Fundamental and clinical study of direct immunoradiometric assay in human renin concentration

International Nuclear Information System (INIS)

Kurimoto, Fumihiko; Horiuchi, Junko; Sakurai, Hyoichiro; Suzuki, Hiromichi; Takita, Takashi; Saruta, Takao.

1988-01-01

'Renin RIA Pasteur' kit for directly measuring renin concentration in human plasma (PRC) was fundamentally and clinically evaluated. A standard curve for PRC was linear in the range of 10 - 640 pg/ml. Reproducibility, recovery, and stability were satisfactory. There was a significantly positive correlation between direct PRC and conventional plasma renin activity (PRA) and indirect PRC. PRC was directly measured in 119 healthy volunteers and 15 patients with primary aldosteronism (4), Cushing's syndrome (6), or non-functioning tumor (5). The basal PRC was 32.4 +- 18.8 pg/ml for men and 37.9 +- 22.6 pg/ml for women. PRC for primary aldosteronism was below detectable levels, and remained unchanged even after the administratin of ACTH. In the case of Cushing's syndrome, mean PRC and PRA were 19 pg/ml and 1.2 ng/ml/hr, and did not respond to ACTH. Although the administration of ATCH was significantly associated with a decreased PRC, there was only tendency toward the decreased PRA in the case of non-functioning tumors. The results indicate the usefulness of the present kit in terms of its ability to directly measure PRC without any complicated procedures. (Namekawa, K.)

Clinical significance of determination of SAC/PRA value in patients with primary aldosteronism

International Nuclear Information System (INIS)

Li Liren; Dai Yaozong; Liu Jiumin

2003-01-01

Objective: To investigate the diagnostic significance of determining SAC/PRA valve in hyperaldosteronism. Methods: Plasma renin activity (PRA) and angiotensin (AT-II) as well as serum aldosterone contents were measured with RIA in 48 patients with primary aldosteronism and 30 controls. The SAC/PRA value was calculated. Results: Contents of PRA, AT-II and Aldo in blood of patients with primary aldosteronism were very significantly different from those in controls (p < 0.001) (PRA 0.14 ± 0.08 ng/ml/h vs 0.57 ± 0.08 ng/ml/h; AT-II 21.21 ± 7.55 ng/L vs 36.03 ± 6.11 ng/L; Aldo 1.07 ± 0.34 nmol/L vs 0.33 ± 0.04 nmol/L). Calculated SAC/PRA value was 913 ± 409 (normal upper limit 400). Conclusion: SAC/PRA value is an useful accessory diagnostic criterion for primary aldosteronism

[Renin-angiotensin-aldosterone system activity during head-up tilt testing in patients with vasovagal syncope].

Science.gov (United States)

Gajek, Jacek; Zyśko, Dorota; Mazurek, Walentyna

2005-08-01

The stimulation of renin-angiotensin-aldosterone (RAA) system during tilt table test is caused by sympathetic nervous system activation by orthostatic stress and a serotonin release as well. In healthy individuals increase of plasma renin activity during test with maximal values on the peak of the test was described. The aim of the study was to assess the activation of RAAS in patients with neurally mediated syncope during the tilt table test by means of plasma renin activity and serum aldosterone levels. The study was carried out in 31 patients aged 39.4 +/- 15.0 years (18 women and 13 men) with neurally mediated syncope during tilt test. Plasma renin activity was assessed in the baseline conditions, immediately after the test and 10 minutes after the test using radioenzymatic assay. Aldosterone concentrations were measured radioimmunologically, twice: after 30 minutes supine rest and after the syncope. Plasma renin activity during supine rest was 2.2 +/- 2.4 ng/ml/h, rose after the syncope 2.5-fold to 5.2 +/- 4.5 ng/ml/h (p < 0.001 comparing to baseline) stayed on similar level approximately for the next 10 minutes--4.9 +/- 5.5 ng/ml/h (p = n.s.). In 11 patients (35%) 10 minutes after the test even further increase of PRA was observed. Serum aldosterone level increased significantly immediately after tilt test (90.0 +/- 72.9 vs 178.8 +/- 150.1 pg/ml, p < 0.01). Authors showed, that in patients with NMS plasma renin activity increases and this increase lasts for 10 minutes after the syncope and the concentration of aldosterone increases immediately after tilt test.

Cortisol-induced inhibition of ovine renin and aldosterone responses to hypotension

International Nuclear Information System (INIS)

Wood, C.E.; Silbiger, J.

1987-01-01

Previous studies from this laboratory have demonstrated that in preterm fetal sheep increases in plasma cortisol (F) concentration equal in amplitude to fetal F stress responses suppress plasma renin activity (PRA). The purpose of this study was to investigate the possibility that this negative interaction exists in adult sheep. Cortisol was measured by radioimmunoassay. Five conscious ewes with chronically prepared carotid arterial loops were infused intravenously with F or vehicle for 5 h. One hour after the end of F or vehicle infusion, renin secretion was stimulated by hypotension produced by infusion of sodium nitroprusside. F infusion increased plasma F; during vehicle infusion plasma F did not change. F infusion decreased hematocrit from 29 +/- 2 to 26 +/- 1%. Basal PRA in vehicle- and F-infused groups were 0.4 +/- 0 and 0.2 +/- 0.1 ng angiotensin I-ml -1 -h -1 and did not change. In vehicle-infused ewes, PRA increased from 0.4 +/- 0 to 4.6 +/- 0.4 and plasma aldosterone from 26.0 +/- 1.0 to 173.1 +/- 21.8 pg/ml, while in F-infused ewes, PRA increased from 0.2 +/- 1 to 3.3 +/- 0.4 ng angiotensin I-ml -1 -h -1 and aldosterone from 25.0 +/- 0 to 48.2 +/- 23.2 pg/ml, significantly smaller responses. These results suggest that repeated stress may modulate the responses of the renin-angiotensin system in this species

Hemodynamic, morphometric and autonomic patterns in hypertensive rats - renin-angiotensin system modulation

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Fernanda S. Zamo

2010-01-01

Full Text Available BACKGROUND: Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system. AIMS: To investigate the effects of the time-course of hypertension over 1 hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate; 2 left ventricular hypertrophy; and 3 local and systemic Renin-angiotensin system of the spontaneously hypertensive rats. METHODS: Male spontaneously hypertensive rats were randomized into two groups: young (n=13 and adult (n=12. Hemodynamic signals (blood pressure, heart rate, blood pressure variability (BPV and spectral analysis of the autonomic components of blood pressure were analyzed. LEFT ventricular hypertrophy was measured by the ratio of LV mass to body weight (mg/g, by myocyte diameter (μm and by relative fibrosis area (RFA, %. ACE and ACE2 activities were measured by fluorometry (UF/min, and plasma renin activity (PRA was assessed by a radioimmunoassay (ng/mL/h. Cardiac gene expressions of Agt, Ace and Ace2 were quantified by RT-PCR (AU. RESULTS: The time-course of hypertension in spontaneously hypertensive rats increased BPV and reduced the alpha index in adult spontaneously hypertensive rats. Adult rats showed increases in left ventricular hypertrophy and in RFA. Compared to young spontaneously hypertensive rats, adult spontaneously hypertensive rats had lower cardiac ACE and ACE2 activities, and high levels of PRA. No change was observed in gene expression of Renin-angiotensin system components. CONCLUSIONS: The observed autonomic dysfunction and modulation of Renin-angiotensin system activity are contributing factors to end-organ damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable levels and the consequent

[Differences of blood plasma renin activity, angiotensin II and aldosterone levels in essential or secondary hypertension].

Science.gov (United States)

Song, Ai-ling; Zeng, Zheng-pei; Tong, An-li; Lu, Lin; Chen, Shi; Li, Ming; Fu, Chun-li; Wang, Yong-hui; Sun, Mei-li

2012-04-01

To study on the difference of plasma renin activity (PRA), angiotensin II (Ang II), and aldosterone levels in patients with essential hypertension (EH) or primary aldosteronism (PA) or pheochromocytoma (PHEO), and to analyze the sensitivity and specificity on the diagnosis of PA among patients with hypertension with aldosterone/PRA ratio (ARR). The plasma aldosterone, Ang II and PRA concentrations in supine and upright positions were measured by radioimmunoassay from 413 patients including idiopathic hyperaldosteronism (IHA, n = 111), aldosterone-producing adenoma (APA, n = 118), PHEO (n = 98) and EH (n = 86). ARR was calculated. Plasma aldosterone concentrations in both of supine and upright positions in PHEO group [374 (294, 465) pmol/L and 629 (449, 997) pmol/L] and PA group [471 (346, 632) pmol/L and 673 (499, 825) pmol/L] were higher than those in EH group [277 (224, 332) pmol/L and 427 (341, 501) pmol/L] (P 0.05). The PRA level in both positions of each group were PHEO group [0.3 (0.2, 1.0) µg · L(-1) · h(-1) and 1.4 (0.6, 3.4) µg · L(-1) · h(-1)] > EH group [0.2 (0.1, 0.4) µg · L(-1) · h(-1) and 0.6 (0.4, 1.0) µg · L(-1) · h(-1)] (P PA group [0.1 (0.1, 0.1) µg · L(-1) · h(-1) and 0.2 (0.1, 0.3) µg · L(-1) · h(-1)] (P < 0.01), and APA group [0.1 (0.1, 0.1) µg · L(-1) · h(-1) and 0.1 (0.1, 0.3) µg · L(-1) · h(-1)] < IHA group [0.1 (0.1, 0.2) µg · L(-1) · h(-1) and 0.2 (0.1, 0.3) µg · L(-1) · h(-1)] (supine P < 0.01; upright P < 0.05). APA was divided into 2 types with renin-Ang II-responsive APA (n = 26) and unresponsive APA (n = 92). The plasma aldosterone concentration was lower in supine position but higher in upright position in renin-Ang II-responsive APA than in unresponsive APA patients. ARR in upright was higher in PA group (P < 0.01) but lower in PHEO group (P < 0.05) compared with EH. ARR was higher in APA than in IHA (P < 0.01). The sensitivity and specificity of ARR as 40 (aldosterone unit: ng/dl; PRA unit: µg · L(-1

Therapeutic vaccines against human and rat renin in spontaneously hypertensive rats.

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Zhihua Qiu

Full Text Available Vaccination provides a promising approach for treatment of hypertension and improvement in compliance. As the initiation factor of renin-angiotensin system, renin plays a critical role in hypertension. In this study, we selected six peptides (rR32, rR72, rR215, hR32, hR72, and hR215 belonging to potential epitopes of rat and human renin. The main criteria were as follows: (1 include one of renin catalytic sites or the flap sequence; (2 low/no-similarity when matched with the host proteome; (3 ideal antigenicity and hydrophilicity. The peptides were coupled to keyhole limpet hemocyanin and injected into SpragueDawley (SD rats, spontaneously hypertensive rats (SHRs and Wistar-Kyoto rats. The antisera titers and the binding capacity with renin were detected. The effects of the anti-peptides antibodies on plasma renin activity (PRA and blood pressure were also determined. All peptides elicited strong antibody responses. The antisera titers ranged from 1:32,000 to 1:80,000 in SD rats on day 63. All antisera could bind to renin in vitro. Compared with the control antibody, the antibodies against the rR32, hR32, rR72 and hR72 peptides inhibited PRA level by up to about 50%. Complete cross-reactivity of the anti-rR32 antibody and the anti-hR32 antibody was confirmed. The epitopes rR32 and hR32 vaccines significantly decreased systolic blood pressure (SBP of SHRs up to 15mmHg (175±2 vesus 190±3 mmHg, P = 0.035; 180±2 vesus 195±3 mmHg, P = 0.039, while no obvious effect on SD rats. Additionally, no significant immune-mediated damage was detected in the vaccinated animals. In conclusion, the antigenic peptide hR32 vaccine mimicking the (32Asp catalytic site of human renin may constitute a novel tool for the development of a renin vaccine.

Influence of Aging on Plasma Renin Activity

International Nuclear Information System (INIS)

Cho, K. W.; Kim, S. H.; Kang, S. K.; Choi, H. Y.

1982-01-01

Influence of aging on plasma renin activity was evaluated in healthy normotensive subjects(age range 21-63 years, 413 males) devoid of cardiorenal or endocrinological problems. The age-related decrease of plasma renin activity in the subjects between 21-28 years group and 36-42 years group was slight, but over the 43 years groups was significantly different. The age-related suppression of plasma renin activity was much more smooth and continuous all over the age ranges evaluated. The sexual difference in plasma renin activity was noticed between the subjects of 22 years old group (34 males) and 19 years group (34 females) (p<0.003). The data suggest that the age-related suppression of plasma renin activity appeared in healthy normotensive subjects should be considered in the case of evaluation of low renin essential hypertension.

The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment

DEFF Research Database (Denmark)

Petersen, Morten; Andersen, Jon T; Jimenez-Solem, Espen

2012-01-01

A gene-drug interaction has been indicated between beta-1 selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). We studied the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR) and the genotype...

Active immunization against renin in normotensive marmoset

International Nuclear Information System (INIS)

Michel, J.B.; Guettier, C.; Philippe, M.; Galen, F.X.; Corvol, P.; Menard, J.

1987-01-01

Primate renins (human and monkey) are very similar. We used pure human renin to immunize marmosets (Callithrix jacchus) and thereby produce a chronic blockade of the renin-angiotensinogen reaction. After a control period of 2 months, five male marmosets, on their usual sodium-poor diet, were immunized against pure human renin by three subcutneous injections of 30 μg each, with complete and then incomplete Freund's adjuvant. Three marmosets were injected with adjuvant only and served as controls. Blood sampling and blood pressure measurements were performed weekly. After the third injection, the five marmosets immunized against renin developed a high titer of renin antibodies (50% binding of 125 I-labeled human renin at a dilution of ≥ 1:10,000). The antibodies inhibited the enzymatic activity of both marmoset and human renins. At the same time, systolic blood pressure decreased significantly. Plasma renin enzyme activity was undetectable in the animals. Plasma aldosterone decreased significantly. After 1-4 months with low blood pressure, a normal urinary output, and a normal plasma creatinine, the five marmosets became sick and died within one month. At autopsy an immunological renal disease, characterize by the presence of immunoglobulin and macrophage infiltration colocalized with renin, was found. No immunoglobulin was detectable in extrarenal vessels or in other organs. These experiments demonstrate that, in this primate, a chronic blockade of the renin-angiotensin system can be achieved by active immunization against homologous renin, but this blockade is associated with the development of an autoimmune disease localized in the kidney

Effect of antigravity suit inflation on cardiovascular, PRA, and PVP responses in humans. [Plasma Renin Activity and Plasma VasoPressin

Science.gov (United States)

Kravik, S. E.; Keil, L. C.; Geelen, G.; Wade, C. E.; Barnes, P. R.

1986-01-01

The effects of lower body and abdominal pressure, produced by antigravity suit inflation, on blood pressure, pulse rate, fluid and electrolyte shift, plasma vasopressin and plasma renin activity in humans in upright postures were studied. Five men and two women stood upright for 3 hr with the suit being either inflated or uninflated. In the control tests, the suit was inflated only during the latter part of the trials. Monitoring was carried out with a sphygnomanometer, with sensors for pulse rates, and using a photometer and osmometer to measure blood serum characteristics. The tests confirmed earlier findings that the anti-g suit eliminates increases in plasma renin activity. Also, the headward redistribution of blood obtained in the tests commends the anti-g suit as an alternative to water immersion or bed rest for initial weightlessness studies.

Plasma renin activity profile in normal and hypertensive Filipinos

International Nuclear Information System (INIS)

Guevara, R.; Torres, J. Jr.; Abundo, H.P.; Perez, A.P.

To establish a base line profile of plasma renin activity in normotensive and hypertensive Filipinos, 1.019 cases, 479 males and 540 females with an age range 14 - 89 years (mean - 46 + -20) were studied at the Santo Tomas University Hospital of various life styles from the Metro-Manila area, 248 comprised the normotensive group (male - 122 or 49.2 %, female 126 or 50.8 %) and 771 were hypertensive. Of these, 711 (92.6 %) has essential hypertension and are presented in this report. Plasma Renin Activity was determined by radioimmunoassay using Dainabot Renin-Ricket. Concurrent 24 hr. urine sodium and potassium were determined. Nomograms of plasma renin activity as related to urine sodium excretion were drawn after computerized statistical analysis of data. The normal mean value of plasma renin activity was found to be 1.64 + - 0.81 ng./ml./hr. in the upright position and 1.15 + - .68 ng./ml./hr. in the supine position. Based on the nomogram derived, the values obtained in the 711 cases of essential hypertension were classified into High Renin - 14.3 % Normal Renin - 56.1 % and Low Renin - 29.6 %. This study establishes normal levels of plasma renin activity as well as define and classify same renin activity among hypertensive Filipinos, a useful and practicable guide for treatment and can be of prognostic significance. (author)

Prospective validation of an automated chemiluminescence-based assay of renin and aldosterone for the work-up of arterial hypertension.

