the role of the CaSR in EH was investigated using male spontaneously hypertensive rats (SHRs) and rat and human plasma samples. The percentages of medial wall thickness to external diameter (WT%), total vessel wall cross-sectional area to the total area (WA%) of thoracic arteries, as well as the percentage of wall area occupied by collagen to total vessel wall area (CA%) were determined. Tissue protein expression and plasma concentrations of the CaSR, cyclic adenosine monophosphate (cAMP), renin, and angiotensin II (Ang II) were additionally assessed. WT%, WA%, and CA% were found to increase with increasing BP, whereas the plasma concentration of CaSR was found to decrease. With increasing BP, the levels of smooth muscle actin and calponin decreased, whereas those of osteopontin and proliferating cell nuclear antigen increased. The CaSR level negatively correlated with the levels of cAMP and Ang II, but positively correlated with those of renin. Our data suggest that reduced expression of the CaSR is correlated with activation of the RAS, which induces increased vascular remodeling and VSMC proliferation, and thereby associated with EH in the SHR model and in the Han Chinese population. Our findings provide new insights into the pathogenesis of EH. PMID:27391973

  11. Renin Angiotensin Signaling in Normal Pregnancy and Preeclampsia

    PubMed Central

    Irani, Roxanna A.; Xia, Yang

    2011-01-01

    Summary Many reports indicate that there is an increase in almost all of the components of the renin-angiotensin system (RAS) during an uncomplicated pregnancy, but renin activity, angiotensin II, and aldosterone decrease in preeclampsia (PE) for reasons that are unclear. PE is a life-threatening disorder of late pregnancy characterized by hypertension, proteinuria, increased soluble fms-like tyrosine kinase-1, as well as renal and placental morphologic abnormalities. Although a leading cause of maternal and perinatal morbidity and mortality, the pathogenic mechanisms of PE remain largely undefined. Immunologic mechanisms and aberrations of the RAS have been long considered contributors to the disorder. Bridging these two concepts, numerous studies report the presence of the angiotensin II type I receptor agonistic autoantibody (AT1-AA) found circulating in preeclamptic women. This autoantibody induces many key features of the disorder through AT1 receptor signaling, and has been implicated in the pathogenesis of PE. Here we review the functions of the RAS during normal pregnancy and PE, and highlight the role of AT1-AA in both animal models and in the human disorder. PMID:21266264

  12. Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY): essential study design and rationale of a randomised clinical multicentre trial

    PubMed Central

    Lindhardt, Morten; Currie, Gemma; Pontillo, Claudia; Beige, Joachim; Delles, Christian; von der Leyen, Heiko; Mischak, Harald; Navis, Gerjan; Noutsou, Marina; Ortiz, Alberto; Ruggenenti, Piero Luigi; Rychlik, Ivan; Spasovski, Goce; Rossing, Peter

    2016-01-01

    Introduction Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment in normoalbumuric patients have given mixed results. This might reflect that the large fraction of normoalbuminuric patients are not at risk of progression, thereby reducing power in previous studies. A specific risk classifier based on urinary proteomics (chronic kidney disease (CKD)273) has been shown to identify normoalbuminuric diabetic patients who later progressed to overt kidney disease, and may hold the potential for selection of high-risk patients for early intervention. Combining the ability of CKD273 to identify patients at highest risk of progression with prescription of preventive aldosterone blockade only to this high-risk population will increase power. We aim to confirm performance of CKD273 in a prospective multicentre clinical trial and test the ability of spironolactone to delay progression of early diabetic nephropathy. Methods and analysis Investigator-initiated, prospective multicentre clinical trial, with randomised double-masked placebo-controlled intervention and a prospective observational study. We aim to include 3280 type 2 diabetic participants with normoalbuminuria. The CKD273 classifier will be assessed in all participants. Participants with high-risk pattern are randomised to treatment with spironolactone 25 mg once daily, or placebo, whereas, those with low-risk pattern will be observed without intervention other than standard of care. Treatment or observational period is 3 years. The primary endpoint is development of confirmed microalbuminuria in 2 of 3 first morning voids urine samples. Ethics and dissemination The study will be conducted under International Conference on Harmonisation – Good clinical practice (ICH-GCP) requirements

  13. Inducible Knock-Down of the Mineralocorticoid Receptor in Mice Disturbs Regulation of the Renin-Angiotensin-Aldosterone System and Attenuates Heart Failure Induced by Pressure Overload

    PubMed Central

    Montes-Cobos, Elena; Li, Xiao; Fischer, Henrike J.; Sasse, André; Kügler, Sebastian; Didié, Michael; Toischer, Karl; Fassnacht, Martin; Dressel, Ralf; Reichardt, Holger M.

    2015-01-01

    Mineralocorticoid receptor (MR) inactivation in mice results in early postnatal lethality. Therefore we generated mice in which MR expression can be silenced during adulthood by administration of doxycycline (Dox). Using a lentiviral approach, we obtained two lines of transgenic mice harboring a construct that allows for regulatable MR inactivation by RNAi and concomitant expression of eGFP. MR mRNA levels in heart and kidney of inducible MR knock-down mice were unaltered in the absence of Dox, confirming the tightness of the system. In contrast, two weeks after Dox administration MR expression was significantly diminished in a variety of tissues. In the kidney, this resulted in lower mRNA levels of selected target genes, which was accompanied by strongly increased serum aldosterone and plasma renin levels as well as by elevated sodium excretion. In the healthy heart, gene expression and the amount of collagen were unchanged despite MR levels being significantly reduced. After transverse aortic constriction, however, cardiac hypertrophy and progressive heart failure were attenuated by MR silencing, fibrosis was unaffected and mRNA levels of a subset of genes reduced. Taken together, we believe that this mouse model is a useful tool to investigate the role of the MR in pathophysiological processes. PMID:26605921

  14. Benefits of Renin-Angiotensin Blockade on Retinopathy in Type 1 Diabetes Vary With Glycemic Control

    PubMed Central

    Harindhanavudhi, Tasma; Mauer, Michael; Klein, Ronald; Zinman, Bernard; Sinaiko, Alan; Caramori, M. Luiza

    2011-01-01

    OBJECTIVE Optimal glycemic control slows diabetic retinopathy (DR) development and progression and is the standard of care for type 1 diabetes. However, these glycemic goals are difficult to achieve and sustain in clinical practice. The Renin Angiotensin System Study (RASS) showed that renin-angiotensin system (RAS) blockade can slow DR progression. In the current study, we evaluate whether glycemic control influenced the benefit of RAS blockade on DR progression in type 1 diabetic patients. RESEARCH DESIGN AND METHODS We used RASS data to analyze the relationships between two-steps or more DR progression and baseline glycemic levels in 223 normotensive, normoalbuminuric type 1 diabetic patients randomized to receive 5 years of enalapril or losartan compared with placebo. RESULTS A total of 147 of 223 patients (65.9%) had DR at baseline (47 of 74 patients [63.5%] in placebo and 100 of 149 patients [67.1%] in the combined treatment groups [P = 0.67]). Patients with two-steps or more DR progression had higher baseline A1C than those without progression (9.4 vs. 8.2%, P < 0.001). There was no beneficial effect of RAS blockade (P = 0.92) in patients with baseline A1C ≤7.5%. In contrast, 30 of 112 (27%) patients on the active treatment arms with A1C >7.5% had two-steps or more DR progression compared with 26 of 56 patients (46%) in the placebo group (P = 0.03). CONCLUSIONS RAS blockade reduces DR progression in normotensive, normoalbuminuric type 1 diabetic patients with A1C >7.5%. Whether this therapy could benefit patients with A1C ≤7.5% will require long-term studies of much larger cohorts. PMID:21715517

  15. Renin-angiotensin blockade resets podocyte epigenome through Kruppel-like Factor 4 and attenuates proteinuria.

    PubMed

    Hayashi, Kaori; Sasamura, Hiroyuki; Nakamura, Mari; Sakamaki, Yusuke; Azegami, Tatsuhiko; Oguchi, Hideyo; Tokuyama, Hirobumi; Wakino, Shu; Hayashi, Koichi; Itoh, Hiroshi

    2015-10-01

    Proteinuria is a central component of chronic kidney disease and an independent risk factor for cardiovascular disease. Kidney podocytes have an essential role as a filtration barrier against proteinuria. Kruppel-like Factor 4 (KLF4) is expressed in podocytes and decreased in glomerular diseases leading to methylation of the nephrin promoter, decreased nephrin expression and proteinuria. Treatment with an angiotensin receptor blocker (ARB) reduced methylation of the nephrin promoter in murine glomeruli of an adriamycin nephropathy model with recovery of KLF4 expression and a decrease in albuminuria. In podocyte-specific KLF4 knockout mice, the effect of ARB on albuminuria and the nephrin promoter methylation was attenuated. In cultured human podocytes, angiotensin II reduced KLF4 expression and caused methylation of the nephrin promoter with decreased nephrin expression. In patients, nephrin promoter methylation was increased in proteinuric kidney diseases with decreased KLF4 and nephrin expression. KLF4 expression in ARB-treated patients was higher in patients with than without ARB treatment. Thus, angiotensin II can modulate epigenetic regulation in podocytes and ARB inhibits these actions in part via KLF4 in proteinuric kidney diseases. This study provides a new concept that renin-angiotensin system blockade can exert therapeutic effects through epigenetic modulation of the kidney gene expression. PMID:26108068

  16. Renin-Angiotensin Activation and Oxidative Stress in Early Heart Failure with Preserved Ejection Fraction

    PubMed Central

    Negi, Smita I.; Jeong, Euy-Myoung; Shukrullah, Irfan; Veleder, Emir; Jones, Dean P.; Fan, Tai-Hwang M.; Varadarajan, Sudhahar; Danilov, Sergei M.; Fukai, Tohru; Dudley, Samuel C.

    2015-01-01

    Animal models have suggested a role of renin-angiotensin system (RAS) activation and subsequent cardiac oxidation in heart failure with preserved ejection fraction (HFpEF). Nevertheless, RAS blockade has failed to show efficacy in treatment of HFpEF. We evaluated the role of RAS activation and subsequent systemic oxidation in HFpEF. Oxidative stress markers were compared in 50 subjects with and without early HFpEF. Derivatives of reactive oxidative metabolites (DROMs), F2-isoprostanes (IsoPs), and ratios of oxidized to reduced glutathione (Eh GSH) and cysteine (Eh CyS) were measured. Angiotensin converting enzyme (ACE) levels and activity were measured. On univariate analysis, HFpEF was associated with male sex (p = 0.04), higher body mass index (BMI) (p = 0.003), less oxidized Eh CyS (p = 0.001), lower DROMs (p = 0.02), and lower IsoP (p = 0.03). Higher BMI (OR: 1.3; 95% CI: 1.1–1.6) and less oxidized Eh CyS (OR: 1.2; 95% CI: 1.1–1.4) maintained associations with HFpEF on multivariate analysis. Though ACE levels were higher in early HFpEF (OR: 1.09; 95% CI: 1.01–1.05), ACE activity was similar to that in controls. HFpEF is not associated with significant systemic RAS activation or oxidative stress. This may explain the failure of RAS inhibitors to alter outcomes in HFpEF. PMID:26504834

  17. Renin-Angiotensin-Aldosterone Genotype Influences Ventricular Remodeling in Infants with Single Ventricle

    PubMed Central

    Mital, Seema; Chung, Wendy K.; Colan, Steven D.; Sleeper, Lynn A.; Manlhiot, Cedric; Arrington, Cammon B.; Cnota, James F.; Graham, Eric M.; Mitchell, Michael E.; Goldmuntz, Elizabeth; Li, Jennifer S.; Levine, Jami C.; Lee, Teresa M.; Margossian, Renee; Hsu, Daphne T.

    2011-01-01

    Background We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function and response to enalapril in infants with single ventricle. Methods and Results Single ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with RAAS upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate (eGFR), and response to enalapril were compared between patients with ≥2 homozygous risk genotypes (high-risk), and those with <2 homozygous risk genotypes (low-risk) at two time points - before the superior-cavopulmonary-connection (pre-SCPC) and at age 14 months. Of 230 trial subjects, 154 were genotyped: 38 were high-risk, 116 were low-risk. Ventricular mass and volume were elevated in both groups pre-SCPC. Ventricular mass and volume decreased and eGFR increased after SCPC in the low-risk (p<0.05) but not the high-risk group. These responses were independent of enalapril treatment. Weight and height z-scores were lower at baseline and height remained lower in the high-risk group at 14 months especially in those receiving enalapril (p<0.05). Conclusions RAAS-upregulation genotypes were associated with failure of reverse remodeling after SCPC surgery, less improvement in renal function, and impaired somatic growth, the latter especially in patients receiving enalapril. RAAS genotype may identify a high-risk subgroup of single ventricle patients who fail to fully benefit from volume unloading surgery. Follow-up is warranted to assess longterm impact. Clinical Trial Registration Clinical Trials.gov Identifier NCT00113087 PMID:21576655

  18. Renin angiotensin system: A novel target for migraine prophylaxis.

    PubMed

    Nandha, Ruchika; Singh, Harpal

    2012-03-01

    Migraine constitutes 16% of primary headaches affecting 10-20% of general population according to International Headache Society. Till now nonsteroidalanti-inflammatory drugs (NSAIDS), opioids and triptans are the drugs being used for acute attack of migraine. Substances with proven efficacy for prevention include β-blockers, calcium channel blockers, antiepileptic drugs and antidepressants. All the already available drugs have certain limitations. Either they are unable to produce complete relief or 30-40% patients are no responders or drugs produce adverse effects. This necessitates the search for more efficacious and well-tolerated drugs. A new class of drugs like angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor antagonists have recently been studied for their off label use in prophylaxis of migraine. Studies, done so far, have shown results in favour of their clinical use because of the ability to reduce number of days with headache, number of days with migraine, hours with migraine, headache severity index, level of disability, improved Quality of life and decrease in consumption of specific or nonspecific analgesics. This article reviews the available evidence on the efficacy and safety of these drugs in prophylaxis of migraine and can give physician a direction to use these drugs for chronic migraineurs. Searches of pubmed, Cochrane database, Medscape, Google and clinicaltrial.org were made using terms like ACE inhibitors, angiotensin II receptor antagonists and migraine. Relevant journal articles were chosen to provide necessary information. PMID:22529467

  19. Gastrointestinal potassium binding-more than just lowering serum [K(+)]: patiromer, potassium balance, and the renin angiotensin aldosterone axis.

    PubMed

    Emmett, Michael; Mehta, Ankit

    2016-09-01

    Hyperkalemia limits the use of renin-angiotensin-aldosterone axis (RAAS) blockers in patients with renal insufficiency. This can be managed by efforts to increase kaliuresis and by gastrointestinal potassium binding with sodium polystyrene sulfonate, a relatively ineffective agent. Now with the availability of patiromer, RAAS blockers can be used more liberally. In addition, potassium reduction decreases aldosterone, which may be beneficial. Adverse nonepithelial aldosterone effects such as endothelial dysfunction and cardiac fibrosis may be ameliorated. PMID:27521112

  20. Serum levels of renin, angiotensin-converting enzyme and angiotensin II in patients treated by surgical excision, propranolol and captopril for problematic proliferating infantile haemangioma.

    PubMed

    Sulzberger, L; Baillie, R; Itinteang, T; de Jong, S; Marsh, R; Leadbitter, P; Tan, S T

    2016-03-01

    The role of the renin-angiotensin system (RAS) in the biology of infantile haemangioma (IH) and its accelerated involution induced by β-blockers was first proposed in 2010. This led to the first clinical trial in 2012 using low-dose captopril, an angiotensin-converting enzyme (ACE) inhibitor, demonstrating a similar response in these tumours. This study aimed to compare serial serum levels of the components of the RAS in patients before and after surgical excision, propranolol or captopril treatment for problematic proliferating IH. Patients with problematic proliferating IH underwent measurements of serum levels of plasma renin activity (PRA), ACE and angiotensin II (ATII) before, and 1-2 and 6 months following surgical excision, propranolol or captopril treatment. This study included 27 patients undergoing surgical excision (n = 8), propranolol (n = 11) and captopril (n = 8) treatment. Treatment with either surgical excision or propranolol resulted in significant decrease in the mean levels of PRA. Surgical excision or captopril treatment led to significant decline in the mean levels of ATII. All three treatment modalities had no significant effect on the mean levels of ACE. This study demonstrates the effect of surgical excision, propranolol and captopril treatment in lowering the levels of PRA and ATII, but not ACE, supporting a mechanistic role for the RAS in the biology of IH. PMID:26612192

  1. Clinical trials update from the European Society of Cardiology-Heart Failure meeting 2015: AUGMENT-HF, TITRATION, STOP-HF, HARMONIZE, LION HEART, MOOD-HF, and renin-angiotensin inhibitors in patients with heart and renal failure.

    PubMed

    Pellicori, Pierpaolo; Clark, Andrew L

    2015-09-01

    This article provides an overview on the key trials relevant to the pathophysiology, prevention, and treatment of heart failure (HF) presented at the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) annual meeting held in Seville, Spain in May 2015. Trials reported include AUGMENT-AF (myocardial injections of calcium-alginate hydrogel), a propensity score-matched study of renin-angiotensin system antagonists in patients with HF and severe renal dysfunction, HARMONIZE (sodium zirconium cyclosilicate used to bind potassium), TITRATION, comparing two regimes for introducing LCZ696, STOP-HF, a trial of intramyocardial stromal cell-derived factor-1, MOOD-HF (escitalopram for patients with heart failure and depression), and LION HEART, a trial of intermittent levosimendan therapy. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. PMID:26289928

  2. Hypovolemia in syncope and orthostatic intolerance role of the renin-angiotensin system

    NASA Technical Reports Server (NTRS)

    Jacob, G.; Robertson, D.; Mosqueda-Garcia, R.; Ertl, A. C.; Robertson, R. M.; Biaggioni, I.

    1997-01-01

    PURPOSE: Orthostatic intolerance is the cause of significant disability in otherwise normal patients. Orthostatic tachycardia is usually the dominant hemodynamic abnormality, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety and, in some cases, syncope. It is the most common disorder of blood pressure regulation after essential hypertension. There is a predilection for younger rather than older adults and for women more than men. Its cause is unknown; partial sympathetic denervation or hypovolemia has been proposed. METHODS AND MATERIALS: We tested the hypothesis that reduced plasma renin activity, perhaps from defects in sympathetic innervation of the kidney, could underlie a hypovolemia, giving rise to these clinical symptoms. Sixteen patients (14 female, 2 male) ranging in age from 16 to 44 years were studied. Patients were enrolled in the study if they had orthostatic intolerance, together with a raised upright plasma norepinephrine (> or = 600 pg/mL). Patients underwent a battery of autonomic tests and biochemical determinations. RESULTS: There was a strong positive correlation between the blood volume and plasma renin activity (r = 0.84, P = 0.001). The tachycardic response to upright posture correlated with the severity of the hypovolemia. There was also a correlation between the plasma renin activity measured in these patients and their concomitant plasma aldosterone level. CONCLUSIONS: Hypovolemia occurs commonly in orthostatic intolerance. It is accompanied by an inappropriately low level of plasma renin activity. The degree of abnormality of blood volume correlates closely with the degree of abnormality in plasma renin activity. Taken together, these observations suggest that reduced plasma renin activity may be an important pathophysiologic component of the syndrome of orthostatic intolerance.

  3. 25-Hydroxyvitamin D status, arterial stiffness and the renin-angiotensin system in healthy humans.

    PubMed

    Abdi-Ali, Ahmed; Nicholl, David D M; Hemmelgarn, Brenda R; MacRae, Jennifer M; Sola, Darlene Y; Ahmed, Sofia B

    2014-01-01

    Vitamin D deficiency is associated with increased arterial stiffness. We sought to clarify the influence of vitamin D in modulating angiotensin II-dependent arterial stiffness. Thirty-six healthy subjects (33 ± 2 years, 67% female, mean 25-hydroxyvitamin D 69 ± 4 nmol/L) were studied in high salt balance. Arterial stiffness, expressed as brachial pulse wave velocity (bPWV) and aortic augmentation index (AIx), was measured by tonometry at baseline and in response to angiotensin II infusion (3 ng/kg/min × 30 min then 6 ng/kg/min × 30 min). The primary outcome was change in bPWV after an angiotensin II challenge. Results were analyzed according to plasma 25-hydroxyvitamin D status: deficient (<50 nmol/L) and sufficient (≥ 50 nmol/L). There were no differences in baseline arterial stiffness between vitamin D deficient (25-hydroxyvitamin D 40 ± 2 nmol/L) and sufficient (25-hydroxyvitamin D 80 ± 4 nmol/L) groups. Compared with sufficient vitamin D status, vitamin D deficiency was associated with a decreased arterial response to angiotensin II challenge (Δbrachial pulse wave velocity: 0.48 ± 0.44 m/s versus 1.95 ± 0.22 m/s, p=0.004; Δaortic augmentation index: 9.4 ± 3.4% versus 14.2 ± 2.7%, p=0.3), which persisted for brachial pulse wave velocity response after adjustment for covariates (p=0.03). Vitamin D deficiency is associated with increased arterial stiffness in healthy humans, possibly through an angiotensin II-dependent mechanism. PMID:24164282

  4. Obesity-induced hypertension develops in young rats independently of the renin-angiotensin-aldosterone system.

    PubMed

    Smith, Anita D; Brands, Michael W; Wang, Mong-Heng; Dorrance, Anne M

    2006-03-01

    A correlation exists between obesity and hypertension. In the currently available models of diet-induced obesity, the treatment of rats with a high fat (HF) diet does not begin until adulthood. Our aim was to develop and characterize a model of pre-pubescent obesity-induced hypertension. Male Sprague-Dawley rats were fed a HF diet (35% fat) for 10 weeks, beginning at age 3 weeks. Blood pressure was measured by tail-cuff, and a terminal blood sample was obtained to measure fasting blood glucose, insulin, plasma renin, aldosterone, thiobarbitutic acid reactive substances (TBARS), and free 8-isoprostanes levels. The vascular reactivity in the aorta was assessed using a myograph. Blood pressure was increased in rats fed the HF diet (HF, 161 +/- 2 mm Hg vs. control, 137 +/- 2 mm Hg, P < 0.05). Blood glucose (HF, 155 +/- 4 mg/dL vs. control, 123 +/- 5 mg/dL, P < 0.05), insulin (HF, 232 +/- 63 pM vs. control, 60 +/- 11 pM, P < 0.05), TBARS (expressed as nM of malondialdehyde [MDA]/ml [HF, 1.8 +/- 0.37 nM MDA/ml vs. control 1.05 +/- 0.09 nM MDA/ml, P < 0.05]), and free 8-isoprostanes (HF, 229 +/- 68 pg/ml vs. control, 112 +/- 9 pg/ml, P < 0.05) levels were elevated in the HF diet group. Interestingly, plasma renin and aldosterone levels were not different between the groups. The maximum vasoconstriction to phenylephrine (10(-4) M) was increased in the HF diet group (HF, 26.1 +/- 1.5 mN vs. control 22.3 +/- 1.2 mN, P < 0.05). In conclusion, pre-pubescent rats become hypertensive and have increased oxidative stress and enhanced vasoconstriction when fed a HF diet. Surprisingly, this occurs without the increase in renin or aldosterone levels seen in the adult models of diet-induced obesity. PMID:16514174

  5. Intraventricular haemorrhage and the renin-angiotensin-aldosterone system in very low birthweight infants.

    PubMed

    Leslie, G I; Philips, J B; Cassady, G

    1989-11-01

    Blood volume, plasma renin activity (PRA) and urine aldosterone excretion (UAE) were measured in ten very low birthweight infants who had a Grade 3 or 4 intraventricular haemorrhage (IVH) during the first 2 days after birth. Mean (range) birthweight was 950 (630-1500) g and gestational age was 27 (23-31) weeks. Nine infants were receiving assisted ventilation and one was breathing spontaneously. Eight IVH occurred on the first postnatal day and two on the second; seven were symptomatic and three asymptomatic. PRA was significantly higher than control values on Day 1 only; median 244 (range 91-654) ng/ml per h vs. 64 (4-259) ng/ml per h (P less than 0.01). Infants with symptomatic IVH in the preceding 8 h (n = 6) all had PRA greater than 300 ng/ml per h; none of these infants had received transfusions or volume expansion between IVH and PRA measurement. PRA was less than 100 ng/ml per h in the three infants with asymptomatic IVH and one infant with greater than 24 h interval between IVH and PRA measurement; three of these four had received transfusions prior to PRA measurement. UAE was not significantly different from control values on either Day 1 or Day 2. Blood volume at 22 +/- 3 h postnatal age ranged from 75 to 107 ml/kg. There was an inverse logarithmic correlation between PRA and blood volume (r = 0.883; P less than 0.005), with PRA values exceeding 300 ng/ml per h when blood volume was less than 90 ml/kg. UAE did not correlate with either PRA or blood volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2591335

  6. Regulation of hypothalamic renin-angiotensin system and oxidative stress by aldosterone

    PubMed Central

    Huang, Bing S; Zheng, Hong; Tan, Junhui; Patel, Kaushik P; Leenen, Frans HH

    2011-01-01

    In rats with salt-induced hypertension or post myocardial infarction (MI), AT1 receptor (AT1R) densities and oxidative stress increase and neuronal nitric oxide synthase (nNOS) levels decrease in the paraventricular nucleus (PVN). The present study was designed to determine whether these changes may depend on activation of the aldosterone – “ouabain” neuromodulatory pathway. After intracerebroventricular (icv) infusion of aldosterone (20ng/h) for 14 days, blood pressure (BP) and heart rate (HR) were recorded in conscious Wistar rats, and mRNA and protein for nNOS, endothelial NOS (eNOS), AT1R and NADPH oxidase subunits were assessed in brain tissue. BP and HR were significantly increased by aldosterone. Aldosterone significantly increased mRNA and protein of AT1R, P22phox, P47phox, P67phox and Nox2, and decreased nNOS but not eNOS mRNA and protein in the PVN, and increased angiotensin converting enzyme (ACE) and AT1R binding densities in the PVN and SON. The increases in BP and HR as well as changes in mRNA, proteins and ACE and AT1R binding densities were all largely prevented by concomitant icv infusion of Digibind (to bind “ouabain”) or benzamil (to block presumably epithelial sodium channels). These data indicate that aldosterone via “ouabain” increases in the PVN ACE, AT1R and oxidative stress but decreases nNOS, and suggest that endogenous aldosterone may cause this similar pattern of changes observed in salt sensitive hypertension and heart failure post MI. PMID:21824999

  7. Renin, angiotensins, and angiotensin-converting enzyme in neuroblastoma cells: evidence for intracellular formation of angiotensins.

    PubMed Central

    Okamura, T; Clemens, D L; Inagami, T

    1981-01-01

    The mechanism of formation of various peptide hormones in neuronal cells in the brain is not clear. The question of whether brain angiotensin II is formed by an extracellular mechanism as in the peripheral system or by an intracellular mechanism can be answered by using cloned cells in culture. We have screened several neuroblastoma cell lines of rat and mouse origin and found at least three cell lines that contain renin (EC 3.4.99.19), angiotensin-converting enzyme (dipeptidyl carboxypeptidase; peptidyldipeptide hydrolase, EC 3.4.15.1), and angiotensins I and II. This finding was interpreted to indicate that in these cells angiotensin formation takes place by an intracellular mechanism, in contrast to the extracellular mechanism well known to occur in plasma. This study also demonstrates the existence of viable and cloned cell lines that produce renin. PMID:6273896

  8. Urinary Angiotensinogen as a Potential Biomarker of Intrarenal Renin-angiotensin System Activity in Chinese Patients with Chronic Kidney Disease.

    PubMed

    Xu, Z; Xu, B; Xu, C

    2014-09-01

    Urinary angiotensinogen (AGT) mainly derives from the AGT produced in the proximal tubular cells. Evidence exists that supports the correlation between urinary AGT and circulating AGT. Previous studies measured urinary AGT by radioimmunoassay which is not convenient for clinical practice. In this study, we utilized an enzyme-linked immunosorbent assay (ELISA) based method to quantify urinary AGT. We analysed the relationship between urinary AGT and intrarenal angiotensin II (Ang II) activity in patients with chronic kidney disease (CKD). Urinary and plasma renin activity, AGT, Ang II and aldosterone were measured by radioimmunoassay or ELISA in 128 CKD patients. Furthermore, expression levels of intrarenal renin, AGT, Ang II and Ang II receptor were examined by immunohistochemistry staining (IHCS) in 72 CKD patients undergoing renal biopsy. Average urinary AGT was 2.02 ± 0.55 ng/(mg Cr). Hypertension, urinary protein, urinary Ang II and urinary Type IV collagen (Col IV) positively correlated with urinary AGT. Estimated glomerular filtration rate (eGFR), urinary sodium and serum AGT negatively correlated with urinary AGT. Multiple regression analysis indicated that low serum AGT, high urinary protein, urinary Ang II and urinary Col IV correlated significantly with high urinary AGT. Moreover, we observed positive correlation between urinary AGT and positive IHCS area of AGT, Ang II and Ang II Type 1 receptor inrenal tissue. These data suggest that urinary AGT might be a potential biomarker of intrarenal angiotensin II activity in CKD patients. PMID:25781279

  9. Urinary Angiotensinogen as a Potential Biomarker of Intrarenal Renin-angiotensin System Activity in Chinese Patients with Chronic Kidney Disease

    PubMed Central

    Xu, Z; Xu, B; Xu, C

    2014-01-01

    ABSTRACT Urinary angiotensinogen (AGT) mainly derives from the AGT produced in the proximal tubular cells. Evidence exists that support the correlation between urinary AGT and circulating AGT. Previous studies measured urinary AGT by radioimmunoassay which is not convenient for clinical practice. In this study, we utilized an enzyme-linked immunosorbent assay (ELISA) based method to quantify urinary AGT. We analysed the relationship between urinary AGT and intrarenal angiotensin II (Ang II) activity in patients with chronic kidney disease (CKD). Urinary and plasma renin activity, AGT, Ang II and aldosterone were measured by radioimmunoassay or ELISA in 128 CKD patients. Furthermore, expression levels of intrarenal renin, AGT, Ang II and Ang II receptor were examined by immunohistochemistry staining (IHCS) in 72 CKD patients undergoing renal biopsy. Average urinary AGT was 2.02 ± 0.55 ng/(mg Cr). Hypertension, urinary protein, urinary Ang II and urinary Type IV collagen (Col IV) positively correlated with urinary AGT. Estimated glomerular filtration rate (eGFR), urinary sodium and serum AGT negatively correlated with urinary AGT. Multiple regression analysis indicated that low serum AGT, high urinary protein, urinary Ang II and urinary Col IV correlated significantly with high urinary AGT. Moreover, we observed positive correlation between urinary AGT and positive IHCS area of AGT, Ang II and Ang II Type 1 receptor in renal tissue. These data suggest that urinary AGT might be a potential biomarker of intrarenal angiotensin II activity in CKD patients. PMID:25781279

  10. Role of the renin-angiotensin system in the regulation of intestinal blood flow and sympathetic neurotransmission

    SciTech Connect

    Suvannapura, A.

    1988-01-01

    The aims of the present studies were (1) to determine if endogenous angiotensin II (Ang II) plays a role in the local control of mesenteric blood flow (MBF) following volume depletion in anesthetized dogs, and (2) to investigate the mechanism(s) of actions of Ang II on the facilitation of sympathetic neurotransmission in the rate jejunum. To investigate the role of endogenous Ang II in the control of MBF, a dose of an antagonist of Ang II, saralasin, that has effects mainly localized to the mesenteric circulation was determined. The data demonstrated that blockage of actions of Ang II in the mesenteric circulation resulted in a decrease in intestinal vasoconstriction which occurred following acute hypotensive hemorrhage. The effect of Ang II on the uptake and release of norepinephrine from sympathetic nerve endings in the rat jejunum was investigated. The uptake of norepinephrine in rat jejunum was determined by incubating jejunal slices in Krebs buffer containing 0.01 {mu}M {sup 3}H-norepinephrine. The accumulation of label in the tissue after 10 min incubation was determined by liquid scintillation spectrometry. Intracellular uptake of {sup 3}H-norepinephrine was calculated and shown to be an active process.

  11. Renin-angiotensin-aldosterone system and electrolyte metabolism in rat blood after flight aboard Cosmos-1129 biosatellite

    SciTech Connect

    Kvetnansky, R.; Tigranyan, R.A.; Jindra, A.; Viting, T.A.

    1982-08-01

    Blood plasma aldosterone concentration and renin activity were studied in rats flow in space on the Cosmos 1129 satellite using radioimmunoassay techniques. Immediately after the flight, the animals presented significant decreases in plasma renin activity, as compared to rats in the vivarium control and animals in the synchronous experiment. R. J.

  12. Responses of sympathoadrenal and renin angiotensin systems to stress stimuli in humans during real and simulated microgravity.

    PubMed

    Kvetnansky, R; Koska, J; Ksinantova, L; Noskov, V B; Blazicek, P; Marko, M; Macho, L; Grigoriev, A I; Vigas, M

    2002-07-01

    Changes of plasma hormone levels were investigated in human subjects after exposure to physical exercise (WL) and insulin induced hypoglycemia (ITT) during space flight or after head down bed rest (HDBR). Exaggerated responses of plasma epinephrine (EPI), norepinephrine (NE) and aldosterone (ALD) were observed after WL during space flight as compared to preflight response. Hypoglycemia during space flight induced attenuated responses of EPI, NE and augmented response of ALD. Exposure to WL during HDBR was followed by significantly exaggerated responses of plasma EPI, NE, ALD, PRA and cortisol. In HDBR the responses of plasma EPI, NE and cortisol were reduced and PRA response was exaggerated during ITT. These data indicate that hormonal responses to ITT and WL are similar at real and simulated microgravity. PMID:14977002

  13. Dual Tank Fuel System

    DOEpatents

    Wagner, Richard William; Burkhard, James Frank; Dauer, Kenneth John

    1999-11-16

    A dual tank fuel system has primary and secondary fuel tanks, with the primary tank including a filler pipe to receive fuel and a discharge line to deliver fuel to an engine, and with a balance pipe interconnecting the primary tank and the secondary tank. The balance pipe opens close to the bottom of each tank to direct fuel from the primary tank to the secondary tank as the primary tank is filled, and to direct fuel from the secondary tank to the primary tank as fuel is discharged from the primary tank through the discharge line. A vent line has branches connected to each tank to direct fuel vapor from the tanks as the tanks are filled, and to admit air to the tanks as fuel is delivered to the engine.

  14. Calibrating the impact of dual RAAS blockade on the heart and the kidney - balancing risks and benefits.

    PubMed

    Ziff, O J; Covic, A; Goldsmith, D

    2016-07-01

    Overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in the pathophysiology of heart failure (HF) and chronic kidney disease (CKD). RAAS antagonists can significantly improve clinical outcomes, but monotherapy blocks but one step of the RAAS and can be bypassed through compensatory mechanisms. Providing more complete RAAS blockade by deploying drugs with complementary actions seemed logical - hence the practice of using dual (or triple) RAAS inhibitors. However, RAAS antagonists also exhibit dose-limiting side effects, including acute kidney injury, hyperkalaemia and hypotension, which blunt their overall effectiveness. Despite achieving better RAAS blockade, several trials failed to show clinical outcome improvements. Patients with concomitant CKD and HF (cardiorenal syndrome) are at the greatest risk of these adverse events and therefore the least able to benefit, yet they also have the worst prognosis. This paradox, where those most in need have fewest therapeutic options, poses three questions which are the focus of this review: whether (i) novel therapies that prevent adverse effects can restore therapeutic benefits to patients who would otherwise be RAAS-therapy intolerant, (ii) there are any validated alternatives to their use and (iii) newer approaches to the detection of fluid congestion are ready for implementation. PMID:27278080

  15. Prevention of atrial fibrillation with renin-angiotensin system inhibitors on essential hypertensive patients: a meta-analysis of randomized controlled trials

    PubMed Central

    Zhao, Di; Wang, Ze-Mu; Wang, Lian-Sheng

    2015-01-01

    Abstract We aimed to investigate the effectiveness and safety of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on preventing atrial fibrillation in essential hypertensive patients. Systematic literature retrieval was carried out to obtain randomized controlled trials on the effects of ACEI/ARBs on essential hypertensive patients before December, 2013. Data extraction and quality evaluation were performed. Meta-analysis was performed by Review Manager 5.2.3. Ten high quality studies (11 articles) with a total of 42,892 patients (20,491 patients in the ACEI/ARBs group and 22,401 patients in the β-blocker or the calcium antagonist group) met the inclusion criteria and were included in the meta-analysis. The results showed that ACEI/ARBs reduced the incidence of atrial fibrillation (AF) recurrence compared to calcium antagonists (RR = 0.48; 95%CI, 0.40-0.58; P<0.00001) or β-blockers (RR = 0.39; 95%CI, 0.20-0.74; P = 0.005) in long-term follow-up, respectively. Furthermore, ACEI/ARBs reduced the incidence of congestive heart failure (RR = 0.86; 95%CI, 0.77-0.96; P = 0.007). However, no significant effects were observed on the incidence of new AF, cardiac death, myocardial infarction, and stroke. Our results suggest that ACEI/ARBs may reduce the incidence of AF recurrence and congestive heart failure, with fewer serious adverse effects. PMID:26668582

  16. Dual schedule ignition system

    SciTech Connect

    Remmers, G.M.

    1991-08-13

    This patent describes a time base generator for an ignition system of an internal combustion engine having a crankshaft. It comprises an encoder disk which rotates synchronously with the crankshaft of the engine and includes a plurality of timing features of a predetermined width which are at fixed locations relative to the crankshaft and includes at least one synchronizing feature which is at a fixed location relative to the crankshaft and to at least one of the timing features; detector means for detecting the presence or absence of the timing features and the at least one synchronizing feature and for generating digital signals representative thereof; and pulse generating means for generating a first pulse train from the trailing edge of each timing feature represented in the digital signal and for generating a second pulse train from the leading edge of each timing feature represented in the digital signal whereby the pulses of the second pulse train are advanced from the pulses of the first pulse train by a predetermined angular rotation of the crankshaft determined by the width of each timing feature.

  17. Dual mode nuclear rocket system applications.

    NASA Technical Reports Server (NTRS)

    Boretz, J. E.; Bell, J. M.; Plebuch, R. K.; Priest, C. C.

    1972-01-01

    Mission areas where the dual-mode nuclear rocket system is superior to nondual-mode systems are demonstrated. It is shown that the dual-mode system is competitive with the nondual-mode system even for those specific missions and particular payload configurations where it does not have a clear-cut advantage.

  18. Dual pressure displacement control system

    SciTech Connect

    Louis, J.E.; Klocke, C.C.

    1988-02-02

    This patent describes a dual pressure servo control system for a variable displacement hydraulic unit having displacement setting means positioned by a hydraulic servo mechanism. The hydraulic unit is provided with main loop lines at least one of which is capable of being subjected to high main loop pressure during operation of the hydraulic unit, a control line including a displacement control valve providing a controlled flow of fluid under pressure to the servo mechanism, and a source of fluid under pressure for the control line comprising a low pressure source connected to the control line through a check valve and high pressure source comprising of a high pressure control line connected to the control line downstream of the check valve. The high pressure control line includes a flow restriction limiting flow to the control line means and generating a significant flow induced pressure drop in the high pressure control line once movement in the servo mechanism is initiated.

  19. Apprenticeships in Germany: Modernising the Dual System

    ERIC Educational Resources Information Center

    Deissinger, Thomas; Hellwig, Silke

    2005-01-01

    Purpose ? This paper proposes to investigate the modernisation of the German Dual System for apprenticeships. Design/methodology/approach ? The paper looks at the history of the development of the Dual System and looks at the challenges it faces today. Findings ? The paper finds that Germany, with its long-standing tradition of dual…

  20. Dual spectra well logging system

    SciTech Connect

    Nussbaum, T.W.

    1982-09-07

    A dual spectra well logging system includes a well logging tool which is adapted to pass through a bore hole in an earth formation. The well logging tool includes at least two sensors which sense at least one condition of the earth formation and provides corresponding pulse signals. A circuit connected to the sensors provides a combined pulse signal wherein the pulses of the pulse signal from one sensor has one polarity and the pulses of the pulse signal from the other sensor has pulses of an opposite polarity. A circuit applies the combined pulse signal to a well logging cable which conducts the combined pulse signal to the surface of the earth formation. Surface apparatus includes a network connected to the cable which provides control signals in accordance with the polarity of the pulses in the combined pulse signal. A network connected to the cable inverts the combined pulse signal and provides a combined pulse signal and an inverted combined pulse signal. A first switching network receiving the combined pulse signal passes the pulses derived from the pulses of the one polarity in acccordance with the control signals to provide a first pulse signal while a second switching network receiving the inverted combined pulse signal passes the pulses derived from the pulses of the opposite polarity in accordance with the control signals to provide a second pulse signal. An output network processes the two pulse signals to provide an indication of the earth's condition in accordance with the processed pulse signals.

  1. Lessons from the German Dual System

    ERIC Educational Resources Information Center

    Hyslop, Alisha

    2012-01-01

    Most average Americans know more about the food in Germany than the education structure, but its emphasis on a dual system of education and training has a number of insights to offer to American career and technical educators. This author had the opportunity to observe firsthand the vocational education and training system, or "VET" system as it…

  2. Nonlinear control for dual quaternion systems

    NASA Astrophysics Data System (ADS)

    Price, William D.

    The motion of rigid bodies includes three degrees of freedom (DOF) for rotation, generally referred to as roll, pitch and yaw, and 3 DOF for translation, generally described as motion along the x, y and z axis, for a total of 6 DOF. Many complex mechanical systems exhibit this type of motion, with constraints, such as complex humanoid robotic systems, multiple ground vehicles, unmanned aerial vehicles (UAVs), multiple spacecraft vehicles, and even quantum mechanical systems. These motions historically have been analyzed independently, with separate control algorithms being developed for rotation and translation. The goal of this research is to study the full 6 DOF of rigid body motion together, developing control algorithms that will affect both rotation and translation simultaneously. This will prove especially beneficial in complex systems in the aerospace and robotics area where translational motion and rotational motion are highly coupled, such as when spacecraft have body fixed thrusters. A novel mathematical system known as dual quaternions provide an efficient method for mathematically modeling rigid body transformations, expressing both rotation and translation. Dual quaternions can be viewed as a representation of the special Euclidean group SE(3). An eight dimensional representation of screw theory (combining dual numbers with traditional quaternions), dual quaternions allow for the development of control techniques for 6 DOF motion simultaneously. In this work variable structure nonlinear control methods are developed for dual quaternion systems. These techniques include use of sliding mode control. In particular, sliding mode methods are developed for use in dual quaternion systems with unknown control direction. This method, referred to as self-reconfigurable control, is based on the creation of multiple equilibrium surfaces for the system in the extended state space. Also in this work, the control problem for a class of driftless nonlinear systems is

  3. PERFORMANCE EVALUATION OF THE DUAL DIGESTION SYSTEM

    EPA Science Inventory

    The dual digestion system (DDS) was developed to provide stabilized, pathogen free sludge. DDS consists of a 1-day detention time, pure-oxygen, covered aerobic digester (Step I) followed by an 8-day detention time anaerobic reactor. The temperature in the Step I digester is contr...

  4. 14 CFR 25.399 - Dual control system.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure Control Surface and System Loads § 25.399 Dual control system. (a) Each dual control system must be designed for the pilots operating in opposition, using... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Dual control system. 25.399 Section...

  5. 14 CFR 23.399 - Dual control system.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Structure Control Surface and System Loads § 23.399 Dual control system. (a) Each dual control system must be designed to withstand the force... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Dual control system. 23.399 Section...

  6. Anthropomorphic dual-arm space telemanipulation system

    NASA Technical Reports Server (NTRS)

    Jau, Bruno M.

    1990-01-01

    Dexterous dual-arm manipulations are feasible with the system described and illustrated in the paper. The structure is based on an extensible host arm that carries the dual-arm robot which comprises two 7-DOF arms each of which includes a hand with a thumb and three fingers with 4 DOF each. Joint compliance can be stiffened to any level, and the operator uses arm harnesses and gloves to utilize the robotics in an anthropomorphic fashion. The configuration eliminates coordinate-transformation computations, and the system is found to achieve a control-frequency rate of 1000 Hz for its direct man/machine interfaces based on fiber-optic cables. The electronics control for the system utilizes a sensory system consisting of force, position, and compliance sensors. The robotics system is expected to be a user-friendly device that permits assembly, repair, tethering, and other complex mechanical operations.

  7. Combined Therapy with Renin-Angiotensin System and Calcium Channel Blockers in Type 2 Diabetic Hypertensive Patients with Proteinuria: Effects on Soluble TWEAK, PTX3, and Flow-Mediated Dilation

    PubMed Central

    Yilmaz, Mahmut Ilker; Carrero, Juan Jesús; Martín-Ventura, Jose Luis; Sonmez, Alper; Saglam, Mutlu; Celik, Turgay; Yaman, Halil; Yenicesu, Mujdat; Eyileten, Tayfun; Moreno, Juan Antonio; Egido, Jesús

    2010-01-01

    Background and objectives: Soluble TNF-like weak inducer of apoptosis (sTWEAK) and long pentraxin-3 (PTX3) concentrations have been associated with endothelial function in patients with chronic kidney disease (CKD). This study tested the hypothesis that the improvement in endothelial function after initiation of angiotensin II receptor blocker (valsartan), calcium channel blocker (amlodipine) therapy, or a combination of both is directly linked to the normalization of sTWEAK and PTX3. Design, setting, participants, & measurements: One-hundred-eight diabetic CKD stage I patients with hypertension (56% men, 46.7 ± 5.3 years) were allocated to a 12-week intervention with amlodipine (10 mg/d), valsartan (160 mg/d), or their combination. Plasma levels of sTWEAK, PTX3, and flow-mediated dilation (FMD) were studied during the interventions. Results: All treatment strategies effectively increased FMD and reduced proteinuria, confirming a more prone reduction with the combined therapy. These improvements were followed by significant PTX3 reductions. Valsartan alone and in combination with amlodipine achieved significant incremental raises in sTWEAK plasma levels. More importantly, the changes observed in sTWEAK (β = 0.25, P = 0.006) or PTX3 (β = −0.24, P = 0.007) plasma levels were independently associated with the improvement in ultrasonographically measured FMD. Conclusions: This study shows that treatment with antihypertensive drugs improves FMD and normalizes proteinuria, PTX3, and sTWEAK in diabetic CKD stage I patients with hypertension. The improvement in FMD was independently associated with PTX3 and sTWEAK normalization. Two surrogate biomarkers of endothelial function are therefore identified with potential as therapeutic targets. The study was registered in clinicaltrials.gov as NCT00921570. PMID:20430947

  8. Dietary peptides from the non-digestible fraction of Phaseolus vulgaris L. decrease angiotensin II-dependent proliferation in HCT116 human colorectal cancer cells through the blockade of the renin-angiotensin system.

    PubMed

    Luna-Vital, Diego A; Liang, Katie; González de Mejía, Elvira; Loarca-Piña, Guadalupe

    2016-05-18

    This study aimed to determine the ability of peptides present in the non-digestible fraction (NDF) of common beans to decrease angiotensin II (AngII) through the blockade of RAS and its effect on the proliferation of HCT116 human colorectal cancer cells. Pure synthesized peptides GLTSK and GEGSGA and the peptide fractions (PF) of cultivars Azufrado Higuera and Bayo Madero were used. The cells were pretreated with pure peptides, PF or AGT at their IC50 or IC25 values, in comparison with the simultaneous treatment of peptides and AGT. For western blot and microscopy analysis, 100 μM and 0.5 mg mL(-1) were used for pure peptides and PF treatments, respectively. According to the ELISA tests, GLTSK and GEGSGA decreased (p < 0.05) the conversion rate of AGT to angiotensin I (AngI) by 38 and 28%, respectively. All the peptides tested reduced (p < 0.05) the conversion rate of AngI to AngII from 38 to 50%. When the cells were pretreated with both pure peptides and PF before exposure to AGT, the effectiveness inhibiting cell proliferation was higher than the simultaneous treatment suggesting their preventive effects. GLTSK and GEGSGA interacted with the catalytic site of renin, the angiotensin-I converting enzyme, and the AngII receptor, mainly through hydrogen bonds, polar, hydrophobic and cation-π interactions according to molecular docking. Through confocal microscopy, it was determined that GLTSK and GEGSGA caused the decrease (p < 0.05) of AngII-dependent STAT3 nuclear activation in HCT116 cells by 66 and 23%, respectively. The results suggest that peptides present in the common bean NDF could potentially ameliorate the effects of RAS overexpression in colorectal cancer. PMID:27156533

  9. Fixed-Dose Combinations of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in the Treatment of Hypertension: A Comparison of Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors.

    PubMed

    Hsiao, Fu-Chih; Tung, Ying-Chang; Chou, Shing-Hsien; Wu, Lung-Sheng; Lin, Chia-Pin; Wang, Chun-Li; Lin, Yu-Sheng; Chang, Chee-Jen; Chu, Pao-Hsien

    2015-12-01

    Fixed-dose combinations (FDCs) of different regimens are recommended in guidelines for the treatment of hypertension. However, clinical studies comparing FDCs of angiotensin receptor blocker (ARB)/calcium channel blocker (CCB) and angiotensin-converting enzyme inhibitor (ACE inhibitor)/CCB in hypertensive patients are lacking.Using a propensity score matching of 4:1 ratio, this retrospective claims database study compared 2 FDC regimens, ARB/CCB and ACE inhibitor/CCB, in treating hypertensive patients with no known atherosclerotic cardiovascular disease. All patients were followed for at least 3 years or until the development of major adverse cardiovascular events (MACEs) during the study period. In addition, the effect of medication adherence on clinical outcomes was evaluated in subgroup analysis based on different portions of days covered.There was no significant difference in MACE-free survival (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 0.98-1.50; P = 0.08) and survival free from hospitalization for heart failure (HR: 1.15; 95% CI: 082-1.61; P = 0.431), new diagnosis of chronic kidney disease (HR: 0.98; 95% CI: 071-1.36; P = 0.906), and initiation of dialysis (HR: 0.99; 95% CI: 050-1.92; P = 0.965) between the 2 study groups. The results remained the same within each subgroup of patients with different adherence statuses.ARBs in FDC regimens with CCBs in the present study were shown to be as effective as ACE inhibitors at reducing the risks of MACEs, hospitalization for heart failure, new diagnosis of chronic kidney disease, and new initiation of dialysis in hypertensive patients, regardless of the medication adherence status. PMID:26705234

  10. Satellite dual antenna pointing system

    NASA Technical Reports Server (NTRS)

    Keigler, John E. (Inventor); Hartshorne, Frank A. (Inventor)

    1986-01-01

    A satellite antenna pointing system for separately pointing separated transmit and receive high gain antenna systems includes means for separately and sequentially applying a beacon signal to the transmit and receive antenna systems and a broad beam width antenna which has a coverage area greater than the overall coverage region of the spot beam antenna systems. The system includes ground stations located at or near the periphery of the overall coverage region adapted to receive these beacon signals. At a central control station these beacon signals are compared to provide first signals proportional to the ratio of said beacon signals received from said transmit antenna system and said broad beam width antenna and second signals proportional to the ratio of said beacon signals received from said satellite receive antenna system and said broad beam width antenna. The central station generates from said first signals transmit antenna control signals which are sent to the satellite to control the orientation of said transmit antenna system. Likewise, the central control station generates from the second signals receiver antenna control signals which are applied to the satellite to control the orientation of the satellite receive antenna system.

  11. Dual-Laser Schlieren System

    NASA Technical Reports Server (NTRS)

    Owen, R. B.; Wintherow, W. K.

    1982-01-01

    Proposed schlieren system uses two lasers and two knife edges to simultaneously view perpendicular refractive-index gradients in a test volume. It is improvement over conventional schlieren systems, which monitor gradient along only one axis. Although originally developed to monitor materials-processing experiments in space, it should find application wherever there is need to study two-dimensional temperature, pressure, concentration or other gradients related to index of refraction.

  12. Effects of the cyclooxygenase inhibiting nitric oxide donator naproxcinod versus naproxen on systemic blood pressure in patients with osteoarthritis.

    PubMed

    White, William B; Schnitzer, Thomas J; Fleming, Rosanna; Duquesroix, Brigitte; Beekman, Maarten

    2009-09-15

    Traditional nonsteroidal anti-inflammatory drugs are associated with the destabilization of blood pressure (BP) control, particularly in hypertensive patients treated with blockers of the renin-angiotensin system. To assess the potential impact of nitric oxide donation, the effects of naproxcinod with naproxen and placebo on changes in BP were compared in a randomized clinical trial of 916 patients with osteoarthritis after 13 weeks of therapy. In addition, the effects of naproxcinod versus naproxen and placebo on systolic BP in patients with hypertension treated with renin-angiotensin system blockers were evaluated. Naproxcinod 750 mg twice daily reduced systolic BP compared to naproxen 500 mg twice daily (p <0.02). The 2 doses of naproxcinod showed reductions from baseline in diastolic BP relative to naproxen (p <0.04) and similar changes compared to placebo. In 207 patients with hypertension treated with renin-angiotensin-blocking agents alone or with diuretics, the difference in mean change from baseline in systolic BP between naproxen 500 mg and naproxcinod 750 mg was 6.5 mm Hg in favor of naproxcinod (p <0.02). The proportion of patients in the overall population with systolic BP increases > or =10 mm Hg was greater with naproxen 500 mg (22%) compared to naproxcinod 750 mg (14%, p = 0.04), naproxcinod 375 mg (14%, p = 0.055), and placebo (15.6%, p = 0.155). In conclusion, naproxcinod did not induce elevations of BP seen with naproxen, and it had similar effects on BP to that of placebo in patients with osteoarthritis. PMID:19733721

  13. Dual liquid and gas chromatograph system

    DOEpatents

    Gay, Don D.

    1985-01-01

    A chromatographic system that utilizes one detection system for gas chromatographic and micro-liquid chromatographic determinations. The detection system is a direct-current, atmospheric-pressure, helium plasma emission spectrometer. The detector utilizes a non-transparent plasma source unit which contains the plasma region and two side-arms which receive effluents from the micro-liquid chromatograph and the gas chromatograph. The dual nature of this chromatographic system offers: (1) extreme flexibility in the samples to be examined; (2) extremely low sensitivity; (3) element selectivity; (4) long-term stability; (5) direct correlation of data from the liquid and gas samples; (6) simpler operation than with individual liquid and gas chromatographs, each with different detection systems; and (7) cheaper than a commercial liquid chromatograph and a gas chromatograph.

  14. Dual liquid and gas chromatograph system

    DOEpatents

    Gay, D.D.

    A chromatographic system is described that utilizes one detection system for gas chromatographic and micro-liquid chromatographic determinations. The detection system is a direct-current, atmospheric-pressure, helium plasma emission spectrometer. The detector utilizes a nontransparent plasma source unit which contains the plasma region and two side-arms which receive effluents from the micro-liquid chromatograph and the gas chromatograph. The dual nature of this chromatographic system offers: (1) extreme flexibility in the samples to be examined; (2) extreme low sensitivity; (3) element selectivity; (4) long-term stability; (5) direct correlation of data from the liquid and gas samples; (6) simpler operation than with individual liquid and gas chromatographs, each with different detection systems; and (7) cheaper than a commercial liquid chromatograph and a gas chromatograph.

  15. Dual-keel electrodynamic Maglev system

    SciTech Connect

    He, Jianliang; Rote, D.M.; Wang, Zian; Coffey, H.T.

    1995-12-31

    This paper introduces a new concept for an electrodynamic-suspension maglev system that has a dual-keel arrangement. Each keel consists of a row of superconducting magnets aboard the vehicle. The keels move in troughs in the guideway that are each lined with pairs of figure-eight-shaped null-flux coils. Each pair of null-flux coils is cross-connected to produce null-flux suspension and guidance force. The cross-connected figure-eight null-flux coils in each trough are also energized by a three-phase power supply to produce propulsive force. Preliminary analysis shows that the new system has many advantages over other EDS systems in terms of system performance and dynamic stability.

  16. Dual-keel electrodynamic maglev system

    SciTech Connect

    He, J.; Wang, Z.; Rote, D.M.; Coffey, H.T.; Hull, J.R.; Mulcahy, T.M.; Cai, Y.

    1995-12-31

    A propulsion and stabilization system with a plurality of superconducting magnetic devices affixed to the dual-keels of a vehicle, where the superconducting magnetic devices produce a magnetic field when energized. The system also includes a plurality of figure-eight shaped null-flux coils affixed to opposing vertical sides of slots in a guideway. The figure-eight shaped null-flux coils are vertically oriented, laterally cross-connected in parallel, longitudinally connected in series, and continue the length of the vertical slots providing levitation and guidance force. An external power source energizes the figure-eight shaped null-flux coils to create a magnetic traveling wave that interacts with the magnetic field produced by the superconducting magnets to impart motion to the vehicle.

  17. Dual-keel electrodynamic maglev system

    DOEpatents

    He, Jianliang; Wang, Zian; Rote, Donald M.; Coffey, Howard T.; Hull, John R.; Mulcahy, Thomas M.; Cal, Yigang

    1996-01-01

    A propulsion and stabilization system with a plurality of superconducting magnetic devices affixed to the dual-keels of a vehicle, where the superconducting magnetic devices produce a magnetic field when energized. The system also includes a plurality of figure-eight shaped null-flux coils affixed to opposing vertical sides of slots in a guideway. The figure-eight shaped null-flux coils are vertically oriented, laterally cross-connected in parallel, longitudinally connected in series, and continue the length of the vertical slots providing levitation and guidance force. An external power source energizes the figure-eight shaped null-flux coils to create a magnetic traveling wave that interacts with the magnetic field produced by the superconducting magnets to impart motion to the vehicle.

  18. Dual-keel electrodynamic maglev system

    DOEpatents

    He, J.L.; Wang, Z.; Rote, D.M.; Coffey, H.T.; Hull, J.R.; Mulcahy, T.M.; Cal, Y.

    1996-12-24

    A propulsion and stabilization system is disclosed with a plurality of superconducting magnetic devices affixed to the dual-keels of a vehicle, where the superconducting magnetic devices produce a magnetic field when energized. The system also includes a plurality of figure-eight shaped null-flux coils affixed to opposing vertical sides of slots in a guideway. The figure-eight shaped null-flux coils are vertically oriented, laterally cross-connected in parallel, longitudinally connected in series, and continue the length of the vertical slots providing levitation and guidance force. An external power source energizes the figure-eight shaped null-flux coils to create a magnetic traveling wave that interacts with the magnetic field produced by the superconducting magnets to impart motion to the vehicle. 6 figs.

  19. Costs and energy efficiency of a dual-mode system

    NASA Technical Reports Server (NTRS)

    Heft, R. C.

    1977-01-01

    The life cycle costs of a dual mode system for both public and semiprivate ownership are examined, and the costs in terms of levelized required revenue per passenger mile are presented. The energy use of the dual mode vehicle is analyzed by means of a detailed vehicle simulation program for the control policy and guideway system. Several different propulsion systems are considered.

  20. Discovery and in Vivo Evaluation of Potent Dual CYP11B2 (Aldosterone Synthase) and CYP11B1 Inhibitors.

    PubMed

    Meredith, Erik L; Ksander, Gary; Monovich, Lauren G; Papillon, Julien P N; Liu, Qian; Miranda, Karl; Morris, Patrick; Rao, Chang; Burgis, Robin; Capparelli, Michael; Hu, Qi-Ying; Singh, Alok; Rigel, Dean F; Jeng, Arco Y; Beil, Michael; Fu, Fumin; Hu, Chii-Whei; LaSala, Daniel

    2013-12-12

    Aldosterone is a key signaling component of the renin-angiotensin-aldosterone system and as such has been shown to contribute to cardiovascular pathology such as hypertension and heart failure. Aldosterone synthase (CYP11B2) is responsible for the final three steps of aldosterone synthesis and thus is a viable therapeutic target. A series of imidazole derived inhibitors, including clinical candidate 7n, have been identified through design and structure-activity relationship studies both in vitro and in vivo. Compound 7n was also found to be a potent inhibitor of 11β-hydroxylase (CYP11B1), which is responsible for cortisol production. Inhibition of CYP11B1 is being evaluated in the clinic for potential treatment of hypercortisol diseases such as Cushing's syndrome. PMID:24900631

  1. Dual power, constant speed electric motor system

    DOEpatents

    Kirschbaum, H.S.

    1984-07-31

    A dual capacity permanent split capacitor electric motor system is provided with a stator having main and auxiliary windings. The main stator winding includes two winding sections which are connected in parallel with each other and across a pair of line terminals while the auxiliary winding is connected in series with a capacitor to form a circuit branch which is connected between the line terminals for operation at a first output power level. Switching means are provided to reconnect the main stator winding sections in series with each other and in series with a second capacitor to form a circuit branch which is connected between the line terminals while the stator auxiliary winding is connected directly between the line terminals for operation at a second output power level. Automatic rotation reversal occurs when the motor switches from the first to the second output power level. 6 figs.

  2. Dual power, constant speed electric motor system

    DOEpatents

    Kirschbaum, Herbert S.

    1984-01-01

    A dual capacity permanent split capacitor electric motor system is provided with a stator having main and auxiliary windings. The main stator winding includes two winding sections which are connected in parallel with each other and across a pair of line terminals while the auxiliary winding is connected in series with a capacitor to form a circuit branch which is connected between the line terminals for operation at a first output power level. Switching means are provided to reconnect the main stator winding sections in series with each other and in series with a second capacitor to form a circuit branch which is connected between the line terminals while the stator auxiliary winding is connected directly between the line terminals for operation at a second output power level. Automatic rotation reversal occurs when the motor switches from the first to the second output power level.

  3. Dual arm robotic system with sensory input

    NASA Technical Reports Server (NTRS)

    Ozguner, U.

    1987-01-01

    The need for dual arm robots in space station assembly and satellite maintainance is of increasing significance. Such robots will be in greater demand in the future when numerous tasks will be assigned to them to relieve the direct intervention of humans in space. Technological demands from these robots will be high. They will be expected to perform high speed tasks with a certain degree of autonomy. Various levels of sensing will have to be used in a sophisticated control scheme. Ongoing research in control, sensing and real-time software to produce a two-arm robotic system than can accomplish generic assembly tasks is discussed. The control hierarchy and the specific control approach are discussed. A decentralized implementation of model-reference adaptive control using Variable Structure controllers and the incorporation of tactile feedback is considered.

  4. Signaling Pathways Involved in Renal Oxidative Injury: Role of the Vasoactive Peptides and the Renal Dopaminergic System

    PubMed Central

    Rukavina Mikusic, N. L.; Kravetz, M. C.; Kouyoumdzian, N. M.; Della Penna, S. L.; Rosón, M. I.; Fernández, B. E.; Choi, M. R.

    2014-01-01

    The physiological hydroelectrolytic balance and the redox steady state in the kidney are accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Angiotensin II, atrial natriuretic peptide and intrarenal dopamine play a pivotal role in this interactive network. The balance between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide, by one side, and the prooxidant effect of the renin angiotensin system, by the other side, contributes to ensuring the normal function of the kidney. Different pathological scenarios, as nephrotic syndrome and hypertension, where renal sodium excretion is altered, are associated with an impaired interaction between two natriuretic systems as the renal dopaminergic system and atrial natriuretic peptide that may be involved in the pathogenesis of renal diseases. The aim of this review is to update and comment the most recent evidences about the intracellular pathways involved in the relationship between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide and the prooxidant effect of the renin angiotensin system in the pathogenesis of renal inflammation. PMID:25436148

  5. Economic Efficiency and Investment Timing for Dual Water Systems

    NASA Astrophysics Data System (ADS)

    Leconte, Robert; Hughes, Trevor C.; Narayanan, Rangesan

    1987-10-01

    A general methodology to evaluate the economic feasibility of dual water systems is presented. In a first step, a static analysis (evaluation at a single point in time) is developed. The analysis requires the evaluation of consumers' and producer's surpluses from water use and the capital cost of the dual (outdoor) system. The analysis is then extended to a dynamic approach where the water demand increases with time (as a result of a population increase) and where the dual system is allowed to expand. The model determines whether construction of a dual system represents a net benefit, and if so, what is the best time to initiate the system (corresponding to maximization of social welfare). Conditions under which an analytic solution is possible are discussed and results of an application are summarized (including sensitivity to different parameters). The analysis allows identification of key parameters influencing attractiveness of dual water systems.

  6. A Dual System Model of Preferences under Risk

    ERIC Educational Resources Information Center

    Mukherjee, Kanchan

    2010-01-01

    This article presents a dual system model (DSM) of decision making under risk and uncertainty according to which the value of a gamble is a combination of the values assigned to it independently by the affective and deliberative systems. On the basis of research on dual process theories and empirical research in Hsee and Rottenstreich (2004) and…

  7. Dual frequency dichroic feed performance. [dual feed system for microwave antennas

    NASA Technical Reports Server (NTRS)

    Bathker, D. A.

    1974-01-01

    The NASA Deep Space Net (DSN) in support of the Viking Mars Project in 1976, and for science and technology demonstrations during the Mariner-Venus-Mercury mission in 1974, has developed and implemented a dual (S- and X-band) feed for large ground microwave antennas. This feed provides for a multiplicity of functions; very low listening capability at each downlink (spacecraft-to-earth) band as well as simultaneous diplexed very high cw power uplink (earth-to-spacecraft) at the S-band frequency. Total 64-m antenna system performance, is considered in terms of gain, operating noise temperature and dual beam pointing or boresight coincidence. Because of the unique ability to fold or stow the dual band feed elements for single band operations, the performance definition between single and dual band operations will be reliable and accurate.

  8. Technology, Applications, and Process Challenges of Dual Chamber Systems.

    PubMed

    Werk, Tobias; Ludwig, Imke S; Luemkemann, Joerg; Mahler, Hanns-Christian; Huwyler, Joerg; Hafner, Mathias

    2016-01-01

    Dual-chamber systems provide an option as a drug and device combination product, when home care and emergency lyophilized products are intended. Nevertheless, until today, there are only a few products on the market, due to the challenges and limitations in manufacturability, product formulation, and product stability in a dual-chamber configuration, as well as economic considerations. This review serves to describe currently available dual-chamber systems and to discuss factors to be considered for appropriate selection and establishing fill-finish processes. PMID:26852837

  9. TESTING OF THE DUAL ROTARY FILTER SYSTEM

    SciTech Connect

    Herman, D.; Fowley, M.; Stefanko, D.

    2011-08-29

    The Savannah River National Laboratory (SRNL) installed and tested two hydraulically connected SpinTek rotary microfilter (RMF) units to determine the behavior of a multiple filter system. Both units were successfully controlled by a control scheme written in DELTA-V architecture by Savannah River Remediation (SRR) Process Control Engineering personnel. The control system was tuned to provide satisfactory response to changing conditions during the operation of the multi-filter system. Stability was maintained through the startup and shutdown of one of the filter units while the second was still in operation. The installation configuration originally proposed by the Small Colum Ion Exchange (SCIX) project of independent filter and motor mountings may be susceptible to vibration. Significant stiffening of the filter and motor mounts was required to minimize the vibration. Alignment of the motor to the filter was a challenge in this test configuration. The deployment configuration must be easy to manipulate and allow for fine adjustment. An analysis of the vibration signature of the test system identified critical speeds. Whether it corresponds to the resonance frequency of a rotor radial vibration mode that was excited by rotor unbalance is uncertain based upon the measurements. A relative motion series should be completed on the filter with the final shaft configuration to determine if the resonances exist in the final filter design. The instrumentation selected for deployment, including the concentrate discharge control valve and flow meters, performed well. Automation of the valve control integrated well with the control scheme and when used in concert with the other control variables, allowed automated control of the dual RMF system. The one area of concern with the instrumentation was the condition resulting when the filtrate flow meter operated with less than three gpm. This low flow was at the lower range of performance for the flow meter. This should not be

  10. Design of an ultra-thin dual band infrared system

    NASA Astrophysics Data System (ADS)

    Du, Ke; Cheng, Xuemin; Lv, Qichao; Hu, YiFei

    2014-11-01

    The ultra-thin imaging system using reflective multiple-fold structure has smaller volume and less weight while maintaining high resolution compared with conventional optical systems. The multi-folded approach can significantly extend focal distance within wide spectral range without incurring chromatic aberrations. In this paper, we present a dual infrared imaging system of four-folded reflection with two air-spaced concentric reflective surfaces. The dual brand IR system has 107mm effective focal length, 0.7NA, +/-4° FOV, and 50mm effective aperture with 80mm outer diameter into a 25mm total thickness, which spectral response is 3~12μm.

  11. Estimating the weight of generally configured dual wing systems

    NASA Technical Reports Server (NTRS)

    Cronin, D. L.; Somnay, R. J.

    1985-01-01

    Formulas available for the weight estimation of monoplane wings cannot be said to be appropriate for the estimation of generally configured dual wing systems. In the present paper a method is described which simultaneously generates a structural weight estimate and a fully stressed, quasi-optimal structure for a model of a dual wing system. The method is fast and inexpensive. It is ideally suited to preliminary design. To illustrate the method, a dual wing system and a conventional wing system are sized. Numerical computation is shown to be suitably fast for both cases and, for both cases, convergence to a final configuration is shown to be quite rapid. To illustrate the validity of the method, a conventional wing is sized and its weight obtained by the present method is compared to its weight determined by a reputable weight estimation formula. The results are shown to be very close.

  12. Design of a dynamic dual-foveated imaging system.

    PubMed

    Du, Xiaoyu; Chang, Jun; Zhang, Yunqiang; Wang, Xi; Zhang, Bochuan; Gao, Lei; Xiao, Liping

    2015-10-01

    A new kind of dynamic dual-foveated imaging system in the infrared band is designed and optimized in this paper. Dual-foveated imaging refers to the variation in spatial resolution at the two selected fields across the image. Such variable resolution imaging system is suitable for a variety of applications including monitoring, recognition, and remote operation of unmanned aerial vehicle. In this system, a transmissive spatial light modulator (SLM) is used as an active optical element which is located near the image plane instead of pupil plane creatively in order to divide the two selected fields. PMID:26480118

  13. 40. View of dual projector system located in MWOC facility ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    40. View of dual projector system located in MWOC facility in transmitter building no. 102 by Bessler Company. System used to project images in MWOC on backlit screen system with fiber optic electro/mechanical system linked to computer output to indicate information on screen linked with display from projector system. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

  14. Dual-energy performance of dual kVp in comparison to dual-layer and quantum-counting CT system concepts

    NASA Astrophysics Data System (ADS)

    Kappler, S.; Grasruck, M.; Niederlöhner, D.; Strassburg, M.; Wirth, S.