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Rossi, Gian Paolo; Ceolotto, Giulio; Rossitto, Giacomo; Seccia, Teresa Maria; Maiolino, Giuseppe; Berton, Chiara; Basso, Daniela; Plebani, Mario

2016-09-01

The availability of simple and accurate assays of plasma active renin (DRC) and aldosterone concentration (PAC) can improve the detection of secondary forms of arterial hypertension. Thus, we investigated the performance of an automated chemiluminescent assay for DRC and PAC in referred hypertensive patients. We prospectively recruited 260 consecutive hypertensive patients referred to an ESH Center for Hypertension. After exclusion of six protocol violations, 254 patients were analyzed: 67.3% had primary hypertension, 17.3% an aldosterone producing adenoma (APA), 11.4% idiopathic hyperaldosteronism (IHA), 2.4% renovascular hypertension (RVH), 0.8% familial hyperaldosteronism type 1 (FH-1), 0.4% apparent mineralocorticoid excess (AME), 0.4% a renin-producing tumor, and 3.9% were adrenalectomized APA patients. Bland-Altman plots and Deming regression were used to analyze results. The diagnostic accuracy (area under the curve, AUC of the ROC) of the DRC-based aldosterone-renin ratio (ARRCL) was compared with that of the PRA-based ARR (ARRRIA) using as reference the conclusive diagnosis of APA. At Bland-Altman plot, the DRC and PAC assay showed no bias as compared to the PRA and PAC assay. A tight relation was found between the DRC and the PRA values (concordance correlation coefficient=0.92, pAPA identification the AUC of the ARRCL was higher than that of the ARRRIA [0.974 (95% CI 0.940-0.991) vs. 0.894 (95% CI 0.841-0.933), p=0.02]. This rapid automated chemiluminescent DRC/PAC assay performed better than validated PRA/PAC radioimmunoassays for the identification of APA in referred hypertensive patients.

8C.03: A KEY ROLE FOR ENDOTHELIN-1 IN THE PATHOGENESIS OF PREECLAMPSIA AND THE ASSOCIATED SUPPRESSION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM.

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Verdonk, K; Saleh, L; Smilde, J E; van Ingen, M M; Garrelds, I M; Friesema, E C; Russcher, H; Steegers, E A P; van den Meiracker, A H; Visser, W; Danser, A H J

2015-06-01

Women with preeclampsia (PE) display low renin-angiotensin-aldosterone system (RAAS) activity and a high anti-angiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase-1(sFlt-1) and reduced levels of placental growth factor (PlGF). In the present study, we hypothesized that the RAAS suppression in PE is the consequence of the disturbed angiogenic balance. In a group of pregnant women with hypertensive disease of pregnancy and a group of healthy pregnant women, matched for gestational age (GA) we measured mean arterial blood pressure (MAP), urinary protein-to-creatinine ratio (PCR), and the plasma levels of sFlt-1, PlGF, albumin, creatinine, endothelin-1 (ET-1), renin (concentration and activity, PRC and PRA), angiotensinogen, and aldosterone. Since initial analysis revealed that these parameters strongly correlated with each other, multiple regression analysis was applied to establish independent determinants of ET-1, PRC, aldosterone and PCR. A sFlt-1/PlGF ratio >85 was considered to be representative for a high anti-angiogenic state. Of the 103 pregnant women included, 65 had a sFlt-1/PlGF ratio 85. Plasma ET-1 and creatinine levels were increased in women with a high ratio, whereas PRA and the plasma levels of renin, angiotensinogen, aldosterone and albumin were decreased in these women. The PRA-aldosterone relationship was identical in both groups. Multiple regression analysis revealed that PRC correlated independently with MAP and plasma ET-1 (R2 0.30). In turn, plasma ET-1 correlated positively with sFlt-1 and negatively with PRC (R2 0.52). Independent determinants of plasma aldosterone were GA and PRA (R2 0.56). Finally we found that plasma PlGF, plasma ET-1 and MAP determined PCR (R2 0.69). The high anti-angiogenic state in PE induces ET-1 activation. Together with the increased MAP in PE this factor suppresses renin release, and in parallel (via PRA reduction) aldosterone synthesis. The identical reduction in PRA and

Radioimmunoassay for plasma renin activity

International Nuclear Information System (INIS)

1975-01-01

A radioimmunoassay for the determination of renin activity in blood plasma is described. The plasma sample is mixed with a generator buffer solution also containing an inhibitor for enzymes which convert angiotensin I into other substances. The renin in the plasma sample converts angiotensinogen into angiotensin I. The amount of angiotensin I is then measured with a competitive binding method using 125 I-labelled angiotensin I and antibodies to angiotensin I

Renin Response to Intravenous Furosemide in Hypertension of Chronic Renal Failure

International Nuclear Information System (INIS)

Choe, Kang Won

1978-01-01

It has been suggested that plasma renin activity (PRA) and its response to volume depletion may be abnormal in that it shows little or exaggerated change in patients with chronic renal failure and hypertension. Intravenous furosemide stimulation test was performed in 46 control subjects and 51 patients with chronic renal failure and/or malignant hypertension in order to evaluate PRA response. In contrast to the consistent increase in PRA in control subjects (from 2.5±1.95 to 4.5±2.51 ng/m1/hr), no consistent increase was observed in patients with chronic renal failure, especially in those who showed favorable response to antihypertensive therapy (from 2.5±2.21 to 2.9±2.46 ng/ml/hr). But poor responder to antihypertensive treatment showed considerably higher PRA before and after furosemide stimulation (from 4.9±1.96 to 6.4±1.71 ng/ml/hr) than the responder group did. Moreover, this group seemed to retain the ability to increase PRA in response to intravenous furosemide stimulation. Thus it became apparent that responder group was unable to increase PRA normally in response to furosemide as well as volume depletion, while poor responder seemed to retain that ability. Thus intravenous furosemode may serve as a convenient way to differentiate those who might be benefited by conservative antihypertensive measures from those who would require more drastic measures such as bilateral nephrectomy for their optimal blood pressure control.

Application of determination of PRA, Ang II and IGF-1 levels in the study of typing of essential hypertension

International Nuclear Information System (INIS)

Lu Yongyi; Chen Qun; Yang Yongqing

2010-01-01

Objective: To study the clinical application of determination of plasma renin activity (PRA), Angiotensin II (Ang II ) and insulin-like growth factor-1 (IGF-1) levels in typing of essential hypertension (EH). Methods: Determined the levels of PRA and Aug II in 256 patients with EH and 70 healthy volunteers (as control group) by radioimmunoassay, and measured IGF-1 level by enzyme immunoassay. Research on the typing of EH and the difference between the groups. Results: The PRA and Ang II in control group was (0.432±0.236) μg·L -1 ·h -1 and (31.7±7.4) μg/L respectively. In 256 patients with EH, PRA was increased, normal and decreased in 18.0%, 71.8% and 10.2% respectively, while the level of Ang II was increased, normal and decreased in 12.9%, 76.2% and 10.9% respectively. The IGF-1 levels in 256 patients with EH were increased following the increase of blood pressure. Conclusion: Typing of EH patients with PRA and Ang II as well as the determination of IGF-1 were useful in treating and following up the patients with EH. (authors)

Effects of peripherally and centrally applied ghrelin on the oxidative stress induced by renin angiotensin system in a rat model of renovascular hypertension.

Science.gov (United States)

Boshra, Vivian; Abbas, Amr M

2017-07-26

Renovascular hypertension (RVH) is a result of renal artery stenosis, which is commonly due to astherosclerosis. In this study, we aimed to clarify the central and peripheral effects of ghrelin on the renin-angiotensin system (RAS) in a rat model of RVH. RVH was induced in rats by partial subdiaphragmatic aortic constriction. Experiment A was designed to assess the central effect of ghrelin via the intracerebroventricular (ICV) injection of ghrelin (5 μg/kg) or losartan (0.01 mg/kg) in RVH rats. Experiment B was designed to assess the peripheral effect of ghrelin via the subcutaneous (SC) injection of ghrelin (150 μg/kg) or losartan (10 mg/kg) for 7 consecutive days. Mean arterial blood pressure (MAP), heart rate, plasma renin activity (PRA), and oxidative stress markers were measured in all rats. In addition, angiotensin II receptor type 1 (AT1R) concentration was measured in the hypothalamus of rats in Experiment B. RVH significantly increased brain AT1R, PRA, as well as the brain and plasma oxidative stress. Either SC or ICV ghrelin or losartan caused a significant decrease in MAP with no change in the heart rate. Central ghrelin or losartan caused a significant decrease in brain AT1R with significant alleviation of the brain oxidative stress. Central ghrelin caused a significant decrease in PRA, whereas central losartan caused a significant increase in PRA. SC ghrelin significantly decreased PRA and plasma oxidative stress, whereas SC losartan significantly increased PRA and decreased plasma oxidative stress. The hypotensive effect of ghrelin is mediated through the amelioration of oxidative stress, which is induced by RAS centrally and peripherally.

The renin-angiotensin system in malignant hypertension revisited: plasma renin activity, microangiopathic hemolysis, and renal failure in malignant hypertension

NARCIS (Netherlands)

van den Born, Bert-Jan H.; Koopmans, Richard P.; van Montfrans, Gert A.

2007-01-01

BACKGROUND: Malignant hypertension is a renin-dependent form of hypertension. However, the variations in renin-angiotensin system (RAS) activation in malignant hypertension are not completely understood. A proposed mechanism for ongoing RAS activation is the presence of microangiopathic hemolysis

Plasma Renin Activity in Children with Protein Energy Malnutrition ...

African Journals Online (AJOL)

Plasma renin activity was measured by bio-assay in 100 children with kwashiorkor and in 20 healthy children, and also by radio-immunoassay in another 26 children with kwashiorkor and in another 20 healthy children. Both methods showed that (compared with healthy children) renin activity was significantly increased in ...

Active renin mass concentration to determine aldosterone-to-renin ratio in screening for primary aldosteronism

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Corbin F

2011-07-01

Full Text Available François Corbin1, Pierre Douville2, Marcel Lebel3 1Division of Biochemistry, l'Université de Sherbrooke, Sherbrooke, Quebec, Canada; 2Division of Biochemistry; 3Division of Nephrology, L'Hôtel-Dieu de Québec Hospital and l'Université Laval, Quebec, CanadaBackground: Active renin mass concentration (ARC is independent of the endogenous level of angiotensinogen, and less variable and more reproducible than plasma renin activity. Reference values for the aldosterone-to-renin ratio (ARR using ARC are still undefined. The objective of the present study was to determine the threshold of ARR using ARC measurement to screen for primary aldosteronism.Methods: A total of 211 subjects were included in the study, comprising 78 healthy normotensive controls, 95 patients with essential hypertension, and 38 patients with confirmed primary aldosteronism (20 with surgery-confirmed aldosterone-producing adenoma and 18 with idiopathic adrenal hyperplasia. Blood samples were drawn from ambulatory patients and volunteers in the mid-morning without specific dietary restriction for measuring plasma aldosterone concentration, ARC, and serum potassium.Results: Most normotensive controls and essential hypertension patients had ARR results below 100 pmol/ng, a value which corresponded to 3.3 times the median of these two groups.Conclusion: Patients with ARR values above this level should be considered for further investigation (confirmatory tests or for repeat testing should ARR values be borderline. This study indicates that ARC can be used reliably in determining ARR for primary aldosteronism screening.Keywords: primary aldosteronism, active renin mass concentration, aldosterone-to-renin ratio

Influence of antihypertensive therapy, sodium intake and the concentration of potassium in plasma on concentration of aldosterone and plasma renin activity

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Lalić Tijana

2013-01-01

Full Text Available Introduction: Primary aldosteronism (PA is a group of disorders which are characterized by inadequate and non-suppressible production of aldosterone. The prevalence of PA is increasing in hypertensive population. The golden standard of screening for primary aldosteronism, determination of aldosterone/plasma renin activity (ARR, is influenced by numerous exogenous and endogenous factors. Testing cannot always be conducted under optimal conditions. Objective: To determine influence of antihypertensive drugs and concentrations of potassium and sodium in blood and urine on values of aldosterone and plasma renin activity. Methods: In this retrospective study, we analyzed medical reports of patients admitted to Department of thyroid gland disease in the period from 2009 to 2011, with increased risk for primary aldosteronism. Body weight and height, sodium and potassium in serum and urine, plasma aldosterone concentrations and plasma renin activity, data on medicines and comorbidity were analyzed in all patients. In processing data, statistical methods descriptive analysis, Student T test and univariate linear regression were applied. Result: Of 137 patients, there were more patients with resistant hypertension (53,28% than with adrenal tumors (46,72%. Most patients used calcium channel blockers. Treatment with alpha blockers and calcium channel blockers does not influence ARR. Beta blockers and ACE inhibitors can influence ARR and diuretics and vasodilatators have definite influence. Diabetes mellitus can have higher risk of false negative results. Urine sodium excretion is significantly correlated with plasma aldosteron and serum potassium. Plasma aldosteron and PRA are significantly correlated with concentrations of electrolites in urine. Conclusion: Increased prevalence of primary aldosteronism necessitates need for accurate and better diagnostics.

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.

Science.gov (United States)

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

2015-01-01

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. 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. 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. 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.

Characterization of renin mRNA expression and enzyme activity in rat and mouse mesangial cells

Directory of Open Access Journals (Sweden)

Andrade A.Q.

2002-01-01

Full Text Available Renin is an enzyme involved in the stepwise generation of angiotensin II. Juxtaglomerular cells are the main source of plasma renin, but renin activity has been detected in other cell types. In the present study we evaluated the presence of renin mRNA in adult male Wistar rat and mouse (C-57 Black/6 mesangial cells (MC and their ability to process, store and release both the active and inactive forms of the enzyme. Active renin and total renin content obtained after trypsin treatment were estimated by angiotensinogen consumption analyzed by SDS-PAGE electrophoresis and quantified by angiotensin I generation by HPLC. Renin mRNA, detected by RT-PCR, was present in both rat and mouse MC under basal conditions. Active renin was significantly higher (P<0.05 in the cell lysate (43.5 ± 5.7 ng h-1 10(6 cells than in the culture medium (12.5 ± 2.5 ng h-1 10(6 cells. Inactive prorenin content was similar for the intra- and extracellular compartments (9.7 ± 3.1 and 3.9 ± 0.9 ng h-1 10(6 cells. Free active renin was the predominant form found in both cell compartments. These results indicate that MC in culture are able to synthesize and translate renin mRNA probably as inactive prorenin which is mostly processed to active renin inside the cell. MC secrete both forms of the enzyme but at a lower level compared with intracellular content, suggesting that the main role of renin synthesized by MC may be the intracellular generation of angiotensin II.

Increased activity of digoxin-like substance in low-renin hypertension in acromegaly

Energy Technology Data Exchange (ETDEWEB)

Soszynski, P.; Slowinska-Srzednicka, J.; Zgliczynski, S. (Medical Center for Postgraduate Education, Warsaw (Poland))

1990-01-01

Arterial hypertension is common in acromegaly, but the pathogenesis of this complication remains unknown. To determine the role of an endogenous Na,K pump inhibitor/digoxin-like substance (DLS) in the pathogenesis of hypertension in acromegaly 76 subjects: 28 with acromegaly, 20 with essential hypertension and 28 healthy controls were studied. Serum DLS was measured with the use of radioimmunoassay and bioassay by the inhibition of digoxin-sensitive erythrocyte 86-Rb uptake. In acromegaly, the activity of DLS was significantly increased and plasma renin activity decreased in the hypertensive group, as compared with that of the normotensive group and controls. Moreover, DLS was elevated in the low-renin group of essential hypertension, as compared with that of the normal/high-renin group or controls. The activity of DLS correlated positively with mean arterial pressure and negatively with plasma renin activity, but not with growth hormone levels. In conclusion, an endogenous sodium pump inhibitor/digoxin-like substance may play a role in the pathogenesis of low-renin hypertension in acromegaly.

Increased activity of digoxin-like substance in low-renin hypertension in acromegaly

International Nuclear Information System (INIS)

Soszynski, P.; Slowinska-Srzednicka, J.; Zgliczynski, S.

1990-01-01

Arterial hypertension is common in acromegaly, but the pathogenesis of this complication remains unknown. To determine the role of an endogenous Na,K pump inhibitor/digoxin-like substance (DLS) in the pathogenesis of hypertension in acromegaly 76 subjects: 28 with acromegaly, 20 with essential hypertension and 28 healthy controls were studied. Serum DLS was measured with the use of radioimmunoassay and bioassay by the inhibition of digoxin-sensitive erythrocyte 86-Rb uptake. In acromegaly, the activity of DLS was significantly increased and plasma renin activity decreased in the hypertensive group, as compared with that of the normotensive group and controls. Moreover, DLS was elevated in the low-renin group of essential hypertension, as compared with that of the normal/high-renin group or controls. The activity of DLS correlated positively with mean arterial pressure and negatively with plasma renin activity, but not with growth hormone levels. In conclusion, an endogenous sodium pump inhibitor/digoxin-like substance may play a role in the pathogenesis of low-renin hypertension in acromegaly

Regulation of the renin-angiotensin-aldosterone system in fibromyalgia.

Science.gov (United States)

Maliszewski, Anne M; Goldenberg, Don L; Hurwitz, Shelley; Adler, Gail K

2002-07-01

To assess the function of the renin-angiotensin-aldosterone (RAA) system in women with fibromyalgia (FM) compared to healthy women. Women with FM [n = 14, age 41.0+/-7.2 yrs, body mass index (BMI) 26.4+/-5.4 kg/m2] and healthy women (n = 13, age 40.0+/-7.7 yrs, BMI 25.0+/-5.0 kg/m2) were placed on a low sodium diet (10 mEq sodium/day) for 5 days. After being supine and fasting overnight, subjects received an intravenous infusion of angiotensin II at successive doses of 1, 3, and 10 ng/kg/min for 45 min per dose. Blood pressure (BP), plasma renin activity (PRA), aldosterone, and cortisol were measured at baseline and after each dose of angiotensin II. Prior to sodium restriction, women with FM completed the Hopkins Symptom Checklist-90, which included a question grading the extent of dizziness/faintness on a scale of 0 (none) to 4 (extremely). After dietary sodium restriction, baseline PRA, aldosterone, and supine BP were similar in healthy women and women with FM. Aldosterone and BP rose in response to infused angiotensin II; these responses did not differ significantly between healthy women and women with FM. In women with FM, symptoms of dizziness correlated inversely with BMI (r = -0.81, p < 0.001) and the systolic BP response to 10 ng/kg/min angiotensin II (r = -0.81, p < 0.001). The functioning of the RAA system, including the vascular response to angiotensin II, was intact in women with FM compared to healthy women. However, women with FM who complained of dizziness had a blunted vascular response to angiotensin II. This blunted vascular response may indicate intravascular volume depletion in women with symptoms of dizziness.