    2009-02-01

    Recent publications in the field of Computed Tomography (CT) demonstrate the rising interest in applying dual-energy methods for material classification during clinical routine examinations. Based on today's standard of technology, dual-energy CT can be realized by either scanning with different X-ray spectra or by deployment of energy selective detector technologies. The list of so-called dual-kVp methods contains sequential scans, fast kVp-switching and dual-source CT. Examples of energy selective detectors are scintillator-based energyintegrating dual-layer devices or direct converter with quantum counting electronics. The general difference of the approaches lies in the shape of the effectively detected X-ray energy spectra and in the presence of crossscatter radiation in the case of dual-source devices. This leads to different material classification capabilities for the various techniques. In this work, we present detector response simulations of realistic CT scans with subsequent CT image reconstruction. Analysis of the image data allows direct and objective comparison of the dual-kVp, dual-layer, and quantum counting CT system concepts. The dual-energy performance is benchmarked in terms of image noise and Iodine-bone separation power at given image sharpness and dose exposure. For the case of dual-source devices the effect of cross-scatter radiation, as well as the benefit of additional filtering are taken into account.

  15. Dual- and triple-band AR coatings for IR systems

    NASA Astrophysics Data System (ADS)

    Cohen, Daniel; Stolov, Yevgeni; Azran, Amnon; Gilo, Mordechai

    2013-06-01

    Dual-band infrared camera systems allow viewing and comparison of the 3-5µ and 8-12µ spectrum regions, improve visibility at sunrise/sunset and help distinguish between targets and decoys. They also enhance the ability to defeat many IR countermeasures such as smoke, camouflage and flares. As dual band 3rd generation FLIR systems progress, we introduce coatings for these systems. This paper describes advanced dual band coatings for the 3-5µ and 8-12µ spectrum regions, with reference to single band coatings. Theoretical and measured designs are shown for ZnSe, ZnS, Ge and IG-6 substrates. Triple band AR coatings with additional transmittance at 1.06µ are also demonstrated.

  16. 14 CFR 27.399 - Dual control system.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Dual control system. 27.399 Section 27.399 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Strength Requirements Control Surface and System Loads § 27.399...

  17. 14 CFR 27.399 - Dual control system.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Dual control system. 27.399 Section 27.399 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Strength Requirements Control Surface and System Loads § 27.399...

  18. Special Education Teacher Preparation in Singapore's Dual Education System

    ERIC Educational Resources Information Center

    Walker, Zachary

    2016-01-01

    Global comparisons of teacher education programs should start with an understanding of the school systems that teachers are being prepared for in their local contexts. The purpose of this article is to describe Singapore's dual education system as well as teacher preparation in a country that educates many students with disabilities in a separate…

  19. Solution of a system of dual integral equations.

    NASA Technical Reports Server (NTRS)

    Buell, J.; Kagiwada, H.; Kalaba, R.; Ruspini, E.; Zagustin, E.

    1972-01-01

    The solution of a presented system of differential equations with initial values is shown to satisfy a system of dual integral equations of a type appearing in the study of axisymmetric problems of potential theory. Of practical interest are possible applications in biomechanics, particularly, for the case of trauma due to impact.

  20. Dual fan, dual-duct system meets air quality, energy-efficiency needs

    SciTech Connect

    Schuler, M.

    1996-03-01

    Canada`s Space Centre in Saint-Hubert Quebec is a 300,000 ft{sup 2} (27,871 m{sup 2}) complex that houses the headquarters of the Canadian Space Agency, the Canadian Astronaut Training Centre, mission ground control installations, research facilities, offices and the required support facilities. A comfortable, pleasant research environment was a primary concern for the Space Centre, given its elite clientele. The objectives were high indoor-air quality, design flexibility, energy efficiency and low capital costs. Dual duct systems which are the heart of the mechanical concept allowed the designers to meet these objectives. The Space Centre`s offices, laboratories and conference center are all served by dual-duct systems. All operate using an air economizer cycle. Gas boilers provide them with hot water for heating and steam for humidification while centrifugal chillers provide chilled water for cooling. This article describes the design.

  1. Dual-Use system architecture for a space situational awareness system in Japan

    NASA Astrophysics Data System (ADS)

    Otani, Y.; Kohtake, N.; Ohkami, Y.

    The use of outer space plays a vital role in both defense and civil fields. Since the separation of space activities between civil and defense applications is extremely inefficient, the Dual-Use concept has been considered fundamental for promoting the effective use of space. To the best of the authors' knowledge, most previous studies on Dual-Use focused on the technological aspects, and very few on a system engineering approach to Dual-Use. This left some important issues untouched such as the operational aspects of a system of systems, which need to be understood in a more generic context. This paper presents the results of a conceptual study, system design and management analysis of Dual-Use system architecture. First, an outline of the Dual-Use concept will be described and a definition of Dual-Use given. The effectiveness of applying the Dual-Use system concept to Space Situational Awareness (SSA) for both defense and civil users as a system of systems will then be discussed and investigated with a stakeholders analysis, context diagram and design structure matrix method. It has demonstrated that there is a need for a Dual-Use SSA Data Center which works as a binder between defense and civil systems as well as a data policy for constructing a Dual-Use SSA system.

  2. Dual-frequency and dual-polarization VLBI observations of the stellar system Algol

    NASA Technical Reports Server (NTRS)

    Lestrade, Jean-Francois; Mutel, Robert L.; Preston, Robert A.; Phillips, Robert B.

    1988-01-01

    Results of multiepoch VLBI observations of the stellar system Algol are presented, including dual-polarization and dual-frequency measurements at 2.3 and 8.4 GHz. The brightness temperature of the radio source is generally between 3 x 10 to the 8th K and 5 x 10 to the 9th K and is consistent with gyrosynchrotron emission from energetic electrons with mean energy less than 1 MeV in an active coronal region. Two exceptional events were observed: a high-brightness, broad-band outburst occurring simultaneously at 2.3 and 8.4 GHz, and a short-duration, highly polarized and high-brightness temperature outburst at 1.66 GHz. A simple physical model which includes all three types of emission is suggested.

  3. Study on the gain characteristic of dual MCP cascade system

    NASA Astrophysics Data System (ADS)

    Xie, Jingjing; Zang, Yiqing; Li, Yang; Li, Ye

    2015-03-01

    The low gain of single micro-channel plate (MCP) detector system has a lot of restrictions. So the dual MCP system is widely applied in many fields. Many experiments showed the gain was proportional to initial electron energy in single MCP system. If we improve the initial energy that collide with the second MCP in dual MCP system, it may have beneficial influence on the system gain. In order to check these hypothesis, we use the "Secondary Electric Field Acceleration" cascade structure in experiments. The results show the correctness through the comparison test with conventional 'V' type cascade structure. In this paper, we describe the different between these two structure and discuss the influence factors in their system gain. It gives a reference in the cascade system that with high gain and it also takes a great significance on the weak-light-detection field.

  4. Combustion system for dual fuel engine

    SciTech Connect

    Schaub, F.S.; Smith, J.G.

    1990-10-30

    This patent describes in an dual gas-liquid fuel four cycle engine having cylinders and wherein each cylinder is operatively connected thereto and each cylinder has a piston, two inlet valves, two exhaust valves and a first liquid fuel injector. It comprises: at least one fuel torch cell operatively connected to at least one cylinder, the torch cell having a torch cell nozzle at one end thereof and the other end having appropriate means to connect the torch cell to a fuel supply, a second fuel injector mounted in the torch cell at a predetermined angle to an axis of the torch cell, the torch cell defining an auto-ignition chamber, the second fuel injector being in operative communication with the auto-ignition chamber by an injector nozzle passageway, the injector nozzle passageway entering the auto-ignition chamber at a predetermined angle relative to the axis, and a torch nozzle passage connecting the auto-ignition chamber with the cylinder at a predetermined angle to a top inner portion of a cylinder head.

  5. LABORATORY STUDY OF LIMESTONE REGENERATION IN DUAL ALKALI SYSTEMS

    EPA Science Inventory

    The report describes a series of open- and closed-loop laboratory bench scale experiments which were carried out to study parameters which affect the reaction of limestone with dual alkali flue gas desulfurization system process liquors. It gives details of several sets of operat...

  6. Different but Equal? Assessing European Dual HE Systems

    ERIC Educational Resources Information Center

    Kivinen, Osmo; Nurmi, Jouni

    2010-01-01

    In higher education dual systems, graduates are qualified to apply for jobs in same professional fields along two separated educational routes. The research problem is whether the rival applicants for professional positions are treated equally in the labour market despite their different qualifications. From the graduates point of view, to be…

  7. 46 CFR 111.05-29 - Dual voltage direct current systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Dual voltage direct current systems. 111.05-29 Section... Dual voltage direct current systems. Each dual voltage direct current system must have a suitably sensitive ground detection system which indicates current in the ground connection, has a range of at...

  8. 46 CFR 111.05-29 - Dual voltage direct current systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Dual voltage direct current systems. 111.05-29 Section... Dual voltage direct current systems. Each dual voltage direct current system must have a suitably sensitive ground detection system which indicates current in the ground connection, has a range of at...

  9. 46 CFR 111.05-29 - Dual voltage direct current systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Dual voltage direct current systems. 111.05-29 Section... Dual voltage direct current systems. Each dual voltage direct current system must have a suitably sensitive ground detection system which indicates current in the ground connection, has a range of at...

  10. 46 CFR 111.05-29 - Dual voltage direct current systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Dual voltage direct current systems. 111.05-29 Section... Dual voltage direct current systems. Each dual voltage direct current system must have a suitably sensitive ground detection system which indicates current in the ground connection, has a range of at...

  11. 46 CFR 111.05-29 - Dual voltage direct current systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Dual voltage direct current systems. 111.05-29 Section... Dual voltage direct current systems. Each dual voltage direct current system must have a suitably sensitive ground detection system which indicates current in the ground connection, has a range of at...

  12. Dual-purpose chamber-cooling system

    NASA Technical Reports Server (NTRS)

    Fraze, R. E.

    1968-01-01

    Inexpensive, portable system was designed for cooling small environmental test chambers with a temperature-controlled gas stream evaporated from a cryogenic liquid. The system reduces the temperature of a chamber to any desired point in a fraction of the time required by previous systems.

  13. Using dual-purpose crops in sheep-grazing systems.

    PubMed

    Dove, Hugh; Kirkegaard, John

    2014-05-01

    The utilisation of dual-purpose crops, especially wheat and canola grown for forage and grain production in sheep-grazing systems, is reviewed. When sown early and grazed in winter before stem elongation, later-maturing wheat and canola crops can be grazed with little impact on grain yield. Recent research has sought to develop crop- and grazing-management strategies for dual-purpose crops. Aspects examined have been grazing effects on crop growth, recovery and yield development along with an understanding of the grazing value of the crop fodder, its implications for animal nutrition and grazing management to maximise live-weight gain. By alleviating the winter 'feed gap', the increase in winter stocking rate afforded by grazing crops allows crop and livestock production to be increased simultaneously on the same farm. Integration of dual-purpose wheat with canola on mixed farms provides further systems advantages related to widened operational windows, weed and disease control and risk management. Dual-purpose crops are an innovation that has potential to assist in addressing the global food-security challenge. PMID:24323974

  14. A new method of dual FOV optical system design

    NASA Astrophysics Data System (ADS)

    Zhang, Liang

    2009-07-01

    With the development of scientific technologies, infrared imaging technology has been applied in the fields of industry, medical treatment, and national defense and so on. Infrared detection has the advantages of looking through the smoke, fog, haze, snow, and also could avoid the affection of battlefield flash. Hence, it could achieve the long distance and all-weather scout, especially in nighttime and badness weather conditions.All kinds of single-FOV, dual-FOV, multi-FOV and continuous zoom optical systems have been applied more and more abroad with the research and application of infrared imaging technologies. Therefore, the research of all sorts of dual FOV optical systems would be more important. The system belongs to simple zoom optical systems by having two fields of view. The zoom methods comprise of single zoom, rotary zoom, radial zoom, axial zoom and so on. Basing on the analysis of zoom methods, a new method of zoom optical system has been developed, which realized the dual FOV optical system by sharing secondary imaging lenses. This design method could make the results approaching to diffraction limit, and improve the precision of optical axial. It also has decreased the moving parts and reduced the difficulty of assembly of system.

  15. Demountable dual-FOV zooming optical design for IR system

    NASA Astrophysics Data System (ADS)

    Kang, Wenli; Wang, Nanxi; Gao, Jing; Zhang, Bo; Gao, Shan

    2015-10-01

    Based on a 384×288 uncooled long-wavelength IR detector, a dual-FOV zooming optical system has been designed. To match the requirement of lightweight and flexible optoelectronic system, the zoom lens has been designed demountable. To evaluate the image quality, the MTF and RMS have been mainly considered. Also, the temperature analysis has been done to get the focusing solution. The result showed that the image quality was well and matched the requirement well.

  16. Dual systems of speech category learning across the lifespan

    PubMed Central

    Maddox, W. Todd; Chandrasekaran, Bharath; Smayda, Kirsten; Yi, Han-Gyol

    2013-01-01

    Although categorization is fundamental to speech processing, little is known about the learning systems that mediate auditory categorization and even less is known about changes across the lifespan. Vision research supports dual-learning systems that are grounded in neuroscience and are partially-dissociable. The reflective, rule-based system is prefrontally mediated and uses working memory and executive attention to develop and test rules for classifying in an explicit fashion. The reflexive, information-integration system is striatally mediated and operates by implicitly associating perception with actions that lead to reinforcement. We examine the extent to which dual-learning systems mediate auditory and speech learning in younger and older adults. We examined auditory category learning when a rule-based strategy (Experiment 1) or information-integration strategy (Experiment 2) was optimal, and found an age-related rule-based deficit, but intact information-integration learning. Experiment 3 examined natural auditory category learning, and found an age-related performance deficit. Computational modeling suggested that this was due to older adults’ persistent reliance on sub-optimal, uni-dimensional strategies when two-dimensional strategies were optimal. Working memory capacity was also found to be associated with improved rule-based and natural auditory category learning, but not information-integration category learning. These results suggest that dual-learning systems are operative in speech category learning across the lifespan, and that performance deficits, when present are due to deficiencies in frontally-mediated, rule-based processes. PMID:24364408

  17. Affine root systems and dual numbers

    NASA Astrophysics Data System (ADS)

    Kostyakov, I. V.; Gromov, N. A.; Kuratov, V. V.

    The root systems in Carroll spaces with degenerate metric are defined. It is shown that their Cartan matrices and reflection groups are affine. Due to the geometric consideration the root system structure of affine algebras is determined by a sufficiently simple algorithm.

  18. The German Dual Apprenticeship System: An Analysis of Its Evolution and Present Challenges.

    ERIC Educational Resources Information Center

    Tremblay, Diane-Gabrielle; Le Bot, Irene

    The evolution of Germany's dual apprenticeship system and the challenges now facing it were reviewed. The following topics were considered: (1) the progression from craft guilds to vocational training; (2) the history of Germany's dual apprenticeship system from its organization in the 1970s; (4) apprenticeship in the dual system; (3) Germany's…

  19. Dual use display systems for telerobotics

    NASA Technical Reports Server (NTRS)

    Massimino, Michael J.; Meschler, Michael F.; Rodriguez, Alberto A.

    1994-01-01

    This paper describes a telerobotics display system, the Multi-mode Manipulator Display System (MMDS), that has applications for a variety of remotely controlled tasks. Designed primarily to assist astronauts with the control of space robotics systems, the MMDS has applications for ground control of space robotics as well as for toxic waste cleanup, undersea, remotely operated vehicles, and other environments which require remote operations. The MMDS has three modes: (1) Manipulator Position Display (MPD) mode, (2) Joint Angle Display (JAD) mode, and (3) Sensory Substitution (SS) mode. These three modes are discussed in the paper.

  20. Plasma-sprayed dual density ceramic turbine seal system

    NASA Technical Reports Server (NTRS)

    Clingman, D. L.; Schechter, B.; Cross, K. R.; Cavanagh, J. R.

    1979-01-01

    Dual density, plasma sprayed ceramic coating systems were investigated for possible application as abradable turbine tip seal systems in small gas turbine engines. Abradability, erosion resistance, internal leakage, and microstructural characterization were investigated for polyester and cenosphere filled zirconium oxide composites. Results indicate the polyester system is more abradable but displays significantly less erosion resistance than the cenosphere system. It is also stated that the absence of significant blade tip damage during abradability testing of both systems suggests additional effort may result in a more nearly optimum balance of abradability and erosion resistance.

  1. Regulation of renin release by local and systemic factors.

    PubMed

    Schweda, F; Kurtz, A

    2011-01-01

    The renin-angiotensin system (RAS) is critically involved in the regulation of the salt and volume status of the body and blood pressure. The activity of the RAS is controlled by the protease renin, which is released from the renal juxtaglomerular epithelioid cells into the circulation. Renin release is regulated in negative feedback-loops by blood pressure, salt intake, and angiotensin II. Moreover, sympathetic nerves and renal autacoids such as prostaglandins and nitric oxide stimulate renin secretion. Despite numerous studies there remained substantial gaps in the understanding of the control of renin release at the organ or cellular level. Some of these gaps have been closed in the last years by means of gene-targeted mice and advanced imaging and electrophysiological methods. In our review, we discuss these recent advances together with the relevant previous literature on the regulation of renin release. PMID:22128405

  2. Refrigeration system having dual suction port compressor

    DOEpatents

    Wu, Guolian

    2016-01-05

    A cooling system for appliances, air conditioners, and other spaces includes a compressor, and a condenser that receives refrigerant from the compressor. The system also includes an evaporator that receives refrigerant from the condenser. Refrigerant received from the condenser flows through an upstream portion of the evaporator. A first portion of the refrigerant flows to the compressor without passing through a downstream portion of the evaporator, and a second portion of the refrigerant from the upstream portion of the condenser flows through the downstream portion of the evaporator after passing through the upstream portion of the evaporator. The second portion of the refrigerant flows to the compressor after passing through the downstream portion of the evaporator. The refrigeration system may be configured to cool an appliance such as a refrigerator and/or freezer, or it may be utilized in air conditioners for buildings, motor vehicles, or other such spaces.

  3. Dual energy use systems: District heating survey

    NASA Astrophysics Data System (ADS)

    1980-07-01

    The current status of and problems facing district heating systems operated by electric utilities were identified. The technical and economic factors which can affect the present and future success of district heating systems in the United States were evaluated. A survey of 59 district heating electric utilities was conducted to determine the current status of the industry. Questions developed to obtain data on technical, economic, regulator, and marketing factors were included in the survey. Literature on district heating in the U.S. and abroad was collected from governments, industry and foreign sources and reviewed to aid in evaluating the current and future potential of the industry. Interviews were held with executives of 16 utilities that operate district heating systems in order to determine corporate attitudes. A summary of the literature obtained is provided. Survey results are tabulated and described. The interviews and survey data were used to compile 10 case studies of utilities operating district heating systems under a braod range of circumstances.

  4. Oxidative stress-mediated effects of angiotensin II in the cardiovascular system

    PubMed Central

    Wen, Hairuo; Gwathmey, Judith K; Xie, Lai-Hua

    2014-01-01

    Angiotensin II (Ang II), an endogenous peptide hormone, plays critical roles in the pathophysiological modulation of cardiovascular functions. Ang II is the principle effector of the renin-angiotensin system for maintaining homeostasis in the cardiovascular system, as well as a potent stimulator of NAD(P)H oxidase, which is the major source and primary trigger for reactive oxygen species (ROS) generation in various tissues. Recent accumulating evidence has demonstrated the importance of oxidative stress in Ang II-induced heart diseases. Here, we review the recent progress in the study on oxidative stress-mediated effects of Ang II in the cardiovascular system. In particular, the involvement of Ang II-induced ROS generation in arrhythmias, cell death/heart failure, ischemia/reperfusion injury, cardiac hypertrophy and hypertension are discussed. Ca2+/calmodulin-dependent protein kinase II is an important molecule linking Ang II, ROS and cardiovascular pathological conditions. PMID:24587981

  5. Stochastic image reconstruction for a dual-particle imaging system

    NASA Astrophysics Data System (ADS)

    Hamel, M. C.; Polack, J. K.; Poitrasson-Rivière, A.; Flaska, M.; Clarke, S. D.; Pozzi, S. A.; Tomanin, A.; Peerani, P.

    2016-02-01

    Stochastic image reconstruction has been applied to a dual-particle imaging system being designed for nuclear safeguards applications. The dual-particle imager (DPI) is a combined Compton-scatter and neutron-scatter camera capable of producing separate neutron and photon images. The stochastic origin ensembles (SOE) method was investigated as an imaging method for the DPI because only a minimal estimation of system response is required to produce images with quality that is comparable to common maximum-likelihood methods. This work contains neutron and photon SOE image reconstructions for a 252Cf point source, two mixed-oxide (MOX) fuel canisters representing point sources, and the MOX fuel canisters representing a distributed source. Simulation of the DPI using MCNPX-PoliMi is validated by comparison of simulated and measured results. Because image quality is dependent on the number of counts and iterations used, the relationship between these quantities is investigated.

  6. Dual-Actuator Active Vibration-Control System

    NASA Technical Reports Server (NTRS)

    Kascak, Albert F.; Kiraly, Louis J.; Montague, Gerald T.; Palazzolo, Alan B.; Manchala, Daniel

    1994-01-01

    Dual-actuator active vibration-control (DAAVC) system is developmental system of type described in "Active Vibration Dampers for Rotating Machinery" (LEW-15427). System features sensors and actuators positioned and oriented at bearings to measure and counteract vibrations of shaft along either of two axes perpendicular to axis of rotation. Effective in damping vibrations of helicopter-engine test stand, making it safer to operate engine at speeds near and above first resonance of engine/test-stand system. Opens new opportunities for engine designers to draw more power from engine, and concept applicable to other rotating machines.

  7. Dual-range linearized transimpedance amplifier system

    DOEpatents

    Wessendorf, Kurt O.

    2010-11-02

    A transimpedance amplifier system is disclosed which simultaneously generates a low-gain output signal and a high-gain output signal from an input current signal using a single transimpedance amplifier having two different feedback loops with different amplification factors to generate two different output voltage signals. One of the feedback loops includes a resistor, and the other feedback loop includes another resistor in series with one or more diodes. The transimpedance amplifier system includes a signal linearizer to linearize one or both of the low- and high-gain output signals by scaling and adding the two output voltage signals from the transimpedance amplifier. The signal linearizer can be formed either as an analog device using one or two summing amplifiers, or alternately can be formed as a digital device using two analog-to-digital converters and a digital signal processor (e.g. a microprocessor or a computer).

  8. EVALUATION OF THE LIMESTONE DUAL ALKALI PROTOTYPE SYSTEM PLANT SCHOLZ: SYSTEM DESIGN AND PROGRAM PLAN

    EPA Science Inventory

    The report describes the (Phase I) design of both a limestone dual alkali system at Gulf Power Co.'s Scholz steam plant and a related test program. The limestone dual alkali process will be tested at an existing 20 MWe prototype facility at the Scholz plant. The intent of the pro...

  9. Dual Telecentric Lens System For Projection Onto Tilted Toroidal Screen

    NASA Technical Reports Server (NTRS)

    Gold, Ronald S.; Hudyma, Russell M.

    1995-01-01

    System of two optical assemblies for projecting image onto tilted toroidal screen. One projection lens optimized for red and green spectral region; other for blue. Dual-channel approach offers several advantages which include: simplified color filtering, simplified chromatic aberration corrections, less complex polarizing prism arrangement, and increased throughput of blue light energy. Used in conjunction with any source of imagery, designed especially to project images formed by reflection of light from liquid-crystal light valve (LCLV).

  10. Dual Oculometer System for Aviation Crew Assessment

    NASA Technical Reports Server (NTRS)

    Latorella, Kara; Ellis, Kyle K.; Lynn, William A.; Frasca, Dennis; Burdette, Daniel W.; Feigh, Charles T.; Douglas, Alan L.

    2010-01-01

    Oculometers, eye trackers, are a useful tool for ascertaining the manner in which pilots deploy visual attentional resources, and for assessing the degree to which stimuli capture attention exogenously. The aim of this effort was to obtain oculometer data comfortably, unobtrusively, reliably and with good spatial resolution over a standard B757-like flight deck for both individuals in a crew. We chose to implement two remote, 5-camera Smarteye systems which were crafted for this purpose to operate harmoniously. We present here the results of validation exercises, lessons learned for improving data quality, and initial thoughts on the use of paired oculometer data to reflect crew workload, coordination, and situation awareness, in the aggregate.

  11. Non-Traditional Systemic Treatments for Diabetic Retinopathy: An
Evidence-Based Review

    PubMed Central

    Simó, Rafael; Ballarini, Stefania; Cunha-Vaz, José; Ji, Linong; Haller, Hermann; Zimmet, Paul; Wong, Tien Y.

    2015-01-01

    The rapid escalation in the global prevalence diabetes, with more than 30% being afflicted with diabetic retinopathy (DR), means it is likely that associated vision-threatening conditions will also rise substantially. This means that new therapeutic approaches need to be found that go beyond the current standards of diabetic care, and which are effective in the early stages of the disease. In recent decades several new pharmacological agents have been investigated for their effectiveness in preventing the appearance and progression of DR or in reversing DR; some with limited success while others appear promising. This up-to-date critical review of non-traditional systemic treatments for DR is based on the published evidence in MEDLINE spanning 1980-December 2014. It discusses a number of therapeutic options, paying particular attention to the mechanisms of action and the clinical evidence for the use of renin-angiotensin system blockade, fenofibrate and calcium dobesilate monohydrate in DR. PMID:25989912

  12. Dual energy CT with photon counting and dual source systems: comparative evaluation.

    PubMed

    Atak, Haluk; Shikhaliev, Polad M

    2015-12-01

    Recently, new dual energy (DE) computed tomography (CT) systems-dual source CT (DSCT) and photon counting CT (PCCT) have been introduced. Although these systems have the same clinical targets, they have major differences as they use dual and single kVp acquisitions and different x-ray detection and energy resolution concepts. The purpose of this study was theoretical and experimental comparisons of DSCT and PCCT. The DSCT Siemens Somatom Flash was modeled for simulation study. The PCCT had the same configuration as DSCT except it used a photon counting detector. The soft tissue phantoms with 20, 30, and 38 cm diameters included iodine, CaCO3, adipose, and water samples. The dose (air kerma) was 14 mGy for all studies. The low and high energy CT data were simulated at 80 kVp and 140 kVp for DSCT, and in 20-58 keV and 59-120 keV energy ranges for PCCT, respectively. The experiments used Somatom Flash DSCT system and PCCT system based on photon counting CdZnTe detector with 2  ×  256 pixel configuration and 1  ×  1 mm(2) pixels size. In simulated general CT images, PCCT provided higher contrast-to-noise ratio (CNR) than DSCT with 0.4/0.8 mm Sn filters. The PCCT with K-edge filter provided higher CNR than the PCCT with a Cu filter, and DSCT with 0.4 mm Sn filter provided higher CNR than the DSCT with a 0.8 mm Sn filter. In simulated DE subtracted images, CNR of the DSCT was comparable to the PCCT with a Cu filter. However, DE PCCT with Ho a K-edge filter provided 30-40% higher CNR than the DE DSCT with 0.4/0.8 mm Sn filters. The experimental PCCT provided higher CNR in general imaging compared to the DSCT. In experimental DE subtracted images, the DSCT provided higher CNR than the PCCT with a Cu filter. However, experimental CNR with DE PCCT with K-edge filter was 15% higher than in DE DSCT, which is less than 30-40% increase predicted by the simulation study. It is concluded that ideal PCCT can provide substantial advantages over ideal

  13. Dual energy CT with photon counting and dual source systems: comparative evaluation

    NASA Astrophysics Data System (ADS)

    Atak, Haluk; Shikhaliev, Polad M.

    2015-12-01

    Recently, new dual energy (DE) computed tomography (CT) systems—dual source CT (DSCT) and photon counting CT (PCCT) have been introduced. Although these systems have the same clinical targets, they have major differences as they use dual and single kVp acquisitions and different x-ray detection and energy resolution concepts. The purpose of this study was theoretical and experimental comparisons of DSCT and PCCT. The DSCT Siemens Somatom Flash was modeled for simulation study. The PCCT had the same configuration as DSCT except it used a photon counting detector. The soft tissue phantoms with 20, 30, and 38 cm diameters included iodine, CaCO3, adipose, and water samples. The dose (air kerma) was 14 mGy for all studies. The low and high energy CT data were simulated at 80 kVp and 140 kVp for DSCT, and in 20-58 keV and 59-120 keV energy ranges for PCCT, respectively. The experiments used Somatom Flash DSCT system and PCCT system based on photon counting CdZnTe detector with 2  ×  256 pixel configuration and 1  ×  1 mm2 pixels size. In simulated general CT images, PCCT provided higher contrast-to-noise ratio (CNR) than DSCT with 0.4/0.8 mm Sn filters. The PCCT with K-edge filter provided higher CNR than the PCCT with a Cu filter, and DSCT with 0.4 mm Sn filter provided higher CNR than the DSCT with a 0.8 mm Sn filter. In simulated DE subtracted images, CNR of the DSCT was comparable to the PCCT with a Cu filter. However, DE PCCT with Ho a K-edge filter provided 30-40% higher CNR than the DE DSCT with 0.4/0.8 mm Sn filters. The experimental PCCT provided higher CNR in general imaging compared to the DSCT. In experimental DE subtracted images, the DSCT provided higher CNR than the PCCT with a Cu filter. However, experimental CNR with DE PCCT with K-edge filter was 15% higher than in DE DSCT, which is less than 30-40% increase predicted by the simulation study. It is concluded that ideal PCCT can provide substantial advantages over ideal

  14. The tri-Hamiltonian dual system of supersymmetric two boson system

    NASA Astrophysics Data System (ADS)

    Zhang, Mengxia; Tian, Kai; Zhang, Lei

    2016-09-01

    The dual system of the supersymmetric two boson system is constructed through the approach of tri-Hamiltonian duality, and inferred from this duality, its zero-curvature representation is also figured out. Furthermore, the dual system is shown to be equivalent to a N = 2 supersymmetric Camassa-Holm equation, and this relation results in a new linear spectral problem for the N = 2 supersymmetric Camassa-Holm equation.

  15. A laboratory breadboard system for dual-arm teleoperation

    NASA Technical Reports Server (NTRS)

    Bejczy, A. K.; Szakaly, Z.; Kim, W. S.

    1990-01-01

    The computing architecture of a novel dual-arm teleoperation system is described. The novelty of this system is that: (1) the master arm is not a replica of the slave arm; it is unspecific to any manipulator and can be used for the control of various robot arms with software modifications; and (2) the force feedback to the general purpose master arm is derived from force-torque sensor data originating from the slave hand. The computing architecture of this breadboard system is a fully synchronized pipeline with unique methods for data handling, communication and mathematical transformations. The computing system is modular, thus inherently extendable. The local control loops at both sites operate at 100 Hz rate, and the end-to-end bilateral (force-reflecting) control loop operates at 200 Hz rate, each loop without interpolation. This provides high-fidelity control. This end-to-end system elevates teleoperation to a new level of capabilities via the use of sensors, microprocessors, novel electronics, and real-time graphics displays. A description is given of a graphic simulation system connected to the dual-arm teleoperation breadboard system. High-fidelity graphic simulation of a telerobot (called Phantom Robot) is used for preview and predictive displays for planning and for real-time control under several seconds communication time delay conditions. High fidelity graphic simulation is obtained by using appropriate calibration techniques.

  16. Modeling mineral dissolution and precipitation in dual-porosity systems

    SciTech Connect

    Novak, C.F.; Gelbard, F.

    1991-10-01

    A dual-porosity chemical transport model is applied to saturated fractured porous media. In this model, transport through fractures is advection-dominated while transport between the matrix and the fractures is diffusion-dominated. Recent studies in the literature indicate that conservative tracers and radionuclides in these systems will be retarded by matrix diffusion in the absence of chemical reactions. This study examines systems that include chemical reactions (e.g., dissolution/precipitation and aqueous complexation) and examines changes in retardation caused by precipitation.

  17. Dual autofocusing algorithm for optical lens measurement system

    NASA Astrophysics Data System (ADS)

    Zhang, Zhenjiu; Hu, Hong

    2010-08-01

    In order to develop an on-line optical lens measurement system, a dual autofocusing algorithm consisting of coarse autofocusing and fine autofocusing is proposed to realize the accurate and automatic image grabbing. In the procedure of coarse autofocusing, variance function on the whole image is selected as sharpness evaluation function (SEF), and mean comparison method is applied to realize the hill-climbing algorithm for focal plane searching. A 3-point method is used to initialize the searching direction. In the procedure of fine autofocusing, a conditional dilation method based on mathematical morphology is used to extract the region of interest (ROI), namely, the target images, and a shape factor is employed to eliminate the disturbance regions. Brenner function within ROI is selected as SEF, and single-point comparison method is used to find the focal plane accurately. Compared to the traditional methods, this dual autofocusing algorithm not only can realize high precision focusing, but also has large autofocusing range. The experiment results show that the dual autofocusing technique can guarantee that the focusing position locates in the depth of field. The proposed algorithm is suitable for the on-line optical lens measurement.

  18. The selective equipment removal system dual arm work module

    SciTech Connect

    Noakes, M.W.; Haley, D.C.; Willis, W.D.

    1997-12-31

    The Selective Equipment Removal System (SERS) was previously developed under the Department of Energy`s Robotics Technology Development Program to demonstrate and evaluate mobile telerobotic concepts for performing selective dismantlement using the reconfigurable dual-arm work module (DAWM). DAWM was designed for overhead transporter, crane hook, and mobile vehicle deployment. The DAWM configuration provided two 6-degree-of-freedom (D.O.F.) hydraulic manipulators with a maximum capacity of 240 lbs in the elbows-up configuration and five additional D.O.F. supplying torso rotate for the entire positioning package, linear extension of each arm base, and base rotate for each arm (which added a seventh D.O.F. to the manipulator for elbows-up, elbows-out, and elbows-down operation). Hydraulic manipulators were selected to provide the payload capacity required for anticipated tooling and material handling needs that would be typical of heavy dismantlement tasks. The original design of the dual arm manipulation system was driven by the desire to provide maximum system versatility in the study of deployment options and orientation relative to specific task performance. In FY 1996, the program was directed to provide remote systems support for the dismantlement of the CP5 reactor at Argonne National Lab (ANL) beginning in FY 1997. A study of the tasks involved and the available deployment options led to a rework of the DAWM designated the dual arm work platform (DAWP), which was specifically designed around crane hook deployment, reduced the base D.O.F.`s to four instead of five, and made use of the existing DAWM control system. This paper describes the evolution of the DAWM into the DAWP and the design philosophy involved.

  19. Dual system (energy management/electrical submetering) retrofit

    SciTech Connect

    Hirschfeld, H.E.; Lopes, J.S.

    1998-07-01

    This paper discussed implementation of an innovative and state-of-the-art Dual System, capable of both energy management and electrical submetering, that was installed in a large New York City multi-family residential master-metered housing complex during 1997. Both technical and non-technical issues affected the decision-making process. The selection of the Dual System represented a compromise necessary for the project to overcome barriers and obtain utility rebates. The Dual System enables the sharing of control (EMS) and metering (Submetering) signals through the use of powerline carrier (PLC) communications, minimizing installation costs and resident intrusion. The EMS controls individual apartment electrical heating and cooling equipment by activating remote switching equipment installed on the unit circuits in order to reduce electric consumption, primarily when tenants are not at home. When tenants are at home, they can manually override the system. The submetering application (when implemented) will involve the measurement and billing of electric use in individual apartment units. Without submetering, individual apartment electric costs are allocated based on methods other than actual usage (e.g., number of rooms). With submetering, individual apartments are metered by management, which then allocates and bills utility costs fairly to residents in proportion to actual consumption. Residents would thus pay for what they use and have the incentive to conserve. The project has shown that both EMS and Submetering can be installed in a rental property in a rent-regulated environment and overcome the many barriers encountered. It provides strong and compelling evidence supporting policy favoring submetering as both an energy conservation measure and as an equitable means of allocating building operating costs. Both prior studies and preliminary data from the Project confirm the potential for savings for submetering and EMS (so far, only 5.8% for EMS vs 20% in

  20. The dual systems model: Review, reappraisal, and reaffirmation.

    PubMed

    Shulman, Elizabeth P; Smith, Ashley R; Silva, Karol; Icenogle, Grace; Duell, Natasha; Chein, Jason; Steinberg, Laurence

    2016-02-01

    According to the dual systems perspective, risk taking peaks during adolescence because activation of an early-maturing socioemotional-incentive processing system amplifies adolescents' affinity for exciting, pleasurable, and novel activities at a time when a still immature cognitive control system is not yet strong enough to consistently restrain potentially hazardous impulses. We review evidence from both the psychological and neuroimaging literatures that has emerged since 2008, when this perspective was originally articulated. Although there are occasional exceptions to the general trends, studies show that, as predicted, psychological and neural manifestations of reward sensitivity increase between childhood and adolescence, peak sometime during the late teen years, and decline thereafter, whereas psychological and neural reflections of better cognitive control increase gradually and linearly throughout adolescence and into the early 20s. While some forms of real-world risky behavior peak at a later age than predicted, this likely reflects differential opportunities for risk-taking in late adolescence and young adulthood, rather than neurobiological differences that make this age group more reckless. Although it is admittedly an oversimplification, as a heuristic device, the dual systems model provides a far more accurate account of adolescent risk taking than prior models that have attributed adolescent recklessness to cognitive deficiencies. PMID:26774291

  1. [Role of rennin-angiotensin system in cholinergic agonist carbachol-induced cardiovascular responses in ovine fetus].

    PubMed

    Geng, Chun-Song; Wan, Zhen; Feng, Ya-Hong; Fan, Yi-Sun

    2012-06-25

    To investigate the mechanisms underlying the cholinergic agonist carbachol-induced cardiovascular responses, changes of renin-angiotensin system were examined in fetal hormonal systems. In the ovine fetal model under stressless condition, the cardiovascular function was recorded. Blood samples were collected before (during baseline period) and after the intravenous administration of carbachol. Simultaneously, the levels of angiotensin I (Ang I), angiotensin II (Ang II) and vasopressin in the fetal plasma were detected by immunoradiological method. Also, blood gas, plasma osmolality and electrolyte concentrations were analyzed in blood samples. Results showed that in chronically prepared ovine fetus, intravenous infusion of carbachol led to a significant decrease of heart rate (P < 0.05), and a transient decrease followed by an increase of blood pressure (P < 0.05) within 30 min. After the intravenous infusion of carbachol, blood concentrations of Ang I and Ang II in near-term ovine fetus were both significantly increased (P < 0.05); however, blood concentration of vasopressin, values of blood gas, electrolytes and plasma osmolality in near-term ovine fetus were not significantly changed (P > 0.05). Blood levels of Ang I and Ang II in the atropine (M receptor antagonist) + carbachol intravenous administration group was lower than those in the carbachol group without atropine administration (P < 0.05). In conclusion, this study indicates that the near-term changes of cardiovascular system induced by intravenous administration of carbachol in ovine fetus, such as blood pressure and heart rate, are associated with the changes of hormones of circulatory renin-angiotensin system. PMID:22717634

  2. Dual-circuit, multiple-effect refrigeration system and method

    DOEpatents

    DeVault, Robert C.

    1995-01-01

    A dual circuit absorption refrigeration system comprising a high temperature single-effect refrigeration loop and a lower temperature double-effect refrigeration loop separate from one another and provided with a double-condenser coupling therebetween. The high temperature condenser of the single-effect refrigeration loop is double coupled to both of the generators in the double-effect refrigeration loop to improve internal heat recovery and a heat and mass transfer additive such as 2-ethyl-1-hexanol is used in the lower temperature double-effect refrigeration loop to improve the performance of the absorber in the double-effect refrigeration loop.

  3. Diesel engine dual path exhaust cleaner and burner system

    SciTech Connect

    Stark, T.L.

    1983-02-15

    A dual filter element exhaust cleaner and burner system for diesel engines provides for the trapping of particulates in the engine exhaust gases by their passage through filter elements, as selectively controlled by means of a four-way valve. Collected particulates in a non-active particulate filter element are incinerated by means of a heater, with this filter element, during incineration, being supplied with exhaust gases through a constant flow exhaust gas regulator whereby incineration of the particulates will occur at a controlled rate independent of engine speed.

  4. Dual Heat Pulse, Dual Layer Thermal Protection System Sizing Analysis and Trade Studies for Human Mars Entry Descent and Landing

    NASA Technical Reports Server (NTRS)

    McGuire, Mary Kathleen

    2011-01-01

    NASA has been recently updating design reference missions for the human exploration of Mars and evaluating the technology investments required to do so. The first of these started in January 2007 and developed the Mars Design Reference Architecture 5.0 (DRA5). As part of DRA5, Thermal Protection System (TPS) sizing analysis was performed on a mid L/D rigid aeroshell undergoing a dual heat pulse (aerocapture and atmospheric entry) trajectory. The DRA5 TPS subteam determined that using traditional monolithic ablator systems would be mass expensive. They proposed a new dual-layer TPS concept utilizing an ablator atop a low thermal conductivity insulative substrate to address the issue. Using existing thermal response models for an ablator and insulative tile, preliminary hand analysis of the dual layer concept at a few key heating points indicated that the concept showed potential to reduce TPS masses and warranted further study. In FY09, the followon Entry, Descent and Landing Systems Analysis (EDL-SA) project continued by focusing on Exploration-class cargo or crewed missions requiring 10 to 50 metric tons of landed payload. The TPS subteam advanced the preliminary dual-layer TPS analysis by developing a new process and updated TPS sizing code to rapidly evaluate mass-optimized, full body sizing for a dual layer TPS that is capable of dual heat pulse performance. This paper describes the process and presents the results of the EDL-SA FY09 dual-layer TPS analyses on the rigid mid L/D aeroshell. Additionally, several trade studies were conducted with the sizing code to evaluate the impact of various design factors, assumptions and margins.

  5. Dual-phase evolution in complex adaptive systems

    PubMed Central

    Paperin, Greg; Green, David G.; Sadedin, Suzanne

    2011-01-01

    Understanding the origins of complexity is a key challenge in many sciences. Although networks are known to underlie most systems, showing how they contribute to well-known phenomena remains an issue. Here, we show that recurrent phase transitions in network connectivity underlie emergent phenomena in many systems. We identify properties that are typical of systems in different connectivity phases, as well as characteristics commonly associated with the phase transitions. We synthesize these common features into a common framework, which we term dual-phase evolution (DPE). Using this framework, we review the literature from several disciplines to show that recurrent connectivity phase transitions underlie the complex properties of many biological, physical and human systems. We argue that the DPE framework helps to explain many complex phenomena, including perpetual novelty, modularity, scale-free networks and criticality. Our review concludes with a discussion of the way DPE relates to other frameworks, in particular, self-organized criticality and the adaptive cycle. PMID:21247947

  6. Dual-learning systems during speech category learning

    PubMed Central

    Chandrasekaran, Bharath; Yi, Han-Gyol; Maddox, W. Todd

    2013-01-01

    Dual-systems models of visual category learning posit the existence of an explicit, hypothesis-testing ‘reflective’ system, as well as an implicit, procedural-based ‘reflexive’ system. The reflective and reflexive learning systems are competitive and neurally dissociable. Relatively little is known about the role of these domain-general learning systems in speech category learning. Given the multidimensional, redundant, and variable nature of acoustic cues in speech categories, our working hypothesis is that speech categories are learned reflexively. To this end, we examined the relative contribution of these learning systems to speech learning in adults. Native English speakers learned to categorize Mandarin tone categories over 480 trials. The training protocol involved trial-by-trial feedback and multiple talkers. Experiment 1 and 2 examined the effect of manipulating the timing (immediate vs. delayed) and information content (full vs. minimal) of feedback. Dual-systems models of visual category learning predict that delayed feedback and providing rich, informational feedback enhance reflective learning, while immediate and minimally informative feedback enhance reflexive learning. Across the two experiments, our results show feedback manipulations that targeted reflexive learning enhanced category learning success. In Experiment 3, we examined the role of trial-to-trial talker information (mixed vs. blocked presentation) on speech category learning success. We hypothesized that the mixed condition would enhance reflexive learning by not allowing an association between talker-related acoustic cues and speech categories. Our results show that the mixed talker condition led to relatively greater accuracies. Our experiments demonstrate that speech categories are optimally learned by training methods that target the reflexive learning system. PMID:24002965

  7. Dual-Frequency Airborne Scanning Rain Radar Antenna System

    NASA Technical Reports Server (NTRS)

    Hussein, Ziad A.; Green, Ken

    2004-01-01

    A compact, dual-frequency, dual-polarization, wide-angle-scanning antenna system has been developed as part of an airborne instrument for measuring rainfall. This system is an upgraded version of a prior single-frequency airborne rain radar antenna system and was designed to satisfy stringent requirements. One particularly stringent combination of requirements is to generate two dual-polarization (horizontal and vertical polarizations) beams at both frequencies (13.405 and 35.605 GHz) in such a way that the beams radiated from the antenna point in the same direction, have 3-dB angular widths that match within 25 percent, and have low sidelobe levels over a wide scan angle at each polarization-and-frequency combination. In addition, the system is required to exhibit low voltage standing-wave ratios at both frequencies. The system (see figure) includes a flat elliptical scanning reflector and a stationary offset paraboloidal reflector illuminated by a common-aperture feed system that comprises a corrugated horn with four input ports one port for each of the four frequency-and-polarization combinations. The feed horn is designed to simultaneously (1) under-illuminate the reflectors 35.605 GHz and (2) illuminate the reflectors with a 15-dB edge taper at 13.405 GHz. The scanning mirror is rotated in azimuth to scan the antenna beam over an angular range of 20 in the cross-track direction for wide swath coverage, and in elevation to compensate for the motion of the aircraft. The design of common-aperture feed horn makes it possible to obtain the required absolute gain and low side-lobe levels in wide-angle beam scanning. The combination of the common-aperture feed horn with the small (0.3) focal-length-to-diameter ratio of the paraboloidal reflector makes it possible for the overall system to be compact enough that it can be mounted on a DC-8 airplane.

  8. Importance of dual delivery systems for bone tissue engineering.

    PubMed

    Farokhi, Mehdi; Mottaghitalab, Fatemeh; Shokrgozar, Mohammad Ali; Ou, Keng-Liang; Mao, Chuanbin; Hosseinkhani, Hossein

    2016-03-10

    Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering. PMID:26805518

  9. Dual spectral band reconnaissance systems for multiple platforms

    NASA Astrophysics Data System (ADS)

    Wyatt, Steve H.

    2002-11-01

    Recon/Optical, Inc. (ROI) has a family of digital, dual spectral band (visible/IR) cameras that is readily applicable for reconnaissance missions on virtually any airborne platform available today. Each camera is based on a modular design that allows reconfiguration for a multitude of volumetric and mission constraints. The open architecture facilitates integration as either a reconnaissance system components or as the system master controller. Output data can be formatted to satisfy either NITF or STANAG requirements making the camera adaptable to applications throughout the world. These cameras offer several key features, including a stabilization system, that can be tuned to each platform, optional data compression to optimize data storage and data link performance, and a camera-mounted inertial measurement unit for improved pointing accuracy. These and other core capabilities are especially beneficial to users with unique platform integration requirements. Camera flexibility translates into low-risk integration to a variety of reconnaissance platforms.

  10. Dual annular rotating "windowed" nuclear reflector reactor control system

    DOEpatents

    Jacox, Michael G.; Drexler, Robert L.; Hunt, Robert N. M.; Lake, James A.

    1994-01-01

    A nuclear reactor control system is provided in a nuclear reactor having a core operating in the fast neutron energy spectrum where criticality control is achieved by neutron leakage. The control system includes dual annular, rotatable reflector rings. There are two reflector rings: an inner reflector ring and an outer reflector ring. The reflectors are concentrically assembled, surround the reactor core, and each reflector ring includes a plurality of openings. The openings in each ring are capable of being aligned or non-aligned with each other. Independent driving means for each of the annular reflector rings is provided so that reactor criticality can be initiated and controlled by rotation of either reflector ring such that the extent of alignment of the openings in each ring controls the reflection of neutrons from the core.

  11. A dual-modal retinal imaging system with adaptive optics

    PubMed Central

    Meadway, Alexander; Girkin, Christopher A.; Zhang, Yuhua

    2013-01-01

    An adaptive optics scanning laser ophthalmoscope (AO-SLO) is adapted to provide optical coherence tomography (OCT) imaging. The AO-SLO function is unchanged. The system uses the same light source, scanning optics, and adaptive optics in both imaging modes. The result is a dual-modal system that can acquire retinal images in both en face and cross-section planes at the single cell level. A new spectral shaping method is developed to reduce the large sidelobes in the coherence profile of the OCT imaging when a non-ideal source is used with a minimal introduction of noise. The technique uses a combination of two existing digital techniques. The thickness and position of the traditionally named inner segment/outer segment junction are measured from individual photoreceptors. In-vivo images of healthy and diseased human retinas are demonstrated. PMID:24514529

  12. Dual-imaging system for burn depth diagnosis.

    PubMed

    Ganapathy, Priya; Tamminedi, Tejaswi; Qin, Yi; Nanney, Lillian; Cardwell, Nancy; Pollins, Alonda; Sexton, Kevin; Yadegar, Jacob

    2014-02-01

    Currently, determination of burn depth and healing outcomes has been limited to subjective assessment or a single modality, e.g., laser Doppler imaging. Such measures have proven less than ideal. Recent developments in other non-contact technologies such as optical coherence tomography (OCT) and pulse speckle imaging (PSI) offer the promise that an intelligent fusion of information across these modalities can improve visualization of burn regions thereby increasing the sensitivity of the diagnosis. In this work, we combined OCT and PSI images to classify the degree of burn (superficial, partial-thickness and full-thickness burns). Algorithms were developed to integrate and visualize skin structure (with and without burns) from the two modalities. We have completed the proposed initiatives by employing a porcine burn model and compiled results that attest to the utility of our proposed dual-modal fusion approach. Computer-derived data indicating the varying burn depths were validated through immunohistochemical analysis performed on burned skin tissue. The combined performance of OCT and PSI modalities provided an overall ROC-AUC=0.87 (significant at p<0.001) in classifying different burn types measured after 1-h of creating the burn wounds. Porcine model studies to assess feasibility of this dual-imaging system for wound tracking are underway. PMID:23790396

  13. Dual Fan Separator within the Universal Waste Management System

    NASA Technical Reports Server (NTRS)

    Stapleton, Tom; Converse, Dave; Broyan, James Lee, Jr.

    2014-01-01

    Since NASA's new spacecraft in development for both LEO and Deep Space capability have considerable crew volume reduction in comparison to the Space Shuttle, it is clear that NASA requires a smaller and less expensive commode. The UTAS Universal Waste Management System (UWMS) was designed to address these new constraints, resulting in an 80% volume reduction in the cabin while enhancing performance. Whereas all of the current space commodes use air flow to capture both urine and feces and separate air from the captured air/urine mixture, the UWMS commode and urine fans and the urine separator were combined into a single unit. This unit enables use of a single motor and motor controller, which provides considerable packaging and weight efficiency. In some of the intended platform applications for the UWMS, the urine is pumped to a water reclamation system. The ISS Urine Processor Assembly (UPA) system requires delivered urine to include less than 0.25% air inclusion. Air inclusion in centrifugal urine separators is greatly dependent on its rotational speed. To satisfy this requirement, a gear reducer was included, allowing the fans to rotate at a much higher speed than the separator. This new design, the Dual Fan Separator (DFS) has been designed, prototyped and tested. This paper will outline the studies and analysis performed to develop the design configuration for testing. The studies included a configuration trade study, dynamic stability analysis of the rotating bodies and a performance analysis of included labyrinth seals. NASA is considereing a program to fly the UWMS aboard the ISS as a flight experiment. The goal of the design activity is to elevate the Technical Readiness Level (TRL) of the Dual Fan Separator and determine if the concept is ready to be included in flight experiment deliverable.

  14. Study of the enantioseparation capability of chiral dual system based on chondroitin sulfate C in CE.

    PubMed

    Chen, Jiaquan; Du, Yingxiang; Zhu, Fenxia; Chen, Bin; Zhang, Qi; Du, Shuaijing; Li, Ping

    2015-02-01

    It has been reported that chiral dual system is able to improve the enantioseparation of enantiomers in many cases. Currently, the dual systems involved in CE chiral separation are mostly dual CDs systems, and the polysaccharides-based chiral dual system was reported in only one paper. To the best of our knowledge, the use of chondroitin sulfate C (CSC)-based dual system for enantiomeric separation has not been reported previously. Herein, four CSC-based chiral dual systems, namely CSC/glycogen, CSC/chondroitin sulfate A (CSA), CSC/hydroxypropyl-β-CD (HP-β-CD), as well as CSC/β-CD (β-CD), were evaluated for the first time for their enantioseparation capability by CE in this paper. During the course of the work, the influences of chiral selector concentration and buffer pH values on enantioseparation in dual systems were systematically investigated. Under the optimized conditions, the dual system consisting of CSC and glycogen exhibited better separations toward nefopam, duloxetine, sulconazole, atenolol, laudanosine, and cetirizine enantiomers compared to the single CSC or glycogen system. The combination of CSC and HP-β-CD improved the separation of amlodipine and chlorphenamine enantiomers. However, no synergistic effect was observed in the CSC/CSA and CSC/β-CD systems. PMID:25421375

  15. Stereoscopic Displays And The Human Dual Visual System

    NASA Astrophysics Data System (ADS)

    Clapp, Robert E.

    1986-05-01

    There is only one real world. We "see" that world as extending into three dimensions because we look at it with two visual systems and with two eyes. We are not presented with two "pictures" of the real world, but with two separate sets of inputs into two separate systems. The analog of the eye as a camera has been a constant problem in the visualization of the "seeing" process. Overcoming the persistence of such an approach is the first requirement in developing a true stereoscopic display system. The eye is a dynamic sensing apparatus and supplies the brain with visual inputs. The brain constructs the scene we "see", and is responsible for our perceptions of the visual world. The sensory inputs from the human dual visual system (Ambient - wide FOV, Focal - detail FOV) are combined with other body senses in this perceptual process. Indeed, other body senses, in some degree, direct and control where and at what our eyes look. This process of conceptualization of the "real" world as perceived by ourselves can be related only within limits to the "real" world as perceived by others.. This paper addresses the processes by which our minds (with sensor inputs) work to form our stereoscopic perceptual concepts of the world, real or simulated, and the advantages (and problems) caused by our egocentric reduction of those data inputs. Discussion and evaluation of stereoscopic display systems compares current and future display systems.

  16. Athermalization for infrared dual field-of-view optical system

    NASA Astrophysics Data System (ADS)

    Yang, Changcheng; Li, Shenghui

    2008-03-01

    With the principle of mechanical passive athermalization, a method of making the dual field-of-view (DFOV) switching zoom system for passive athermalization is presented. The long effective focal length (EFL) and short EFL have the same focus shift values of temperature by optical material combination of switching groups. So the long EFL and short EFL of this system achieve the best temperature compensation simultaneously by moving the compensated lens with the same distance, and the system has the best images and parfocality in a large working temperature. A DFOV switching zoom system is designed. It has a relative aperture of f/4.0, 100% cold shield efficiency, the EFL of 180mm/60mm at 3.7-4.8μm. The movement of compensated lens can be achieved with four layers of aluminum/titanium materials. Compared with the MTF of a normal switching zoom system without athermalization, this system needn't move the compensated lens repeatedly to obtain the best images from -30°C to 70°C and enhances the performance of target tracking and recognition.

  17. Dual field of view optical system for colonoscope

    NASA Astrophysics Data System (ADS)

    Katkam, Rajender

    The present dual field of view flexible colonoscope can provide both forward view and radial or backward view of the colon to improve detection of cancerous polyps. The colonoscope has its own illumination that illuminates the parts of the colon viewed by imaging optics. The optical system, limited only by the diffraction effects at the exit pupil over the entire visible spectrum, can provide high resolution and is suitable for color imaging. The flexible colonoscope has an on-board sensor at the proximal end of the colonoscope to improve resolution. The proximal end of colonoscope measures only 8 mm in diameter and 20 mm in length. The present colonoscope has the potential to be scaled down to as small as 6 mm inner diameter from the present 8 mm.

  18. Dual strain gage balance system for measuring light loads

    NASA Technical Reports Server (NTRS)

    Roberts, Paul W. (Inventor)

    1991-01-01

    A dual strain gage balance system for measuring normal and axial forces and pitching moment of a metric airfoil model imparted by aerodynamic loads applied to the airfoil model during wind tunnel testing includes a pair of non-metric panels being rigidly connected to and extending towards each other from opposite sides of the wind tunnel, and a pair of strain gage balances, each connected to one of the non-metric panels and to one of the opposite ends of the metric airfoil model for mounting the metric airfoil model between the pair of non-metric panels. Each strain gage balance has a first measuring section for mounting a first strain gage bridge for measuring normal force and pitching moment and a second measuring section for mounting a second strain gage bridge for measuring axial force.

  19. Study of dual-channel infrared spectroradiometer systems

    NASA Technical Reports Server (NTRS)

    Wrubel, J. A.

    1973-01-01

    A dual channel infrared spectroradiometer system was installed at a high altitude facility where spectral data were obtained from F2/H2, FLOX/CH4, FLOX/B2H6, OF2/CH4, and OF2/B2H6 propellant combinations. A good HF emission spectra was obtained for tests with the OF2B2H6 propellant combination. Subsequently, data were obtained on the LOX/GH2 propellant combination at sea level and altitude conditions that were inconsistent because the calculation of plume properties led to physically unrealistic results. The inconsistencies resulted from measurement accuracy not being within the narrow limits required by the data reduction scheme. Although the anticipated program results were not obtained, the data gathered are useful for guiding future experimental efforts and formulations of less sensitive analytical models.

  20. The competitive advantage of a dual-transporter system.

    PubMed

    Levy, Sagi; Kafri, Moshe; Carmi, Miri; Barkai, Naama

    2011-12-01

    Cells use transporters of different affinities to regulate nutrient influx. When nutrients are depleted, low-affinity transporters are replaced by high-affinity ones. High-affinity transporters are helpful when concentrations of nutrients are low, but the advantage of reducing their abundance when nutrients are abundant is less clear. When we eliminated such reduced production of the Saccharomyces cerevisiae high-affinity transporters for phosphate and zinc, the elapsed time from the initiation of the starvation program until the lack of nutrients limited growth was shortened, and recovery from starvation was delayed. The latter phenotype was rescued by constitutive activation of the starvation program. Dual-transporter systems appear to prolong preparation for starvation and to facilitate subsequent recovery, which may optimize sensing of nutrient depletion by integrating internal and external information about nutrient availability. PMID:22158820

  1. Method and system for dual resolution translation stage

    DOEpatents

    Halpin, John Michael

    2014-04-22

    A dual resolution translation stage includes a stage assembly operable to receive an optical element and a low resolution adjustment device mechanically coupled to the stage assembly. The dual resolution stage also includes an adjustable pivot block mechanically coupled to the stage assembly. The adjustable pivot block includes a pivot shaft. The dual resolution stage further includes a lever arm mechanically coupled to the adjustable pivot block. The lever arm is operable to pivot about the pivot shaft. The dual resolution stage additionally includes a high resolution adjustment device mechanically coupled to the lever arm and the stage assembly.

  2. Dual Systems Competence [Image Omitted] Procedural Processing: A Relational Developmental Systems Approach to Reasoning

    ERIC Educational Resources Information Center

    Ricco, Robert B.; Overton, Willis F.

    2011-01-01

    Many current psychological models of reasoning minimize the role of deductive processes in human thought. In the present paper, we argue that deduction is an important part of ordinary cognition and we propose that a dual systems Competence [image omitted] Procedural processing model conceptualized within relational developmental systems theory…

  3. Dual redundant arm system operational quality measures and their applications - Static measures

    NASA Technical Reports Server (NTRS)

    Lee, Sukhan; Kim, Sungbok

    1990-01-01

    The authors present dual-arm system static operational quality measures which quantify the efficiency and capability of a dual-arm system in generating Cartesian velocities and static forces. First, they define and analyze the kinematic interactions between the two arms incurred by the various modes of dual-arm cooperation, such as transport, assembly, and grasping modes of cooperation, and specify the kinematic constraints imposed on individual arms in Cartesian space due to the kinematic interactions. Dual-arm static manipulability is presented. Finally, dual-arm operational quality is scaled by a task-oriented operational quality measure (TOQs) obtained by the comparison between the desired and actual static manipulabilities. TOQs is used in the optimization of dual-arm joint configurations. Simulation results are shown.

  4. Control system for cheng dual-fluid cycle engine system

    SciTech Connect

    Cheng, D.Y.

    1987-07-21

    A dual-fluid heat engine is described which is operated to produce co-generated process steam having: a chamber; compressor means for introducing a first gaseous working fluid comprising air into the chamber, the compressor means having a predetermined pressure ratio (CPR); means for introducing a second liquid-vapor working fluid comprising water in the form of a vapor within the chamber at a defined water/air working fluid ratio (XMIX); means for heating the water vapor and air in the chamber at a defined specific heat input rate (SHIR); turbine means responsive to the mixture of the first and second working fluids for converting the energy associated with the mixture to mechanical energy, the temperature of the mixture entering the turbine means defining the turbine inlet temperature (TIT) and having a design maximum turbine inlet temperature (TITmax); counterflow heat exchanger means for transferring residual thermal energy from the exhausted mixture of first and second working fluids to the incoming working fluid water to thereby preheat the same to water vapor prior to its introduction within the chamber; means for diverting water vapor from the chamber, if desired, for co-generated process steam; and wherein the improvement comprises: means for operating the engine under partial load conditions such that when substantially no co-generated process steam is required. The engine control path follows a locus of peak efficiency points resulting in declining TIT as the load decreases, and such that XMIX and SHIR are selected so that for a given value of TIT, XMIX is at or near XMIX peak, where XMIX peak occurs when conditions are met simultaneously.

  5. The German 'Dual System' of Occupational Training: A Much-Replicated but Oft-Failed Transfer.

    ERIC Educational Resources Information Center

    Wilson, David N.

    Germany's Dual System, which consists of in-school and in-enterprise components, facilitates entry into 374 recognized technical, white-collar and blue-collar occupations listed in training regulations that are grounded in legislation. The Dual System's origins and development in Germany were examined along with several attempts to replicate the…

  6. The Improved Dual-view Field Goniometer System FIGOS

    PubMed Central

    Schopfer, Jürg; Dangel, Stefan; Kneubühler, Mathias; Itten, Klaus I.

    2008-01-01

    In spectrodirectional Remote Sensing (RS) the Earth's surface reflectance characteristics are studied by means of their angular dimensions. Almost all natural surfaces exhibit an individual anisotropic reflectance behaviour due to the contrast between the optical properties of surface elements and background and the geometric surface properties of the observed scene. The underlying concept, which describes the reflectance characteristic of a specific surface area, is called the bidirectional reflectance distribution function (BRDF). BRDF knowledge is essential for both correction of directional effects in RS data and quantitative retrieval of surface parameters. Ground-based spectrodirectional measurements are usually performed with goniometer systems. An accurate retrieval of the bidirectional reflectance factors (BRF) from field goniometer measurements requires hyperspectral knowledge of the angular distribution of the reflected and the incident radiation. However, prior to the study at hand, no operational goniometer system was able to fulfill this requirement. This study presents the first dual-view field goniometer system, which is able to simultaneously collect both the reflected and the incident radiation at high angular and spectral resolution and, thus, providing the necessary spectrodirectional datasets to accurately retrieve the surface specific BRF. Furthermore, the angular distribution of the incoming diffuse radiation is characterized for various atmospheric conditions and the BRF retrieval is performed for an artificial target and compared to laboratory spectrodirectional measurement results obtained with the same goniometer system. Suggestions for further improving goniometer systems are given and the need for intercalibration of various goniometers as well as for standardizing spectrodirectional measurements is expressed.

  7. Design of camera and spectrometer dual-use system

    NASA Astrophysics Data System (ADS)

    Qi, Yong-hong; Xue, Bin; Zhao, Yi-yi; Tao, Jin-you

    2013-08-01

    Imaging spectrometers based on prism-grating-prism (PGP) have advantage of direct vision, as a basis for the design of an optical system for a spectrometer and camera dual-use, the system can plug the light splitting element to switch between the spectrometer and camera. This paper has discussed the working principles and structure of the PGP and spectrometer, collimating and focusing lens design principles, then the design result has been presented. The spectral range of the system is 400-800nm, the pixel size of CCD used is 10um × 10um, 1010 × 1018 pixels, the object space numerical aperture is 0.1. In order to reduce the cost and eliminate aberration, collimating lens and focusing lens have symmetric structure, in order to improve the diffraction efficiency, PGP uses the volume phase holographic transmission grating. After optimization the design by ZEMAX software, the whole spectral range resolution is better than 1nm in average, the MTF at Nyquist frequency is greater than 0.7, the length of the whole system is 87mm.

  8. General equilibrium characteristics of a dual-lift helicopter system

    NASA Technical Reports Server (NTRS)

    Cicolani, L. S.; Kanning, G.

    1986-01-01

    The equilibrium characteristics of a dual-lift helicopter system are examined. The system consists of the cargo attached by cables to the endpoints of a spreader bar which is suspended by cables below two helicopters. Results are given for the orientation angles of the suspension system and its internal forces, and for the helicopter thrust vector requirements under general circumstances, including nonidentical helicopters, any accelerating or static equilibrium reference flight condition, any system heading relative to the flight direction, and any distribution of the load to the two helicopters. Optimum tether angles which minimize the sum of the required thrust magnitudes are also determined. The analysis does not consider the attitude degrees of freedom of the load and helicopters in detail, but assumes that these bodies are stable, and that their aerodynamic forces in equilibrium flight can be determined independently as functions of the reference trajectory. The ranges of these forces for sample helicopters and loads are examined and their effects on the equilibrium characteristics are given parametrically in the results.

  9. Abradable dual-density ceramic turbine seal system

    NASA Technical Reports Server (NTRS)

    Clingman, D. L.; Schechter, B.; Cross, K. R.; Cavanagh, J. R.

    1981-01-01

    A plasma sprayed dual density ceramic abradable seal system for direct application to the HPT seal shroud of small gas turbine engines. The system concept is based on the thermal barrier coating and depends upon an additional layer of modified density ceramic material adjacent to the gas flow path to provide the desired abradability. This is achieved by codeposition of inert fillers with yttria stabilized zirconia (YSZ) to interrupt the continuity of the zirconia struture. The investigation of a variety of candidate fillers, with hardness values as low as 2 on Moh's scale, led to the conclusion that solid filler materials in combination with a YSZ matrix, regardless of their hardness values, have a propensity for compacting rather than shearing as originally expected. The observed compaction is accompanied by high energy dissipation in the rub interaction, usually resulting in the adhesive transfer of blade material to the stationary seal member. Two YSZ based coating systems which incorported hollow alumino silicate spheres as density reducing agents were surveyed over the entire range of compositions from 100 percent filler to 100 percent YSZ. Abradability and erosion characteristics were determined, hardness and permeability characterized, and engine experience acquired with several system configurations.

  10. In-Flight performance of MESSENGER's Mercury dual imaging system

    USGS Publications Warehouse

    Hawkins, S.E.; Murchie, S.L.; Becker, K.J.; Selby, C.M.; Turner, F.S.; Noble, M.W.; Chabot, N.L.; Choo, T.H.; Darlington, E.H.; Denevi, B.W.; Domingue, D.L.; Ernst, C.M.; Holsclaw, G.M.; Laslo, N.R.; Mcclintock, W.E.; Prockter, L.M.; Robinson, M.S.; Solomon, S.C.; Sterner, R.E.

    2009-01-01

    The Mercury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft, launched in August 2004 and planned for insertion into orbit around Mercury in 2011, has already completed two flybys of the innermost planet. The Mercury Dual Imaging System (MDIS) acquired nearly 2500 images from the first two flybys and viewed portions of Mercury's surface not viewed by Mariner 10 in 1974-1975. Mercury's proximity to the Sun and its slow rotation present challenges to the thermal design for a camera on an orbital mission around Mercury. In addition, strict limitations on spacecraft pointing and the highly elliptical orbit create challenges in attaining coverage at desired geometries and relatively uniform spatial resolution. The instrument designed to meet these challenges consists of dual imagers, a monochrome narrow-angle camera (NAC) with a 1.5?? field of view (FOV) and a multispectral wide-angle camera (WAC) with a 10.5?? FOV, co-aligned on a pivoting platform. The focal-plane electronics of each camera are identical and use a 1024??1024 charge-coupled device detector. The cameras are passively cooled but use diode heat pipes and phase-change-material thermal reservoirs to maintain the thermal configuration during the hot portions of the orbit. Here we present an overview of the instrument design and how the design meets its technical challenges. We also review results from the first two flybys, discuss the quality of MDIS data from the initial periods of data acquisition and how that compares with requirements, and summarize how in-flight tests are being used to improve the quality of the instrument calibration. ?? 2009 SPIE.

  11. Dual redundant arm system operational quality measures and their applications - Dynamic measures

    NASA Technical Reports Server (NTRS)

    Lee, Sukhan; Kim, Sungbok

    1990-01-01

    Dual-arm dynamic operation quality measures are presented which quantify the efficiency and capability of generating Cartesian accelerations by two cooperative arms based on the analysis of dual-arm dynamic interactions. Dual-arm dynamic manipulability is defined as the efficiency of generating Cartesian accelerations under the dynamic and kinematic interactions between individual arms and an object under manipulation. The analysis of dual-arm dynamic interactions is based on the so-called Cartesian space agent model of an arm, which represents an individual arm as a force source acting upon a point mass with the effective Cartesian space arm dynamics and an environment or an object under manipulation. The Cartesian space agent model of an arm makes it possible to derive the dynamic and kinematic constraints involved in the transport, assembly and grasping modes of dual-arm cooperation. A task-oriented operational quality measure, (TOQd) is defined by evaluating dual-arm dynamic manipulability in terms of given task requirements. TOQd is used in dual-arm joint configuration optimization. Simulation results are shown. A complete set of forward dynamic equations for a dual-arm system is derived, and dual-arm dynamic operational quality measures for various modes of dual-arm cooperation allowing sliding contacts are established.

  12. A Dual Gold Nanoparticle System for Mesenchymal Stem Cell Tracking

    PubMed Central

    Ricles, L.M.; Nam, S.Y.; Treviño, E.A.; Emelianov, S.Y.; Suggs, L.J.