[The changes in renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome].

Science.gov (United States)

Cui, Jia; Dou, Jingtao; Yang, Guoqing; Zang, Li; Jin, Nan; Chen, Kang; Du, Jin; Gu, Weijun; Wang, Xianling; Yang, Lijuan; Lyu, Zhaohui; Ba, Jianming; Mu, Yiming; Lu, Juming; Li, Jiangyuan; Pan, Changyu

2015-07-01

Cushing's syndrome is a clinical condition resulting from chronic exposure to excess glucocorticoid. As a consequence, long-term hypercortisolism contributes significantly to the development of systemic disorders by direct and/or indirect effects. The present study was to analyze the changes of renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome on the standard posture test. We retrospectively reviewed 150 patients with histologically confirmed Cushing's syndrome treated at the PLA General Hospital between 2002 and 2014. Among them, 128 patients were diagnosed as adreno-cortico-tropic-hormone (ACTH)-independent Cushing's syndrome, and 22 were ACTH-dependent Cushing's syndrome. All patients were undertaken the posture test. Plasma renin activity (PRA), angiotensin II, plasma aldosterone concertration (PAC) levels were measured before and after the test. Basal plasma PRA [0.5 (0.2,1.3)µg·L(-1)·h(-1), angiotensin II [(48.9±20.1) ng/L] and PAC [(285.0±128.1) pmol/L] levels were within the normal range in supine position. Compared with the subjects with ACTH-independent Cushing's syndrome, the basal PAC levels were higher in subjects with ACTH-dependent Cushing's syndrome [(348.0±130.4) pmol/L vs (274.2±125.0) pmol/L, PCushing's syndrome [(49.7±26.4)%] was significantly lower than that in those with ACTH-independent Cushing's syndrome [(81.2±69.3)%] upon upright posture stimulation (PCushing's syndrome was similar to that in normal control. The basal PAC level and its response to upright posture are differently associated with ACTH level in Cushing's syndrome.

Effect of Diuresis on Plasma Renin Activity and Aldosterone Concentration in Normal and Toxemic Pregnancy

Energy Technology Data Exchange (ETDEWEB)

Sung, H. K.; Lee, H. S.; Cho, S. S.; Koh, J. H.; Lee, J. K.; Kim, H. S. [Korea Atomic Emergy Research Institute, Seoul (Korea, Republic of)

1973-03-15

The changes of plasma renin activity, aldosterone concentration, serum sodium, and potassium levels were studied before and after the water loading followed by diuretics injection. The materials were: 13 non-, 11 normal-, and 11 toxemic pregnancy cases. The plasma renin activity and aldosterone concentration of the cord and postpartum blood were also measured. Following were the results: 1. The plasma renin activity was elevated significantly in normal pregnancy, and slightly in toxemic pregnancy. The serum sodium levels were decreased in pregnancy. 2. The plasma aldosterone concentration was slightly decreased in normal pregnancy, and slightly increased in toxemic pregnancy, however, statistically insignificant. 3. The plasma renin activity of the cord and postpartum blood were lower than those of pregnancy cases. 4. The changes of plasma renin activity after the diuretic administration showed an initial increase, which recovered within 2 hours. These changes were the least in normal pregnancy, and the most in toxemic pregnancy. 5. The changes of plasma aldosterone concentration after the diuretic administration were similar to those of plasma renin activity, although the variations were not so wide.

Effect of Diuresis on Plasma Renin Activity and Aldosterone Concentration in Normal and Toxemic Pregnancy

International Nuclear Information System (INIS)

Sung, H. K.; Lee, H. S.; Cho, S. S.; Koh, J. H.; Lee, J. K.; Kim, H. S.

1973-01-01

The changes of plasma renin activity, aldosterone concentration, serum sodium, and potassium levels were studied before and after the water loading followed by diuretics injection. The materials were: 13 non-, 11 normal-, and 11 toxemic pregnancy cases. The plasma renin activity and aldosterone concentration of the cord and postpartum blood were also measured. Following were the results: 1. The plasma renin activity was elevated significantly in normal pregnancy, and slightly in toxemic pregnancy. The serum sodium levels were decreased in pregnancy. 2. The plasma aldosterone concentration was slightly decreased in normal pregnancy, and slightly increased in toxemic pregnancy, however, statistically insignificant. 3. The plasma renin activity of the cord and postpartum blood were lower than those of pregnancy cases. 4. The changes of plasma renin activity after the diuretic administration showed an initial increase, which recovered within 2 hours. These changes were the least in normal pregnancy, and the most in toxemic pregnancy. 5. The changes of plasma aldosterone concentration after the diuretic administration were similar to those of plasma renin activity, although the variations were not so wide.

Direct renin inhibition — a new way of targeting the renin system

Directory of Open Access Journals (Sweden)

Morris J Brown

2006-06-01

Full Text Available The renin system plays a key role in the pathology of hypertension and is influenced, both directly and indirectly, by most antihypertensive agents. The system is the target of several established classes of antihypertensive agents including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers. Of currently available drugs, only the beta-blockers suppress renin secretion, but these also reduce heart rate and cardiac output. Calcium channel blockers and diuretics cause a modest activation of the renin system secondary to the fall in renal afferent arteriolar pressure and reduction in filtered sodium load. Aliskiren is the first orally available direct inhibitor that blocks the renin system at its rate limiting step and is shown to reduce angiotensin I and II and plasma renin activity.

Obstructive Sleep Apnea and Aldosterone

Science.gov (United States)

Svatikova, Anna; Olson, Lyle J.; Wolk, Robert; Phillips, Bradley G.; Adachi, Taro; Schwartz, Gary L.; Somers, Virend K.

2009-01-01

Background: Obstructive sleep apnea (OSA) is a major risk factor for hypertension and has been associated with increased risk for cardiovascular morbidity. A dysregulated renin-angiotensin-aldosterone system may contribute to excess sodium retention and hypertension and may be activated in OSA. We tested the hypothesis that serum levels of aldosterone and plasma renin activity (PRA) are increased by apneic sleep in subjects without cardiovascular disease, compared to healthy control subjects. Methods and Results: Plasma aldosterone level was measured in 21 subjects with moderate to severe OSA and was compared to 19 closely matched healthy subjects. Plasma renin activity (PRA) was measured in 19 OSA patients and in 20 healthy controls. Aldosterone and PRA were measured before sleep (9pm), after 5 hrs of untreated OSA (2am) and in the morning after awakening (6am). There were no baseline (9pm) differences in serum aldosterone levels and PRA between the healthy controls and OSA patients (aldosterone: 55.2 ± 9 vs 56.0 ± 9 pg/mL; PRA: 0.99 ± 0.15 vs 1.15 ± 0.15 ng/mL/hr). Neither several hours of untreated severe OSA nor CPAP treatment affected aldosterone levels and PRA in OSA patients. Diurnal variation of both aldosterone and PRA was observed in both groups, in that morning renin and aldosterone levels were higher than those measured at night before sleep. Conclusions: Our study shows that patients with moderate to severe OSA without co-existing cardiovascular disease have plasma aldosterone and renin levels similar to healthy subjects. Neither untreated OSA nor CPAP treatment acutely affect plasma aldosterone or renin levels. Citation: Svatikova A; Olson LJ; Wolk R; Phillips BG; Adachi T; Schwartz GL; Somers VK. Obstructive sleep apnea and aldosterone. SLEEP 2009;32(12):1589-1592. PMID:20041594

The role of vascular protein and renin in chronic two-kidney, one clip Goldblatt hypertension

International Nuclear Information System (INIS)

Nakada, T.; Yamori, Y.

1982-01-01

Chronic hypertension was induced in rats by application of a clip for 17 or 20 weeks to the unilateral renal artery and leaving the contrarenal vessel intact. Some of the rats received antihypertensive treatment with phenoxybenzamine (POB). 3 H-proline was injected into all rats in the 17th experimental week to observe the in vivo incorporation rates of 3 H-proline into vascular non-collagenous protein and vascular collagen. Plasma renin activity (PRA) of decapitated rats was assayed in the terminal stage of the experiment. Significant differences were noted between 2K-1C hypertensive rats and sham-operated normotensive rats, the former rats having significantly higher incorporation rates of 3 H-proline into non-collagenous protein and collagen of testicular or mesenteric artery. These results indicate that increased synthesis of vascular non-collagenous protein as well as collagen, especially of small arteries, plays a major role for the pathogenesis of chronic hypertension in 2K-1C rats, and renin does not contribute to elevation of the blood pressure in the maintenance phase of this type of experimental hypertension

PRISIM: a computer program that makes PRA useful

International Nuclear Information System (INIS)

Fussell, J.B.; Campbell, D.J.; Glynn, J.C.; Burdick, G.R.

1986-01-01

PRISIM is an IBM personal computer program that translates probabilistic risk assessment (PRA) information and calculates additional PRA type information for use by those who are not PRA experts. Specifically, PRISIM was developed for the US Nuclear Regulatory Commission for use by their resident inspectors at nuclear power plants. Inspector activities are either scheduled or are in response to a particular status of a plant. PRISIM is useful for either activity

ANGIOTONIN-ACTIVATOR, RENIN- AND ANGIOTONIN-INHIBITOR, AND THE MECHANISM OF ANGIOTONIN TACHYPHYLAXIS IN NORMAL, HYPERTENSIVE, AND NEPHRECTOMIZED ANIMALS.

Science.gov (United States)

Page, I H; Helmer, O M

1940-03-31

1. Angiotonin does not exert its vasoconstrictor effect in the absence of a substance contained in red blood cells and serum which we have called "angiotonin-activator." A fraction has been separated from blood in which angiotonin-activator is concentrated. It contains little or no reninactivator. 2. Repeated intravenous injections of angiotonin into animals causes the pressor response gradually to lessen and finally to disappear (the phenomenon of tachyphylaxis), but much more slowly than when renin is injected. When the response to angiotonin is abolished, renin also fails to act. Large doses of renin reduce and finally abolish the responsiveness to angiotonin. Exhaustion of renin-activator in the blood abolishes the response to renin without abolishing the response to angiotonin. 3. Blood from animals made tachyphylactic by infusion of angiotonin contains greatly reduced amounts of angiotonin-activator. An inhibitor also appears in the blood. 4. Bilateral nephrectomy prolongs and greatly enhances the rise of arterial pressure following injection of angiotonin and renin. The enhancement reaches a maximum in from 24 to 30 hours after operation. Blood from these animals exhibits greatly increased ability to activate angiotonin and renin when tested in isolated perfused organs. Large amounts of angiotonin are required to reduce the amount of activator in their blood. Renin-activator is simultaneously but little affected. 5. Tranfusion of blood from an animal made tachyphylactic to angiotonin into a nephrectomized dog reduces the response of the latter to angiotonin. Angiotonin when added to the blood of the recipient of the transfusion and perfused through a rabbit's ear also exhibits greatly reduced vasoconstrictor action. 6. Transfusion of normal blood in large amounts into nephrectomized or hypertensive dogs reduces the recipient's response to renin. If renintachyphylaxis is established in the donor, transfusion abolishes the response to renin in the recipient

Combination therapy with renin-angiotensin-aldosterone system inhibitor telmisartan and serine protease inhibitor camostat mesilate provides further renoprotection in a rat chronic kidney disease model

Directory of Open Access Journals (Sweden)

Yuki Narita

2016-02-01

Full Text Available We previously reported that camostat mesilate (CM had renoprotective and antihypertensive effects in rat CKD models. In this study, we examined if CM has a distinct renoprotective effect from telmisartan (TE, a renin-angiotensin-aldosterone system (RAS inhibitor, on the progression of CKD. We evaluated the effect of CM (400 mg/kg/day and/or TE (10 mg/kg/day on renal function, oxidative stress, renal fibrosis, and RAS components in the adenine-induced rat CKD model following 5-weeks treatment period. The combination therapy with CM and TE significantly decreased the adenine-induced increase in serum creatinine levels compared with each monotherapy, although all treatment groups showed similar reduction in blood pressure. Similarly, adenine-induced elevation in oxidative stress markers and renal fibrosis markers were significantly reduced by the combination therapy relative to each monotherapy. Furthermore, the effect of the combination therapy on plasma renin activity (PRA and plasma aldosterone concentration (PAC was similar to that of TE monotherapy, and CM had no effect on both PRA and PAC, suggesting that CM has a distinct pharmacological property from RAS inhibition. Our findings indicate that CM could be a candidate drug for an add-on therapy for CKD patients who had been treated with RAS inhibitors.

Calcium channel blocker prevents stress-induced activation of renin and aldosterone in conscious pig

International Nuclear Information System (INIS)

Ceremuzynski, L.K.; Klos, J.; Barcikowski, B.; Herbaczynska-Cedro, K.

1991-01-01

A considerable amount of data suggest the involvement of calcium-mediated processes in the activation of the renin-angiotensin-aldosterone (RAA) cascade. To investigate the effect of calcium-channel inhibition on the RAA system, the authors studied 21 conscious pigs. Blood renin and aldosterone levels increased by subjecting animals to 24 hours of immobilization stress. Renin and aldosterone levels were repeatedly measured by radioimmunoassay in blood samples taken periodically over 24 hours from a chronically implanted arterial cannula. Pretreatment of the animals (N = 11) with nisoldipine, 2 x 20 mg p.o. daily for 2 days before and on the day of immobilization, transiently attenuated the stress-induced increase of plasma renin activity and completely prevented the rise of aldosterone, as compared to nontreated controls (N = 10). The finding that nisoldipine suppresses RAA activation induced by a nonpharmacologic stimulus in the conscious intact animal may have clinical implications

Iminopyrimidinones: A novel pharmacophore for the development of orally active renin inhibitors

Energy Technology Data Exchange (ETDEWEB)

McKittrick, Brian A.; Caldwell, John P.; Bara, Thomas; Boykow, George; Chintala, Madhu; Clader, John; Czarniecki, Michael; Courneya, Brandy; Duffy, Ruth; Fleming, Linda; Giessert, Rachel; Greenlee, William J.; Heap, Charles; Hong, Liwu; Huang, Ying; Iserloh, Ulrich; Josien, Hubert; Khan, Tanweer; Korfmacher, Walter; Liang, Xian; Mazzola, Robert; Mitra, Soumya; Moore, Kristina; Orth, Peter; Rajagopalan, Murali; Roy, Sudipta; Sakwa, Samuel; Strickland, Corey; Vaccaro, Henry; Voigt, Johannes; Wang, Hongwu; Wong, Jesse; Zhang, Rumin; Zych, Andrew (Merck); (Albany MR)

2015-04-01

The development of renin inhibitors with favorable oral pharmacokinetic profiles has been a longstanding challenge for the pharmaceutical industry. As part of our work to identify inhibitors of BACE1, we have previously developed iminopyrimidinones as a novel pharmacophore for aspartyl protease inhibition. In this letter we describe how we modified substitution around this pharmacophore to develop a potent, selective and orally active renin inhibitor.

Effect of antigravity suit inflation on cardiovascular, PRA, and PVP responses in humans.

Science.gov (United States)

Kravik, S E; Keil, L C; Geelen, G; Wade, C E; Barnes, P R; Spaul, W A; Elder, C A; Greenleaf, J E

1986-08-01

Blood pressure, pulse rate (PR), serum osmolality and electrolytes, as well as plasma vasopressin (PVP) and plasma renin activity (PRA), were measured in five men and two women [mean age 38.6 +/- 3.9 (SE) yr] before, during, and after inflation of an antigravity suit that covered the legs and abdomen. After 24 h of fluid deprivation the subjects stood quietly for 3 h: the 1st h without inflation, the 2nd with inflation to 60 Torr, and the 3rd without inflation. A similar control noninflation experiment was conducted 10 mo after the inflation experiment using five of the seven subjects except that the suit was not inflated during the 3-h period. Mean arterial pressure increased by 14 +/- 4 (SE) Torr (P less than 0.05) with inflation and decreased by 15 +/- 5 Torr (P less than 0.05) after deflation. Pulse pressure (PP) increased by 7 +/- 2 Torr (P less than 0.05) with inflation and PR decreased by 11 +/- 5 beats/min (P less than 0.05); PP and PR returned to preinflation levels after deflation. Plasma volume decreased by 6.1 +/- 1.5% and 5.3 +/- 1.6% (P less than 0.05) during hours 1 and 3, respectively, and returned to base line during inflation. Inflation decreased PVP from 6.8 +/- 1.1 to 5.6 +/- 1.4 pg/ml (P less than 0.05) and abolished the significant rise in PRA during hour 1. Both PVP and PRA increased significantly after deflation: delta = 18.0 +/- 5.1 pg/ml and 4.34 +/- 1.71 ng angiotensin I X ml-1 X h-1, respectively. Serum osmolality and Na+ and K+ concentrations were unchanged during the 3 h of standing.(ABSTRACT TRUNCATED AT 250 WORDS)

Probabilistic risk assessment course documentation. Volume 1: PRA fundamentals

International Nuclear Information System (INIS)

Breeding, R.J.; Leahy, T.J.; Young, J.