    2015-01-01

    Stem cell-based therapies have demonstrated improved outcomes in preclinical and clinical trials for treating cardiovascular ischemic diseases. However, the contribution of stem cells to vascular repair is poorly understood. To elucidate these mechanisms, many have attempted to monitor stem cells following their delivery in vivo, but these studies have been limited by the fact that many contrast agents, including nanoparticles, are commonly passed on to non-stem cells in vivo. Specifically, cells of the reticuloendothelial system, such as macrophages, frequently endocytose free contrast agents, resulting in the monitoring of macrophages instead of the stem cell therapy. Here we demonstrate a dual gold nanoparticle system which is capable of monitoring both delivered stem cells and infiltrating macrophages using photoacoustic imaging. In vitro analysis confirmed preferential labeling of the two cell types with their respective nanoparticles and the maintenance of cell function following nanoparticle labeling. In addition, delivery of the system within a rat hind limb ischemia model demonstrated the ability to monitor stem cells and distinguish and quantify macrophage infiltration. These findings were confirmed by histology and mass spectrometry analysis. This work has important implications for cell tracking and monitoring cell-based therapies. PMID:25709814

  13. A laboratory simulation of a single-axis dual-level precision pointing system

    NASA Technical Reports Server (NTRS)

    Bullock, G. F.; Morrell, F. R.; Romanczyk, K. C.

    1973-01-01

    The laboratory simulation of a scaled single-axis dual-level control system for a large space telescope is demonstrated. The dual-level control system consists of a coarse-body-pointing system and a fine-pointing system, which uses an image motion compensator, an image dissector tube, and digital electronics. The results of the simulation indicate that the dual-level system can be used to provide tracking capability within one-tenth of a diffraction-limited image diameter of a 3-meter f/100 telescope for stars up to a +12.3 visual magnitude.

  14. 14 CFR 105.43 - Use of single-harness, dual-parachute systems.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Use of single-harness, dual-parachute... TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES PARACHUTE OPERATIONS Parachute Equipment and Packing § 105.43 Use of single-harness, dual-parachute systems. No person may conduct a...

  15. 14 CFR 105.43 - Use of single-harness, dual-parachute systems.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Use of single-harness, dual-parachute... TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES PARACHUTE OPERATIONS Parachute Equipment and Packing § 105.43 Use of single-harness, dual-parachute systems. No person may conduct a...

  16. 14 CFR 105.43 - Use of single-harness, dual-parachute systems.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Use of single-harness, dual-parachute... TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES PARACHUTE OPERATIONS Parachute Equipment and Packing § 105.43 Use of single-harness, dual-parachute systems. No person may conduct a...

  17. 14 CFR 105.43 - Use of single-harness, dual-parachute systems.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Use of single-harness, dual-parachute... TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES PARACHUTE OPERATIONS Parachute Equipment and Packing § 105.43 Use of single-harness, dual-parachute systems. No person may conduct a...

  18. 14 CFR 105.43 - Use of single-harness, dual-parachute systems.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Use of single-harness, dual-parachute... TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES PARACHUTE OPERATIONS Parachute Equipment and Packing § 105.43 Use of single-harness, dual-parachute systems. No person may conduct a...

  19. A Dual Communication and Imaging Underwater Acoustic System

    NASA Astrophysics Data System (ADS)

    Fu, Tricia C.

    A dual communication and imaging underwater acoustic system is proposed and developed throughout this dissertation. Due to the wide variation in underwater channel characteristics, the research here focuses more on robustness to multipath in the shallow underwater acoustic environment, rather than high bit-rate applications and signaling schemes. Lower bit-rate (in the hundreds of bits per second (bps) to low kbps), applications such as the transfer of ecological telemetry data, e.g. conductivity or temperature data, are the primary focus of this dissertation. The parallels between direct sequence spread spectrum in digital communication and pulse-echo with pulse compression in imaging, and channel estimation in communication and range profile estimation in imaging are drawn, leading to a unified communications and imaging platform. A digital communication algorithm for channel order and channel coefficient estimation and symbol demodulation using Matching Pursuit (MP) with Generalized Multiple Hypothesis Testing (GMHT) is implemented in programmable DSP in real time with field experiment results in varying underwater environments for the single receiver (Rx), single transmitter (Tx) case. The custom and off-the-shelf hardware used in the single receiver, single transmitter set of experiments are detailed as well. This work is then extended to the single-input multiple-output (SIMO) case, and then to the full multiple-input multiple-output (MIMO) case. The results of channel estimation are used for simple range profile imaging reconstructions. Successful simulated and experimental results for both transducer array configurations are presented and analyzed. Non-real-time symbol demodulation and channel estimation is performed using experimental data from a scaled testing environment. New hardware based on cost-effective fish-finder transducers for a 6 Rx--1 Tx and 6 Rx--4 Tx transducer array is detailed. Lastly, in an application that is neither communication nor

  20. Vortex dynamics in self-dual Chern-Simons-Higgs systems

    SciTech Connect

    Kim, Y. ); Lee, K. )

    1994-02-15

    We consider vortex dynamics in self-dual Chern-Simons-Higgs systems. We show that the naive Aharonov-Bohm phase is the inverse of the statistical phase expected from the vortex spin, and that the self-dual configurations of vortices are degenerate in energy but not in angular momentum. We also use the path integral formalism to derive the dual formulation of Chern-Simons-Higgs systems in which vortices appear as charged particles. We argue that in addition to the electromagnetic interaction, there is an additional interaction between vortices, the so-called Magnus force, and that these forces can be put together into a single dual electromagnetic'' interaction. This dual electromagnetic interaction leads to the right statistical phase. We also derive and study the effective action for slowly moving vortices, which contains terms both linear and quadratic in the vortex velocity. We show that vortices can be bounded to each other by the Magnus force.

  1. 32-megapixel dual-color CCD imaging system

    NASA Astrophysics Data System (ADS)

    Stubbs, Christopher W.; Marshall, Stuart; Cook, Kenneth H.; Hills, Robert F.; Noonan, Joseph; Akerlof, Carl W.; Alcock, Charles R.; Axelrod, Timothy S.; Bennett, D.; Dagley, K.; Freeman, K. C.; Griest, Kim; Park, Hye-Sook; Perlmutter, Saul; Peterson, Bruce A.; Quinn, Peter J.; Rodgers, A. W.; Sosin, C.; Sutherland, W. J.

    1993-07-01

    We have developed an astronomical imaging system that incorporates a total of eight 2048 X 2048 pixel CCDs into two focal planes, to allow simultaneous imaging in two colors. Each focal plane comprises four 'edge-buttable' detector arrays, on custom Kovar mounts. The clocking and bias voltage levels for each CCD are independently adjustable, but all the CCDs are operated synchronously. The sixteen analog outputs (two per chip) are measured at 16 bits with commercially available correlated double sampling A/D converters. The resulting 74 MBytes of data per frame are transferred over fiber optic links into dual-ported VME memory. The total readout time is just over one minute. We obtain read noise ranging from 6.5 e- to 10 e- for the various channels when digitizing at 34 Kpixels/sec, with full well depths (MPP mode) of approximately 100,000 e- per 15 micrometers X 15 micrometers pixel. This instrument is currently being used in a search of gravitational microlensing from compact objects in our Galactic halo, using the newly refurbished 1.3 m telescope at the Mt. Stromlo Observatory, Australia.

  2. Verification of the dual integral glow analysis dosimetry system

    NASA Astrophysics Data System (ADS)

    Wagner, Eric Christopher

    2000-10-01

    The Dual Integral Glow Analysis (DINGA) method is a unique approach to the determination of the low-LET dose deposited within a thermoluminescent personnel dosimeter. DINGA creates its estimate of the dose deposited by utilizing the integrals of a sub-section of the glow curves obtained from opposite sides of one or more thermoluminescent detectors (TLDs) and knowledge of the TLDs thermophysical parameters. The performance of DINGA is evaluated with computational simulations for a variety of heating methods and error tolerance is also examined by introducing errors into the inputs the DINGA code. It has been found that DINGA's dose estimates are off approximately, in the worst case, the same percentage as the input parameter was varied. Experimental measurements are performed using a hot-gas heating method for large personnel doses and a laser heating method for smaller personnel doses with LiF: Mg, Ti (TLD-100) dosimeters. The dosimeters are exposed to select radiation fields generated by either certified sources or fields characterized by certified equipment. The DINGA dosimetry system is found to correctly report shallow and deep dose well within the limits required for certification by the National Voluntary Accreditation Program. The worst performance quotient is 0.19, well below the strictest limit of 0.30.

  3. Compact dual field of view SWIR/MWIR optical system

    NASA Astrophysics Data System (ADS)

    Vizgaitis, Jay N.; Witte, Kyle; Littleton, Roy; Perconti, Philip

    2011-06-01

    This paper discusses the design and development of a dual field of view, all-refractive infrared optical system that images the mid-wave infrared (MWIR) light in one field of view and the short wave infrared (SWIR) light in the narrower second field of view onto the same detector. The narrow field of view images the SWIR radiation at a slow f/number of 10.0, while the wide field of view images the MWIR radiation at f/1.9. The field of view is changed via a single lens that changes its axial position within the lens, resulting in an axial zoom and an overall magnification change of 6X. The change in focal length and f/number at the same time enables an increased focal length without having to increase the aperture size by the ratio of the focal length change. The large field of view change is achieved by both the motion of the lens, and the use of the spectral properties of the materials that change with wavelength. The change in spectral bands is accomplished via the use of a spectral filter wheel.

  4. Power extraction from vortex-induced vibration of dual mass system

    NASA Astrophysics Data System (ADS)

    Nishi, Yoshiki

    2013-01-01

    This study theoretically examines energy extraction through the vortex-induced vibration (VIV) of a dual mass system. The theory involves a dynamic system comprising two cylinders connected with a few springs, dampers, and a generator. The governing equation for the system is composed of equations of translational motion for the two cylinders and an equation of rotation for the wake oscillator, which is introduced for describing a hydrodynamic lift force acting on a primary cylinder. The harmonic solution of the equations is derived by adopting an averaging method. The analytical solution obtained for a dual mass case is reduced to one for a single mass case by considering a limit of infinite in-between damping and zero mass of secondary cylinder. The calculation shows enhancement of power extraction by the dual mass system, surpassing that by single mass system. This advantage of the dual mass system holds under both constant and variable flow velocities.

  5. Cross Coupling Compensation Strategy and System Test of Dual-Driving Synchronous Control

    NASA Astrophysics Data System (ADS)

    Lu, Hong; Fan, Wei; Xie, Shitong

    This paper focus on the synchronous control of dual-driving system, a cross coupling compensation strategy is proposed to guarantee the synchronization. Based on the stable single servo system, dual-driving synchronous control system is designed. The performance of the dual-driving system adopted cross-coupled strategy' is theoretically analyzed and simulated. Furthermore, the parameters of the speed loop and position loop is regulated to optimize the system. By using frequency domain analysis method to tune parameters of control system, dual-driving synchronous motion is finally well achieved. The results of the performance analysis and the simulation test indicates that this synchronous control scheme has fast response, small dynamic error and robustness to external disturbance.

  6. Sample Analysis Code System for the Dual Channel Counter.

    Energy Science and Technology Software Center (ESTSC)

    1994-09-14

    Version 00 RADCOMPT automates gross alpha and gross beta sample analysis calculations and, in many cases, warns the technologist when a hazard level is being approached or when it has been exceeded. The RADCOMPT program is unique in that it corrects for crosstalk between channels, and in this way provides increased accuracy and efficiency. Even though it is designed explicitly for the analyses of air samples and wipe samples, it can also be used formore » other sample types. It is designed to be used with a dual channel counter (in which one channel is used for alpha detection and the other for beta detection), but may be used with two single channel counters employed for the same purpose. In addition, it provides an automated means for the execution of the following radiological sample analyses protocol: A. Calibration of the counting system B. Calculation of sample activity or air activity concentrations (with the activities of air activity concentrations at the top and bottom of the two-sided 95 percent confidence interval also specified). C. Determination of minimum sample counting times required for detection and/or quantification of specified alpha and beta activities or air activity concentrations. In addition, alternate counting times are determined for alternate activities such that the specified alpha and beta activities are at the top of the 95% confidence interval, increasing the confidence that the activities measured are below the specified limits. D. Calculation of the minimum detectable activities or air activity concentrations. E. Determination of air sample volumes required for detection and/or quantification of specified alpha and beta air activity concentrations. F. Calculation of long-lived activities or air activity concentrations based on radon daughter and thoron daughter decay. G. Calculation of employees DAC-Hours and estimated Committed Effective Dose Equivalent. H. Varying calibration constants (to coincide with possible adjustments to

  7. Dual Fan Separator within the Universal Waste Management System

    NASA Technical Reports Server (NTRS)

    Stapleton, Tom; Converse, Dave; Broyan, James Lee, Jr.

    2014-01-01

    Since NASA's new spacecraft in development for both LEO and Deep Space capability have considerable crew volume reduction in comparison to the Space Shuttle, the need became apparent for a smaller commode. In response the Universal Waste Management System (UWMS) was designed, resulting in an 80% volume reduction from the last US commode, while enhancing performance. The ISS WMS and previous shuttle commodes have a fan supplying air flow to capture feces and a separator to capture urine and separate air from the captured air/urine mixture. The UWMS combined both rotating equipment components into a single unit, referred to at the Dual Fan Separator (DFS). The combination of these components resulted in considerable packaging efficiency and weight reduction, removing inter-component plumbing, individual mounting configurations and required only a single motor and motor controller, in some of the intended UWMS platform applications the urine is pumped to the ISS Urine Processor Assembly (UPA) system. It requires the DFS to include less than 2.00% air inclusion, by volume, in the delivered urine. The rotational speed needs to be kept as low as possible in centrifugal urine separators to reduce air inclusion in the pumped fluid, while fans depend on rotational speed to develop delivered head. To satisfy these conflicting requirements, a gear reducer was included, allowing the fans to rotate at a much higher speed than the separator. This paper outlines the studies and analysis performed to develop the DFS configuration. The studies included a configuration trade study, dynamic stability analysis of the rotating bodies and a performance analysis of included labyrinth seals. NASA is considering a program to fly the UWMS aboard the ISS as a flight experiment. The goal of this activity is to advance the Technical Readiness Level (TRL) of the DFS and determine if the concept is ready to be included as part of the flight experiment deliverable.

  8. Toward an Automatic Calibration of Dual Fluoroscopy Imaging Systems

    NASA Astrophysics Data System (ADS)

    Al-Durgham, Kaleel; Lichti, Derek; Kuntze, Gregor; Sharma, Gulshan; Ronsky, Janet

    2016-06-01

    High-speed dual fluoroscopy (DF) imaging provides a novel, in-vivo solution to quantify the six-degree-of-freedom skeletal kinematics of humans and animals with sub-millimetre accuracy and high temporal resolution. A rigorous geometric calibration of DF system parameters is essential to ensure precise bony rotation and translation measurements. One way to achieve the system calibration is by performing a bundle adjustment with self-calibration. A first-time bundle adjustment-based system calibration was recently achieved. The system calibration through the bundle adjustment has been shown to be robust, precise, and straightforward. Nevertheless, due to the inherent absence of colour/semantic information in DF images, a significant amount of user input is needed to prepare the image observations for the bundle adjustment. This paper introduces a semi-automated methodology to minimise the amount of user input required to process calibration images and henceforth to facilitate the calibration task. The methodology is optimized for processing images acquired over a custom-made calibration frame with radio-opaque spherical targets. Canny edge detection is used to find distinct structural components of the calibration images. Edge-linking is applied to cluster the edge pixels into unique groups. Principal components analysis is utilized to automatically detect the calibration targets from the groups and to filter out possible outliers. Ellipse fitting is utilized to achieve the spatial measurements as well as to perform quality analysis over the detected targets. Single photo resection is used together with a template matching procedure to establish the image-to-object point correspondence and to simplify target identification. The proposed methodology provided 56,254 identified-targets from 411 images that were used to run a second-time bundle adjustment-based DF system calibration. Compared to a previous fully manual procedure, the proposed methodology has

  9. Safe transport of diborane in a dual refrigerant system: A concept

    NASA Technical Reports Server (NTRS)

    Stone, G. R.

    1972-01-01

    Mobile transport system, that can be carried by truck and parked in storage area, consists of an inner container capable of holding 363 kg of diborane and an external, dual refrigeration unit which uses liquid nitrogen and Freon-14.

  10. Enhanced mechanical energy extraction from transverse galloping using a dual mass system

    NASA Astrophysics Data System (ADS)

    Vicente-Ludlam, D.; Barrero-Gil, A.; Velazquez, A.

    2015-03-01

    This paper offers a theoretical study of energy extraction through transverse galloping using a dual-mass system. To this end, a two-degree-of-freedom model is developed where fluid forces on the galloping body are described resorting to quasi-steady hypothesis; the model is solved approximately by using the Harmonic Balance Method. Three possible configurations of the dual-mass system have been analyzed. Two of them show an improvement in the efficiency of energy extraction with respect to that of the single mass configuration when the mechanical properties of the dual-mass system are appropriately chosen. In addition, the dual-mass system promotes a broadening of the values of the incident flow velocities at which the efficiency is kept high.

  11. Dual interferometer system for measuring index of refraction

    NASA Astrophysics Data System (ADS)

    Goodwin, Eric Peter

    The optical power of a lens is determined by the surface curvature and the refractive index, n. Knowledge of the index is required for accurate lens design models and for examining material variations from sample to sample. The refractive index of glass can be accurately measured using a prism spectrometer, but measuring the index of soft contact lens materials presents many challenges. These materials are non-rigid, thin, and must remain hydrated in a saline solution during testing. Clearly an alternative to a prism spectrometer must be used to accurately measure index. A Dual Interferometer System has been designed, built and characterized as a novel method for measuring the refractive index of transparent optical materials, including soft contact lens materials. The first interferometer is a Low Coherence Interferometer in a Twyman-Green configuration with a scanning reference mirror. The contact lens material sample is placed in a measurement cuvette, where it remains hydrated. By measuring the locations of the multiple optical interfaces, the physical thickness t of the material is measured. A new algorithm has been developed for processing the low coherence signals obtained from the reflection at each optical interface. The second interferometer is a Mach-Zehnder interferometer with a tunable HeNe laser light source. This interferometer measures the optical path length (OPL) of the test sample in the cuvette in transmission as a function of five wavelengths in the visible spectrum. This is done using phase-shifting interferometry. Multiple thickness regions are used to solve 2pi phase ambiguities in the OPL. The outputs of the two interferometers are combined to determine the refractive index as a function of wavelength: n(lambda) = OPL(lambda)/t. Since both t and OPL are measured using a detector array, n is measured at hundreds of thousands of data points. A measurement accuracy of 0.0001 in refractive index is achieved with this new instrument, which is

  12. Technology requirements for advanced earth orbital transportation systems. Volume 3: Summary report - dual mode propulsion

    NASA Technical Reports Server (NTRS)

    Hepler, A. K.; Bangsund, E. L.

    1978-01-01

    The impact of dual-mode propulsion on cost-effective technology requirements for advanced earth-orbital transportation systems is considered. Additional objectives were to determine the advantages of the best dual mode concept relative to the LO2/LH2 concept of the basic study. Normal technology requirements applicable to horizontal take-off and landing single-stage-to-orbit systems utilizing dual mode rocket propulsion were projected to the 1985 time period. These technology projections were then incorporated in a vehicle parametric design analysis for two different operational concepts of a dual mode propulsion system. The resultant performance, weights and costs of each concept were compared. The selected propulsion concept was evaluated to confirm the parametric trending/scaling of weights and to optimize the configuration.

  13. [Pharmacovigilance update].

    PubMed

    Livio, F

    2013-01-01

    Main pharmacovigilance updates in 2012 are reviewed here. Dabigatran: elderly patients with renal failure are at higher risk of bleeding. Dual renin-angiotensin-aldosterone system blockade comprising aliskiren is harmful. Incretins: low risk of acute pancreatitis. Interaction between fusidic acid and statins: many reports of rhabdomyolysis. Interactions between boceprevir/telaprevir and antiretroviral therapies: complex, but manageable. Citalopram, ondansetron: maximum recommended doses are reduced. Atomoxetine: significant increase in blood pressure and heart rate in a fraction of exposed patients. Agomelatine: elevated liver enzymes are common. Fingolimod: bradycardia and heart blocks after first dose - stronger safety recommendations regarding use in patients with heart conditions and strengthened cardiovascular monitoring. PMID:23367709

  14. The dual axis radiographic hydrodynamic test (DARHT) facility personnel safety system (PSS) control system

    SciTech Connect

    Jacquez, Edward B

    2008-01-01

    The mission of the Dual Axis Radiograph Hydrodynamic Test (DARHT) Facility is to conduct experiments on dynamic events of extremely dense materials. The PSS control system is designed specifically to prevent personnel from becoming exposed to radiation and explosive hazards during machine operations and/or the firing site operation. This paper will outline the Radiation Safety System (RSS) and the High Explosive Safety System (HESS) which are computer-controlled sets of positive interlocks, warning devices, and other exclusion mechanisms that together form the PSS.

  15. Reductions of self-dual Yang-Mills fields and classical systems

    NASA Astrophysics Data System (ADS)

    Chakravarty, S.; Ablowitz, M. J.; Clarkson, P. A.

    1990-08-01

    One-dimensional reductions of the self-dual Yang-Mills equations yield various classical systems depending on the choice of the Lie algebra associated with the self-dual fields. Included are the Euler-Arnold equations for rigid bodies in n dimensions, the Kovalevskaya top, and a generalization of the Nahm equation which is related to a classical third-order differential equation possessing a movable natural boundary in the complex plane.

  16. Technology requirements for advanced earth-orbital transportation systems, dual-mode propulsion

    NASA Technical Reports Server (NTRS)

    Haefeli, R. C.; Littler, E. G.; Hurley, J. B.; Winter, M. G.

    1977-01-01

    The application of dual-mode propulsion concepts to fully reusable single-stage-to-orbit (SSTO) vehicles is discussed. Dual-mode propulsion uses main rocket engines that consume hydrocarbon fuels as well as liquid hydrogen fuel. Liquid oxygen is used as the oxidizer. These engine concepts were integrated into transportation vehicle designs capable of vertical takeoff, delivering a payload to earth orbit, and return to earth with a horizontal landing. Benefits of these vehicles were assessed and compared with vehicles using single-mode propulsion (liquid hydrogen and oxygen engines). Technology requirements for such advanced transportation systems were identified. Figures of merit, including life-cycle cost savings and research costs, were derived for dual-mode technology programs, and were used for assessments of potential benefits of proposed technology activities. Dual-mode propulsion concepts display potential for significant cost and performance benefits when applied to SSTO vehicles.

  17. Parameter Identification of Chaotic Systems by a Novel Dual Particle Swarm Optimization

    NASA Astrophysics Data System (ADS)

    Jiang, Yunxiang; Lau, Francis C. M.; Wang, Shiyuan; Tse, Chi K.

    In this paper, we propose a dual particle swarm optimization (PSO) algorithm for parameter identification of chaotic systems. We also consider altering the search range of individual particles adaptively according to their objective function value. We consider both noiseless and noisy channels between the original system and the estimation system. Finally, we verify the effectiveness of the proposed dual PSO method by estimating the parameters of the Lorenz system using two different data acquisition schemes. Simulation results show that the proposed method always outperforms the traditional PSO algorithm.

  18. Research on dual spectrum solar-blind ultraviolet corona detection system

    NASA Astrophysics Data System (ADS)

    Yang, Feng; Gu, Yan; Sun, Jianning; Pan, Jingsheng; Zhu, Bo; Wang, Qi; Lu, Xiaoqing

    2015-04-01

    A dual spectrum solar-blind ultraviolet (UV) corona detection system is designed in this paper. A common optical axis using a dichroic mirror is applied to this system in order to make visible light and ultraviolet light spectroscopy to ultraviolet detector and visible detectors. A high speed circuit of image processing based on TMS320DM642 DSP and a circuit that is used into system control and power management based on microcontroller are designed for the presented system. On the basis of the multi-threaded programming ideas, real-time image acquisition of ultraviolet and visible detectors, ultraviolet image noise reduction, image registration, dual spectral integration, Characteristic superimposing, serial communication and image display are achieved by using the DSP image processing circuit. Experimental results show that the dual spectrum solar-blind ultraviolet corona detection system has a good performance of corona detection based on ultraviolet and visible image fusion.

  19. An acoustic dual filter in the audio frequencies with two local resonant systems

    NASA Astrophysics Data System (ADS)

    Liu, Zhao-qun; Zhang, Hui; Zhang, Shu-yi; Fan, Li

    2014-08-01

    We report an acoustic dual filter to realize the sound regulation in the audio frequency range, in which resonant vibrations of two membrane-air and metal-elastomer systems generate two sound transmission peaks and a sound blocking below 3000 Hz. The local vibrational profiles manifest that the transmission peak at lower frequency is mainly dependent on the resonant vibration of the membrane-air system, and the coupling vibrations of two systems generate the blocking frequency and transmission peak at higher frequency. Importantly, two transmission peaks can be controlled independently. It is feasible to realize the acoustic device in sound shield and dual filters.

  20. Compact wearable dual-mode imaging system for real-time fluorescence image-guided surgery

    NASA Astrophysics Data System (ADS)

    Zhu, Nan; Huang, Chih-Yu; Mondal, Suman; Gao, Shengkui; Huang, Chongyuan; Gruev, Viktor; Achilefu, Samuel; Liang, Rongguang

    2015-09-01

    A wearable all-plastic imaging system for real-time fluorescence image-guided surgery is presented. The compact size of the system is especially suitable for applications in the operating room. The system consists of a dual-mode imaging system, see-through goggle, autofocusing, and auto-contrast tuning modules. The paper will discuss the system design and demonstrate the system performance.

  1. Compact wearable dual-mode imaging system for real-time fluorescence image-guided surgery.

    PubMed

    Zhu, Nan; Huang, Chih-Yu; Mondal, Suman; Gao, Shengkui; Huang, Chongyuan; Gruev, Viktor; Achilefu, Samuel; Liang, Rongguang

    2015-09-01

    A wearable all-plastic imaging system for real-time fluorescence image-guided surgery is presented. The compact size of the system is especially suitable for applications in the operating room. The system consists of a dual-mode imaging system, see-through goggle, autofocusing, and auto-contrast tuning modules. The paper will discuss the system design and demonstrate the system performance. PMID:26358823

  2. Dual nozzle design update. [on liquid rocket engines for advanced earth-to-orbit transportation systems

    NASA Technical Reports Server (NTRS)

    Obrien, C. J.

    1982-01-01

    Dual-nozzle engines, such as the dual-throat and dual-expander engines, are being evaluated for advanced earth-to-orbit transportation systems. Potential derivatives of the Space Shuttle and completely new vehicles might benefit from these advanced engines. In this paper, progress in the design of single-fuel and dual-fuel dual-nozzle engines is summarized. Dual-nozzle engines include those burning propellants such as LOX/RP-1/LH2, LOX/LC3H8/LH2, LOX/LCH4/LH2, LOX/LH2/LH2, LOX/LCH4/LCH4, LOX/LC3H8/C3H8 and N2O4/MMH/LH2. Engine data are applicable for thrust levels from 200,000 through 670,000 lbF. The results indicate that several versions of these engines utilize state-of-the-art technology and that even advanced versions of these engines do not require a major breakthrough in technology.

  3. The design and solving for initial structure of dual field of view IR system

    NASA Astrophysics Data System (ADS)

    Wang, Xue-xin; Jiao, Ming-yin; Yang, Bin

    2009-07-01

    In this paper, the zoom theory of IR dual field-of-view zoom optical lens (FOVs) is introduced. The process of how to solve the focal length and spaces of every group element by using performance parameters of infrared dual FOV optical system is described and the solving method for initial structure of single lens and double separate lens used as group is presented in detail. Particularly, great emphasis is give to discuss how to solve the initial structure for every group with PW method. Finally, the design results for 8μm~12μm dual field-of-view zoom infrared systems using the method mentioned above is presented and evaluated for each field by diffraction modulation transfer function(MTF), which shows that the design makes a good system with high image quality.

  4. Projection-type dual-view three-dimensional display system based on integral imaging.

    PubMed

    Jeong, Jinsoo; Lee, Chang-Kun; Hong, Keehoon; Yeom, Jiwoon; Lee, Byoungho

    2014-09-20

    A dual-view display system provides two different images in different directions. Most of them only present two-dimensional images for observers. In this paper, we propose a projection-type dual-view three-dimensional (3D) display system based on integral imaging. To assign directivities to the images, a projection-type display and dual-view screen with lenticular lenses are implemented. The lenticular lenses split the collimated image from the projection device into two different directions. The separated images are integrated by a single lens array in front of the screen, and full-parallax 3D images are observed in two different viewing regions. The visibility of the reconstructed 3D images can be improved by using high-density lenticular lenses and a high numerical aperture lens array. We explain the principle of the proposed method and verify the feasibility of the proposed system with simulations and experimental results. PMID:25322119

  5. Comparison of Analytical Predictions and Experimental Results for a Dual Brayton Power System (Discussion on Test Hardware and Computer Model for a Dual Brayton System)

    NASA Technical Reports Server (NTRS)

    Johnson, Paul K.

    2007-01-01

    NASA Glenn Research Center (GRC) contracted Barber-Nichols, Arvada, CO to construct a dual Brayton power conversion system for use as a hardware proof of concept and to validate results from a computational code known as the Closed Cycle System Simulation (CCSS). Initial checkout tests were performed at Barber- Nichols to ready the system for delivery to GRC. This presentation describes the system hardware components and lists the types of checkout tests performed along with a couple issues encountered while conducting the tests. A description of the CCSS model is also presented. The checkout tests did not focus on generating data, therefore, no test data or model analyses are presented.

  6. Dual manifold system and method for fluid transfer

    SciTech Connect

    Doktycz, Mitchel J.; Bryan, William Louis; Kress, Reid

    2003-05-27

    A dual-manifold assembly is provided for the rapid, parallel transfer of liquid reagents from a microtiter plate to a solid state microelectronic device having biological sensors integrated thereon. The assembly includes aspiration and dispense manifolds connected by a plurality of conduits. In operation, the aspiration manifold is actuated such that the aspiration manifold is seated onto an array of reagent-filled wells of the microtiter plate. The wells are pressurized to force reagent through conduits toward the dispense manifold. A pressure pulse provided by a standard ink-jet printhead ejects nanoliter-to-picoliter droplets of reagent through an array of printhead orifices and onto test sites on the surface of the microelectronic device.

  7. Bimusicalism: The Implicit Dual Enculturation of Cognitive and Affective Systems.

    PubMed

    Wong, Patrick C M; Roy, Anil K; Margulis, Elizabeth Hellmuth

    2009-12-01

    One prominent example of globalization and mass cultural exchange is bilingualism, whereby world citizens learn to understand and speak multiple languages. Music, similar to language, is a human universal, and subject to the effects of globalization. In two experiments, we asked whether bimusicalism exists as a phenomenon, and whether it can occur even without explicit formal training and extensive music-making. Everyday music listeners who had significant exposure to music of both Indian (South Asian) and Westerners traditions (IW listeners) and listeners who had experience with only Indian or Western culture (I or W listeners) participated in recognition memory and tension judgment experiments where they listened to Western and Indian music. We found that while I and W listeners showed an in-culture bias, IW listeners showed equal responses to music from both cultures, suggesting that dual mental and affective sensitivities can be extended to a nonlinguistic domain. PMID:20657798

  8. Dual manifold system and method for fluid transfer

    DOEpatents

    Doktycz, Mitchel J.; Bryan, William Louis; Kress, Reid

    2003-09-30

    A dual-manifold assembly is provided for the rapid, parallel transfer of liquid reagents from a microtiter plate to a solid state microelectronic device having biological sensors integrated thereon. The assembly includes aspiration and dispense manifolds connected by a plurality of conduits. In operation, the aspiration manifold is actuated such that the aspiration manifold is seated onto an array of reagent-filled wells of the microtiter plate. The wells are pressurized to force reagent through conduits toward the dispense manifold. A pressure pulse provided by a standard ink-jet printhead ejects nanoliter-to-picoliter droplets of reagent through an array of printhead orifices and onto test sites on the surface of the microelectronic device.

  9. Bimusicalism: The Implicit Dual Enculturation of Cognitive and Affective Systems

    PubMed Central

    Wong, Patrick C. M.; Roy, Anil K.; Margulis, Elizabeth Hellmuth

    2010-01-01

    One prominent example of globalization and mass cultural exchange is bilingualism, whereby world citizens learn to understand and speak multiple languages. Music, similar to language, is a human universal, and subject to the effects of globalization. In two experiments, we asked whether bimusicalism exists as a phenomenon, and whether it can occur even without explicit formal training and extensive music-making. Everyday music listeners who had significant exposure to music of both Indian (South Asian) and Westerners traditions (IW listeners) and listeners who had experience with only Indian or Western culture (I or W listeners) participated in recognition memory and tension judgment experiments where they listened to Western and Indian music. We found that while I and W listeners showed an in-culture bias, IW listeners showed equal responses to music from both cultures, suggesting that dual mental and affective sensitivities can be extended to a nonlinguistic domain. PMID:20657798

  10. Optimal Spacing of Dual-axis Trackers for Concentrating Photovoltaic Systems

    NASA Astrophysics Data System (ADS)

    Kim, Yong Sin; Winston, Roland

    2011-12-01

    The levelized cost of energy (LCOE) is widely used to compare the cost of energy generation across technologies. In a utility-scale concentrating photovoltaic (CPV) system, the spacing of dual-axis trackers must be balanced with total energy harvested from modules to minimize LCOE. In this paper, a spacing method of dual-axis trackers in a CPV system is presented. Based on the definition of LCOE, a cost function is defined and optimized in terms of spacing related parameters. Various methods to estimate hourly direct normal irradiance (DNI) are investigated and m-by-n tracker array configurations to minimize the cost function are discussed.

  11. Effect of Operating Parameters on a Dual-Stage High Velocity Oxygen Fuel Thermal Spray System

    NASA Astrophysics Data System (ADS)

    Khan, Mohammed N.; Shamim, Tariq

    2014-08-01

    High velocity oxygen fuel (HVOF) thermal spray systems are being used to apply coatings to prevent surface degradation. The coatings of temperature sensitive materials such as titanium and copper, which have very low melting points, cannot be applied using a single-stage HVOF system. Therefore, a dual-stage HVOF system has been introduced and modeled computationally. The dual-spray system provides an easy control of particle oxidation by introducing a mixing chamber. In addition to the materials being sprayed, the thermal spray coating quality depends to a large extent on flow behavior of reacting gases and the particle dynamics. The present study investigates the influence of various operating parameters on the performance of a dual-stage thermal spray gun. The objective is to develop a predictive understanding of various parameters. The gas flow field and the free jet are modeled by considering the conservation of mass, momentum, and energy with the turbulence and the equilibrium combustion sub models. The particle phase is decoupled from the gas phase due to very low particle volume fractions. The results demonstrate the advantage of a dual-stage system over a single-stage system especially for the deposition of temperature sensitive materials.

  12. A dual-systems perspective on addiction: contributions from neuroimaging and cognitive training.

    PubMed

    McClure, Samuel M; Bickel, Warren K

    2014-10-01

    Dual-systems theories explain lapses in self-control in terms of a conflict between automatic and deliberative modes of behavioral control. Numerous studies have now tested whether the brain areas that control behavior are organized in a manner consistent with dual-systems models. Brain regions directly associated with the mesolimbic dopamine system, the nucleus accumbens and ventromedial prefrontal cortex in particular, capture some of the features assumed by automatic processing. Regions in the lateral prefrontal cortex are more closely linked to deliberative processing and the exertion of self-control in the suppression of impulses. While identifying these regions crudely supports dual-systems theories, important modifications to what constitutes automatic and deliberative behavioral control are also suggested. Experiments have identified various means by which automatic processes may be sculpted. Additional work decomposes deliberative processes into component functions such as generalized working memory, reappraisal of emotional stimuli, and prospection. The importance of deconstructing dual-systems models into specific cognitive processes is clear for understanding and treating addiction. We discuss intervention possibilities suggested by recent research, and focus in particular on cognitive training approaches to bolster deliberative control processes that may aid quit attempts. PMID:25336389

  13. A dual-systems perspective on addiction: contributions from neuroimaging and cognitive training

    PubMed Central

    McClure, Samuel M.; Bickel, Warren K.