1985-08-01

The full range of PRA topics is presented, with a special emphasis on systems analysis and PRA applications. Systems analysis topics include system modeling such as fault tree and event tree construction, failure rate data, and human Reliability. The discussion of PRA applications is centered on past and present PRA based programs, such as WASH-1400 and the Interim Reliability Evaluation Program, as well as on some of the potential future applications of PRA. The relationship of PRA to generic safety issues such as station blackout and Anticipated Transient Without Scram (ATWS) is also discussed. In addition to system modeling, the major PRA tasks of accident process analysis, and consequence analysis are presented. An explanation of the results of these activities, and the techniques by which these results are derived, forms the basis for a discussion of these topics. An additional topic which is presented in this course is the topic of PRA management, organization, and evaluation. 84 figs., 41 tabs

Peptides and neurotransmitters that affect renin secretion

Science.gov (United States)

Ganong, W. F.; Porter, J. P.; Bahnson, T. D.; Said, S. I.

1984-01-01

Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the

Uses of PRA in nuclear reactor regulation

International Nuclear Information System (INIS)

Congel, F.

1987-01-01

For the past five years, more than ten probabilistic risk assessment (PRA) studies were conducted by the owners of nuclear utilities and were submitted for the review of US Nuclear Regulatory Commission staff. These PRA studies were reviewed under various types of regulatory activities depending on the nature of plant licensing stage. The reviews of these PRAs provided very valuable uses to both the staff and the licensees on safety matters of the plant operation. The licensees developed perspectives using PRA models on the safety profiles of their plants. These PRA perspectives influenced licensees' major decisions to implement improvements to plant design and operating and emergency procedures to reduce and/or eliminate the plant's vulnerability to core damage accidents. The staff's review of these PRAs particularly emphasized the dominant accident sequences. The resulting findings led to the identification of dominant risk contributors, critical areas of plant locations, mechanisms leading to potential early containment failures, and instances of noncompliances of staff's deterministic criteria. Specific examples include single failure criterion and separation requirements to assess the need for any additional measures to further improve the safety of the plant. Some of these PRAs were reviewed under regulatory activities other than safety review such as environmental review, final design review, and licensing hearings. Most importantly, the risk profiles of generic PRAs will continue to be used in reviewing and evaluating unresolved safety issues and other generic issues. The major regulatory uses of PRAs, a summary of full scope PRA review, a summary of plant improvements as a result of PRA reviews, and the future role of PRA reviews are presented

Plasma volume, osmolality, vasopressin, and renin activity during graded exercise in man

Science.gov (United States)

Convertino, V. A.; Keil, L. C.; Bernauer, E. M.; Greenleaf, J. E.

1981-01-01

The influence of work intensity on plasma volume, osmolality, vasopressin and renin activity and the interrelationships between these responses are investigated. Plasma volume, renin activity and osmotic, sodium and arginine vasopressin concentrations were measured in venous blood samples taken from 15 healthy male subjects before and after six minutes of bicycle ergometer exercise at 100, 175 and 225 W. Plasma volume is found to decrease significantly with increasing work intensity, while increases in Na(+) concentration, osmolality and vasopressin are only observed to be significant when the work intensity exceeds 40% maximal aerobic capacity and plasma resin activity increased linearly at all work levels. In addition, significant correlations are observed between plasma volume and osmolality and sodium changes, and between vasopressin and osmolality and sodium content changes. Data thus support the hypotheses that (1) vasopressin may be the primary controlling endocrine for fluid and electrolyte levels following exercise; (2) an exercise intensity greater than 40% maximal aerobic capacity is required to stimulate vasopressin release through changes in plasma osmolality; and (3) the stimulation of the renin-angiotensin system is a more general stress response.

Development of insights from PRAs for non-PRA people

International Nuclear Information System (INIS)

Reilly, H.J.; Meale, B.M.

1992-01-01

A probabilistic risk assessment (PRA) of the Savannah River K-Reactor was completed in 1990. The PRA estimated the frequency of core damage accidents caused by operational occurrences during power operation of the reactor. The US Department of Energy (DOE) requested Idaho National Engineering Laboratory (INEL) to prepare guidance based on the PRA for use by DOE personnel at the Savannah River Site (SRS). The document had the purpose of informing the DOE system engineers and site representatives about how the information in the PRA might be used to help guide their activities. Opportunities existed to develop a document somewhat different than those developed previously by other programs. The opportunities existed because the audience is different: the principal audience for the document consists of DOE engineers who have continuing oversight responsibility for activities performed by the operating contractor at the K-Reactor, but who may not be knowledgeable about PRA

Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study

DEFF Research Database (Denmark)

Krum, Henry; Massie, Barry; Abraham, William T

2011-01-01

AIMS: The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs......S for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II-IV symptoms, and elevated plasma...... levels of BNP. Methods Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open-label run-in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run-in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril...

Insights on PRA Review Practices: Necessity for Model Shaking

Energy Technology Data Exchange (ETDEWEB)

Kim, Inn Seock; Jang, Mi suk; Kim, Seoung Rae [NESS, Daejeon (Korea, Republic of)

2016-05-15

Probabilistic risk assessment (PRA) is increasingly used as a technique to help ensure design and operational safety of nuclear power plants (NPPs) in the nuclear industry. Hence, there is considerable interest in the PRA quality, and as a result, a peer review of the PRA model is typically performed to ensure its technical adequacy as part of the PRA development process or for any other reason (e.g., regulatory requirement). For the PRA model to be used as a valuable vehicle for risk-informed applications, it is essential that the PRA model must yield correct and physically meaningful accident sequences and minimal cutsets for specific plant configurations or conditions relating to the applications. Hence, the existing peer review guidelines need to be updated to reflect these insights so that risk-informed applications could be more actively pursued with confidence.

Predicting the onset of Addison's disease: ACTH, renin, cortisol and 21-hydroxylase autoantibodies

Science.gov (United States)

Baker, Peter R.; Nanduri, Priyaanka; Gottlieb, Peter A.; Yu, Liping; Klingensmith, Georgeanna J.; Eisenbarth, George S.; Barker, Jennifer M.

2016-01-01

Summary Context Autoantibodies to 21-hydroxylase (21OH-AA) precede onset of autoimmune Addison's disease (AD). Progression to AD can take months to years, and early detection of metabolic decompensation may prevent morbidity and mortality. Objective To define optimal methods of predicting progression to overt AD (defined by subnormal peak cortisol response to Cosyntropin) in 21OH-AA+ individuals. Design, Setting and Participants Individuals were screened for 21OH-AA at the Barbara Davis Center from 1993 to 2011. Subjects positive for 21OH-AA (n = 87) were tested, and the majority prospectively followed for the development of Addison's disease, including seven diagnosed with AD upon 21OH-AA discovery (discovered), seven who progressed to AD (progressors) and 73 nonprogressors. Main Outcome Measured Plasma renin activity (PRA), ACTH, baseline cortisol, peak cortisol and 21OH-AA were measured at various time points relative to diagnosis of AD or last AD-free follow-up. Results Compared with nonprogressors, in the time period 2 months–2 years prior to the onset of AD, progressors were significantly more likely to have elevated ACTH (11–22 pm, P < 1E-4), with no significant differences in mean PRA (P = 0·07) or baseline cortisol (P = 0·08), and significant but less distinct differences seen with 21OH-AA levels (P < 1E-4) and poststimulation cortisol levels (P = 6E-3). Conclusion Moderately elevated ACTH is a more useful early indicator of impending AD than 21OH-AA, PRA or peak cortisol, in the 2 months–2 years preceding the onset of AD. PMID:22066755

Urinary renin and angiotensinogen in type 2 diabetes

DEFF Research Database (Denmark)

Persson, Frederik; Lu, Xifeng; Rossing, Peter

2013-01-01

Urinary levels of renin-angiotensin-aldosterone system (RAAS) components may reflect renal RAAS activity and/or the renal efficacy of RAAS inhibition. Our aim was to determine whether urinary angiotensinogen and renin are circulating RAAS-independent markers during RAAS blockade.......Urinary levels of renin-angiotensin-aldosterone system (RAAS) components may reflect renal RAAS activity and/or the renal efficacy of RAAS inhibition. Our aim was to determine whether urinary angiotensinogen and renin are circulating RAAS-independent markers during RAAS blockade....

Radioimmunoassay - renin - angiotensin. Principles of radioimmunoassay and their application in measuring renin and angiotensin

Energy Technology Data Exchange (ETDEWEB)

Krause, D K; Hummerich, W; Poulsen, K [eds.

1978-01-01

Typical pitfalls such as impurity of 'standard', tracer damage, crossreactivity of antiserum, unspecific binding of protecting proteins, blank effects with negative results, charcoal stripping, invisible coprecipitate or uncertainty in the analysis of the calibration curve (graph, logit-log, polynormal or spline function) can occur in any type of radioimmunoassay; they are detailed in the general part of this book. The special position occupied by radioimmunological quantification of parameters of the renin-angiotensin system creates additional, even more serious problems. While the radioimmunological determination of the decapeptide angiotensin I no longer causes major obstacles, measurement of the biologically active octapeptide angiotensin II is still only possible in a few centers. The (indirect) determination of plasma renin is characterized by a situation where the enzyme renin may be clearly defined in theory as a specific 10-11-leucine-leucine-endopeptidase cleaving only a decapeptide, but the actual renin assay, however, measures various forms of renin and other angiotensin-forming (or angiotensin-destroying) enzymes at the same time.

Increased renin production in mice with deletion of peroxisome proliferator-activated receptor-gamma in juxtaglomerular cells

DEFF Research Database (Denmark)

Desch, Michael; Schreiber, Andrea; Schweda, Frank

2010-01-01

We recently found that endogenous (free fatty acids) and pharmacological (thiazolidinediones) agonists of nuclear receptor Peroxisome proliferator-activated receptor (PPAR)gamma stimulate renin transcription. In addition, the renin gene was identified as a direct target of PPARgamma. The mouse re...

Comparative biochemistry of renins and angiotensins in the vertebrates.

Science.gov (United States)

Nakajima, T; Khosla, M C; Sakakibara, S

1978-09-01

Comparative biochemistry of renins and angiotensins was discussed. Renin extracted from hog kidney was different from that from mouse submaxillary glands in immunoreactivity and carbohydrate content. Rat kidney renin was also different from hog kidney renin in the amino acid composition. The presence of big and big-big renins was pointed out immunochemically. These big renins were considered to be precursors of kidney renin. Angiotensins in mammalian and nonmammalian species produced by renal or extrarenal renin have been differentiated by some biochemical and pharmacological criteria. Some of these angiotensins were analyzed sequentially. The replacements of amino acid residues at positions 1, 5, and/or 9 of angiotensin I have been demonstrated in nonmammalian species. Specific pressor activities have been determined using synthetic angiotensins by a 4 point assay in rat. Specific pressor activities of various angiotensins were obtained from the dose-blood pressure-response curves using a single angiotensin sample per assay rat.

Activity assays and immunoassays for plasma Renin and prorenin: information provided and precautions necessary for accurate measurement

DEFF Research Database (Denmark)

Campbell, Duncan J; Nussberger, Juerg; Stowasser, Michael

2009-01-01

into focus the differences in information provided by activity assays and immunoassays for renin and prorenin measurement and has drawn attention to the need for precautions to ensure their accurate measurement. CONTENT: Renin activity assays and immunoassays provide related but different information...... provided by these assays and of the precautions necessary to ensure their accuracy....

Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors

Science.gov (United States)

Okada, Yoshiyuki; Jarvis, Sara S; Best, Stuart A; Bivens, Tiffany B; Adams-Huet, Beverley; Levine, Benjamin D; Fu, Qi

2013-01-01

Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n= 7), or a diuretic, hydrochlorothiazide (n= 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P < 0.01), while MSNA responses were different between hydrochlorothiazide and aliskiren (P= 0.006 pre/post × drug). Both supine and upright MSNA became greater after hydrochlorothiazide treatment (supine, 72 ± 18 post vs. 64 ± 15 bursts (100 beats)−1 pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)−1; P= 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)−1), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)−1; P= 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P= 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r= 0.74, P= 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin–angiotensin–aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive

Renal hemodynamics and renin-angiotensin system activity in humans with multifocal renal artery fibromuscular dysplasia.

Science.gov (United States)

van Twist, Daan J L; Houben, Alphons J H M; de Haan, Michiel W; de Leeuw, Peter W; Kroon, Abraham A

2016-06-01

Fibromuscular dysplasia (FMD) is the second most common cause of renovascular hypertension. Nonetheless, knowledge on the renal microvasculature and renin-angiotensin system (RAS) activity in kidneys with FMD is scarce. Given the fairly good results of revascularization, we hypothesized that the renal microvasculature and RAS are relatively spared in kidneys with FMD. In 58 hypertensive patients with multifocal renal artery FMD (off medication) and 116 matched controls with essential hypertension, we measured renal blood flow (Xenon washout method) per kidney and drew blood samples from the aorta and both renal veins to determine renin secretion and glomerular filtration rate per kidney. We found that renal blood flow and glomerular filtration rate in FMD were comparable to those in controls. Although systemic renin levels were somewhat higher in FMD, renal renin secretion was not elevated. Moreover, in patients with unilateral FMD, no differences between the affected and unaffected kidney were observed with regard to renal blood flow, glomerular filtration rate, or renin secretion. In men, renin levels and renin secretion were higher as compared with women. The renal blood flow response to RAS modulation (by intrarenal infusion of angiotensin II, angiotensin-(1-7), an angiotensin II type 1 receptor blocker, or a nitric oxide synthase blocker) was also comparable between FMD and controls. Renal blood flow, glomerular filtration, and the response to vasoactive substances in kidneys with multifocal FMD are comparable to patients with essential hypertension, suggesting that microvascular function is relatively spared. Renin secretion was not increased and the response to RAS modulation was not affected in kidneys with FMD.

The renin-angiotensin system in kidney development

DEFF Research Database (Denmark)

Jensen, B L; Stubbe, J; Madsen, K

2004-01-01

Recent data from studies in rodents with targeted gene disruption and pharmacological antagonists have shown that the renin-angiotensin-aldosterone system (RAAS) and cyclooxygenase type-2 (COX-2) are necessary for late stages of kidney development. The present review summarizes data on the develo......Recent data from studies in rodents with targeted gene disruption and pharmacological antagonists have shown that the renin-angiotensin-aldosterone system (RAAS) and cyclooxygenase type-2 (COX-2) are necessary for late stages of kidney development. The present review summarizes data...... on the developmental changes of RAAS and COX-2 and the pathways by which they are activated; their possible interplay and the mechanisms by which they affect kidney development. Intrarenal and circulating renin and angiotensin II (ANG II) are stimulated at birth in most mammals. In rats, renin and ANG II stay...... glucocorticoid concentration and by a low NaCl intake. Studies with selective inhibitors of COX-2 and COX-2 null mice show that COX-2 activity stimulates renin secretion from JG-cells during postnatal kidney development and that lack of COX-2 activity leads to pathological change in cortical architecture...

Controlled treatment of primary hypertension with propranolol and spironolactone. A crossover study with special reference to initial plasma renin activity.

Science.gov (United States)

Karlberg, B E; Kågedal, B; Tegler, L; Tolagen, K; Bergman, B

1976-03-31

Twenty-seven patients with hypertension were randomly allocated to a 10 month crossover study. Treatment consisted of spironolactone (200 mg/day for 2 months), propranolol (320 mg/day for 2 months) and combined administration of both drugs at half the dosage. Between treatment periods placebo was given for 2 months. Fourteen patients were previously untreated. The average pretreatment blood pressure for the entire group was 188/114 +/- 16/7(mean +/- standard deviation) mm Hg supine and 188/118 +/- 20/9 mm Hg standing. Both spironolactone and propranolol reduced blood pressure significantly in both the supine and standing positions. Upright plasma renin activity was determined by radioimmunoassay of angiotensin I. The average initial level was 1.9 +/- 1.2 (range 0.4 to 5.0) ng/ml/hr. There was a close correlation between plasma renin activity and the effects of the drugs: With increasing renin level the response to propranolol was better whereas the opposite was true for spironolactone. The combination of spironolactone and propranolol decreased the blood pressure still further in the supine and standing positions, irrespective of initial plasma renin activity. All patients achieved a normal supine pressure. Blood pressure and plasma renin activity returned toward pretreatment values during placebo administration. It is concluded that pretreatment levels of plasma renin activity can predict the antihypertensive response to propranolol and spironolactone. The combination of the two drugs, which have different modes of action, will effectively reduce blood pressure in hypertension. The results support the concept that the renin-angiotensin-aldo-sterone system may be involved in primary hypertension.

Local renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy.

Science.gov (United States)

Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

1999-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.

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

DEFF Research Database (Denmark)

Nielsen, L Ringholm; Pedersen-Bjergaard, U; Thorsteinsson, B

2009-01-01

AIMS: To investigate whether increased risk of severe hypoglycaemia in early pregnancy is related to pregnancy-induced changes in renin-angiotensin system (RAS) activity in women with type 1 diabetes (T1DM). METHODS: Severe hypoglycaemic events the year preceding pregnancy were recorded...... retrospectively in 107 consecutive pregnant women with T1DM. Events during pregnancy were recorded prospectively. Measurements of ACE, renin and angiotensinogen were determined at 8, 14, 21, 27 and 33 weeks and postpartum. RESULTS: The rate of severe hypoglycaemia was 1.1 and 5.3 events/patient-year the year...... preceding pregnancy and postpartum ACE activity (relative rate of severe hypoglycaemia above versus below median ACE activity: 4.4 (CI: 1.7-11.9), p=0.003). No association was found between severe hypoglycaemia during pregnancy and renin angiotensin system activity at 8 weeks. CONCLUSIONS: In early...

Renal renin secretion as regulator of body fluid homeostasis

DEFF Research Database (Denmark)

Damkjær, Mads; Isaksson, Gustaf L; Stubbe, Jane

2013-01-01

The renin-angiotensin system is essential for body fluid homeostasis and blood pressure regulation. This review focuses on the homeostatic regulation of the secretion of active renin in the kidney, primarily in humans. Under physiological conditions, renin secretion is determined mainly by sodium...