    2014-01-01

    Dual-systems theories explain lapses in self-control in terms of a conflict between automatic and deliberative modes of behavioral control. Numerous studies have now tested whether the brain areas that control behavior are organized in a manner consistent with dual-systems models. Brain regions directly associated with the mesolimbic dopamine system, the nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC) in particular, capture some of the features assumed by automatic processing. Regions in the lateral prefrontal cortex (lPFC) are more closely linked to deliberative processing and the exertion of self-control in the suppression of impulses. While identifying these regions crudely supports dual-system theories, important modifications to what constitutes automatic and deliberative behavioral control are also suggested. Experiments have identified various means by which automatic processes may be sculpted. Additional work decomposes deliberative processes into component functions such as generalized working memory, reappraisal of emotional stimuli, and prospection. The importance of deconstructing dual-systems models into specific cognitive processes is clear for understanding and treating addiction. We discuss intervention possibilities suggested by recent research, and focus in particular on cognitive training approaches to bolster deliberative control processes that may aid quit attempts. PMID:25336389

  14. The Potential of Dual Camera Systems for Multimodal Imaging of Cardiac Electrophysiology and Metabolism

    PubMed Central

    Holcomb, Mark R.; Woods, Marcella C.; Uzelac, Ilija; Wikswo, John P.; Gilligan, Jonathan M.; Sidorov, Veniamin Y.

    2013-01-01

    Fluorescence imaging has become a common modality in cardiac electrodynamics. A single fluorescent parameter is typically measured. Given the growing emphasis on simultaneous imaging of more than one cardiac variable, we present an analysis of the potential of dual camera imaging, using as an example our straightforward dual camera system that allows simultaneous measurement of two dynamic quantities from the same region of the heart. The advantages of our system over others include an optional software camera calibration routine that eliminates the need for precise camera alignment. The system allows for rapid setup, dichroic image separation, dual-rate imaging, and high spatial resolution, and it is generally applicable to any two-camera measurement. This type of imaging system offers the potential for recording simultaneously not only transmembrane potential and intracellular calcium, two frequently measured quantities, but also other signals more directly related to myocardial metabolism, such as [K+]e, NADH, and reactive oxygen species, leading to the possibility of correlative multimodal cardiac imaging. We provide a compilation of dye and camera information critical to the design of dual camera systems and experiments. PMID:19657065

  15. A novel dual-frequency loading system for studying mechanobiology of load-bearing tissue.

    PubMed

    Zhang, Chunqiu; Qiu, Lulu; Gao, Lilan; Guan, Yinjie; Xu, Qiang; Zhang, Xizheng; Chen, Qian

    2016-12-01

    In mechanobiological research, an appropriate loading system is an essential tool to mimic mechanical signals in a native environment. To achieve this goal, we have developed a novel loading system capable of applying dual-frequency loading including both a low-frequency high-amplitude loading and a high-frequency low-amplitude loading, according to the mechanical conditions experienced by bone and articular cartilage tissues. The low-frequency high-amplitude loading embodies the main force from muscular contractions and/or reaction forces while the high-frequency low-amplitude loading represents an assistant force from small muscles, ligaments and/or other tissue in order to maintain body posture during human activities. Therefore, such dual frequency loading system may reflect the natural characteristics of complex mechanical load on bone or articular cartilage than the single frequency loading often applied during current mechanobiological experiments. The dual-frequency loading system is validated by experimental tests using precision miniature plane-mirror interferometers. The dual-frequency loading results in significantly more solute transport in articular cartilage than that of the low-frequency high-amplitude loading regiment alone, as determined by quantitative fluorescence microscopy of tracer distribution in articular cartilage. Thus, the loading system can provide a new method to mimic mechanical environment in bone and cartilage, thereby revealing the in vivo mechanisms of mechanosensation, mechanotransduction and mass-transport, and improving mechanical conditioning of cartilage and/or bone constructs for tissue engineering. PMID:27612712

  16. The convertible engine: A dual-mode propulsion system

    NASA Technical Reports Server (NTRS)

    Mcardle, Jack G.

    1988-01-01

    A variable inlet guide vane (VIGV) convertible engine that could be used to power future high-speed rotorcraft was tested on an outdoor stand. The engine ran stably and smoothly in the turbofan, turboshaft, and dual (combined fan and shaft) power modes. In the turbofan mode with the VIGV open, fuel consumption was comparable to that of a conventional turbofan engine. In the turboshaft mode with the VIGV closed, fuel consumption was higher than that of present turboshaft engines because power was wasted in churning fan-tip air flow. In dynamic performance tests with a specially built digital engine control and using a waterbrake dynamometer for shaft load, the engine responded effectively to large steps in thrust command and shaft torque. Previous mission analyses of a conceptual X-wing rotorcraft capable of 400-knot cruise speed were revised to account for more fan-tip churning power loss that was originally estimated. The calculations confirm that using convertible engines rather than separate life and cruise engines would result in a smaller, lighter craft with lower fuel use and direct operating cost.

  17. Removal of ammonia from urine vapor by a dual-catalyst system

    NASA Technical Reports Server (NTRS)

    Budininkas, P.

    1977-01-01

    The feasibility of removing ammonia from urine vapor by a low-temperature dual-catalyst system has been demonstrated. The process is based on the catalytic oxidation of ammonia to a mixture of nitrogen, nitrous oxide, and water, followed by a catalytic decomposition of the nitrous oxide into its elements. Potential ammonia oxidation and nitrous oxide decomposition catalysts were first screened with artificial gas mixtures, then tested with the actual urine vapor produced by boiling untreated urine. A suitable dual-catalyst bed arrangement was found that achieved the removal of ammonia and also organic carbon, and recovered water of good quality from urine vapor.

  18. Three dimensional laser microfabrication in diamond using a dual adaptive optics system.

    PubMed

    Simmonds, Richard D; Salter, Patrick S; Jesacher, Alexander; Booth, Martin J

    2011-11-21

    Femtosecond laser fabrication of controlled three dimensional structures deep in the bulk of diamond is facilitated by a dual adaptive optics system. A deformable mirror is used in parallel with a liquid crystal spatial light modulator to compensate the extreme aberrations caused by the refractive index mismatch between the diamond and the objective immersion medium. It is shown that aberration compensation is essential for the generation of controlled micron-scale features at depths greater than 200 μm, and the dual adaptive optics approach demonstrates increased fabrication efficiency relative to experiments using a single adaptive element. PMID:22109438

  19. Quantum interference of stored dual-channel spin-wave excitations in a single tripod system

    SciTech Connect

    Wang Hai; Li Shujing; Xu Zhongxiao; Zhao Xingbo; Zhang Lijun; Li Jiahua; Wu Yuelong; Xie Changde; Peng Kunchi; Xiao Min

    2011-04-15

    We present an experimental demonstration of dual-channel memory in a single tripod atomic system. The total readout signal exhibits either constructive or destructive interference when the dual-channel spin-wave excitations (SWEs) are retrieved by two reading beams with a controllable relative phase. When the two reading beams have opposite phases, the SWEs will remain in the medium, which can be retrieved later with two in-phase reading beams. Such a phase-sensitive storage and retrieval scheme can be used to measure and control the relative phase between the two SWEs in the memory medium, which may find applications in quantum-information processing.

  20. Dispersion-compensating dual-mode optical fibers desirable for erbium-doped-fiber-amplified systems

    SciTech Connect

    Eguchi, Masashi

    2001-06-01

    A broadband dispersion-compensating dual-mode optical fiber with a double-layer profile core is proposed to compensate for positive dispersion in conventional single-mode optical fibers operating near 1.55 {mu}m. This wavelength band is suitable for erbium-doped-fiber-amplified systems. It is known that the first higher-order mode of dual-mode fibers exhibits large negative waveguide dispersion, and double-layer profile core fibers are dispersion-shifted fibers whose transmission and bending losses are lower than those of simple core-cladding dispersion-shifted fibers. Such advantages are attractive for commercial devices or modules. Here, a dispersion-compensating dual-mode fiber with a double-layer profile core that satisfies both low bending loss and broadband dispersion compensation is proposed. {copyright} 2001 Optical Society of America

  1. The German Dual System of Vocational Education and Implications for Human Resource Development in America.

    ERIC Educational Resources Information Center

    Theuerkauf, Walter E.; Weiner, Andreas

    The dual job training system in Germany is an essential market parameter of the country's economy and a part of the country's growth policy. By improving human capital (by providing training in high-tech sectors) it will also help safeguard Germany's future as a major industrial nation. Training primarily takes place in handicraft and industrial…

  2. An enzyme-responsive controlled release system based on a dual-functional peptide.

    PubMed

    Li, X; Burger, S; O'Connor, A J; Ong, L; Karas, J A; Gras, S L

    2016-04-14

    A new controlled release system was developed by loading a dual-functional peptide (DFP) on a mesoporous silica material. One-pot synthesis produced a DFP that was stimuli responsive, releasing a therapeutic peptide by protease cleavage. The design provides new steps towards smart biomaterials. PMID:26998533

  3. The Emerging Roles of Coaches in the Malaysian Dual Training System

    ERIC Educational Resources Information Center

    Othman, Ahmad; Abdullah, Nor Hazana; Sulaiman, Mohamad; Shamsuddin, Alina

    2011-01-01

    This paper discusses the new task of industry personnel as coaches in the National Dual Training System (NDTS), a newly introduced training initiative for producing k-workers in Malaysia. The decision to introduce this initiative was made by the Malaysian Cabinet on the 19th May 2004 with the hope that it will resolve the issue of skilled workers…

  4. Dual Water Systems: Characterization and Performance for Distribution of Reclaimed Water (WaterRF Report 4333)

    EPA Science Inventory

    The research tasks included: an inventory of cases where dual systems have been implemented; formulation of a protocol to identify claimed benefits, costs, and risks; collection of data (quantitative and anecdotal) to assess performance; display of data in the form of performance...

  5. Grazing initiation timing affects net rturn to dual-purpose wheat systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Limited experimental data are available to allow direct evaluation of the effects of grazing initiation timing on net returns to dual-purpose wheat systems. The objectives were to simulate the effect of grazing initiation dates on net returns to a wheat (Triticum aestivum L.) – cattle (Bos taurus) ...

  6. Diversity of free-living amoebae in a dual distribution (potable and recycled) water system

    EPA Science Inventory

    Free-living amoebae are known to facilitate the growth of water associated pathogens. This study, for the first time, explored the diversity of free-living amoebae in a dual distribution (potable and recycled) water system in Rouse Hill NSW, Australia. Water and biofilm samples w...

  7. A low-cost dual-camera imaging system for aerial applicators

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agricultural aircraft provide a readily available remote sensing platform as low-cost and easy-to-use consumer-grade cameras are being increasingly used for aerial imaging. In this article, we report on a dual-camera imaging system we recently assembled that can capture RGB and near-infrared (NIR) i...

  8. Development of the Dual Aerodynamic Nozzle Model for the NTF Semi-Span Model Support System

    NASA Technical Reports Server (NTRS)

    Jones, Greg S.; Milholen, William E., II; Goodliff, Scott L.

    2011-01-01

    The recent addition of a dual flow air delivery system to the NASA Langley National Transonic Facility was experimentally validated with a Dual Aerodynamic Nozzle semi-span model. This model utilized two Stratford calibration nozzles to characterize the weight flow system of the air delivery system. The weight flow boundaries for the air delivery system were identified at mildly cryogenic conditions to be 0.1 to 23 lbm/sec for the high flow leg and 0.1 to 9 lbm/sec for the low flow leg. Results from this test verified system performance and identified problems with the weight-flow metering system that required the vortex flow meters to be replaced at the end of the test.

  9. Design of triode extraction system for a dual hollow cathode ion source

    NASA Astrophysics Data System (ADS)

    Wang, Jing-Hui; Zhu, Kun; Zhao, Wei-Jiang; Liu, Ke-Xin

    2011-02-01

    A triode extraction system is designed for a dual hollow cathode ion source being developed at the Institute of Heavy Ion Physics, Peking University. Basic parameters of the plasma are selected after examining the operation principle of the ion source, then the triode extraction system is designed and optimized by using software PBGUNS (for Particle Beam GUN Simulations). The physical design of the system is given in this paper.

  10. A dual cone-beam CT system for image guided radiotherapy: Initial performance characterization

    SciTech Connect

    Li Hao; Bowsher, James; Yin Fangfang; Giles, William

    2013-02-15

    Purpose: The purpose of this study is to evaluate the performance of a recently developed benchtop dual cone-beam computed tomography (CBCT) system with two orthogonally placed tube/detector sets. Methods: The benchtop dual CBCT system consists of two orthogonally placed 40 Multiplication-Sign 30 cm flat-panel detectors and two conventional x-ray tubes with two individual high-voltage generators sharing the same rotational axis. The x-ray source to detector distance is 150 cm and x-ray source to rotational axis distance is 100 cm for both subsystems. The objects are scanned through 200 Degree-Sign of rotation. The dual CBCT system utilized 110 Degree-Sign of projection data from one detector and 90 Degree-Sign from the other while the two individual single CBCTs utilized 200 Degree-Sign data from each detector. The system performance was characterized in terms of uniformity, contrast, spatial resolution, noise power spectrum, and CT number linearity. The uniformities, within the axial slice and along the longitudinal direction, and noise power spectrum were assessed by scanning a water bucket; the contrast and CT number linearity were measured using the Catphan phantom; and the spatial resolution was evaluated using a tungsten wire phantom. A skull phantom and a ham were also scanned to provide qualitative evaluation of high- and low-contrast resolution. Each measurement was compared between dual and single CBCT systems. Results: Compared to single CBCT, the dual CBCT presented: (1) a decrease in uniformity by 1.9% in axial view and 1.1% in the longitudinal view, as averaged for four energies (80, 100, 125, and 150 kVp); (2) comparable or slightly better contrast (0{approx}25 HU) for low-contrast objects and comparable contrast for high-contrast objects; (3) comparable spatial resolution; (4) comparable CT number linearity with R{sup 2}{>=} 0.99 for all four tested energies; (5) lower noise power spectrum in magnitude. Dual CBCT images of the skull phantom and the

  11. Measurement and research on improving the performance of dual-temperature refrigerator system

    NASA Astrophysics Data System (ADS)

    Jwo, Ching-Song; Lin, Ming-Wei; Lin, Chien-Yu; Hsu, Ching-Wei; Chen, Sih-Li

    2010-08-01

    This study presents a "cold-stored liquid-vapor heat exchanger" to improve the performance of dual-temperature refrigerator system, for the installation of "cold-stored liquid-vapor heat exchanger" to measure the improving the performance of system. The study designs four different experimental models for making analytical discussion, and these models include: Model-A, dual-temperature refrigerator system (control group); Model-B, electronic expansion valve, which replaces mechanical evaporating pressure regulating valve; Model-C, dual-temperature refrigerator system equipped with a "traditional liquid heat exchanger" and Model-D, dual-temperature refrigerator system equipped with an "cold-stored liquid-vapor heat exchanger" developed by the study. As known from analysis of the experimental data, under the operation of Model-B, the overheating situation at the return conduit of medium-temperature evaporator can be effectively controlled. Furthermore, the model can enhance the refrigeration speed, and improve the problems of accumulation of refrigerator oil as well as the shutdown and instability of pump appeared in traditional evaporating pressure regulating valve. After making analysis and comparison under the operation of Model-C, the COP of dual-temperature refrigerator is found improved by around 21.7%. When experimental analysis and comparison are made under the operation of Model-D, it is found that air-cooled liquid-gas heat exchanger can effectively provide better overcooling degree, and this device can improve the exhaust of compressor and excessively high temperature of machine shell. Eventually, the overall COP can be effectively improved by around 29.5%.

  12. Off-axis point spread function reconstruction from a dual deformable mirror adaptive optics system

    NASA Astrophysics Data System (ADS)

    Keskin, O.; Conan, R.; Bradley, C.; Blain, C.

    2008-07-01

    In AO applications, PSF reconstruction is used in calibrating image analysis techniques for astrometry, and in the deconvolution of images to enhance their contrast. The partial correction provided by the AO system is due to the finite sampling of the wavefront sensor, the DM (limited number of freedoms on the DM, i.e., the number of actuators) and the finite bandwidth of the control system. Furthermore, the correction provided by an AO system degrades across the field of view, depending on the angular separation between the guide star and the target object (anisoplanatism). In this paper, an end to end numerical model of an off-axis dual DM AO system has been implemented to accommodate for the anisoplanatic errors that degrade the performance of AO systems at greater angular distances from the guide star. An improved off-axis PSF reconstruction methodology has been developed and numerically evaluated for the dual DM (Woofer/Tweeter) off-axis AO architecture.

  13. Converting dual-duct constant-volume systems to variable-volume systems without retrofitting the terminal boxes

    SciTech Connect

    Liu, M.; Claridge, D.E.

    1999-07-01

    Dual-duct constant-air-volume systems can be converted to variable-air-volume systems by installing hot air dampers in the main hot air ducts. No terminal box retrofit is needed. The detailed retrofit procedures and control sequences are described in this paper. Results from a case study building are also presented.

  14. Tests of a Dual-systems Model of Speech Category Learning.

    PubMed

    Maddox, W Todd; Chandrasekaran, Bharath

    2014-10-01

    In the visual domain, more than two decades of work posits the existence of dual category learning systems. The reflective system uses working memory to develop and test rules for classifying in an explicit fashion. The reflexive system operates by implicitly associating perception with actions that lead to reinforcement. Dual-systems models posit that in learning natural categories, learners initially use the reflective system and with practice, transfer control to the reflexive system. The role of reflective and reflexive systems in second language (L2) speech learning has not been systematically examined. Here monolingual, native speakers of American English were trained to categorize Mandarin tones produced by multiple talkers. Our computational modeling approach demonstrates that learners use reflective and reflexive strategies during tone category learning. Successful learners use talker-dependent, reflective analysis early in training and reflexive strategies by the end of training. Our results demonstrate that dual-learning systems are operative in L2 speech learning. Critically, learner strategies directly relate to individual differences in category learning success. PMID:25264426

  15. Tests of a Dual-systems Model of Speech Category Learning

    PubMed Central

    Maddox, W. Todd; Chandrasekaran, Bharath

    2013-01-01

    In the visual domain, more than two decades of work posits the existence of dual category learning systems. The reflective system uses working memory to develop and test rules for classifying in an explicit fashion. The reflexive system operates by implicitly associating perception with actions that lead to reinforcement. Dual-systems models posit that in learning natural categories, learners initially use the reflective system and with practice, transfer control to the reflexive system. The role of reflective and reflexive systems in second language (L2) speech learning has not been systematically examined. Here monolingual, native speakers of American English were trained to categorize Mandarin tones produced by multiple talkers. Our computational modeling approach demonstrates that learners use reflective and reflexive strategies during tone category learning. Successful learners use talker-dependent, reflective analysis early in training and reflexive strategies by the end of training. Our results demonstrate that dual-learning systems are operative in L2 speech learning. Critically, learner strategies directly relate to individual differences in category learning success. PMID:25264426

  16. Comparison between single- and dual-electrode ion source systems for low-energy ion transport

    SciTech Connect

    Vasquez, M. Jr.; Tokumura, S.; Kasuya, T.; Maeno, S.; Wada, M.

    2012-11-06

    Extraction of ions with energies below 100 eV has been demonstrated using a hot-cathode multi-cusp ion source equipped with extraction electrodes made of thin wires. Two electrode geometries, a single-electrode system, and a dual-electrode system were built and tested. The single-electrode configuration showed high ion beam current densities at shorter distances from the electrode but exhibited rapid attenuation as the distance from the electrode increased. Beam angular spread measurements showed similar beam divergence for both electrode configurations at low plasma densities. At high plasma densities and low extraction potentials, the single-electrode system showed the angular spread twice as large as that of the dual-electrode system. Energy distribution analyses showed a broader energy spread for ion beams extracted from a single-electrode set-up.

  17. Effects of mixing system and pilot fuel quality on diesel-biogas dual fuel engine performance.

    PubMed

    Bedoya, Iván Darío; Arrieta, Andrés Amell; Cadavid, Francisco Javier

    2009-12-01

    This paper describes results obtained from CI engine performance running on dual fuel mode at fixed engine speed and four loads, varying the mixing system and pilot fuel quality, associated with fuel composition and cetane number. The experiments were carried out on a power generation diesel engine at 1500 m above sea level, with simulated biogas (60% CH(4)-40% CO(2)) as primary fuel, and diesel and palm oil biodiesel as pilot fuels. Dual fuel engine performance using a naturally aspirated mixing system and diesel as pilot fuel was compared with engine performance attained with a supercharged mixing system and biodiesel as pilot fuel. For all loads evaluated, was possible to achieve full diesel substitution using biogas and biodiesel as power sources. Using the supercharged mixing system combined with biodiesel as pilot fuel, thermal efficiency and substitution of pilot fuel were increased, whereas methane and carbon monoxide emissions were reduced. PMID:19683439

  18. Dual-Use Aspects of System Health Management

    NASA Technical Reports Server (NTRS)

    Owens, P. R.; Jambor, B. J.; Eger, G. W.; Clark, W. A.

    1994-01-01

    System Health Management functionality is an essential part of any space launch system. Health management functionality is an integral part of mission reliability, since it is needed to verify the reliability before the mission starts. Health Management is also a key factor in life cycle cost reduction and in increasing system availability. The degree of coverage needed by the system and the degree of coverage made available at a reasonable cost are critical parameters of a successful design. These problems are not unique to the launch vehicle world. In particular, the Intelligent Vehicle Highway System, commercial aircraft systems, train systems, and many types of industrial production facilities require various degrees of system health management. In all of these applications, too, the designers must balance the benefits and costs of health management in order to optimize costs. The importance of an integrated system is emphasized. That is, we present the case for considering health management as an integral part of system design, rather than functionality to be added on at the end of the design process. The importance of maintaining the system viewpoint is discussed in making hardware and software tradeoffs and in arriving at design decisions. We describe an approach to determine the parameters to be monitored in any system health management application. This approach is based on Design of Experiments (DOE), prototyping, failure modes and effects analyses, cost modeling and discrete event simulation. The various computer-based tools that facilitate the approach are discussed. The approach described originally was used to develop a fault tolerant avionics architecture for launch vehicles that incorporated health management as an integral part of the system. Finally, we discuss generalizing the technique to apply it to other domains. Several illustrations are presented.

  19. Third generation infrared system calibration using dual band thermoelectric thermal reference sources and test systems to calibrate uncooled IRFPAs

    NASA Astrophysics Data System (ADS)

    Finfrock, David K.; Kolander, William L.

    2008-04-01

    As dual band, 3rd generation FLIR systems progress from the research lab into the field, supporting technologies must also advance. This paper describes advances in Thermoelectric Thermal Reference Sources (TTRS) from single band (3 to 5 or 8 to 12 microns) to dual band in one assembly (3 to 5 and 8 to 12 microns). It will describe the optical, system, electrical, and mechanical parameters of dual band TTRS units. It provides IR system design engineers with the critical parameters of dual band TTRS units to aid in their design process. TTRS assemblies provide a temperature controllable radiometrically uniform surface. When viewed by theFLIR system detectors, the TTRS enables the system electronics to perform gain and offset calibration as well as DC restoration for each pixel's preamp Some of the parameters for 3rd Generation FLIR system TTRS units included in this paper will be: Emissivity of BB surfaces. Apparent thermal radiometric uniformity. How this is predicted and measured. Window material wavelength transmission (Hermetically sealed units only). TTRS emitter surface temperatures as a function of heat sink temperatures. Trade-off between uniformity, power consumption, and transient performance. Power consumption, Thermal interfaces and required heat sinking Types and accuracy of Temperature sensors mounted on emitter surface. Also included in this paper is a description of a Thermoelectric Black Body Test Apparatus that can be used to generate temperature coefficients needed to "burn" Proms for uncooled IRFPAs during their production and burn in processing.

  20. Dual-mode microwave system to enhance early detection of cancer

    NASA Technical Reports Server (NTRS)

    Carr, K. L.; El-Mahdi, A. M.; Shaeffer, J.

    1981-01-01

    A dual-mode microwave system has been developed that will permit early detection of cancer. The system combines the use of the passive microwave radiometer with an active transmitter. The active transmitter will provide localized heating to enhance early detection by taking advantage of the differential heating (i.e., tumor temperature with respect to surrounding tissue) associated with the thermal characteristics of tumors.

  1. Design of a dual port volume measuring system

    SciTech Connect

    Klevgard, P.A.

    1990-09-01

    A volume measuring system is described which uses the ideal gas law and pressure measurements to determine an unknown vessel's volume when a gas expands into that vessel from a known volume. The design, the engineering principles, the calibration, and the accuracy of this computer-controlled system are all discussed. A set of electrical and mechanical drawings of the system is included. 3 refs., 6 figs.

  2. Biomechanical study comparing a new combined rod-plate system with conventional dual-rod and plate systems.

    PubMed

    Sha, Mo; Ding, Zheng-Qi; Ting, Hu S; Kang, Liang-Qi; Zhai, Wen-Liang; Liu, Hui

    2013-02-01

    Most anterior spinal instrumentation systems are designed as either a plate or dual-rod system and have corresponding limitations. Dual-rod designs may offer greater adjustability; however, this system also maintains a high profile and lacks a locking design. Plate systems are designed to be stiffer, but the fixed configuration is not adaptable to the variety of vertebral body shapes. The authors designed a new combined rod-plate system (D-rod) to overcome these limitations and compared its biomechanical performance with the conventional dual-rod and plate system. Eighteen pig spinal specimens were divided into 3 groups (6 per group). An L1 corpectomy was performed and fixed with the D-rod (group A; n=6), Z-plate (Sofamor Danek, Memphis, Tennessee) (group B; n=6), or Ventrofix (Synthes, Paoli, Pennsylvania) (group C; n=6) system. T13-L2 range of motion was measured with a 6 degrees of freedom (ie, flexion-extension, lateral bending, and axial rotation) spine simulator under pure moments of 6.0 Nm. The D-rod and Ventrofix specimens were significantly stiffer than the Z-plate specimens (P<.05) based on results obtained from lateral bending and flexion-extension tests. The D-rod and Z-plate specimens were significantly stiffer than the Ventrofix specimens (P<.05) in axial rotation. The D-rod combines the advantages of the plate and dual-rod systems, where the anterior rod exhibits the design of a low-profile locking plate, enhanced stability, and decreased interference of the surrounding vasculature. The posterior rods function in compression and distraction, and the dual-rod system offers greater adjustability and control over screw placement. The results indicate that it may provide adequate stability for anterior thoracolumbar reconstruction. PMID:23383624

  3. System-Level Logistics for Dual Purpose Canister Disposal

    SciTech Connect

    Kalinina, Elena A.

    2014-06-03

    The analysis presented in this report investigated how the direct disposal of dual purpose canisters (DPCs) may be affected by the use of standard transportation aging and disposal canisters (STADs), early or late start of the repository, and the repository emplacement thermal power limits. The impacts were evaluated with regard to the availability of the DPCs for emplacement, achievable repository acceptance rates, additional storage required at an interim storage facility (ISF) and additional emplacement time compared to the corresponding repackaging scenarios, and fuel age at emplacement. The result of this analysis demonstrated that the biggest difference in the availability of UNF for emplacement between the DPC-only loading scenario and the DPCs and STADs loading scenario is for a repository start date of 2036 with a 6 kW thermal power limit. The differences are also seen in the availability of UNF for emplacement between the DPC-only loading scenario and the DPCs and STADs loading scenario for the alternative with a 6 kW thermal limit and a 2048 start date, and for the alternatives with a 10 kW thermal limit and 2036 and 2048 start dates. The alternatives with disposal of UNF in both DPCs and STADs did not require additional storage, regardless of the repository acceptance rate, as compared to the reference repackaging case. In comparison to the reference repackaging case, alternatives with the 18 kW emplacement thermal limit required little to no additional emplacement time, regardless of the repository start time, the fuel loading scenario, or the repository acceptance rate. Alternatives with the 10 kW emplacement thermal limit and the DPCs and STADs fuel loading scenario required some additional emplacement time. The most significant decrease in additional emplacement time occurred in the alternative with the 6 kW thermal limit and the 2036 repository starting date. The average fuel age at emplacement ranges from 46 to 88 years. The maximum fuel age at

  4. Trigonometric Sutherland systems and their Ruijsenaars duals from symplectic reduction

    SciTech Connect

    Feher, L.; Ayadi, V.

    2010-10-15

    Beside its usual interpretation as a system of n indistinguishable particles moving on the circle, the trigonometric Sutherland system can be viewed alternatively as a system of distinguishable particles on the circle or on the line, and these three physically distinct systems are in duality with corresponding variants of the rational Ruijsenaars-Schneider system. We explain that the three duality relations, first obtained by Ruijsenaars in 1995, arise naturally from the Kazhdan-Kostant-Sternberg symplectic reductions of the cotangent bundles of the group U(n) and its covering groups U(1)xSU(n) and RxSU(n), respectively. This geometric interpretation enhances our understanding of the duality relations and simplifies Ruijsenaars' original direct arguments that led to their discovery.

  5. Adaptive optics ophthalmologic systems using dual deformable mirrors

    SciTech Connect

    Jones, S; Olivier, S; Chen, D; Sadda, S; Joeres, S; Zawadzki, R; Werner, J S; Miller, D

    2007-02-01

    Adaptive Optics (AO) have been increasingly combined with a variety of ophthalmic instruments over the last decade to provide cellular-level, in-vivo images of the eye. The use of MEMS deformable mirrors in these instruments has recently been demonstrated to reduce system size and cost while improving performance. However, currently available MEMS mirrors lack the required range of motion for correcting large ocular aberrations, such as defocus and astigmatism. In order to address this problem, we have developed an AO system architecture that uses two deformable mirrors, in a woofer/tweeter arrangement, with a bimorph mirror as the woofer and a MEMS mirror as the tweeter. This setup provides several advantages, including extended aberration correction range, due to the large stroke of the bimorph mirror, high order aberration correction using the MEMS mirror, and additionally, the ability to ''focus'' through the retina. This AO system architecture is currently being used in four instruments, including an Optical Coherence Tomography (OCT) system and a retinal flood-illuminated imaging system at the UC Davis Medical Center, a Scanning Laser Ophthalmoscope (SLO) at the Doheny Eye Institute, and an OCT system at Indiana University. The design, operation and evaluation of this type of AO system architecture will be presented.

  6. Characteristics of neural and humoral systems involved in the regulation of blood pressure in snakes.

    PubMed

    Breno, Maria Cristina; Prezoto, Benedito Carlos; Borgheresi, Rosa A M B; Lazari, Maria Fátima M; Yamanouye, Norma

    2007-07-01

    Cardiovascular function is affected by many mechanisms, including the autonomic system, the kallikrein-kinin system (KKS), the renin-angiotensin system (RAS) and the endothelin system. The function of these systems seems to be fairly well preserved throughout the vertebrate scale, but evolution required several adaptations. Snakes are particularly interesting for studies related to the cardiovascular function because of their elongated shape, their wide variation in size and length, and because they had to adapt to extremely different habitats and gravitational influences. To keep the normal cardiovascular control the snakes developed anatomical and functional adaptations and interesting structural peculiarities are found in their autonomic, KKS, RAS and endothelin systems. Our laboratory has characterized some biochemical, pharmacological and physiological properties of these systems in South American snakes. This review compares the components and function of these systems in snakes and other vertebrates, and focuses on differences found in snakes, related with receptor or ligand structure and/or function in autonomic system, RAS and KKS, absence of components in KKS and the intriguing identity between a venom and a plasma component in the endothelin system. PMID:17046304

  7. Considerations of a Dual-systems Model of Cognitive Development and Risky Driving

    PubMed Central

    Lambert, Ann E.; Simons-Morton, Bruce G.; Cain, Sarah A.; Weisz, Sarah; Cox, Daniel J.

    2014-01-01

    The dual-systems model of adolescent risk-taking postulates that risk-taking during adolescence partially results from an imbalance in the development of the executive and the socio-emotional cognitive systems. While supported by behavioral and neuroanatomical data, translational research linking the model with real-world driving or laboratory driving simulation is sparse. This paper discusses the model as it relates to adolescent driving and reviews empirical studies that have applied it in a driving-specific context. While, the studies reviewed provided partial support, each lacked a critical component necessary to fully test the model. Thus, a strong test has yet to be implemented; however, the dual-systems model holds promise for advancing the understanding of teen driving risk and guiding applications for prevention and policy. PMID:25983529

  8. Calibration of a dual-PTZ camera system for stereo vision

    NASA Astrophysics Data System (ADS)

    Chang, Yau-Zen; Hou, Jung-Fu; Tsao, Yi Hsiang; Lee, Shih-Tseng

    2010-08-01

    In this paper, we propose a calibration process for the intrinsic and extrinsic parameters of dual-PTZ camera systems. The calibration is based on a complete definition of six coordinate systems fixed at the image planes, and the pan and tilt rotation axes of the cameras. Misalignments between estimated and ideal coordinates of image corners are formed into cost values to be solved by the Nelder-Mead simplex optimization method. Experimental results show that the system is able to obtain 3D coordinates of objects with a consistent accuracy of 1 mm when the distance between the dual-PTZ camera set and the objects are from 0.9 to 1.1 meters.

  9. DualTrust: A Distributed Trust Model for Swarm-Based Autonomic Computing Systems

    SciTech Connect

    Maiden, Wendy M.; Dionysiou, Ioanna; Frincke, Deborah A.; Fink, Glenn A.; Bakken, David E.

    2011-02-01

    For autonomic computing systems that utilize mobile agents and ant colony algorithms for their sensor layer, trust management is important for the acceptance of the mobile agent sensors and to protect the system from malicious behavior by insiders and entities that have penetrated network defenses. This paper examines the trust relationships, evidence, and decisions in a representative system and finds that by monitoring the trustworthiness of the autonomic managers rather than the swarming sensors, the trust management problem becomes much more scalable and still serves to protect the swarm. We then propose the DualTrust conceptual trust model. By addressing the autonomic manager’s bi-directional primary relationships in the ACS architecture, DualTrust is able to monitor the trustworthiness of the autonomic managers, protect the sensor swarm in a scalable manner, and provide global trust awareness for the orchestrating autonomic manager.

  10. Novel technique for low-jitter dual-laser synchronization in a thin film deposition system

    SciTech Connect

    Mukherjee, Pritish; Cuff, John B.; Witanachchi, Sarath

    2001-05-01

    The need for precise laser pulse synchronization in a dual-laser ablation system to optimize the quality of the deposited thin films has been previously demonstrated. We present, in this article, a novel technique for the synchronization of an excimer and a CO{sub 2} laser with synchronization having a temporal fluctuation (jitter) of less than {+-}14 ns. This is several times better than the best precision of temporal synchronization possible using traditional electronic techniques and is crucial for the application of dual-laser ablation in the manufacturing of thin films. Evidence for reproducibility in the ablation of targets using this system is presented by analyzing the initial stages of the ablated plasma using a time-gated charge coupled device imaging system.