Control of the renal renin system by local factors

DEFF Research Database (Denmark)

Wagner, C; Jensen, B L; Krämer, B K

1998-01-01

prostanoid, both stimulate renin secretion and renin gene expression by activating cAMP formation in JG cells. Although the direct effect of NO on JG cells is less clear, its overall effect in vivo seems to be to stimulate the renin system. Evidence is emerging that stimulation by NO is related to the c......AMP pathway, and cGMP-induced inhibition of cAMP-phosphodiesterase III (PDE-III) may mediate this effect. ETs, on the other hand, appear to inhibit the renin system, in particular in those pathways activated by cAMP, acting via Ca2+- and protein kinase C-related mechanisms. There is increasing evidence...... that both NO and PGs could be involved in the physiological regulatory mechanisms by which salt intake affects the renin system....

Review of PRA methodology for LMFBR

International Nuclear Information System (INIS)

Yang, J. E.

1999-02-01

Probabilistic Risk Assessment (PRA) has been widely used as a tool to evaluate the safety of NPPs (Nuclear Power Plants), which are in the design stage as well as in operation. Recently, PRA becomes one of the licensing requirements for many existing and new NPPs. KALIMER is a Liquid Metal Fast Breeder Reactor (LMFBR) being developed by KAERI. Since the design concept of KALIMER is similar to that of the PRISM plant developed by GE, it would be appropriate to review the PRA methodology of PRISM as the first step of KALIMER PRA. Hence, in this report summarizes the PRA methodology of PRISM plant, and the required works for the PSA of KALIMER based on the reviewed results. The PRA technology of PRISM plant consists of following five major tasks: (1) development of initiating event list, (2) development of system event tree, (3) development of core response event tree, (4) development of containment response event tree, and (5) consequences and risk estimation. The estimated individual and societal risk measures show that the risk from a PRISM module is substantially less than the NRC goal. Each task is compared to the PRA methodology of Light Water Reactor (LWR)/Pressurized Heavy Water Reactor (PHWR). In the report, each task of PRISM PRA methodology is reviewed and compared to the corresponding part of LWR/PHWR PSA performed in Korea. The parts that are not modeled appropriately in PRISM PRA are identified, and the recommendations for KALIMER PRA are stated. (author). 14 refs., 9 tabs., 4 figs

New sensitive direct radioimmunoassay for human plasma renin and its clinical application

International Nuclear Information System (INIS)

Higaki, J.; Ogihara, T.; Imai, N.; Kumahara, Y.; Hontani, S.; Nishiura, M.; Ogawa, H.; Hirose, S.; Murakami, K.

1984-01-01

A new sensitive direct radioimmunoassay for human plasma renin has been developed. Renin was purified from Haas' preparation utilizing a pepstatin-C 6 -Sepharose affinity chromatography. Antiserum, prepared by immunizing rabbits with the purified renin, was used for the direct radioimmunoassay at a final dilution of 1:30,000. The antibody was specific for human renal and plasma renin, but did not cross-react with cathepsin D, trypsin, or renins of mouse, dog, and rat. Radioimmunoassay was performed by the double antibody technique using the delayed tracer addition method. In this method, a standard curve was obtained over a range from 0.2 to 8.0 ng/ml. The values from this assay correlated well with total renin activity measured as the generation rate of angiotensin I after trypsin activation, but correlated weakly with active renin activity. This finding disclosed that both active and inactive renin were detected by this method. In normal participants, plasma renin concentration determined by direct radioimmunoassay was increased by standing and furosemide injection. The plasma renin concentration determined by direct radioimmunoassay of patients with essential hypertension was not significantly different from values in normal controls. The values were higher in patients with renovascular hypertension, malignant hypertension and Bartter's syndrome, but lower in patients with primary aldosteronism than in normal controls. 20 references, 7 figures

Renin blood test

Science.gov (United States)

... page: //medlineplus.gov/ency/article/003698.htm Renin blood test To use the sharing features on this page, ... renin test measures the level of renin in blood. How the Test is Performed A blood sample is needed . How ...

Use of PRA in the nuclear regulatory field in South Africa

International Nuclear Information System (INIS)

Hill, T.F.

1994-01-01

The nuclear regulatory authority in South Africa (since 1988 the Council for Nuclear Safety (CNS)), established in 1973 nuclear safety criteria against which to assess the level of safety of any facility using radioactive material. It is a regulatory requirement in South Africa to develop and maintain a living PRA for each facility and thereby to provide the necessary information to demonstrate compliance against these criteria. All safety submissions to the CNS must include at least a risk statement based on an accepted PRA study. The function of the CNS is to regulate all activities in South Africa involving the use of radioactive material and posing a significant risk to the public or plant personnel. This includes most aspects of the nuclear fuel cycle and the Koeberg NPS (two 2775 MW(th) PWRs). A PRA study including source terms for the two Koeberg units was presented by the contractor in 1979. This included the risk due to power and shutdown states and non reactor related accidents involving spent fuel storage, fuel handling and waste treatment related activities. At least 20 PRA studies have been performed for other nuclear facilities in the country. The CNS maintains an in-house PRA capability to perform independent assessments of licensee submission, to participate in developments of PRA methodology in the regulatory field, to perform pro-active safety work and to assist in regulatory decision making. Present ongoing work includes the development of a risk monitor, a risk management system, improvement in PRA codes, models, data collection and analysis, off-site risk assessment methodology and associated regulatory policy. (author). 1 fig

Seabrook Station Level 2 PRA Update to Include Accident Management

International Nuclear Information System (INIS)

Lutz, Robert; Lucci, Melissa; Kiper, Kenneth; Henry, Robert

2006-01-01

A ground-breaking study was recently completed as part of the Seabrook Level 2 PRA update. This study updates the post-core damage phenomena to be consistent with the most recent information and includes accident management activities that should be modeled in the Level 2 PRA. Overall, the result is a Level 2 PRA that fully meets the requirements of the ASME PRA Standard with respect to modeling accident management in the LERF assessment and NRC requirements in Regulatory Guide 1.174 for considering late containment failures. This technical paper deals only with the incorporation of operator actions into the Level 2 PRA based on a comprehensive study of the Seabrook Station accident response procedures and guidance. The paper describes the process used to identify the key operator actions that can influence the Level 2 PRA results and the development of success criteria for these key operator actions. This addresses a key requirement of the ASME PRA Standard for considering SAMG. An important benefit of this assessment was the identification of Seabrook specific accident management insights that can be fed back into the Seabrook Station accident management procedures and guidance or the training provided to plant personnel for these procedures and guidance. (authors)

PRA research and the development of risk-informed regulation at the U.S. nuclear regulatory commission

International Nuclear Information System (INIS)

Siu, Nathan; Collins, Dorothy

2008-01-01

Over the years, Probabilistic Risk Assessment (PRA) research activities conducted at the U.S. Nuclear Regulatory Commission (NRC) have played an essential role in support of the agency's move towards risk-informed regulation. These research activities have provided the technical basis for NRC's regulatory activities in key areas; provided PRA methods, tools, and data enabling the agency to meet future challenges; supported the implementation of NRC's 1995 PRA Policy Statement by assessing key sources of risk; and supported the development of necessary technical and human resources supporting NRC's risk-informed activities. PRA research aimed at improving the NRC's understanding of risk can positively affect the agency's regulatory activities, as evidenced by three case studies involving research on fire PRA, Human Reliability Analysis (HRA), and Pressurized Thermal Shock (PTS) PRA. These case studies also show that such research can take a considerable amount of time, and that the incorporation of research results into regulatory practice can take even longer. The need for sustained effort and appropriate lead time is an important consideration in the development of a PRA research program aimed at helping the agency address key sources of risk for current and potential future facilities

Living alone and activation of the renin-angiotensin-aldosterone-system: Differential effects depending on alexithymic personality features.

Science.gov (United States)

Terock, Jan; Hannemann, Anke; Janowitz, Deborah; Völzke, Henry; Nauck, Matthias; Freyberger, Harald-Jürgen; Wallaschofski, Henri; Grabe, Hans Jörgen

2017-05-01

Living alone is considered as a chronic stress factor predicting different health conditions and particularly cardiovascular disease (CVD). Alexithymia is associated with increased psychological distress, less social skills and fewer close relationships, making alexithymic subjects particularly susceptible to chronic stress imposed by "living alone". Only few studies investigated the renin-angiotensin-aldosterone-system (RAAS) activity in response to chronic stress. We aimed at evaluating the effects of "living alone" as a paradigm for chronic stress on RAAS activity and putatively differential effects depending on alexithymic personality features. Alexithymia and serum concentrations of renin and aldosterone were measured in 944 subjects from the population-based SHIP-1 study. Subgroups were formed using the median of the Toronto Alexithymia Scale-20 (TAS-20) and a cohabitation status of "living alone" or "living together". Analyses were adjusted for various psychosocial, behavioral and metabolic risk factors. "Living alone" was associated with elevated plasma renin (p<0.01, β=0.138) but not aldosterone concentrations in the total sample. On subgroup level, we found associations of "living alone" and elevated renin concentrations only in subjects low in TAS-20 scores (p<0.01, β=0.219). Interactional effects of alexithymia×cohabitation status were found for the aldosterone-to-renin ratio (p=0.02, β=-0.234). The association of chronic stress imposed by "living alone" with increased RAAS activity contributes to explain the relationship of this psychosocial stress condition and increased risk for CVD. In contrast, alexithymic subjects may be less affected by the deleterious effects of "living alone". Copyright © 2017 Elsevier Inc. All rights reserved.

Expression and nutritional regulation of the (pro)renin receptor in rat visceral adipose tissue.

Science.gov (United States)

Achard, V; Tassistro, V; Boullu-Ciocca, S; Grino, M

2011-12-01

Early life nutritional environment plays an important role in the development of visceral adipose tissue and interacts with nutritional regulations in adulthood, leading to metabolic dysregulations. We hypothesized that the renin-angiotensin system may play a role in the programming-induced development of visceral adipose tissue. We studied, using a model of programming of overweight and glucose intolerance, obtained by post-natal overfeeding with consecutive highfat diet, the status of plasma renin activity and mesenteric adipose renin-angiotensin system, including the recently identified (pro)renin receptor, in adult rats. Post-natal overfeeding or high-fat feeding lead to overweight with increased visceral fat mass and adipocytes surface. When both paradigms were associated, adipocytes surface showed a disproportionate increase. A strong immunoreactivity for (pro)renin receptor was found in stromal cells. Plasma renin activity increased in programmed animals whereas (pro)renin receptor expressing cells density was stimulated by high-fat diet. There was a positive, linear relationship between plasma renin activity and (pro)renin receptor expressing cells density and adipocytes surface. Our experiments demonstrate that association of post-natal overfeeding and high-fat diet increased plasma renin activity and adipose (pro)renin receptor expression. Such phenomenon could explain, at least in part, the associated disproportionate adipocyte hypertrophy and its accompanying increased glucose intolerance.

Linkage of PRA models. Phase 1, Results

Energy Technology Data Exchange (ETDEWEB)

Smith, C.L.; Knudsen, J.K.; Kelly, D.L.

1995-12-01

The goal of the Phase I work of the ``Linkage of PRA Models`` project was to postulate methods of providing guidance for US Nuclear Regulator Commission (NRC) personnel on the selection and usage of probabilistic risk assessment (PRA) models that are best suited to the analysis they are performing. In particular, methods and associated features are provided for (a) the selection of an appropriate PRA model for a particular analysis, (b) complementary evaluation tools for the analysis, and (c) a PRA model cross-referencing method. As part of this work, three areas adjoining ``linking`` analyses to PRA models were investigated: (a) the PRA models that are currently available, (b) the various types of analyses that are performed within the NRC, and (c) the difficulty in trying to provide a ``generic`` classification scheme to groups plants based upon a particular plant attribute.

Linkage of PRA models. Phase 1, Results

International Nuclear Information System (INIS)

Smith, C.L.; Knudsen, J.K.; Kelly, D.L.

1995-12-01

The goal of the Phase I work of the ''Linkage of PRA Models'' project was to postulate methods of providing guidance for US Nuclear Regulator Commission (NRC) personnel on the selection and usage of probabilistic risk assessment (PRA) models that are best suited to the analysis they are performing. In particular, methods and associated features are provided for (a) the selection of an appropriate PRA model for a particular analysis, (b) complementary evaluation tools for the analysis, and (c) a PRA model cross-referencing method. As part of this work, three areas adjoining ''linking'' analyses to PRA models were investigated: (a) the PRA models that are currently available, (b) the various types of analyses that are performed within the NRC, and (c) the difficulty in trying to provide a ''generic'' classification scheme to groups plants based upon a particular plant attribute

Interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats.

Science.gov (United States)

Yang, Ke-Ke; Sui, Yi; Zhou, Hui-Rong; Zhao, Hai-Lu

2017-05-01

Renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway both play important roles in carcinogenesis, but the interplay of renin-angiotensin system and adenosine monophosphate-activated protein kinase in carcinogenesis is not clear. In this study, we researched the interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase in renal carcinogenesis of uninephrectomized rats. A total of 96 rats were stratified into four groups: sham, uninephrectomized, and uninephrectomized treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Renal adenosine monophosphate-activated protein kinase and its downstream molecule acetyl coenzyme A carboxylase were detected by immunohistochemistry and western blot at 10 months after uninephrectomy. Meanwhile, we examined renal carcinogenesis by histological transformation and expressions of Ki67 and mutant p53. During the study, fasting lipid profiles were detected dynamically at 3, 6, 8, and 10 months. The results indicated that adenosine monophosphate-activated protein kinase expression in uninephrectomized rats showed 36.8% reduction by immunohistochemistry and 89.73% reduction by western blot. Inversely, acetyl coenzyme A carboxylase expression increased 83.3% and 19.07% in parallel to hyperlipidemia at 6, 8, and 10 months. The histopathology of carcinogenesis in remnant kidneys was manifested by atypical proliferation and carcinoma in situ, as well as increased expressions of Ki67 and mutant p53. Intervention with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker significantly prevented the inhibition of adenosine monophosphate-activated protein kinase signaling pathway and renal carcinogenesis in uninephrectomized rats. In conclusion, the novel findings suggest that uninephrectomy-induced disturbance in adenosine monophosphate-activated protein kinase signaling pathway resulted in hyperlipidemia and

IRIS PRA preliminary results and future direction

International Nuclear Information System (INIS)

Finnicum, D.J.; Kling, C.L.; Carelli, M.D.

2004-01-01

Westinghouse is currently conducting the pre-application licensing of the International Reactor Innovative and Secure (IRIS) on behalf of the IRIS Consortium. One of the key aspects of the IRIS design is the concept of safety-by-design. The PRA (Probabilistic Risk Analysis) is being used as an integral part of the design process. As part of this effort, a PRA of the initial design was generated to address 2 key areas. First, the IRIS PRA supported the evaluation of IRIS design issues by providing a solid risk basis for design and analyses required for the pre-licensing evaluation of the IRIS design. The PRA provides the tool for quantifying the benefit of the safety-by-design approach. Second, the current PRA task is beginning the preparation of the more complete PRA analyses and documentation eventually required for Design Certification. One of the key risk-related goals for IRIS is to reduce the EPZ (Emergency Protection Zone) to within the exclusion area by demonstrating that the off-site doses are consistent with the US Protective Action Guidelines (PAGs) for initiation of emergency response so that the required protective actions would be limited to the exclusion area. The results of the preliminary PRA indicated a core damage frequency of 1.2 E-08 for internal initiators. This is a very good result but much work is needed to meet the ambitious goal of no emergency response. The next phase of the PRA analyses will involve a two-fold expansion of the PRA. First, as the design and analyses approach a greater level of detail, the assumptions used for the initial PRA will be reviewed and the models will be revised as needed to reflect the improved knowledge of the system design and performance. Furthermore, as the full plant design advances, the PRA will be expanded to incorporate risk associated with external challenges such as seismic and fire, and to address low power and shutdowns modes of operation. As with the initial work, the PRA will serve as a tool to

Regulation of renin secretion by renal juxtaglomerular cells

DEFF Research Database (Denmark)

Friis, Ulla G; Madsen, Kirsten; Stubbe, Jane

2013-01-01

A major rate-limiting step in the renin-angiotensin-aldosterone system is the release of active renin from endocrine cells (juxtaglomerular (JG) cells) in the media layer of the afferent glomerular arterioles. The number and distribution of JG cells vary with age and the physiological level...

PRA studies: results, insights and applications

International Nuclear Information System (INIS)

Levine, S.; Stetson, F.T.

1983-01-01

This paper deals with Probalistic Risk Assessment (PRA) studies and their results. The PRA is a combination of logic structures and analytical techniques that can be used to estimate the likelihood and consequences of events that have not been observed because of their low frequency occurrence. At first attitudes concerning PRA reports were controversial principally because of their new techniques and complex multidisciplinary nature. However these attitudes changed following the accident at Three Mile Island in 1979. Many people after this event came to appreciate the risks associated with the operation of nuclear power plants, and since the TMI accident there has been a rapid expansion, in the use of PRA in the US and other countries. (NEA) [fr

Effect of breed on plasma endothelin-1 concentration, plasma renin activity, and serum cortisol concentration in healthy dogs

DEFF Research Database (Denmark)

Höglund, K.; Lequarré, A.-S.; Ljungvall, I.

2016-01-01

BACKGROUND: There are breed differences in several blood variables in healthy dogs. OBJECTIVE: Investigate breed variation in plasma endothelin-1 (ET-1) concentration, plasma renin activity, and serum cortisol concentration. ANIMALS: Five-hundred and thirty-one healthy dogs of 9 breeds examined...... at 5 centers (2-4 breeds/center). METHODS: Prospective observational study. Circulating concentrations of ET-1 and cortisol, and renin activity, were measured using commercially available assays. Absence of organ-related or systemic disease was ensured by thorough clinical investigations, including...