  11. Development of a Dual-PIV system for high-speed flow applications

    NASA Astrophysics Data System (ADS)

    Schreyer, Anne-Marie; Lasserre, Jean J.; Dupont, Pierre

    2015-10-01

    A new Dual-particle image velocimetry (Dual-PIV) system for application in supersonic flows was developed. The system was designed for shock wave/turbulent boundary layer interactions with separation. This type of flow places demanding requirements on the system, from the large range of characteristic frequencies O(100 Hz-100 kHz) to spatial and temporal resolutions necessary for the measurement of turbulent quantities (Dolling in AIAA J 39(8):1517-1531, 2001; Dupont et al. in J Fluid Mech 559:255-277, 2006; Smits and Dussauge in Turbulent shear layers in supersonic flow, 2nd edn. Springer, New York, 2006). While classic PIV systems using high-resolution CCD sensors allow high spatial resolution, these systems cannot provide the required temporal resolution. Existing high-speed PIV systems provide temporal and CMOS sensor resolutions, and even laser pulse energies, that are not adapted to our needs. The only obvious solution allowing sufficiently high spatial resolution, access to high frequencies, and a high laser pulse energy is a multi-frame system: a Dual-PIV system, consisting of two synchronized PIV systems observing the same field of view, will give access to temporal characteristics of the flow. The key technology of our system is frequency-based image separation: two lasers of different wavelengths illuminate the field of view. The cross-pollution with laser light from the respective other branches was quantified during system validation. The overall system noise was quantified, and the prevailing error of only 2 % reflects the good spatial and temporal alignment. The quality of the measurement system is demonstrated with some results on a subsonic jet flow including the spatio-temporal inter-correlation functions between the systems. First measurements in a turbulent flat-plate boundary layer at Mach 2 show the same satisfactory data quality and are also presented and discussed.

  12. A CAD system based on spherical dual representations

    SciTech Connect

    Roach, J.W.; Paripati, P.K.; Wright, J.S.

    1987-08-01

    Computer-aided design (CAD) systems typically have many different functions: drafting, two-dimensional modeling, three-dimensional modeling, finite element analysis, and fit and tolerancing of parts. The authors report on the construction of a CAD system based on shape representation ideas used in the vision community to determine the shape of an object from its image. In the long term, they propose to construct a combined CAD and sensing system based on the same underlying object models. Considerable advantages follow from building a model-driven sensor fusion system that uses a common geometric model. In a manufacturing environment, for example, a library of objects can be built up and its models used in a vision and touch sensing system integrated into an automated assembly line to discriminate between objects and determine orientation and distance. If such a system could be made robust and highly reliable, then some of the most difficult problems that plague attempts to create a fully flexible automated environment would be solved.

  13. Dual sensitivity mode system for monitoring processes and sensors

    DOEpatents

    Wilks, Alan D.; Wegerich, Stephan W.; Gross, Kenneth C.

    2000-01-01

    A method and system for analyzing a source of data. The system and method involves initially training a system using a selected data signal, calculating at least two levels of sensitivity using a pattern recognition methodology, activating a first mode of alarm sensitivity to monitor the data source, activating a second mode of alarm sensitivity to monitor the data source and generating a first alarm signal upon the first mode of sensitivity detecting an alarm condition and a second alarm signal upon the second mode of sensitivity detecting an associated alarm condition. The first alarm condition and second alarm condition can be acted upon by an operator and/or analyzed by a specialist or computer program.

  14. A unified teleoperated-autonomous dual-arm robotic system

    NASA Technical Reports Server (NTRS)

    Hayati, Samad; Lee, Thomas S.; Tso, Kam Sing; Backes, Paul G.; Lloyd, John

    1991-01-01

    A description is given of complete robot control facility built as part of a NASA telerobotics program to develop a state-of-the-art robot control environment for performing experiments in the repair and assembly of spacelike hardware to gain practical knowledge of such work and to improve the associated technology. The basic architecture of the manipulator control subsystem is presented. The multiarm Robot Control C Library (RCCL), a key software component of the system, is described, along with its implementation on a Sun-4 computer. The system's simulation capability is also described, and the teleoperation and shared control features are explained.

  15. The critical role of the central nervous system (pro)renin receptor in regulating systemic blood pressure.

    PubMed

    Xu, Quanbin; Jensen, Dane D; Peng, Hua; Feng, Yumei

    2016-08-01

    The systemic renin-angiotensin system (RAS) has long been recognized as a critically important system in blood pressure (BP) regulation. However, extensive evidence has shown that a majority of RAS components are also present in many tissues and play indispensable roles in BP regulation. Here, we review evidence that RAS components, notably including the newly identified (pro)renin receptor (PRR), are present in the brain and are essential for the central regulation of BP. Binding of the PRR to its ligand, prorenin or renin, increases BP and promotes progression of cardiovascular diseases in an angiotensin II-dependent and -independent manner, establishing the PRR a promising antihypertensive drug target. We also review the existing PRR blockers, including handle region peptide and PRO20, and propose a rationale for blocking prorenin/PRR activation as a therapeutic approach that does not affect the actions of the PRR in vacuolar H(+)-ATPase and development. Finally, we summarize categories of currently available antihypertensive drugs and consider future perspectives. PMID:27113409

  16. Development of dual solid cryogens for high reliability refrigeration system

    NASA Technical Reports Server (NTRS)

    Caren, R. P.; Coston, R. M.

    1967-01-01

    High reliability solid cryogen refrigeration system consists of a container initially filled with a solid cryogen which is coupled thermally to an infrared detector by means of a link of high thermal conductivity extending from a heat exchanger within the cryogen container.

  17. Dual Source Mass Spectrometer and Sample Handling System

    NASA Technical Reports Server (NTRS)

    Brinckerhoff, W. B.; Mahaffy, P. R.; Cornish, T. J.; Cheng, A. F.; Niemann, H. B.; Harpold, D. N.; Gorevan, S. P.; Rafeek, S.; Yucht, D.

    2002-01-01

    We present details of a miniature integrated time-of-flight mass spectrometer and sample handling system under development to address some of the needs for in situ sample analysis on landed missions. Additional information is contained in the original extended abstract.

  18. Regional Policy and Innovation: A French-Style Dual System?

    ERIC Educational Resources Information Center

    Brochier, Damien; And Others

    1994-01-01

    This article focuses on the Rhone-Alpes region's policy for the development of alternating training based on cooperation between the occupational branches and the national educational system. It discusses the following: France's 1987 law on apprenticeship that provided an opportunity for its emergence; cooperative apprenticeship as the culmination…

  19. Computer-aided detection of breast masses on mammograms: performance improvement using a dual system

    NASA Astrophysics Data System (ADS)

    Wei, Jun; Sahiner, Berkman; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Helvie, Mark A.; Roubidoux, Marilyn A.; Petrick, Nicholas; Ge, Jun; Zhou, Chuan

    2005-04-01

    We have developed a computer-aided detection (CAD) system for breast masses on mammograms. In this study, our purpose was to improve the performance of our mass detection system by using a new dual system approach which combines a CAD system optimized with "average" masses with another CAD system optimized with subtle masses. The latter system is trained to provide high sensitivity in detecting subtle masses. For an unknown mammogram, the two systems are used in parallel to detect suspicious objects. A feed-forward backpropagation neural network trained to merge the scores of the two linear discriminant analysis (LDA) classifiers from the two systems makes the final decision in differentiation of true masses from normal tissue. A data set of 86 patients containing 172 mammograms with biopsy-proven masses was partitioned into a training set and an independent test set. This data set is referred to as the average data set. A second data set of 214 prior mammograms was used for training the second CAD system for detection of subtle masses. When the single CAD system trained on the average data set was applied to the test set, the Az for false positive (FP) classification was 0.81 and the FP rates were 2.1, 1.5 and 1.3 FPs/image at the case-based sensitivities of 95%, 90% and 85%, respectively. With the dual CAD system, the Az was 0.85 and the FP rates were improved to 1.7, 1.2 and 0.8 FPs/image at the same case-based sensitivities. Our results indicate that the dual CAD system can improve the performance of mass detection on mammograms.

  20. Dual-row needle arrays under an electromagnetic thermotherapy system for bloodless liver resection surgery.

    PubMed

    Huang, Sheng Chieh; Chang, Yi Yuan; Chao, Ying Jui; Shan, Yan Shen; Lin, Xi Zhang; Lee, Gwo Bin

    2012-03-01

    Electromagnetic thermotherapy has been extensively investigated recently and may become a new surgical modality for a variety of medical applications. It applies a high-frequency alternating magnetic field to heat up magnetic materials inserted within the human body to generate tissue coagulation or cell apoptosis. Using a new procedure with dual-row needle arrays under an electromagnetic thermotherapy system with a feedback temperature control system, this study demonstrates bloodless porcine liver resection, which is challenging using existing methods. In vitro experiments showed that hollowed, stainless-steel needles could be heated up to more than 300 °C within 30 s when centered under the induction coils of the electromagnetic thermotherapy system. In order to generate a wide ablation zone and to prevent the dual-row needle arrays from sticking to the tissue after heating, a constant temperature of 120 °C was applied using a specific treatment protocol. The temperature distribution in the porcine livers was also measured to explore the effective coagulation area. Liver resection was then performed in Lan-Yu pigs. Experimental results showed that seven pigs underwent liver resection without bleeding during surgery and no complications afterward. The dual-row needle arrays combined with the electromagnetic thermotherapy system are thus shown to be promising for bloodless tissue resection. PMID:22194233

  1. Hydrophobic interaction chromatography in dual salt system increases protein binding capacity.

    PubMed

    Senczuk, Anna M; Klinke, Ralph; Arakawa, Tsutomu; Vedantham, Ganesh; Yigzaw, Yinges

    2009-08-01

    Hydrophobic interaction chromatography (HIC) uses weakly hydrophobic resins and requires a salting-out salt to promote protein-resin interaction. The salting-out effects increase with protein and salt concentration. Dynamic binding capacity (DBC) is dependent on the binding constant, as well as on the flow characteristics during sample loading. DBC increases with the salt concentration but decreases with increasing flow rate. Dynamic and operational binding capacity have a major raw material cost/processing time impact on commercial scale production of monoclonal antibodies. In order to maximize DBC the highest salt concentration without causing precipitation is used. We report here a novel method to maintain protein solubility while increasing the DBC by using a combination of two salting-out salts (referred to as dual salt). In a series of experiments, we explored the dynamic capacity of a HIC resin (TosoBioscience Butyl 650M) with combinations of salts. Using a model antibody, we developed a system allowing us to increase the dynamic capacity up to twofold using the dual salt system over traditional, single salt system. We also investigated the application of this novel approach to several other proteins and salt combinations, and noted a similar protein solubility and DBC increase. The observed increase in DBC in the dual salt system was maintained at different linear flow rates and did not impact selectivity. PMID:19382248

  2. System-level Analysis of Food Moisture Content Requirements for the Mars Dual Lander Transit Mission

    NASA Technical Reports Server (NTRS)

    Levri, Julie A.; Perchonok, Michele H.

    2004-01-01

    In order to ensure that adequate water resources are available during a mission, any net water loss from the habitat must be balanced with an equivalent amount of required makeup water. Makeup water may come from a variety of sources, including water in shipped tanks, water stored in prepackaged food, product water from fuel cells, and in-situ water resources. This paper specifically addresses the issue of storing required makeup water in prepackaged food versus storing the water in shipped tanks for the Mars Dual Lander Transit Mission, one of the Advanced Life Support Reference Missions. In this paper, water mass balances have been performed for the Dual Lander Transit Mission, to determine the necessary requirement of makeup water under nominal operation (i.e. no consideration of contingency needs), on a daily basis. Contingency issues are briefly discussed with respect to impacts on makeup water storage (shipped tanks versus storage in prepackaged food). The Dual Lander Transit Mission was selected for study because it has been considered by the Johnson Space Center Exploration Office in enough detail to define a reasonable set of scenario options for nominal system operation and contingencies. This study also illustrates the concept that there are multiple, reasonable life support system scenarios for any one particular mission. Thus, the need for a particular commodity can depend upon many variables in the system. In this study, we examine the need for makeup water as it depends upon the configuration of the rest of the life support system.

  3. Advanced electric heat pump dual-stroke compressor and system development

    NASA Astrophysics Data System (ADS)

    Veyo, S. E.; Fagan, T. J.

    1983-12-01

    The development of an advanced electric heat pump is discussed. A two-capacity, residential, advanced electric heat pump utilizing a unique dual-stroke compressor was developed. Two nearly identical preprototype split systems of nominally 3.5 tons maximum cooling capacity were designed, built and laboratory tested. The estimated annual energy efficiency of this advanced system is 20 percent better than a two-speed electric heat pump available at contract inception in 1979. This superior performance is due to the synergism of a high-efficiency, dual-stroke reciprocating compressor, a dual-strength high-efficiency single-speed single-phase hermetic drive motor, a single-width, single-entry high-efficiency indoor blower with backward curved cambered plate blades, a high-efficiency multivane axial flow outdoor fan, high-efficiency two-speed air mover motors and a microprocessor control system. The relative proportions of heat exchangers, air flows and compressor size as well as the ratio between high and low capacity were optimized so as to minimize the annual cost of ownership in a northern climate. Constraints placed upon the optimization and design process to ensure comfort provide heating air with a temperature of at least 90(0)F and provide cooling with a sensible-to-total capacity ratio of not more than 0.7. System performance was measured in the laboratory in accordance with applicable codes and procedures. Performance data plus hardware details are provided.

  4. Contrasting single and multi-component working-memory systems in dual tasking.

    PubMed

    Nijboer, Menno; Borst, Jelmer; van Rijn, Hedderik; Taatgen, Niels

    2016-05-01

    Working memory can be a major source of interference in dual tasking. However, there is no consensus on whether this interference is the result of a single working memory bottleneck, or of interactions between different working memory components that together form a complete working-memory system. We report a behavioral and an fMRI dataset in which working memory requirements are manipulated during multitasking. We show that a computational cognitive model that assumes a distributed version of working memory accounts for both behavioral and neuroimaging data better than a model that takes a more centralized approach. The model's working memory consists of an attentional focus, declarative memory, and a subvocalized rehearsal mechanism. Thus, the data and model favor an account where working memory interference in dual tasking is the result of interactions between different resources that together form a working-memory system. PMID:26859518

  5. A testbed for a unified teleoperated-autonomous dual-arm robotic system

    NASA Technical Reports Server (NTRS)

    Hayati, S.; Lee, T.; Tso, K.; Backes, P.; Lloyd, J.

    1990-01-01

    This paper describes a complete robot control facility built at the Jet Propulsion Laboratory as part of NASA a telerobotics program to develop a state-of-the-art robot control environment for laboratory based space-like experiments. This system, which is now fully operational, has the following features: separation of the computing facilities into local and remote sites, autonomous motion generation in joint or Cartesian coordinates, dual-arm force reflecting teleoperation with voice interaction between the operator and the robots, shared control between the autonomously generated motions and operator controlled teleoperation, and dual-arm coordinated trajectory generation. The system has been used to carry out realistic experiments such as the exchange of an Orbital Replacement Unit (ORU), bolt turning, and door opening, using a mixture of autonomous actions and teleoperation, with either a single arm or two cooperating arms.

  6. Comparison of Analytical Predictions and Experimental Results for a Dual Brayton Power System

    NASA Technical Reports Server (NTRS)

    Johnson, Paul

    2007-01-01

    NASA Glenn Research Center (GRC) contracted Barber- Nichols, Arvada, CO to construct a dual Brayton power conversion system for use as a hardware proof of concept and to validate results from a computational code known as the Closed Cycle System Simulation (CCSS). Initial checkout tests were performed at Barber- Nichols to ready the system for delivery to GRC. This presentation describes the system hardware components and lists the types of checkout tests performed along with a couple issues encountered while conducting the tests. A description of the CCSS model is also presented. The checkout tests did not focus on generating data, therefore, no test data or model analyses are presented.

  7. System, Apparatus and Method Employing a Dual Head Laser

    NASA Technical Reports Server (NTRS)

    Coyle, Donald B. (Inventor); Stysley, Paul R. (Inventor); Poulios, Demetrios (Inventor)

    2015-01-01

    A system, apparatus and method employing a laser with a split-head, V-assembly gain material configuration. Additionally, the present invention is directed to techniques to better dissipate or remove unwanted energies in laser operations. The present invention is also directed to techniques for better collimated laser beams, with single spatial mode quality (TEM00), with improved efficiency, in extreme environments, such as in outer space.

  8. A dual-respiration chamber system with automated calibration.

    PubMed

    Schoffelen, P F; Westerterp, K R; Saris, W H; Ten Hoor, F

    1997-12-01

    This study characterizes respiration chambers with fully automated calibration. The system consists of two 14-m3 pull-type chambers. Care was taken to provide a friendly environment for the subjects, with the possibility of social contact during the experiment. Gas analysis was automated to correct for analyzer drift and barometric pressure variations and to provide ease of use. Methods used for checking the system's performance are described. The gas-analysis repeatability was within 0.002%. Results of alcohol combustion (50-350 ml/min CO2) show an accuracy of 0.5 +/- 2.0 (SD) % for O2 consumption and -0.3 +/- 1.6% for CO2 production for 2- to 24-h experiments. It is concluded that response time is not the main factor with respect to the smallest practical measurement interval (duration); volume, mixing, gas-analysis accuracy, and levels of O2 consumption and CO2 production are at least equally important. The smallest practical interval was 15-25 min, as also found with most chamber systems described in the literature. We chose to standardize 0.5 h as the minimum measurement interval. PMID:9390982

  9. The natriuretic peptides system in the pathophysiology of heart failure: from molecular basis to treatment.

    PubMed

    Volpe, Massimo; Carnovali, Marino; Mastromarino, Vittoria

    2016-01-01

    After its discovery in the early 1980s, the natriuretic peptide (NP) system has been extensively characterized and its potential influence in the development and progression of heart failure (HF) has been investigated. HF is a syndrome characterized by the activation of different neurohormonal systems, predominantly the renin-angiotensin (Ang)-aldosterone system (RAAS) and the sympathetic nervous system (SNS), but also the NP system. Pharmacological interventions have been developed to counteract the neuroendocrine dysregulation, through the down modulation of RAAS with ACE (Ang-converting enzyme) inhibitors, ARBs (Ang receptor blockers) and mineralcorticoid antagonists and of SNS with β-blockers. In the last years, growing attention has been paid to the NP system. In the present review, we have summarized the current knowledge on the NP system, focusing on its role in HF and we provide an overview of the pharmacological attempts to modulate NP in HF: from the negative results of the study with neprilysin (NEP) inhibitors, alone or associated with an ACE inhibitor and vasopeptidase inhibitors, to the most recently and extremely encouraging results obtained with the new pharmacological class of Ang receptor and NEP inhibitor, currently defined ARNI (Ang receptor NEP inhibitor). Indeed, this new class of drugs to manage HF, supported by the recent results and a vast clinical development programme, may prompt a conceptual shift in the treatment of HF, moving from the inhibition of RAAS and SNS to a more integrated target to rebalance neurohormonal dysregulation in HF. PMID:26637405

  10. Predicted and measured performance of a shaped reflector in a dual-gridded reflector system

    NASA Astrophysics Data System (ADS)

    Evans, G. D.; Malik, D. P. S.

    Current and proposed satellite communications systems demand dual-linearly polarized transmit/receive antennas for contoured and/or multiple-beam coverages. The proven means of satisfying these requirements is by the use of dual-gridded reflectors with multiple feed blocks for a contoured beam. In this paper practical issues and advantages concerning the choice of using a shaped reflector to replace one of the multiple feed antennas (MFAs) within a dual-gridded pair are addressed. For single contoured beam applications a shaped reflector has several important advantages. Primarily it allows a single feed system to replace a whole feed cluster and associated beamforming networks. In a study for the Orion satellites this resulted in a total mass saving of 7.5 kg per feed block and a considerable reduction in hardware complexity. This resulted in a total mass saving of 15 kg which translates to an extra 6 months life for the spacecraft. The use of a single focussed feed also results in the illumination efficiency being improved by approximately 20%. Interestingly the requirements for the Orion satellites are for both spot beams of one polarization and for a contoured beam of the orthogonal polarization to cover all the spots, for both North America and Europe. These requirements have been met by the use of two dual-gridded reflector systems; one antenna in each system being a multiple-beam-antenna and the other a shaped reflector. This paper uses as an example a realistic MFA design devised during the Orion contract procurement stage and its performance is compared with that of an equivalent shaped reflector design optimized at single and multiple frequencies. The susceptibility to predict in service thermal distortions of the two designs is then assessed. Finally some recent results are presented of measured and predicted feed cross-polar radiation collimated by a gridded shaped reflector; the feed being at the focus of an unshaped reflector behind the shaped dish.

  11. Dual mode fuel injection system and fuel injector for same

    SciTech Connect

    Lawrence, Keith E.; Tian, Ye

    2005-09-20

    A fuel injection system has the ability to produce two different spray patterns depending on the positioning of a needle control valve member. Positioning of the needle control valve member determines which of the two needle control chambers are placed in a low pressure condition. First and second needle valve members have closing hydraulic surfaces exposed to fluid pressure in the two needle control chambers. The injector preferably includes a homogenous charge nozzle outlet set and a conventional nozzle outlet set controlled respectively, by the first and second needle valve members.

  12. Development of a dual-view endoscope system

    NASA Astrophysics Data System (ADS)

    Sekiya, Takaomi; Ito, Eiichi; Kanai, Moriyasu; Matsumoto, Mitsuhiro

    2006-02-01

    We demonstrate a new endoscope system for laparoscopic surgery that provides two different views simultaneously. One is a 'wide view' and the other is an 'enlarged view' derived from the wide view with an optical image-shifting mechanism. By using this endoscope, surgeons can observe a surgical area as an enlarged view without moving or rotating the endoscope. Moreover, the wide view is useful for examining the outside of a surgical area. They can move the enlarged view within the area of the wide view by using the image-shifting mechanism. This system consists of a rigid scope and a 'zoom unit.' The rigid scope includes a set of optical lenses for the wide view angle (120 degrees) and light-guide fibers built in for illumination. These fibers are connected to a light source directly. The zoom unit includes imaging optical elements and two CCD cameras. In the zoom unit, an image provided by the rigid scope is divided into two ways by a half-mirror. One image is captured by the first CCD camera with relay lenses for a wide view. The other passes through a Porro prism (II), which is used to shift the enlarged view vertically and horizontally, and zoom lenses with a three variable power. Then, the image is captured by the second CCD camera for an enlarged view. A working distance between the tip of the rigid scope and the surface of viscera is 100mm that is sufficient for surgical operation.

  13. Dual camera system for acquisition of high resolution images

    NASA Astrophysics Data System (ADS)

    Papon, Jeremie A.; Broussard, Randy P.; Ives, Robert W.

    2007-02-01

    Video surveillance is ubiquitous in modern society, but surveillance cameras are severely limited in utility by their low resolution. With this in mind, we have developed a system that can autonomously take high resolution still frame images of moving objects. In order to do this, we combine a low resolution video camera and a high resolution still frame camera mounted on a pan/tilt mount. In order to determine what should be photographed (objects of interest), we employ a hierarchical method which first separates foreground from background using a temporal-based median filtering technique. We then use a feed-forward neural network classifier on the foreground regions to determine whether the regions contain the objects of interest. This is done over several frames, and a motion vector is deduced for the object. The pan/tilt mount then focuses the high resolution camera on the next predicted location of the object, and an image is acquired. All components are controlled through a single MATLAB graphical user interface (GUI). The final system we present will be able to detect multiple moving objects simultaneously, track them, and acquire high resolution images of them. Results will demonstrate performance tracking and imaging varying numbers of objects moving at different speeds.

  14. Modeling of magnetic Barkhausen noise in single and dual easy axis systems in steel

    NASA Astrophysics Data System (ADS)

    Krause, Thomas W.; Mandal, Kalyan; Atherton, David L.

    1999-04-01

    Angular dependent magnetic Barkhausen noise (MBN) signals measured on plate steel, and on the inside and outside surfaces of sections of seam welded and spiral welded 2% Mn steel pipe are modeled by considering a system of dipole moments. The relative orientation of dipole moments is fixed within the material, but their magnitude grows in the presence of an applied field. Growth of the moments is proportional to the magnetic field projected along a particular moment axis. A single easy axis material consists of an isotropically aligned population of moments, giving the background, upon which is superimposed a population of moments with relative orientations that result in a net moment within the sample. A dual easy axis system is proposed to consist of: (i) a second population of moments with orientations resulting in a net moment with orientation different from that of the first and (ii) interactions, possibly quadrupolar in nature, that occur between the individual moments of each population. The model is used to explain differences in the angular-dependent MBN signal between the seam welded pipe, with a single easy axis, and the spiral welded pipe, with a dual easy axis. The source of the dual easy axis system in the spiral welded pipe, which is different on the two pipe surfaces, is considered in terms of the asymmetric manufacturing processes, relative to the pipe axis, applied during its production.

  15. [Production of sugar syrup containing rare sugar using dual-enzyme coupled reaction system].

    PubMed

    Han, Wenjia; Zhu, Yueming; Bai, Wei; Izumori, Ken; Zhang, Tongcun; Sun, Yuanxia

    2014-01-01

    Enzymatic conversion is very important to produce functional rare sugars, but the conversion rate of single enzymes is generally low. To increase the conversion rate, a dual-enzyme coupled reaction system was developed. Dual-enzyme coupled reaction system was constructed using D-psicose-3-epimerase (DPE) and L-rhamnose isomerase (L-RhI), and used to convert D-fructose to D-psicose and D-allose. The ratio of DPE and L-RhI was 1:10 (W/W), and the concentration of DPE was 0.05 mg/mL. The optimum temperature was 60 degrees C and pH was 9.0. When the concentration of D-fructose was 2%, the reaction reached its equilibrium after 10 h, and the yield of D-psicose and D-allose was 5.12 and 2.04 g/L, respectively. Using the dual-enzymes coupled system developed in the current study, we could obtain sugar syrup containing functional rare sugar from fructose-rich raw material, such as high fructose corn syrup. PMID:24818483

  16. Dual spark plug ignition system for motorcycle internal combustion engine

    SciTech Connect

    Hoeptner, H.W.

    1991-04-02

    This patent describes an ignition system for a motorcycle two cylinder internal combustion engine, the system including magnetically coupled primary and secondary coil means, two spark plugs at each of the cylinders, a source of electrical current, and a single set of contacts controlling electrical current flow to the primary coil means for producing high voltage outputs from the secondary coil means to be delivered to all four of the spark plugs, the secondary coil means including certain secondary coil means operatively connected via the primary coil means with both the of spark plugs at one cylinder, a single cam controlling only the contacts, and a single magnetic core between the primary coil means and both the secondary coil means, and wherein the spark plugs include: two plugs at one cylinder and connected with the certain secondary coil means, two plugs at the second cylinder and connected with the other secondary coil means, the primary coil means including certain primary coil means magnetically coupled to the certain secondary coil means, and other primary coil means magnetically coupled to the other secondary coil means, the certain and other primary coil means being connected in series, electrically, the two spark plugs at one cylinder being electrically connected to opposite ends of the certain secondary coil means, and the two spark plugs at the other cylinder are electrically connected to opposite ends of the other secondary coil means. It comprises the cam driven by the engine for controlling opening of the contacts, the cam rotatable about a first axis, carrier means carrying the contacts, and adjustably rotatable about the axis.

  17. Toward a dual-learning systems model of speech category learning

    PubMed Central

    Chandrasekaran, Bharath; Koslov, Seth R.; Maddox, W. T.

    2014-01-01

    More than two decades of work in vision posits the existence of dual-learning systems of category learning. The reflective system uses working memory to develop and test rules for classifying in an explicit fashion, while the reflexive system operates by implicitly associating perception with actions that lead to reinforcement. Dual-learning systems models hypothesize that in learning natural categories, learners initially use the reflective system and, with practice, transfer control to the reflexive system. The role of reflective and reflexive systems in auditory category learning and more specifically in speech category learning has not been systematically examined. In this article, we describe a neurobiologically constrained dual-learning systems theoretical framework that is currently being developed in speech category learning and review recent applications of this framework. Using behavioral and computational modeling approaches, we provide evidence that speech category learning is predominantly mediated by the reflexive learning system. In one application, we explore the effects of normal aging on non-speech and speech category learning. Prominently, we find a large age-related deficit in speech learning. The computational modeling suggests that older adults are less likely to transition from simple, reflective, unidimensional rules to more complex, reflexive, multi-dimensional rules. In a second application, we summarize a recent study examining auditory category learning in individuals with elevated depressive symptoms. We find a deficit in reflective-optimal and an enhancement in reflexive-optimal auditory category learning. Interestingly, individuals with elevated depressive symptoms also show an advantage in learning speech categories. We end with a brief summary and description of a number of future directions. PMID:25132827

  18. Analysis of a generalized dual reflector antenna system using physical optics

    NASA Technical Reports Server (NTRS)

    Acosta, Roberto J.; Lagin, Alan R.

    1992-01-01

    Reflector antennas are widely used in communication satellite systems because they provide high gain at low cost. Offset-fed single paraboloids and dual reflector offset Cassegrain and Gregorian antennas with multiple focal region feeds provide a simple, blockage-free means of forming multiple, shaped, and isolated beams with low sidelobes. Such antennas are applicable to communications satellite frequency reuse systems and earth stations requiring access to several satellites. While the single offset paraboloid has been the most extensively used configuration for the satellite multiple-beam antenna, the trend toward large apertures requiring minimum scanned beam degradation over the field of view 18 degrees for full earth coverage from geostationary orbit may lead to impractically long focal length and large feed arrays. Dual reflector antennas offer packaging advantages and more degrees of design freedom to improve beam scanning and cross-polarization properties. The Cassegrain and Gregorian antennas are the most commonly used dual reflector antennas. A computer program for calculating the secondary pattern and directivity of a generalized dual reflector antenna system was developed and implemented at LeRC. The theoretical foundation for this program is based on the use of physical optics methodology for describing the induced currents on the sub-reflector and main reflector. The resulting induced currents on the main reflector are integrated to obtain the antenna far-zone electric fields. The computer program is verified with other physical optics programs and with measured antenna patterns. The comparison shows good agreement in far-field sidelobe reproduction and directivity.

  19. Extremely sensitive dual imaging system in solid phantoms

    PubMed Central

    Barnoy, Eran A.; Fixler, Dror; Popovtzer, Rachela; Nayhoz, Tsviya; Ray, Krishanu

    2016-01-01

    Herein we describe promising results from the combination of fluorescent lifetime imaging microscopy (FLIM) and diffusion reflection (DR) medical imaging techniques. Three different geometries of gold nanoparticles (GNPs) were prepared: spheres of 20nm diameter, rods (GNRs) of aspect ratio (AR) 2.5, and GNRs of AR 3.3. Each GNP geometry was then conjugated using PEG linkers estimated to be 10nm in length to each of 3 different fluorescent dyes: Fluorescein, Rhodamine B, and Sulforhodamine B. DR provided deep-volume measurements (up to 1cm) from within solid, tissue-imitating phantoms, indicating GNR presence corresponding to the light used by recording light scattered from the GNPs with increasing distance to a photodetector. FLIM imaged solutions as well as phantom surfaces, recording both the fluorescence lifetimes as well as the fluorescence intensities. Fluorescence quenching was observed for Fluorescein, while metal-enhanced fluorescence (MEF) was observed in Rhodamine B and Sulforhodamine B – the dyes with an absorption peak at a slightly longer wavelength than the GNP plasmon resonance peak. Our system is highly sensitive due to the increased intensity provided by MEF, and also because of the inherent sensitivity of both FLIM and DR. Together, these two modalities and MEF can provide a lot of meaningful information for molecular and functional imaging of biological samples. PMID:27239085

  20. Optimization of electrostatic dual-grid beam-deflection system

    NASA Technical Reports Server (NTRS)

    Hudson, W. R.; Lathem, W. C.; Power, J. L.; Banks, B. A.

    1972-01-01

    Tests were performed to minimize accelerator grid erosion of a 5-cm diameter Kaufman ion thruster due to direct beam impingement. Several different screen hole diameters, pillow-shape-square screen holes, and dished screen grids were tried. The optimization was accomplished by copper plating the accelerator grid before testing each grid configuration on a thruster for a 2-hour run. The thruster beam sputtered copper and molybdenum from the accelerator grid where the beam impinged. The observed erosion patterns and measured accelerator currents were used to determine how to modify the accelerator system. The lowest erosion was obtained for a 50-percent open area pillow-shape-square-aperture screen grid, dished 0.043 centimeter convex toward the accelerator grid, which was positioned with the center of the screen grid 0.084 centimeter from the accelerator grid. During this investigation the accelerator current was reduced from 120 to 55 microamperes and was also more uniformly distributed over the area of the accelerator grid.

  1. Optical system design of a new type infrared dual-band seeker

    NASA Astrophysics Data System (ADS)

    Yongli, Ma; Liu, Wenzhe; Wang, Wensheng

    2010-08-01

    Based on the appearance of infrared dual-band device and the technical parameters of infrared seeker, a new-type Cassegrain optical system is designed. The main advantages of the system are large field-of-view, infrared dual-band common path and compact structure. In the Cassegrain optical system, the working wavelengths are 3.7μm~4.8μm and 8μm~12μm, the field-of-view 4° and the aperture 240mm. The paraboloidal primary mirror and hyperboloidal secondary mirror are all replaced by spherical surfaces. So the problems of high machining accuracy and alignment become much easier. In order to balance the aberrations, two compensating lenses are used in the system. The amounts of compensating lenses are much less than other optical systems. So the new optical system becomes much more economy, light and compact. The total length of system is 170mm. The ratio of total length to focal length is 0.62. So it can meet the operating requirement of seeker in limited space. Moreover, the system has a good performance of athermalization between negative 40°c and positive 50°c. The design results of the system show that the MTF value of each field is greater than 0.7 when the cut-off frequency is 11 lp / mm. Wavefront aberration is less than 0.038λ.

  2. Towards Small-Sized Long Tail Business with the Dual-Directed Recommendation System

    NASA Astrophysics Data System (ADS)

    Takahashi, Masakazu; Yamada, Takashi; Tsuda, Kazuhiko; Terano, Takao

    This paper describes a novel architecture to promote retail businesses using information recommendation systems. The main features of the architecture are 1) Dual-directed Recommendation system, 2) Portal site for three kinds of users: Producers, Retailers, and Consumers, which are considered to be Prosumers, and 3) Agent-based implementation. We have developed a web-based system DAIKOC (Dynamic Advisor for Information and Knowledge Oriented Communities) with the above architecture. In this paper, we focus on the recommendation functions to extract the items that will achieve the large sales in the future from the ID (IDentification)-POS (Point-Of-Sales) data.

  3. 10 kWe dual-mode space nuclear power system for military and scientific applications

    NASA Astrophysics Data System (ADS)

    Malloy, John; Westerman, Kurt; Rochow, Richard; Scoles, Stephen

    The Small Externally-fueled Heat Pipe Thermionic Reactor concept is used as the basis of a 10 kWe dual-mode space power system scheme that generates both arcjet propulsion system power and direct (hydrogen propellant-heating) thrust. This direct-thrust feature allows the nuclear-power system to move a payload from LEO to GEO in less than one month, using half as much propellant as a cryogenic-fuel chemical rocket. The nuclear reactor uses 36 thermionic heat-pipe modules, which produce electricity within the reactor and remove waste heat.

  4. Dual-mode spectral imaging system employing a focus variable lens

    NASA Astrophysics Data System (ADS)

    Förster, Erik; Stürmer, Moritz; Wallrabe, Ulrike; Korvink, Jan; Bohnert, Patrick; Brunner, Robert

    2016-04-01

    This paper presents a dual-mode spectral imaging system, which allows switching between pure lateral imaging and the spectrally resolved recording of spatial information. The optical system was equipped with tunable functionalities in order to achieve high flexibility, cover a wide range of object distances, and address extended field angles. A fluidic membrane lens was used for the variable focus, and the recording of the laterally extended scene was made possible by successively adjusting the different tilting angles to the different object positions. The capability and performance of the spectral imaging system were assessed using various test scenes, with different aimed field positions and changing object distances.