PRA and Risk Informed Analysis

International Nuclear Information System (INIS)

Bernsen, Sidney A.; Simonen, Fredric A.; Balkey, Kenneth R.

2006-01-01

The Boiler and Pressure Vessel Code (BPVC) of the American Society of Mechanical Engineers (ASME) has introduced a risk based approach into Section XI that covers Rules for Inservice Inspection of Nuclear Power Plant Components. The risk based approach requires application of the probabilistic risk assessments (PRA). Because no industry consensus standard existed for PRAs, ASME has developed a standard to evaluate the quality level of an available PRA needed to support a given risk based application. The paper describes the PRA standard, Section XI application of PRAs, and plans for broader applications of PRAs to other ASME nuclear codes and standards. The paper addresses several specific topics of interest to Section XI. Important consideration are special methods (surrogate components) used to overcome the lack of PRA treatments of passive components in PRAs. The approach allows calculations of conditional core damage probabilities both for component failures that cause initiating events and failures in standby systems that decrease the availability of these systems. The paper relates the explicit risk based methods of the new Section XI code cases to the implicit consideration of risk used in the development of Section XI. Other topics include the needed interactions of ISI engineers, plant operating staff, PRA specialists, and members of expert panels that review the risk based programs

Aliskiren and valsartan combination therapy for the management of hypertension

Directory of Open Access Journals (Sweden)

Benjamin J Epstein

2010-08-01

Full Text Available Benjamin J EpsteinDepartments of Pharmacotherapy and Translational Research and Medicine, Colleges of Pharmacy and Medicine, University of Florida, Gainesville, Florida, USA and East Coast Institute for Research, Jacksonville, Florida, USAAbstract: Combination therapy is necessary for most patients with hypertension, and agents that inhibit the renin-angiotensin-aldosterone system (RAAS are mainstays in hypertension management, especially for patients at high cardiovascular and renal risk. Single blockade of the RAAS with an angiotensin-converting enzyme (ACE inhibitor or angiotensin receptor blocker (ARB confers some cardiorenal protection; however, these agents do not extinguish the RAAS as evidenced by a reactive increase in plasma renin activity (PRA, a cardiovascular risk marker, and incomplete cardiorenal protection. Dual blockade with an ACE inhibitor and an ARB offers no additional benefit in patients with hypertension and normal renal and left ventricular function. Indeed, PRA increases synergistically with dual blockade. Aliskiren, the first direct renin inhibitor (DRI to become available has provided an opportunity to study the merit of DRI/ARB combination treatment. By blocking the first and rate-limiting step in the RAAS, aliskiren reduces PRA by at least 70% and buffers the compensatory increase in PRA observed with ACE inhibitors and ARBs. The combination of a DRI and an ARB or an ACE inhibitor is an effective approach for lowering blood pressure; available data indicate that such combinations favorably affect proteinuria, left ventricular mass index, and brain natriuretic peptide in patients with albuminuria, left ventricular hypertrophy, and heart failure, respectively. Ongoing outcome studies will clarify the role of aliskiren and aliskiren-based combination RAAS blockade in patients with hypertension and those at high cardiorenal risk.Keywords: aliskiren, valsartan, single-pill combination, hypertension, renin

Interleukin-1 inhibits renin gene expression in As4.1 cells but not in native juxtaglomerular cells

DEFF Research Database (Denmark)

Jensen, B L; Lehle, U; Müller, Maja

1998-01-01

) cells and in the mouse tumor cell line As4.1, which expresses renin mRNA. Renin mRNA levels and secretion of active renin were not significantly changed by IL-1beta in native JG cells. Activation of adenylyl cyclase by forskolin increased renin secretion and renin mRNA levels three- and fivefold......, respectively. These stimulatory responses to forskolin were not altered by IL-1beta. In contrast to native JG cells, renin mRNA abundance was markedly suppressed by IL-1beta in As4.1 cells, whereas secretion of active renin and the stability of renin mRNA were not changed. In As4.1 cells forskolin did...... not change renin secretion or renin mRNA abundance in the absence or in the presence of IL-1beta. These findings suggest that IL-1beta has no direct influence on renin secretion and renin mRNA abundance at the level of native JG cells....

Potent radiolabeled human renin inhibitor, [3H]SR42128: enzymatic, kinetic, and binding studies to renin and other aspartic proteases

International Nuclear Information System (INIS)

Cumin, F.; Nisato, D.; Gagnol, J.P.; Corvol, P.

1987-01-01

The in vitro binding of [ 3 H]SR42128 (Iva-Phe-Nle-Sta-Ala-Sta-Arg), a potent inhibitor of human renin activity, to purified human renin and a number of other aspartic proteases was examined. SR42128 was found to be a competitive inhibitor of human renin, with a K/sub i/ of 0.35 nM at pH 5.7 and 2.0 nM at pH 7.4; it was thus more effective at pH 5.7 than at pH 7.4. Scatchard analysis of the interaction binding of [ 3 H]SR42128 to human renin indicated that binding was reversible and saturable at both pH 5.7 and pH 7.4. There was a single class of binding sites, and the K/sub D/ was 0.9 nM at pH 5.7 and 1 nM at pH 7.4. The association rate was 10 times more rapid at pH 5.7 than at pH 7.4, but there was no difference between the rates of dissociation of the enzyme-inhibitor complex at the two pHs. The effect of pH on the binding of [ 3 H]SR42128 to human renin, cathepsin D, pepsin, and gastricsin was also examined over the pH range 3-8. All the aspartic proteases had a high affinity for the inhibitor at low pH. However, at pH 7.4, [ 3 H]SR42128 was bound only to human renin and to none of the other aspartic proteases. Competitive binding studies with [ 3 H]SR42128 and a number of other inhibitors on human renin or cathepsin D were used to examine the relationships between structure and activity in these systems. The study as a whole indicates that pH plays a major role in the binding of [ 3 H]SR42128 to aspartic proteases and that the nature of the inhibitor residue reacting with the renin S 2 subsites is of critical importance for the specificity of the renin-inhibitor interaction

Practical PRA applications at Consumers Power Company

International Nuclear Information System (INIS)

Blanchard, D.P.

1985-01-01

Consumers Power Company has completed two probabilistic risk assessments (PRAs), one each at its Big Rock Point and Midland plants and is in the process of performing a third study at its Palisades Plant. Each PRA is summarized briefly in this paper. Each PRA has been used to evaluate specific plant design features and make operating and design recommendations to plant and Company management as well as to the regulator. This paper is a sumary of those issues on which Consumers Power Company has applied PRAs to date. The technique used in applying PRA to these issues has varied as more was learned about the plants from the PRA and about PRA itself. Some issue resolutions involved deriving technical arguments from small parts of the PRA only, such as the logic models or consequence analysis. Still others required use of the entire PRA including sequence quantification, plant and containment response, consequence analysis and eventually cost-benefit evaluation of proposed resolutions. The benefits derived from these analyses have also varied and include not only a perceived reduction in the risks associated with plant operation but also economic benefit to the Company in that cost-effective alternatives to resolving safety issues have been permitted

Standardized procedure for tsunami PRA by AESJ

International Nuclear Information System (INIS)

Kirimoto, Yukihiro; Yamaguchi, Akira; Ebisawa, Katsumi

2013-01-01

After Fukushima Accident (March 11, 2011), the Atomic Energy Society of Japan (AESJ) started to develop the standard of Tsunami Probabilistic Risk Assessment (PRA) for nuclear power plants in May 2011. As Japan is one of the countries with frequent earthquakes, a great deal of efforts has been made in the field of seismic research since the early stage. To our regret, the PRA procedures guide for tsunami has not yet been developed although the importance is held in mind of the PRA community. Accordingly, AESJ established a standard to specify the standardized procedure for tsunami PRA considering the results of investigation into the concept, the requirements that should have and the concrete methods regarding tsunami PRA referring the opinions of experts in the associated fields in December 2011 (AESJ-SC-RK004:2011). (author)

Probabilistic risk assessment (PRA) reference document. Final report

International Nuclear Information System (INIS)

Murphy, J.A.

1984-09-01

This document describes the current status of probabilistic risk assessment (PRA) as practiced in the nuclear reactor regulatory process. The PRA studies that have been completed or are under way are reviewed. The levels of maturity of the methodologies used in a PRA are discussed. Insights derived from PRAs are listed. The potential uses of PRA results for regulatory purposes are discussed. This document was issued for comment in February 1984 entitled Probabilistic Risk Assessment (PRA): Status Report and Guidance for Regulatory Application. The comments received on the draft have been considered for this final version of the report

Vanadate-induced inhibition of renin secretion is unrelated to inhibition Na,K-ATPase activity

Energy Technology Data Exchange (ETDEWEB)

Churchill, P.C.; Rossi, N.F.; Churchill, M.C.; Ellis, V.R. (Wayne State Univ. School of Medicine, Detroit, MI (USA))

1990-01-01

There is evidence that three inhibitors of Na,K-ATPase activity-ouabain, K-free extracellular fluid, and vanadate--inhibit renin secretion by increasing Ca{sup 2+} concentration in juxtaglomerular cells, but in the case of vanadate, it is uncertain whether the increase in Ca{sup 2+} is due to a decrease in Ca{sup 2+} efflux or to an increase in Ca{sup 2+} influx through potential operated Ca channels. In the present experiments, the rat renal cortical slice preparation was used to compare and contrast the effects of ouabain, of K-free fluid, and of vanadate on renin secretion, in the absence and presence of methoxyverapamil, A Ca channel blocker. Basal renin secretory rate averaged 7.7 {plus minus} 0.3 GU/g/60 min, and secretory rate was reduced to nearly zero by 1 mM ouabain, by K-free fluid, by 0.5 mM vanadate, and by K-depolarization. Although 0.5 {mu}M methoxyverapamil completely blocked the inhibitory effect of K-depolarization, it failed to antagonize the inhibitory effects of ouabain, of K-free fluid, and of vanadate.

Practical Application of PRA as an Integrated Design Tool for Space Systems

Science.gov (United States)

Kalia, Prince; Shi, Ying; Pair, Robin; Quaney, Virginia; Uhlenbrock, John

2013-01-01

This paper presents the application of the first comprehensive Probabilistic Risk Assessment (PRA) during the design phase of a joint NASA/NOAA weather satellite program, Geostationary Operational Environmental Satellite Series R (GOES-R). GOES-R is the next generation weather satellite primarily to help understand the weather and help save human lives. PRA has been used at NASA for Human Space Flight for many years. PRA was initially adopted and implemented in the operational phase of manned space flight programs and more recently for the next generation human space systems. Since its first use at NASA, PRA has become recognized throughout the Agency as a method of assessing complex mission risks as part of an overall approach to assuring safety and mission success throughout project lifecycles. PRA is now included as a requirement during the design phase of both NASA next generation manned space vehicles as well as for high priority robotic missions. The influence of PRA on GOES-R design and operation concepts are discussed in detail. The GOES-R PRA is unique at NASA for its early implementation. It also represents a pioneering effort to integrate risks from both Spacecraft (SC) and Ground Segment (GS) to fully assess the probability of achieving mission objectives. PRA analysts were actively involved in system engineering and design engineering to ensure that a comprehensive set of technical risks were correctly identified and properly understood from a design and operations perspective. The analysis included an assessment of SC hardware and software, SC fault management system, GS hardware and software, common cause failures, human error, natural hazards, solar weather and infrastructure (such as network and telecommunications failures, fire). PRA findings directly resulted in design changes to reduce SC risk from micro-meteoroids. PRA results also led to design changes in several SC subsystems, e.g. propulsion, guidance, navigation and control (GNC

Regulation of human renin expression in chorion cell primary cultures

International Nuclear Information System (INIS)

Duncan, K.G.; Haidar, M.A.; Baxter, J.D.; Reudelhuber, T.L.

1990-01-01

The human renin gene is expressed in the kidney, placenta, and several other sites. The release of renin or its precursor, prorenin, can be affected by several regulatory agents. In this study, primary cultures of human placental cells were used to examine the regulation of prorenin release and renin mRNA levels and of the transfected human renin promoter linked to chloramphenicol acetyltransferase reporter sequences. Treatment of the cultures with a calcium ionophore alone, calcium ionophore plus forskolin (that activates adenylate cyclase), or forskolin plus a phorbol ester increased prorenin release and renin mRNA levels 1.3 endash to 6 endash fold, but several classes of steroids did not affect prorenin secretion or renin RNA levels. These results suggest that (i) the first 584 base pairs of the renin gene 5'endash flanking DNA do not contain functional glucocorticoid or estrogen response elements, (ii) placental prorenin release and renin mRNA are regulated by calcium ion and by the combinations of cAMP with either C kinase or calcium ion, and (iii) the first 100 base pairs of the human renin 5'endash flanking DNA direct accurate initiation of transcription and can be regulated by cAMP. Thus, some control of renin release in the placenta (and by inference in other tissues) occurs via transcriptional influences on its promoter

The tsunami probabilistic risk assessment (PRA). Example of accident sequence analysis of tsunami PRA according to the standard for procedure of tsunami PRA for nuclear power plants

International Nuclear Information System (INIS)

Ohara, Norihiro; Hasegawa, Keiko; Kuroiwa, Katsuya

2013-01-01

After the Fukushima Daiichi nuclear power plant (NPP) accident, standard for procedure of tsunami PRA for NPP had been established by the Standardization Committee of AESJ. Industry group had been conducting analysis of Tsunami PRA for PWR based on the standard under the cooperation with electric utilities. This article introduced overview of the standard and examples of accident sequence analysis of Tsunami PRA studied by the industry group according to the standard. The standard consisted of (1) investigation of NPP's composition, characteristics and site information, (2) selection of relevant components for Tsunami PRA and initiating events and identification of accident sequence, (3) evaluation of Tsunami hazards, (4) fragility evaluation of building and components and (5) evaluation of accident sequence. Based on the evaluation, countermeasures for further improvement of safety against Tsunami could be identified by the sensitivity analysis. (T. Tanaka)

PRA -- Now that operators have it, what do they do with it?

International Nuclear Information System (INIS)

Rasmussen, M.A.; Kolo, R.J.

1996-01-01

Many utilities have had Probabilistic Risk Assessment (PRA) projects underway for several years in order to satisfy the NRC Generic Letter 88-20 requirement for an Individual Plant Examination, or IPE. Typically the studies have reached the conclusion that there are significant differences in the contribution of different plant components to preventing core damage should a major plant transient occur. How nuclear plant operators can use this knowledge to DECREASE the overall risk of performing the routine tasks of testing and maintenance is not an easy task. 10CFR50.65; ''The Maintenance Rule,'' requires that any plant maintenance performed with the unit on line be evaluated for risk. Byron Station will satisfy the 10CFR50.65 requirement by using PRA methodology to evaluate testing and maintenance activities performed with the unit at power. The challenge is to effectively use the results of PRA studies to aid in plant operations without having to make on shift plant operations personnel experts in PRA. At Byron, PRA is used to help build the weekly work schedules. Operations personnel tasked with reviewing the work schedule are the departmental experts on the use of the PRA results. The on shift SRO's role in implementing the program is to accurately execute and monitor the work week schedule as written, and to react to unforeseen equipment failures with an appropriate level of response. The response to such emergent work items is also predefined. Handling emergent work in a prescribed manner minimizes the overall risk to the unit and also eliminates the need to have PRA expertise available to make emergent work risk evaluations. Thus the on shift operators' required knowledge of PRA methods and intricacies is minimized. PRA is just another of the many tools used by the shift operator to run the plant in a safe, conservative manner

Observations on PRA and its applications

International Nuclear Information System (INIS)

Yeh, Y.-C.; Shieh, S.-L.

2004-01-01

An overview on the experience of PRA and its prospective application in Taiwan's three nuclear power plants is presented. Through the PRA, plant design improvements are performed and several engineering findings are illuminated. The sensitivity study including the internal, seismic, and typhoon events are conducted to justify items that can significantly reduce core meltdown risk. Its resulted plant betterment plans are thus highlighted accordingly. For PRA application, a risk-based inspection program for allocating inspection human resources has been resulted following the importance ranking of each component. The developing risk-based regulation to rationalize technical specification and maintenance program will also be entailed. To enhance the accuracy of the PRA model and its reproducibility, several issues are considered to have high priority for improvement such as external event data and analyses, uncertainty, common mode failure, human reliability, and the relative component importance. Highlight of their significance along with some typical sensitivity analyses are discussed for further investigation. (author)

Role of PRA in new NPP projects

International Nuclear Information System (INIS)

Julin, A.; Sandberg, J.; Virolainen, R.

2012-01-01

In Finland, a plant specific, Level 1 and 2 Probabilistic Risk Analysis (PRA) is required as a prerequisite for issuing the construction license and operating license. The use of PRA in various applications and the main insights are presented. These applications include e.g. PRA support to the design of SSCs (Systems, Structures and Components), definition of pre-service and in-service inspection programs, evaluation of the safety classification of SSCs, development of procedures, training and in definition of risk informed technical specifications, periodic testing and on-line preventive maintenance programs. In addition, PRA shall be used to assess the adequacy and coverage of the phase and system commissioning programs. Also the potential risks related to commissioning tests during nuclear test phase, shall be assessed with the help of PRA. In OL3 project, risk informed approach has been applied on a large scale for the first time in the design, construction and commissioning of a new NPP unit. Pre-nuclear commissioning tests have started at OL3 site and the plant is foreseen to begin commercial operation in 2013. Decisions have been made to launch new NPP projects. Teollisuuden Voima Oyj (TVO) is planning to build a new unit (OL4) at Olkiluoto site and a new utility, Fennovoima, is planning to build one unit at one of two alternative green field sites in Northern parts of Finland. Insights from PRAs of operating NPPs have been used in the evaluation of possible new sites to ensure that the site specific concerns and environmental conditions are adequately taken into account in the design of SSCs. Although the seismic activity at the Olkiluoto site is low, a comprehensive seismic risk analysis is being conducted. Its results support the review of the deterministic seismic design. For new sites, a probabilistic seismic hazard analysis has been carried out for the determination of the design earthquake. Experiences from OL3 licensing have been utilized in the

The aldo-keto reductase AKR1B7 coexpresses with renin without influencing renin production and secretion.