  5. IMAGE ANALYSIS ALGORITHMS FOR DUAL MODE IMAGING SYSTEMS

    SciTech Connect

    Robinson, Sean M.; Jarman, Kenneth D.; Miller, Erin A.; Misner, Alex C.; Myjak, Mitchell J.; Pitts, W. Karl; Seifert, Allen; Seifert, Carolyn E.; Woodring, Mitchell L.

    2010-06-11

    The level of detail discernable in imaging techniques has generally excluded them from consideration as verification tools in inspection regimes where information barriers are mandatory. However, if a balance can be struck between sufficient information barriers and feature extraction to verify or identify objects of interest, imaging may significantly advance verification efforts. This paper describes the development of combined active (conventional) radiography and passive (auto) radiography techniques for imaging sensitive items assuming that comparison images cannot be furnished. Three image analysis algorithms are presented, each of which reduces full image information to non-sensitive feature information and ultimately is intended to provide only a yes/no response verifying features present in the image. These algorithms are evaluated on both their technical performance in image analysis and their application with or without an explicitly constructed information barrier. The first algorithm reduces images to non-invertible pixel intensity histograms, retaining only summary information about the image that can be used in template comparisons. This one-way transform is sufficient to discriminate between different image structures (in terms of area and density) without revealing unnecessary specificity. The second algorithm estimates the attenuation cross-section of objects of known shape based on transition characteristics around the edge of the object’s image. The third algorithm compares the radiography image with the passive image to discriminate dense, radioactive material from point sources or inactive dense material. By comparing two images and reporting only a single statistic from the combination thereof, this algorithm can operate entirely behind an information barrier stage. Together with knowledge of the radiography system, the use of these algorithms in combination can be used to improve verification capability to inspection regimes and improve

  6. A dual-channel fusion system of visual and infrared images based on color transfer

    NASA Astrophysics Data System (ADS)

    Pei, Chuang; Jiang, Xiao-yu; Zhang, Peng-wei; Liang, Hao-cong

    2013-09-01

    A dual-channel fusion system of visual and infrared images based on color transfer The increasing availability and deployment of imaging sensors operating in multiple spectrums has led to a large research effort in image fusion, resulting in a plethora of pixel-level image fusion algorithms. However, most of these algorithms have gray or false color fusion results which are not adapt to human vision. Transfer color from a day-time reference image to get natural color fusion result is an effective way to solve this problem, but the computation cost of color transfer is expensive and can't meet the request of real-time image processing. We developed a dual-channel infrared and visual images fusion system based on TMS320DM642 digital signal processing chip. The system is divided into image acquisition and registration unit, image fusion processing unit, system control unit and image fusion result out-put unit. The image registration of dual-channel images is realized by combining hardware and software methods in the system. False color image fusion algorithm in RGB color space is used to get R-G fused image, then the system chooses a reference image to transfer color to the fusion result. A color lookup table based on statistical properties of images is proposed to solve the complexity computation problem in color transfer. The mapping calculation between the standard lookup table and the improved color lookup table is simple and only once for a fixed scene. The real-time fusion and natural colorization of infrared and visual images are realized by this system. The experimental result shows that the color-transferred images have a natural color perception to human eyes, and can highlight the targets effectively with clear background details. Human observers with this system will be able to interpret the image better and faster, thereby improving situational awareness and reducing target detection time.

  7. Dual-tagging system for the affinity purification of mammalian protein complexes

    SciTech Connect

    Giannone, Richard J; McDonald, W Hayes; Hurst, Gregory {Greg} B; Huang, Ying; Wu, Jun; Liu, Yie; Wang, Yisong

    2007-01-01

    Although affinity purification coupled with mass spectrometry (MS) provides a powerful tool to study protein-protein interactions, this strategy has encountered numerous difficulties when adapted to mammalian cells. Here we describe a Gateway{reg_sign}-compatible dual-tag affinity purification system that integrates regulatable expression, tetracysteine motifs, and various combinations of affinity tags to facilitate the cloning, detection, and purification of bait proteins and their interacting partners. Utilizing the human telomere binding protein TRF2 as a benchmark, we demonstrate bait protein recoveries upwards of approximately 16% from as little as 1-7 x 10{sup 7} cells and successfully identify known TRF2 interacting proteins, suggesting that our dual-tag affinity purification approach is a capable new tool for expanding the capacity to explore mammalian proteomic networks.

  8. Self-consistent dual boson approach to single-particle and collective excitations in correlated systems

    NASA Astrophysics Data System (ADS)

    Stepanov, E. A.; van Loon, E. G. C. P.; Katanin, A. A.; Lichtenstein, A. I.; Katsnelson, M. I.; Rubtsov, A. N.

    2016-01-01

    We propose an efficient dual boson scheme, which extends the dynamical mean-field theory paradigm to collective excitations in correlated systems. The theory is fully self-consistent both on the one- and on the two-particle level, thus describing the formation of collective modes as well as the renormalization of electronic and bosonic spectra on equal footing. The method employs an effective impurity model comprising both fermionic and bosonic hybridization functions. Only single- and two-electron Green's functions of the reference problem enter the theory, due to the optimal choice of the self-consistency condition for the effective bosonic bath. We show that the theory is naturally described by a dual Luttinger-Ward functional and obeys the relevant conservation laws.

  9. Theoretical thermodynamics connections between Dual (Left-Handed) and Direct (Right Handed) systems: Entropy, temperature, pressure and heat capacity

    NASA Astrophysics Data System (ADS)

    Flores, J. C.; Palma-Chilla, L.

    2015-11-01

    Spectral frequencies for Dual systems, a subclass of Left Handed materials, are straight connected to their corresponding Direct counterparts (conventional materials). This allows us to link the thermodynamics properties of both. We found analytically these connections for temperature, pressure and heat capacity. Entropies are also correlated being a basic tool to attach thermodynamically both categories of systems. It is explicitly showed that the Dual has negative temperatures and positive pressures.

  10. Testing and analysis of dual-mode adaptive landing gear, taxi mode test system for YF-12A

    NASA Technical Reports Server (NTRS)

    Gamon, M. A.

    1979-01-01

    The effectiveness of a dual mode adaptive landing gear system in reducing the dynamic response of an airplane during ground taxiing was studied. The dynamic taxi tests of the YF-12A research airplane are presented. A digital computer program which simulated the test conditions is discussed. The dual mode system as tested provides dynamic taxi response reductions of 25 percent at the cg and 30 to 45 percent at the cockpit.

  11. [Combination treatment of hypertension in 2015].

    PubMed

    Špinar, Jindřich; Vítovec, Jiří; Špinarová, Lenka; Bendová, Miroslava

    2015-05-01

    We present an overview of the present views on combination treatment and on fixed combinations in the treatment of hypertension according to guidelines of ESH/ESC and ČSH from 2013. The most frequently recommended dual combinations include a blocker of the renin-angiotensin system (ACEI or sartan) and a calcium channel blocker, and further a blocker of the renin-angiotensin system and a diuretic and a calcium channel blocker and a diuretic. In 2014 a fixed-dose combination of an ACE inhibitor (perindopril), a calcium channel blocker (amlodipine) and an diuretic (indapamide) appeared on the Czech market. Within the PIANIST study including 4 731 insufficiently controlled hypertensives, a fixed-dose triple combination of perindopril, amlodipine and indapamide led to a decrease in blood pressure by 28.3/13.8 mm Hg and to a sufficient control of hypertension in 92 % of patients. The advantage of fixed combinations primarily consists in greater compliance of patients and thereby in a better control of hypertension. About 1/3 of hypertensives need a triple combination for a satisfactory blood pressure control. PMID:26075856

  12. An 8.4-GHz dual-maser front-end system for Parkes reimplementation

    NASA Technical Reports Server (NTRS)

    Trowbridge, D. L.; Loreman, J. R.; Brunzie, T. J.; Quinn, R.

    1990-01-01

    An 8.4-GHz front-end system consisting of a feedhorn, a waveguide feed assembly, dual masers, and downconverters was reimplemented at Parkes as part of the Parkes Canberra Telemetry Array for the Voyager Neptune encounter. The front-end system was originally assembled by the European Space Agency and installed on the Parkes antenna for the Giotto project. It was also used on a time-sharing basis by the Deep Space Network as part of the Parkes Canberra Telemetry Array to enhance the data return from the Voyager Uranus encounter. At the conclusion of these projects in 1986, part of the system was then shipped to JPL on loan for reimplementation at Parkes for the Voyager Neptune encounter. New design and implementation required to make the system operable at Parkes included new microwave front-end control cabinets, closed-cycle refrigeration monitor system, noise-adding radiometer system, front-end controller assembly, X81 local oscillator multiplier, and refurbishment of the original dual 8.4-GHz traveling-wave masers and waveguide feed system. The front-end system met all requirements during the encounter and was disassembled in October 1989 and returned to JPL.

  13. An 8.4-GHz dual-maser front-end system for Parkes reimplementation

    NASA Astrophysics Data System (ADS)

    Trowbridge, D. L.; Loreman, J. R.; Brunzie, T. J.; Quinn, R.

    1990-02-01

    An 8.4-GHz front-end system consisting of a feedhorn, a waveguide feed assembly, dual masers, and downconverters was reimplemented at Parkes as part of the Parkes Canberra Telemetry Array for the Voyager Neptune encounter. The front-end system was originally assembled by the European Space Agency and installed on the Parkes antenna for the Giotto project. It was also used on a time-sharing basis by the Deep Space Network as part of the Parkes Canberra Telemetry Array to enhance the data return from the Voyager Uranus encounter. At the conclusion of these projects in 1986, part of the system was then shipped to JPL on loan for reimplementation at Parkes for the Voyager Neptune encounter. New design and implementation required to make the system operable at Parkes included new microwave front-end control cabinets, closed-cycle refrigeration monitor system, noise-adding radiometer system, front-end controller assembly, X81 local oscillator multiplier, and refurbishment of the original dual 8.4-GHz traveling-wave masers and waveguide feed system. The front-end system met all requirements during the encounter and was disassembled in October 1989 and returned to JPL.

  14. Advancing the application of systems thinking in health: exploring dual practice and its management in Kampala, Uganda

    PubMed Central

    2014-01-01

    Background Many full-time Ugandan government health providers take on additional jobs – a phenomenon called dual practice. We describe the complex patterns that characterize the evolution of dual practice in Uganda, and the local management practices that emerged in response, in five government facilities. An in-depth understanding of dual practice can contribute to policy discussions on improving public sector performance. Methods A multiple case study design with embedded units of analysis was supplemented by interviews with policy stakeholders and a review of historical and policy documents. Five facility case studies captured the perspective of doctors, nurses, and health managers through semi-structured in-depth interviews. A causal loop diagram illustrated interactions and feedback between old and new actors, as well as emerging roles and relationships. Results The causal loop diagram illustrated how feedback related to dual practice policy developed in Uganda. As opportunities for dual practice grew and the public health system declined over time, government providers increasingly coped through dual practice. Over time, government restrictions to dual practice triggered policy resistance and protest from government providers. Resulting feedback contributed to compromising the supply of government providers and, potentially, of service delivery outcomes. Informal government policies and restrictions replaced the formal restrictions identified in the early phases. In some instances, government health managers, particularly those in hospitals, developed their own practices to cope with dual practice and to maintain public sector performance. Management practices varied according to the health manager’s attitude towards dual practice and personal experience with dual practice. These practices were distinct in hospitals. Hospitals faced challenges managing internal dual practice opportunities, such as those created by externally-funded research projects based

  15. Enhanced genome editing in mammalian cells with a modified dual-fluorescent surrogate system.

    PubMed

    Zhou, Yan; Liu, Yong; Hussmann, Dianna; Brøgger, Peter; Al-Saaidi, Rasha Abdelkadhem; Tan, Shuang; Lin, Lin; Petersen, Trine Skov; Zhou, Guang Qian; Bross, Peter; Aagaard, Lars; Klein, Tino; Rønn, Sif Groth; Pedersen, Henrik Duelund; Bolund, Lars; Nielsen, Anders Lade; Sørensen, Charlotte Brandt; Luo, Yonglun

    2016-07-01

    Programmable DNA nucleases such as TALENs and CRISPR/Cas9 are emerging as powerful tools for genome editing. Dual-fluorescent surrogate systems have been demonstrated by several studies to recapitulate DNA nuclease activity and enrich for genetically edited cells. In this study, we created a single-strand annealing-directed, dual-fluorescent surrogate reporter system, referred to as C-Check. We opted for the Golden Gate Cloning strategy to simplify C-Check construction. To demonstrate the utility of the C-Check system, we used the C-Check in combination with TALENs or CRISPR/Cas9 in different scenarios of gene editing experiments. First, we disrupted the endogenous pIAPP gene (3.0 % efficiency) by C-Check-validated TALENs in primary porcine fibroblasts (PPFs). Next, we achieved gene-editing efficiencies of 9.0-20.3 and 4.9 % when performing single- and double-gene targeting (MAPT and SORL1), respectively, in PPFs using C-Check-validated CRISPR/Cas9 vectors. Third, fluorescent tagging of endogenous genes (MYH6 and COL2A1, up to 10.0 % frequency) was achieved in human fibroblasts with C-Check-validated CRISPR/Cas9 vectors. We further demonstrated that the C-Check system could be applied to enrich for IGF1R null HEK293T cells and CBX5 null MCF-7 cells with frequencies of nearly 100.0 and 86.9 %, respectively. Most importantly, we further showed that the C-Check system is compatible with multiplexing and for studying CRISPR/Cas9 sgRNA specificity. The C-Check system may serve as an alternative dual-fluorescent surrogate tool for measuring DNA nuclease activity and enrichment of gene-edited cells, and may thereby aid in streamlining programmable DNA nuclease-mediated genome editing and biological research. PMID:26755436

  16. Light-splitting photovoltaic system utilizing two dual-junction solar cells

    SciTech Connect

    Xiong, Kanglin; Yang, Hui; Lu, Shulong; Dong, Jianrong; Zhou, Taofei; Wang, Rongxin; Jiang, Desheng

    2010-12-15

    There are many difficulties limiting the further development of monolithic multi-junction solar cells, such as the growth of lattice-mismatched material and the current matching constraint. As an alternative approach, the light-splitting photovoltaic system is investigated intensively in different aspects, including the energy loss mechanism and the choice of energy bandgaps of solar cells. Based on the investigation, a two-dual junction system has been implemented employing lattice-matched GaInP/GaAs and InGaAsP/InGaAs cells grown epitaxially on GaAs and InP substrates, respectively. (author)

  17. Off-Line Programming System of Multi-Axis Platform for Dual Beam Laser Welding

    NASA Astrophysics Data System (ADS)

    Yang, Jian-Zhong; Zhang, Yan; Chen, Ji-Hong; Wang, Wei-Qiang; Liu, Yi

    The multi-axis platform of dual beam laser welding (DBLW) can guarantee a good synchronism on double sides, adaptation and precision, thus it can be widely applied. On this platform, this paper studies critical technology of off-line programming of DBLW. It presents a U-oriented on double sides trajectory planning method based on the traditional method derived from single beam laser welding. Then a calibration strategy of structural parameters is rendered and G codes are produced by a postprocessor. At last the researchers develops the off-line programming system on CAM platforms and a simulation conducted proves the system satisfying the need.

  18. Dual cameras acquisition and display system of retina-like sensor camera and rectangular sensor camera

    NASA Astrophysics Data System (ADS)

    Cao, Nan; Cao, Fengmei; Lin, Yabin; Bai, Tingzhu; Song, Shengyu

    2015-04-01

    For a new kind of retina-like senor camera and a traditional rectangular sensor camera, dual cameras acquisition and display system need to be built. We introduce the principle and the development of retina-like senor. Image coordinates transformation and interpolation based on sub-pixel interpolation need to be realized for our retina-like sensor's special pixels distribution. The hardware platform is composed of retina-like senor camera, rectangular sensor camera, image grabber and PC. Combined the MIL and OpenCV library, the software program is composed in VC++ on VS 2010. Experience results show that the system can realizes two cameras' acquisition and display.

  19. A Peroxidase/Dual Oxidase System Modulates Midgut Epithelial Immunity in Anopheles gambiae

    PubMed Central

    Kumar, Sanjeev; Molina-Cruz, Alvaro; Gupta, Lalita; Rodrigues, Janneth; Barillas-Mury, Carolina

    2012-01-01

    Extracellular matrices in diverse biological systems are crosslinked by dityrosine covalent bonds catalyzed by the peroxidase/oxidase system. We show that the Immunomodulatory Peroxidase (IMPer), an enzyme secreted by the mosquito Anopheles gambiae midgut, and dual oxidase (Duox) form a dityrosine network that decreases gut permeability to immune elicitors and protects the microbiota by preventing activation of epithelial immunity. It also provides a suitable environment for malaria parasites to develop within the midgut lumen without inducing nitric oxide synthase expression. Disruption of this barrier results in strong and effective pathogen-specific immune responses. PMID:20223948

  20. A peroxidase/dual oxidase system modulates midgut epithelial immunity in Anopheles gambiae.

    PubMed

    Kumar, Sanjeev; Molina-Cruz, Alvaro; Gupta, Lalita; Rodrigues, Janneth; Barillas-Mury, Carolina

    2010-03-26

    Extracellular matrices in diverse biological systems are cross-linked by dityrosine covalent bonds catalyzed by the peroxidase/oxidase system. We show that a peroxidase, secreted by the Anopheles gambiae midgut, and dual oxidase form a dityrosine network that decreases gut permeability to immune elicitors. This network protects the microbiota by preventing activation of epithelial immunity. It also provides a suitable environment for malaria parasites to develop within the midgut lumen without inducing nitric oxide synthase expression. Disruption of this barrier results in strong and effective pathogen-specific immune responses. PMID:20223948

  1. Application of portable fluorescence spectrophotometry for integrity testing of recycled water dual distribution systems.

    PubMed

    Hambly, Adam C; Henderson, Rita K; Baker, Andy; Stuetz, Richard M; Khan, Stuart J

    2015-01-01

    Water utilities supplying recycled water to households via a "third-pipe" or "dual reticulation" system have a need for a rapid, portable method to detect cross-connections within potable water reticulation networks. This study evaluates portable fluorimetry as a technique for cross-connection detection in the field. For the first time, an investigation of a full-scale dual reticulation water-recycling network has been carried out to identify cross-connections using a portable fluorimeter. We determined that this can be carried out with a 3 mL water sample, and unlike methods that are currently in use for cross-connection detection, can be achieved quickly without disruption to water flow or availability within the network. It was also revealed that fluorescence trigger values could be established with high levels of confidence by sampling less than 2.5% of the network. Fluorescence analysis was also able to uncover a single, real cross-connection event. As such, this paper is a fundamental demonstration of fluorescence as a reliable, highly portable technique for cross-connection detection within dual reticulation water recycling networks and further establishes the abilities of fluorescence devices as valuable field instruments for water quality monitoring. PMID:25506735

  2. Equations of motion of slung load systems with results for dual lift

    NASA Technical Reports Server (NTRS)

    Cicolani, Luigi S.; Kanning, Gerd

    1990-01-01

    General simulation equations are derived for the rigid body motion of slung load systems. These systems are viewed as consisting of several rigid bodies connected by straight-line cables or links. The suspension can be assumed to be elastic or inelastic, both cases being of interest in simulation and control studies. Equations for the general system are obtained via D'Alembert's principle and the introduction of generalized velocity coordinates. Three forms are obtained. Two of these generalize previous case-specific results for single helicopter systems with elastic or inelastic suspensions. The third is a new formulation for inelastic suspensions. It is derived from the elastic suspension equations by choosing the generalized coordinates so as to separate motion due to cable stretching from motion with invariant cable lengths. The result is computationally more efficient than the conventional formulation, and is readily integrated with the elastic suspension formulation and readily applied to the complex dual lift and multilift systems. Equations are derived for dual lift systems. Three proposed suspension arrangements can be integrated in a single equation set. The equations are given in terms of the natural vectors and matrices of three-dimensional rigid body mechanics and are tractable for both analysis and programming.

  3. Cat-eye target imaging system research and dual-channel DSP implementation

    NASA Astrophysics Data System (ADS)

    Zheng, Zheng; Zhang, Haiyang; Shi, Guang; Han, Lei; Zhao, Changming

    2013-09-01

    In modern warfare, well-equipped and trained snipers have become a mortal malady for the combat troops. How to accurately, timely and quickly find and destroy snipers becomes a research focus of national military experts. In order to effectively detect faint echo signal of cat-eye target and get the snipers' position information in the detection area, a small size of dual-channel active laser detection system with monochrome and color Charge-couple Devices(CCD) is designed, which is based on the laser imaging principle of cat-eye effect, associated tests are also conducted. The dual-channel video capture can obtain more information of target area, while taking advantage of the high sensitivity of monochrome CCD will also provide more accurate grayscale information for the video image processing. In order to achieve the miniaturization of system, we choose a video processing board whose size is only 54mm*90mm as hardware platform to complete the algorithm. For verifying the feasibility and accuracy of algorithm, we ultimately build a full set of experimental detection system. The test results show that the system can accurately detect and mark typical cat-eye target from background under different distances, which verifies the rationality and validity of the proposed system and has certain practicality and promotion in the active laser detection system research areas.

  4. The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities.

    PubMed

    Schmaier, A H

    2016-01-01

    The contact activation system (CAS) and kallikrein/kinin system (KKS) are older recognized biochemical pathways that include several proteins that skirt the fringes of the blood coagulation, fibrinolytic, complement and renin-angiotensin fields. These proteins initially were proposed as part of the hemostatic pathways because their deficiencies are associated with prolonged clinical assays. However, the absence of bleeding states with deficiencies of factor XII (FXII), prekallikrein (PK) and high-molecular-weight kininogen indicates that the CAS and KKS do not contribute to hemostasis. Since the discovery of the Hageman factor 60 years ago much has been learned about the biochemistry, cell biology and animal physiology of these proteins. The CAS is a pathophysiologic surface defense mechanism against foreign proteins, organisms and artificial materials. The KKS is an inflammatory response mechanism. Targeting their activation through FXIIa or plasma kallikrein inhibition when blood interacts with the artificial surfaces of modern interventional medicine or in acute attacks of hereditary angioedema restores vascular homeostasis. FXII/FXIIa and products that arise with PK deficiency also offer novel ways to reduce arterial and venous thrombosis without an effect on hemostasis. In summary, there is revived interest in the CAS and KKS due to better understanding of their activities. The new appreciation of these systems will lead to several new therapies for a variety of medical disorders. PMID:26565070

  5. Poissons, grenouilles, femmes et hommes: the appropriation and retention of archetypal systems for reproduction.

    PubMed

    Naftolin, F; Lavy, G; Palumbo, A; DeCherney, A H

    1988-09-01

    In contradistinction to other biological systems, the reproductive mechanisms in sexually reproducing species are unique in that their success relies upon a synchronous interaction between two separate individuals. Reproduction has become increasingly more efficient as higher forms have developed internal fertilization and gestation. Although our anthropomorphic perspective has dominated the understanding of reproductive processes, 'recent discoveries' make it clear that this reproductive efficiency has been gained by retention of previously present biological mechanisms whose origins are in the vestigial excretory tracts and ducts which are the precursors of the reproductive tract. We refer to these as 'archetypal systems'. They include the interaction between sex steroid sensitive tissues and sex steroids, the renin-angiotensin system and the macrophage/monokine response to infection. Through these mechanisms the reproductive tracts have maintained control over the microenvironment in which the reproductive processes occur. Thus, gamete development in male and female, and fertilization and early embryonic existence in the female tract prior to implantation still occur in compartments which are extracorporeal, i.e., separated from blood or subendothelial spaces, and are controlled by cellular mechanisms found in ancient excretory tracts. Since the majority of the changes between lower forms and contemporary mammals are anatomical modifications which have favoured the success of these extracorporeal events within the developing, generally land-based mammals, we should take special note of lower animals, understanding the evolutionary appropriation of mechanisms designed to furnish the suitable microenvironment from the surrounding tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3067547

  6. Application of combined controller based on CMAC and nonlinear PID in dual redundant telescope tracking system

    NASA Astrophysics Data System (ADS)

    Li, Heng; Ren, Changzhi; Song, Libin; Wu, Jun

    2014-07-01

    The direct drive tracking system of Telescope is one multivariable, nonlinear and strong coupling complex mechanical control system which is disturbed by some nonlinear disturbance such torque ripple, wind disturbance during the tracking process. the traditional PID control cannot fundamentally solved the contradiction between static and dynamic performance, tracking data and disturbance .This paper explores a kind of CMAC with nonlinear PID parallel composite control method for dual redundant telescope tracing servo system. The simulation result proves that combined algorithm based on CMAC and PID realizes the servo system without overshoot and accelerates the response of the system. What's more, CMAC feedforward control improves anti-disturbance ability and the control precision of the servo system.

  7. Experimental Investigation of Low-Jitter and Wide-Band Dual Cascaded PLL System

    NASA Astrophysics Data System (ADS)

    Telba, Ahmed; Qasim, Syed Manzoor

    2011-08-01

    Jitter is a matter of great concern for high-speed digital designers because of its ability to degrade the overall system performance. Designing a low-jitter and wide-band phase locked loop (PLL) system is of practical importance because of its application in high speed digital systems. This paper experimentally investigates a low-jitter and wide-band dual cascaded PLL system using a single crystal oscillator. The first PLL used in the system employs a voltage-controlled crystal oscillator (VCXO) to eliminate the input jitter whereas the second PLL provides wide bandwidth. Field Programmable Gate Array (FPGA) is used to generate a jittered clock source which is then passed through the proposed system to achieve wide-band and low-jitter signal. Experimental results are presented to validate the proposed technique for different carrier frequencies.

  8. Research on the electro-optical assistant landing system based on the dual camera photogrammetry algorithm

    NASA Astrophysics Data System (ADS)

    Mi, Yuhe; Huang, Yifan; Li, Lin

    2015-08-01

    Based on the location technique of beacon photogrammetry, Dual Camera Photogrammetry (DCP) algorithm was used to assist helicopters landing on the ship. In this paper, ZEMAX was used to simulate the two Charge Coupled Device (CCD) cameras imaging four beacons on both sides of the helicopter and output the image to MATLAB. Target coordinate systems, image pixel coordinate systems, world coordinate systems and camera coordinate systems were established respectively. According to the ideal pin-hole imaging model, the rotation matrix and translation vector of the target coordinate systems and the camera coordinate systems could be obtained by using MATLAB to process the image information and calculate the linear equations. On the basis mentioned above, ambient temperature and the positions of the beacons and cameras were changed in ZEMAX to test the accuracy of the DCP algorithm in complex sea status. The numerical simulation shows that in complex sea status, the position measurement accuracy can meet the requirements of the project.

  9. A preliminary study on a dual-modality OPT/micro-CT system

    NASA Astrophysics Data System (ADS)

    Yang, Yujie; Di, Dong; Shi, Liangliang; Wang, Jun; Hui, Hui; Yang, Xin; Tian, Jie

    2015-03-01

    Optical projection tomography (OPT) is a mesoscopic scale optical imaging technique for specimens between 1mm and 10mm. Although OPT is widely used for in vivo and ex vivo imaging, its applications in high intensity tissues such as bone and thick samples are limited due to the strong absorption of the light. In contrast, X-ray micro-CT is suitable for high intensity tissue imaging but its contrast of soft tissue is poor. Therefore, imaging tools with both strong penetration and high contrast are in great demand. To address this issue, we develop a dual-modality system integrating both OPT and micro-CT. In this paper, this dual-modality system is applied to dynamic imaging of a clearing process of a mouse paw. The clearing process is essential in OPT when imaging thick or intensity tissues since it can make high intensity tissues optically transparent. In our experiment, we scan the mouse paw with our system - before, during and after optical clearing. Each time we scan CT first and then the OPT. After acquisition, 3-dimentional volumes of OPT and CT are reconstructed separately. Then we use a rigid image registration algorithm to register these volumes. Finally, the volumes are merged together. The experimental results show our bimodal system performs better than single OPT or CT system when processing tissues with both high intensity and soft parts.

  10. A Dual-Field Sensing Scheme for a Guidance System for the Blind

    PubMed Central

    Lin, Qing; Han, Youngjoon

    2016-01-01

    An electronic guidance system is very helpful in improving blind people’s perceptions in a local environment. In our previous work “Lin, Q.; Han, Y. A Context-Aware-Based Audio Guidance System for Blind People Using a Multimodal Profile Model. Sensors 2014, 14, 18670–18700”, a context-aware guidance system using a combination of a laser scanner and a camera was proposed. By using a near-field graphical model, the proposed system could interpret a near-field scene in very high resolution. In this paper, our work is extended by adding a far-field graphical model. The integration of the near-field and the far-field models constitutes a dual-field sensing scheme. In the near-field range, reliable inference of the ground and object status is obtained by fusing range data and image data using the near-field graphical model. In the far-field range, which only the camera can cover, the far-field graphical model is proposed to interpret far-field image data based on appearance and spatial prototypes built using the near-field interpreted data. The dual-field sensing scheme provides a solution for the guidance systems to optimise their scene interpretation capability using simple sensor configurations. Experiments under various local conditions were conducted to show the efficiency of the proposed scheme in improving blind people’s perceptions in urban environments. PMID:27187388

  11. Kinetic modeling of Moorella thermoacetica growth on single and dual-substrate systems.

    PubMed

    Schmitt, Elliott; Bura, Renata; Gustafson, Rick; Ehsanipour, Mandana

    2016-10-01

    Acetic acid is an important chemical raw material that can be produced directly from sugars in lignocellulosic biomass. Development of kinetic models that capture the bioconversion dynamics of multiple sugar systems will be critical to optimization and process control in future lignocellulosic biorefinery processes. In this work, a kinetic model was developed for the single- and dual-substrate conversion of xylose and glucose to acetic acid using the acetogen Moorella thermoacetica. Batch fermentations were performed experimentally at 20 g L(-1) total sugar concentration using synthetic glucose, xylose, and a mixture of glucose and xylose at a 1:1 ratio. The product yield, calculated as total product formed divided by total sugars consumed, was 79.2, 69.9, and 69.7 % for conversion of glucose, xylose, and a mixture of glucose and xylose (1:1 ratio), respectively. During dual-substrate fermentation, M. thermoacetica demonstrated diauxic growth where xylose (the preferred substrate) was almost entirely consumed before consumption of glucose began. Kinetic parameters were similar for the single-substrate fermentations, and a strong linear correlation was determined between the maximum specific growth rate μ max and substrate inhibition constant, K s . Parameters estimated for the dual-substrate system demonstrated changes in the specific growth rate of both xylose and glucose consumption. In particular, the maximum growth rate related to glucose tripled compared to the single-substrate system. Kinetic growth is affected when multiple substrates are present in a fermentation system, and models should be developed to reflect these features. PMID:27262717

  12. Conceptual Design for a Dual-Bell Rocket Nozzle System Using a NASA F-15 Airplane as the Flight Testbed

    NASA Technical Reports Server (NTRS)

    Jones, Daniel S.; Ruf, Joseph H.; Bui, Trong T.; Martinez, Martel; St. John, Clinton W.

    2014-01-01

    The dual-bell rocket nozzle was first proposed in 1949, offering a potential improvement in rocket nozzle performance over the conventional-bell nozzle. Despite the performance advantages that have been predicted, both analytically and through static test data, the dual-bell nozzle has still not been adequately tested in a relevant flight environment. In 2013 a proposal was constructed that offered a NASA F-15 airplane as the flight testbed, with the plan to operate a dual-bell rocket nozzle during captive-carried flight. If implemented, this capability will permit nozzle operation into an external flow field similar to that of a launch vehicle, and facilitate an improved understanding of dual-bell nozzle plume sensitivity to external flow-field effects. More importantly, this flight testbed can be utilized to help quantify the performance benefit with the dual-bell nozzle, as well as to advance its technology readiness level. This presentation provides highlights of a technical paper that outlines this ultimate goal, including plans for future flights to quantify the external flow field of the airplane near the nozzle experiment, as well as details on the conceptual design for the dual-bell nozzle cold-flow propellant feed system integration within the NASA F-15 Propulsion Flight Test Fixture. The current study shows that this concept of flight research is feasible, and could result in valuable flight data for the dual-bell nozzle.

  13. Conceptual Design for a Dual-Bell Rocket Nozzle System Using a NASA F-15 Airplane as the Flight Testbed

    NASA Technical Reports Server (NTRS)

    Jones, Daniel S.; Ruf, Joseph H.; Bui, Trong T.; Martinez, Martel; St. John, Clinton W.

    2014-01-01

    The dual-bell rocket nozzle was first proposed in 1949, offering a potential improvement in rocket nozzle performance over the conventional-bell nozzle. Despite the performance advantages that have been predicted, both analytically and through static test data, the dual-bell nozzle has still not been adequately tested in a relevant flight environment. In 2013 a proposal was constructed that offered a NASA F-15 airplane as the flight testbed, with the plan to operate a dual-bell rocket nozzle during captive-carried flight. If implemented, this capability will permit nozzle operation into an external flow field similar to that of a launch vehicle, and facilitate an improved understanding of dual-bell nozzle plume sensitivity to external flow-field effects. More importantly, this flight testbed can be utilized to help quantify the performance benefit with the dual-bell nozzle, as well as to advance its technology readiness level. Toward this ultimate goal, this paper provides plans for future flights to quantify the external flow field of the airplane near the nozzle experiment, as well as details on the conceptual design for the dual-bell nozzle cold-flow propellant feed system integration within the NASA F-15 Propulsion Flight Test Fixture. The current study shows that this concept of flight research is feasible, and could result in valuable flight data for the dual-bell nozzle.

  14. Conceptual Design for a Dual-Bell Rocket Nozzle System Using a NASA F-15 Airplane as the Flight Testbed

    NASA Technical Reports Server (NTRS)

    Jones, Daniel S.; Ruf, Joseph H.; Bui, Trong T.; Martinez, Martel; St. John, Clinton W.

    2014-01-01

    The dual-bell rocket nozzle was first proposed in 1949, offering a potential improvement in rocket nozzle performance over the conventional-bell nozzle. Despite the performance advantages that have been predicted, both analytically and through static test data, the dual-bell nozzle has still not been adequately tested in a relevant flight environment. In 2013 a proposal was constructed that offered a National Aeronautics and Space Administration (NASA) F-15 airplane as the flight testbed, with the plan to operate a dual-bell rocket nozzle during captive-carried flight. If implemented, this capability will permit nozzle operation into an external flow field similar to that of a launch vehicle, and facilitate an improved understanding of dual-bell nozzle plume sensitivity to external flow-field effects. More importantly, this flight testbed can be utilized to help quantify the performance benefit with the dual-bell nozzle, as well as to advance its technology readiness level. Toward this ultimate goal, this report provides plans for future flights to quantify the external flow field of the airplane near the nozzle experiment, as well as details on the conceptual design for the dual-bell nozzle cold-flow propellant feed system integration within the NASA F-15 Propulsion Flight Test Fixture. The current study shows that this concept of flight research is feasible, and could result in valuable flight data for the dual-bell nozzle.

  15. Research Study to Identify Technology Requirements for Advanced Earth-Orbital Transportation Systems, Dual-Mode Propulsion

    NASA Technical Reports Server (NTRS)

    1977-01-01

    The results of a study of dual mode propulsion concepts ap