Science.gov (United States)

Machura, Katharina; Iankilevitch, Elina; Neubauer, Björn; Theuring, Franz; Kurtz, Armin

2013-03-01

On the basis of evidence that within the adult kidney, the aldo-keto reductase AKR1B7 (aldo-keto reductase family 1, member 7, also known as mouse vas deferens protein, MVDP) is selectively expressed in renin-producing cells, we aimed to define a possible role of AKR1B7 for the regulation and function of renin cells in the kidney. We could confirm colocalization and corecruitment of renin and of AKR1B7 in wild-type kidneys. Renin cells in AKR1B7-deficient kidneys showed normal morphology, numbers, and intrarenal distribution. Plasma renin concentration (PRC) and renin mRNA levels of AKR1B7-deficient mice were normal at standard chow and were lowered by a high-salt diet directly comparable to wild-type mice. Treatment with a low-salt diet in combination with an angiotensin-converting enzyme inhibitor strongly increased PRC and renin mRNA in a similar fashion both in AKR1B7-deficient and wild-type mice. Under this condition, we also observed a strong retrograde recruitment of renin-expressing cell along the preglomerular vessels, however, without a difference between AKR1B7-deficient and wild-type mice. The isolated perfused mouse kidney model was used to study the acute regulation of renin secretion by ANG II and by perfusion pressure. Regarding these parameters, no differences were observed between AKR1B7-deficient and wild-type kidneys. In summary, our data suggest that AKR1B7 is not of major relevance for the regulation of renin production and secretion in spite of its striking coregulation with renin expression.

Estrogen and progesterone receptors have distinct roles in the establishment of the hyperplastic phenotype in PR-A transgenic mice

Energy Technology Data Exchange (ETDEWEB)

Simian, Marina; Bissell, Mina J.; Barcellos-Hoff, Mary Helen; Shyamala, Gopalan

2009-05-11

Expression of the A and B forms of progesterone receptor (PR) in an appropriate ratio is critical for mammary development. Mammary glands of PR-A transgenic mice, carrying an additional A form of PR as a transgene, exhibit morphological features associated with the development of mammary tumors. Our objective was to determine the roles of estrogen (E) and progesterone (P) in the genesis of mammary hyperplasias/preneoplasias in PR-A transgenics. We subjected PR-A mice to hormonal treatments and analyzed mammary glands for the presence of hyperplasias and used BrdU incorporation to measure proliferation. Quantitative image analysis was carried out to compare levels of latency-associated peptide and transforming growth factor beta 1 (TGF{beta}1) between PR-A and PR-B transgenics. Basement membrane disruption was examined by immunofluorescence and proteolytic activity by zymography. The hyperplastic phenotype of PR-A transgenics is inhibited by ovariectomy, and is reversed by treatment with E + P. Studies using the antiestrogen ICI 182,780 or antiprogestins RU486 or ZK 98,299 show that the increase in proliferation requires signaling through E/estrogen receptor alpha but is not sufficient to give rise to hyperplasias, whereas signaling through P/PR has little impact on proliferation but is essential for the manifestation of hyperplasias. Increased proliferation is correlated with decreased TGF{beta}1 activation in the PR-A transgenics. Analysis of basement membrane integrity showed loss of laminin-5, collagen III and collagen IV in mammary glands of PR-A mice, which is restored by ovariectomy. Examination of matrix metalloproteases (MMPs) showed that total levels of MMP-2 correlate with the steady-state levels of PR, and that areas of laminin-5 loss coincide with those of activation of MMP-2 in PR-A transgenics. Activation of MMP-2 is dependent on treatment with E and P in ovariectomized wild-type mice, but is achieved only by treatment with P in PR-A mice. These data

Giant renin secretory granules in beige mouse renal afferent arterioles

DEFF Research Database (Denmark)

Jensen, B L; Rasch, Ruth; Nyengaard, Jens Randel

1997-01-01

The mutant beige mouse (C57BL/6 bg) has a disease characterised by abnormally enlarged cytoplasmic granules in a variety of cells. With the purpose of establishing a suitable cellular model for studying renin secretion, the present study was undertaken to compare renin granule morphology in beige...... (average granular volume 0.681 microm3), whereas 1-2 large granules were present per cell in beige mice. The volume of afferent arteriole that contained secretory granules was lower in the beige mice. We conclude that the beige mouse synthesizes, stores and releases active renin. Renin secretory granules...... in beige mice are grossly enlarged with 1-2 granules per juxtaglomerular cell. Compared with control mice, a similar amount of total renin granule volume per afferent arteriole is contained in a smaller part of beige mouse afferent arteriole. Granular cells from beige mice could therefore be a valuable...

Use of PRA in Shuttle Decision Making Process

Science.gov (United States)

Boyer, Roger L.; Hamlin, Teri L.

2010-01-01

How do you use PRA to support an operating program? This presentation will explore how the Shuttle Program Management has used the Shuttle PRA in its decision making process. It will reveal how the PRA has evolved from a tool used to evaluate Shuttle upgrades like Electric Auxiliary Power Unit (EAPU) to a tool that supports Flight Readiness Reviews (FRR) and real-time flight decisions. Specific examples of Shuttle Program decisions that have used the Shuttle PRA as input will be provided including how it was used in the Hubble Space Telescope (HST) manifest decision. It will discuss the importance of providing management with a clear presentation of the analysis, applicable assumptions and limitations, along with estimates of the uncertainty. This presentation will show how the use of PRA by the Shuttle Program has evolved overtime and how it has been used in the decision making process providing specific examples.

Study on the dynamic changes of the renin angiotensin system (RAS) in patients with acute pancreatitis

International Nuclear Information System (INIS)

An Yuliang; Zhou Li

2002-01-01

Objective: To assess the severity of acute pancreatitis (AP) by observing the changes of the plasma renin activity (PRA) and plasma angiotensin-II levels in those patients. Methods: Plasma concentrations of the PRA and AGT-II were determined with RIA in patients with severe acute pancreatitis (SAP), mild acute pancreatitis (MAP), acute cholecystitis (AC), acute appendicitis (AA), acute phase of peptic ulcer (PU, only AGT-II was measured) and in healthy controls (HC). In SAP and MAP patients, a second determination was done. Results: The plasma levels of the PRA and AGT-II within 24 hours after admission were 3.84 ±1.92 ng/ml·h, 386.68 ±178.53 pg/ml in SAP. A group; 1.88 ± 0.93 ng/ml·h, 142.68 ± 83.57 pg/ml in MAP. A group; 0.68 ±0.45 ng/ml·h, 43.51 ± 31.04 pg/ml in HC group. These variables are significantly higher in SAP. A and MAP. A groups than those in other groups. During the recovery period, they were 1.34 ± 0.76 ng/ml·h, 44.71 ± 27.93 pg/ml in SAP. R group, and 1.18 ± 0.69 ng/ml·h, 41.82 ± 17.88 pg/ml in MAP. R group. There were significant differences (p < 0.05) when comparing the SAP. A group with MAP. A group, and comparing HC group with SAP. A group and with MAP. A group respectively. The paired compartment of the AP (SAP. R/SAP. A and MAP. R/MAP. A) are also significantly differences (p < 0.05). For the same group of AP patients at different stage (SAP. R/SAP. A and MAP. R/MAP. A) those were also significant difference (p < 0.05 ). There are also significant (p < 0.05) difference comparing those values in SAP. A and MAP. A group with the AC, AA and PU group respectively. Conclusion: 1. RAAS are activated in patients with AP on account of the circulatory hypovolemia with various causes. The degree of activation is positively correlated to the seriousness of the disease process. Increase of the plasma level of AGT-II in patients with AP is a compensatory mechanism but it exacerbates the microcirculation impediment of the pancreas

Radioimmunoassay of renin in human renal tissues

International Nuclear Information System (INIS)

Wowra, B.

1981-01-01

A method has been developed to quantitatively determine renin in human kidney tissue. The angiotensin I split off angiotensinogs by renin was radioimmunologically determined. The renin-renin substrate reaction rate followed a saturation kinetics, as it increased the larger the substrate content in the incubation medium until it acquired a maximum value; the reaction rate decreased with substrate concentrations over 40 mg/ml incubation medium. The discontinuance of the renin reaction after incubation by adding acid, boiling and neutralizing again, gave highest renin values. The RIA scattering was 8.3% for double determination of the same sample, for the determination in different RIA additions 7.0%. The detection limit was 20 pg angiotensin I. A direct comparison of radioimmunoassay and bioassay exhibited a very significant agreement of both methods, where the radioimmunologically measured renin values were on average four times larger than those obtained using biological technique. The definition of the so-called normal values for absolute and specific renin concentration in human kidney tissue enabled one to assess the renin values in various syndromes. (orig./MG) [de

Radioimmunoassay of renin-angiotensin-aldosterone in patients with adrenal tumors

International Nuclear Information System (INIS)

Slavnov, V.N.; Yakovlev, A.A.; Yugrinov, O.G.; Gandzha, T.I.

1983-01-01

The results are presented of a study of the renin-angiotensin-aldosterone system in 89 patients with aldosteronoma, corticosteroma, pheochromocytoma and hypertension. Radioimmunoassay was used to measure aldosterone concentration and renin activity in the peripheral blood and blood from vena cava inferior, the renal and adrenal veins, the circadian cycle of their content and the responsiveness of the glomerular zone of the adrenal cortex and the juxtaglomerular renal system under the influence of lasix intake and the change over from a horizontal into vertical position. Patients with adrenal tumors have shown disorders of renin-angiotensin-aldosterone function. Radioimmunoassay of the renin-angiotensin-aldosterone system promotes early detection of adrenal tumors in the general population of patients with hypertension and can be used for control over therapeutic efficacy

Methodologic issues in the measurement of urinary renin

NARCIS (Netherlands)

L.C.W. Roksnoer (Lodi); K. Verdonk (Koen); I.M. Garrelds (Ingrid); J.M. van Gool (Jeanette); R. Zietse (Bob); E.J. Hoorn (Ewout); A.H.J. Danser (Jan)

2014-01-01

textabstractBackground and objectives Alge et al. recently reported that urinary renin may be a prognostic biomarker for AKI after cardiac surgery. However, their urinary renin levels far exceeded published plasma renin levels, whereas normally, urinary renin is,10%of plasma renin. This result

Reno-Cerebral Reflex Activates the Renin-Angiotensin System, Promoting Oxidative Stress and Renal Damage After Ischemia-Reperfusion Injury.

Science.gov (United States)

Cao, Wei; Li, Aiqing; Li, Jiawen; Wu, Chunyi; Cui, Shuang; Zhou, Zhanmei; Liu, Youhua; Wilcox, Christopher S; Hou, Fan Fan

2017-09-01

A kidney-brain interaction has been described in acute kidney injury, but the mechanisms are uncertain. Since we recently described a reno-cerebral reflex, we tested the hypothesis that renal ischemia-reperfusion injury (IRI) activates a sympathetic reflex that interlinks the renal and cerebral renin-angiotensin axis to promote oxidative stress and progression of the injury. Bilateral ischemia-reperfusion activated the intrarenal and cerebral, but not the circulating, renin-angiotensin system (RAS), increased sympathetic activity in the kidney and the cerebral sympathetic regulatory regions, and induced brain inflammation and kidney injury. Selective renal afferent denervation with capsaicin or renal denervation significantly attenuated IRI-induced activation of central RAS and brain inflammation. Central blockade of RAS or oxidative stress by intracerebroventricular (ICV) losartan or tempol reduced the renal ischemic injury score by 65% or 58%, respectively, and selective renal afferent denervation or reduction of sympathetic tone by ICV clonidine decreased the score by 42% or 52%, respectively (all p renal damage and dysfunction persisted after controlling blood pressure with hydralazine. This study uncovered a novel reflex pathway between ischemic kidney and the brain that sustains renal oxidative stress and local RAS activation to promote ongoing renal damage. These data suggest that the renal and cerebral renin-angiotensin axes are interlinked by a reno-cerebral sympathetic reflex that is activated by ischemia-reperfusion, which contributes to ischemia-reperfusion-induced brain inflammation and worsening of the acute renal injury. Antioxid. Redox Signal. 27, 415-432.

2C.07: INVOLVEMENT OF THE RENIN-ANGIOTENSIN SYSTEM IN A PREMATURE AGING MOUSE MODEL.

Science.gov (United States)

Van Thiel, B S; Ridwan, Y; Garrelds, I M; Vermeij, M; Groningen, M C Clahsen-Van; Danser, A H J; Essers, J; Van Der Pluijm, I

2015-06-01

Changes in the renin-angiotensin system (RAS), known for its critical role in the regulation of blood pressure and sodium homeostasis, may contribute to aging and age-related diseases. Here we characterized the RAS and kidney pathology in mice with genomic instability due to a defective nucleotide excision repair gene (Ercc1d/- mice). These mice display premature features of aging, including vascular dysfunction. Studies were performed in male and female Ercc1d/- mice and their wild type controls (Ercc1+/+) at the age of 12 or 18 weeks before and after treatment with losartan. The renin-activatable near-infrared fluorescent probe ReninSense 680™ was applied in vivo to allow non-invasive imaging of renin activity. Plasma renin concentrations (PRC) were additionally measured ex vivo by quantifying Ang I generation in the presence of excess angiotensinogen. Kidneys were harvested and examined for markers of aging, and albumin was determined in urine. Kidneys of 12-week old Ercc1d/- mice showed signs of aging, including tubular anisokaryosis, cell-senescence and increased apoptosis. This was even more pronounced at the age of 18 weeks. Yet, urinary albumin was normal at 12 weeks. The ReninSense 680™ probe showed increased intrarenal renin activity in Ercc1d/- mice versus Ercc1+/+ mice, both at 12 and 18 weeks of age, while PRC in these mice tended to be lower compared to Ercc1+/+ mice. Renin was higher in male than female mice, both in the kidney and in plasma, and losartan increased kidney and plasma renin in both Ercc1d/- and Ercc1+/+ mice. Rapidly aging Ercc1d/- mice display an activated intrarenal RAS, as evidenced by the increased fluorescence detected with the ReninSense 680™ probe. This increased RAS activity may contribute to the disturbed kidney pathology in these mice. The increased intrarenal activity detected with the ReninSense 680™ probe in male vs. female mice, as well as after losartan treatment, are in full agreement with the literature, and

Studies on renin release in vitro

DEFF Research Database (Denmark)

Skøtt, O

1989-01-01

1) Measurements of renin secretion from single arterioles at time intervals down to 20 seconds showed that the renin secretion is episodic, the amount of renin released during each episode corresponding to the estimated content of one secretory granule. 2) A decrease in osmolality elicits episodi...

Direct renin inhibition in chronic kidney disease

DEFF Research Database (Denmark)

Persson, Frederik; Rossing, Peter; Parving, Hans-Henrik

2013-01-01

that renin inhibition could hold potential for improved treatment in patients with chronic kidney disease, with diabetic nephropathy as an obvious group of patients to investigate, as the activity of the renin-angiotensin-aldosterone system is enhanced in these patients and as there is an unmet need....... In addition, combination treatment seemed safe and effective also in patients with impaired kidney function. These initial findings formed the basis for the design of a large morbidity and mortality trial investigating aliskiren as add-on to standard treatment. The study has just concluded, but was terminated...... early as a beneficial effect was unlikely and there was an increased frequency of side effects. Also in non-diabetic kidney disease a few intervention studies have been carried out, but there is no ongoing hard outcome study. In this review we provide the current evidence for renin inhibition in chronic...

PRA: A Perspective on Strengths, Current Limitations, And Possible Improvements

International Nuclear Information System (INIS)

Mosleh, Ail

2014-01-01

Probabilistic risk assessment (PRA) has been used in various technological fields to assist regulatory agencies, managerial decision makers, and systems designers in assessing and mitigating the risks inherent in these complex arrangements. Has PRA delivered on its promise? How do we gage PRA performance? Are our expectations about value of PRA realistic? Are there disparities between what we get and what we think we are getting form PRA and its various derivatives? Do current PRAs reflect the knowledge gained from actual events? How do we address potential gaps? These are some of the questions that have been raised over the years since the inception of the field more than forty years ago. This paper offers a brief assessment of PRA as a technical discipline in theory and practice, its key strengths and weaknesses, and suggestions on ways to address real and perceived shortcomings

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism.

Science.gov (United States)

Kobori, H; Ichihara, A; Suzuki, H; Takenaka, T; Miyashita, Y; Hayashi, M; Saruta, T

1997-08-01

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

PRA: A PERSPECTIVE ON STRENGTHS, CURRENT LIMITATIONS, AND POSSIBLE IMPROVEMENTS

Directory of Open Access Journals (Sweden)

ALI MOSLEH

2014-02-01

Full Text Available Probabilistic risk assessment (PRA has been used in various technological fields to assist regulatory agencies, managerial decision makers, and systems designers in assessing and mitigating the risks inherent in these complex arrangements. Has PRA delivered on its promise? How do we gage PRA performance? Are our expectations about value of PRA realistic? Are there disparities between what we get and what we think we are getting form PRA and its various derivatives? Do current PRAs reflect the knowledge gained from actual events? How do we address potential gaps? These are some of the questions that have been raised over the years since the inception of the field more than forty years ago. This paper offers a brief assessment of PRA as a technical discipline in theory and practice, its key strengths and weaknesses, and suggestions on ways to address real and perceived shortcomings.

Management and Organization Influences in PRA

International Nuclear Information System (INIS)

Gertman, D.I.; Hallbert, B. P.; Blackman, H. S.

1998-01-01

The authors present a research program which aimed at increasing the quality of comprehensiveness of contemporary PRA (Probability Risk Assessment) by providing a tool that allows for incorporating M and O in PRA, at improving the quality of NRC assessments, at conducting research to support the risk informed regulation process, at identifying impact of management and organization, safety culture, workplace environment, down-sizing and deregulation on human performance and reliability

76 FR 81998 - Methodology for Low Power/Shutdown Fire PRA

Science.gov (United States)

2011-12-29

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0295] Methodology for Low Power/Shutdown Fire PRA AGENCY..., ``Methodology for Low Power/Shutdown Fire PRA--Draft Report for Comment.'' DATES: Submit comments by March 01... risk assessment (PRA) method for quantitatively analyzing fire risk in commercial nuclear power plants...

Effects of Intrarenal and Intravenous Infusion of the Phosphodiesterase 3 Inhibitor Milrinone on Renin Secretion

Science.gov (United States)

Kumagai, Kazuhiro; Reid, Ian A.

1994-01-01

We have reported that administration of the phosphodiesterase III inhibitor milrinone increases renin secretion in conscious rabbits. The aim of the present study was to determine if the increase in renin secretion results from a direct renal action of milrinone, or from an indirect extrarenal effect of the drug. This was accomplished by comparing the effects of intrarenal and intravenous infusion of graded doses of milrinone on plasma renin activity in unilaterally nephrectomized conscious rabbits. Milrinone was infused into the renal artery in doses of 0.01, 0.1 and 1.0 micro-g/kg/min, and intravenously in the same rabbits in doses of 0.01, 0.1, 1.0 and 10 micro-g/kg/min. Each dose was infused for 15 min. No intrarenal dose of milrinone altered plasma renin activity or arterial pressure, although at the highest dose, there was a small increase in heart rate. Intravenous infusion of milrinone at 1.0 micro-g/kg/min increased plasma renin activity to 176 +/- 55% of the control value (P less than 0.05). Heart rate increased but arterial pressure did not change. Intravenous infusion of milrinone at 1O micro-g/kg/min increased plasma renin activity to 386 +/- 193% of control in association with a decrease in arterial pressure and an increase in heart rate. These results confirm that milrinone increases renin secretion, and indicate that the stimulation is due to an extrarenal effect of the drug.

PRA-Code Upgrade to Handle a Generic Problem

International Nuclear Information System (INIS)

Wilson, J. R.

1999-01-01

During the probabilistic risk assessment (PRA) for the proposed Yucca Mountain nuclear waste repository, a problem came up that could not be handled by most PRA computer codes. This problem deals with dependencies between sequential events in time. Two similar scenarios that illustrate this problem are LOOP nonrecovery and sequential wearout failures with units of time. The purpose of this paper is twofold: To explain the problem generically, and to show how the PRA code at the INEEL, SAPHIRE, has been modified to solve this problem correctly

The role of the renin-angiotensin-aldosterone system in heart failure

Directory of Open Access Journals (Sweden)

Thomas Unger

2004-03-01

Full Text Available Activity of the renin-angiotensin-aldosterone system (RAAS is increased in patients with heart failure, and its maladaptive mechanisms may lead to adverse effects such as cardiac remodelling and sympathetic activation. Elevated renin activity has been demonstrated in patients with dilated cardiomyopathy. (Third-generation synthetic non-peptide renin inhibitors, with more favourable properties than earlier renin inhibitors, lower ambulatory blood pressure and may have a role to play in other cardiovascular disease. Chymase, a protease inhibitor stored in mast cells that generates angiotensin II (Ang II (in addition to angiotensin-converting enzyme [ACE], has been linked to extracellular matrix remodelling in heart failure. Again, chymase inhibitors have been developed to investigate its functions in vitro and in vivo. Bradykinin is thought to contribute to the cardioprotective effect of ACE inhibition through modification of nitric oxide release, calcium handling and collagen accumulation. Ang II is believed to influence a number of molecular and structural changes in the heart, mostly mediated through the AT1-receptor. The importance of the RAAS in heart failure is shown by the survival benefit conferred by treatment with ACE inhibitors.

Genetic variation and activity of the renin-angiotensin system and severe hypoglycemia in type 1 diabetes

DEFF Research Database (Denmark)

Pedersen-Bjergaard, U.; Dhamrait, S.S.; Sethi, A.A.

2008-01-01

BACKGROUND: The deletion-allele of the angiotensin-converting enzyme (ACE) gene and elevated ACE activity are associated with increased risk of severe hypoglycemia in type 1 diabetes. We explored whether genetic and phenotypic variations in other components of the renin-angiotensin system...... are similarly associated. METHODS: Episodes of severe hypoglycemia were recorded in 171 consecutive type 1 diabetic outpatients during a 1-year follow-up. Participants were characterized at baseline by gene polymorphisms in angiotensinogen, ACE, angiotensin-II receptor types 1 (AT1R) and 2 (AT2R), and by plasma...... associate with high risk of severe hypoglycemia in type 1 diabetes. A potential preventive effect of renin-angiotensin system blocking drugs in patients with recurrent severe hypoglycemia merits further investigation Udgivelsesdato: 2008/3...

77 FR 10576 - Methodology for Low Power/Shutdown Fire PRA

Science.gov (United States)

2012-02-22

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0295] Methodology for Low Power/Shutdown Fire PRA AGENCY.../Shutdown Fire PRA.'' In response to request from members of the public, the NRC is extending the public... risk assessment (PRA) method for quantitatively analyzing fire risk in commercial nuclear power plants...

Individual plant examination and future PRA applications

International Nuclear Information System (INIS)

Monty, B.S.; Sursock, J.P.; Thierry, R.J.

1992-01-01

PRA is being used in many areas of plant operation as has been demonstrated in previous studies. With the U.S. NRC's emphasis on the use of risk to identify plant vulnerabilities and the development of plant specific PRA models for all plants, it is expected that the use of PRA will be expanded. Key areas where this is expected to occur include the development of risk-based Technical Specifications, risk management, and risk-centered maintenance programs. This paper focuses on the Individual Plant Examination requirement and the possible uses of risk-based methods in controlling plant operation to enhance plant safety and availability, and how the IPE requirement will potentially further this area of development. (orig./DG)

PRA (Probabilistic Risk Assessments) Participation versus Validation

Science.gov (United States)

DeMott, Diana; Banke, Richard

2013-01-01

Probabilistic Risk Assessments (PRAs) are performed for projects or programs where the consequences of failure are highly undesirable. PRAs primarily address the level of risk those projects or programs posed during operations. PRAs are often developed after the design has been completed. Design and operational details used to develop models include approved and accepted design information regarding equipment, components, systems and failure data. This methodology basically validates the risk parameters of the project or system design. For high risk or high dollar projects, using PRA methodologies during the design process provides new opportunities to influence the design early in the project life cycle to identify, eliminate or mitigate potential risks. Identifying risk drivers before the design has been set allows the design engineers to understand the inherent risk of their current design and consider potential risk mitigation changes. This can become an iterative process where the PRA model can be used to determine if the mitigation technique is effective in reducing risk. This can result in more efficient and cost effective design changes. PRA methodology can be used to assess the risk of design alternatives and can demonstrate how major design changes or program modifications impact the overall program or project risk. PRA has been used for the last two decades to validate risk predictions and acceptability. Providing risk information which can positively influence final system and equipment design the PRA tool can also participate in design development, providing a safe and cost effective product.

Summary of PRA assessment of transient accident risks, human factors considerations, and PRA methods and applications

International Nuclear Information System (INIS)

Carnino, A.

1984-01-01

This chapter reviews the progress made in the probabilistic risk assessment (PRA) area to help in solving operational transient problems and to integrate human factors considerations, as discussed at the American Nuclear Society Topical Meeting on Anticipated and Abnormal Plant Transients in Light Water Reactors. Topics considered include core-melt frequency, external events (e.g., fires, floods), diagnostic errors, and operator aids. It is concluded that confidence in PRA results, predictions and uses for decisions in both the safety of the plants and their availability will improve

The Angra 1 fire PRA project

International Nuclear Information System (INIS)

Silva, Luiz E. Massiere de C.; Kassawara, Robert

2009-01-01

The Angra 1 Fire PRA (Probabilistic Risk Assessment) is under development by ELETRONUCLEAR jointly with EPRI (Electric Power Research Institute). The project was started January of 2007 and it is foreseen to be finished in the middle of the next year. The study is being conducted according to the newest methodology developed by EPRI and NRC/RES (U.S. Nuclear Regulatory Commission - Office of Regulatory Research) published in 2005 as Fire PRA Methodology for Nuclear Power Facilities (NUREG/CR-6850 or EPRI TR-1011989) [1]. Starting from the Internal Events Angra 1 PRA model Level 1 the project aims to be a comprehensive plant-specific fire analysis to identify the possible consequences of a fire in the plant vital areas which threaten the integrity of systems relevant to the safety, challenging the safety functions and representing a risk of accident that can lead to a core damage. The main tasks include the plant boundary and partitioning, the fire PRA component selection and the identification of the possible fire scenarios (ignition, propagation, detection, extinction and hazards) considering human failure events to establish the fire-induced risk model for quantification of the risk for nuclear core damage taking into account the plant design and its fire protection resources. This work presents a general discussion on the methodology applied to the completed steps of the project. (author)

Constellation Probabilistic Risk Assessment (PRA): Design Consideration for the Crew Exploration Vehicle

Science.gov (United States)

Prassinos, Peter G.; Stamatelatos, Michael G.; Young, Jonathan; Smith, Curtis

2010-01-01

Managed by NASA's Office of Safety and Mission Assurance, a pilot probabilistic risk analysis (PRA) of the NASA Crew Exploration Vehicle (CEV) was performed in early 2006. The PRA methods used follow the general guidance provided in the NASA PRA Procedures Guide for NASA Managers and Practitioners'. Phased-mission based event trees and fault trees are used to model a lunar sortie mission of the CEV - involving the following phases: launch of a cargo vessel and a crew vessel; rendezvous of these two vessels in low Earth orbit; transit to th$: moon; lunar surface activities; ascension &om the lunar surface; and return to Earth. The analysis is based upon assumptions, preliminary system diagrams, and failure data that may involve large uncertainties or may lack formal validation. Furthermore, some of the data used were based upon expert judgment or extrapolated from similar componentssystemsT. his paper includes a discussion of the system-level models and provides an overview of the analysis results used to identify insights into CEV risk drivers, and trade and sensitivity studies. Lastly, the PRA model was used to determine changes in risk as the system configurations or key parameters are modified.

Different antihypertensive effect of beta-blocking drugs in low and normal-high renin hypertension.

Science.gov (United States)

Kralberg, B E; Tolagen, K

1976-05-31

The treatment response to beta-adrenoceptor blocking drugs was compared in two groups of patients with primary (essential) hypertension and different renin levels. Each group consisted of 25 patients and was equally distributed regarding age, severity and stage of hypertension. In the first group (group 1), the mean upright plasma renin activity was 0.8 ng ml-1h-1 (range 0.3 to 1.5) and the patients were considered to have low renin hypertension. In the other group (group 2) the patients had a mean plasma renin activity of 2.1 ng ml-1h-1 (range 1.1 to 5.1) and were considered to have normal to high renin hypertension. In both groups the patients were initially treated with beta-blocking drugs; in group 1 with a beta-blocker corresponding to an average dose of 311 mg propranolol a day for at least eight weeks and in group 2 with propranolol 320 mg a day in a fixed dose for eight weeks. The hypotensive response differed significantly between the two groups (p less than 0.001). In group 1 the pretreatment blood pressure was 197/117 mm Hg supine and 198/120 mm Hg standing. During treatment blood pressure decreased only 5/3 mm Hg supine and 9/5 mm Hg standing. The pretreatment blood pressure in group 2 was 187/114 mm Hg supine and 186/117 mm Hg standing. Beta-blocking therapy reduced blood pressure 36/23 and 34/18 mm Hg, respectively (both p less than 0.001). Pulse rates fell significantly in the two groups, both in the lying and standing positions. In 17 patients with low renin hypertension (group 1), a volume-depleting drug was added (spironolactone, 14 patients; thiazides, 3 patients) and this achieved a marked fall in blood pressure levels of 38/16 mm Hg supine and 37/19 mm Hg standing (both p less than 0.001). These results suggest the following: (1) Most patients with normal to high plasma renin activity respond well to moderate doses of propranolol. (2) Propranolol given in the same doses is almost without antihypertensive effect in patients with low renin

How the chemical industry can benefit from PRA

International Nuclear Information System (INIS)

Guymer, P.; Kaiser, G.D.; Mc Kelvey, T.W.; Hannaman, G.W.

1986-01-01

Probabilistic Risk Assessment (PRA) is a method of quantifying the frequency of occurrence and the magnitude of the consequences of accidents in systems that contain hazardous materials such as radioactive fission products, and toxic, flammable or explosive chemicals. The frequency and the magnitude of the consequences are the basic elements of any definition or risk, which is often simply expressed as the product of frequency and magnitude, summed over all accident sequences. PRA is now a mature technique that has been used to estimate risk for a number of industrial facilities. In this paper the author gives examples of beneficial uses of PRA

Urinary Angiotensinogen and Renin Excretion are Associated with Chronic Kidney Disease

Directory of Open Access Journals (Sweden)

Annett Juretzko

2017-04-01

Full Text Available Background/Aims: Several studies sought to identify new biomarkers for chronic kidney disease (CKD. As the renal renin-angiotensin system is activated in CKD, urinary angiotensinogen or renin excretion may be suitable candidates. We tested whether urinary angiotensinogen or renin excretion is elevated in CKD and whether these parameters are associated with estimated glomerular filtration rate (eGFR. We further tested whether urinary angiotensinogen or renin excretion may convey additional information beyond that provided by albuminuria. Methods: We measured urinary and plasma angiotensinogen, renin, albumin and creatinine in 177 CKD patients from the Greifswald Approach to Individualized Medicine project and in 283 healthy controls from the Study of Health in Pomerania. The urinary excretion of specific proteins is given as protein-to-creatinine ratio. Receiver operating characteristic (ROC curves, spearman correlation coefficients and linear regression models were calculated. Results: Urinary angiotensinogen [2,511 (196-31,909 vs. 18.6 (8.3-44.0 pmol/g, *P<0.01] and renin excretion [0.311 (0.135-1.155 vs. 0.069 (0.045-0.148 pmol/g, *P<0.01] were significantly higher in CKD patients than in healthy controls. The area under the ROC curve was significantly larger when urinary angiotensinogen, renin and albumin excretion were combined than with urinary albumin excretion alone. Urinary angiotensinogen (ß-coefficient -2.405, standard error 0.117, P<0.01 and renin excretion (ß-coefficient -0.793, standard error 0.061, P<0.01 were inversely associated with eGFR. Adjustment for albuminuria, age, sex, systolic blood pressure and body mass index did not significantly affect the results. Conclusion: Urinary angiotensinogen and renin excretion are elevated in CKD patients. Both parameters are negatively associated with eGFR and these associations are independent of urinary albumin excretion. In CKD patients urinary angiotensinogen and renin excretion may

Urinary Angiotensinogen and Renin Excretion are Associated with Chronic Kidney Disease.

Science.gov (United States)

Juretzko, Annett; Steinbach, Antje; Hannemann, Anke; Endlich, Karlhans; Endlich, Nicole; Friedrich, Nele; Lendeckel, Uwe; Stracke, Sylvia; Rettig, Rainer

2017-01-01

Several studies sought to identify new biomarkers for chronic kidney disease (CKD). As the renal renin-angiotensin system is activated in CKD, urinary angiotensinogen or renin excretion may be suitable candidates. We tested whether urinary angiotensinogen or renin excretion is elevated in CKD and whether these parameters are associated with estimated glomerular filtration rate (eGFR). We further tested whether urinary angiotensinogen or renin excretion may convey additional information beyond that provided by albuminuria. We measured urinary and plasma angiotensinogen, renin, albumin and creatinine in 177 CKD patients from the Greifswald Approach to Individualized Medicine project and in 283 healthy controls from the Study of Health in Pomerania. The urinary excretion of specific proteins is given as protein-to-creatinine ratio. Receiver operating characteristic (ROC) curves, spearman correlation coefficients and linear regression models were calculated. Urinary angiotensinogen [2,511 (196-31,909) vs. 18.6 (8.3-44.0) pmol/g, *P<0.01] and renin excretion [0.311 (0.135-1.155) vs. 0.069 (0.045-0.148) pmol/g, *P<0.01] were significantly higher in CKD patients than in healthy controls. The area under the ROC curve was significantly larger when urinary angiotensinogen, renin and albumin excretion were combined than with urinary albumin excretion alone. Urinary angiotensinogen (ß-coefficient -2.405, standard error 0.117, P<0.01) and renin excretion (ß-coefficient -0.793, standard error 0.061, P<0.01) were inversely associated with eGFR. Adjustment for albuminuria, age, sex, systolic blood pressure and body mass index did not significantly affect the results. Urinary angiotensinogen and renin excretion are elevated in CKD patients. Both parameters are negatively associated with eGFR and these associations are independent of urinary albumin excretion. In CKD patients urinary angiotensinogen and renin excretion may convey additional information beyond that provided by

Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels

Directory of Open Access Journals (Sweden)

Zhen-Ye Zhang

2017-09-01

Full Text Available Large-conductance calcium-activated potassium channels (BK channels belong to a family of Ca2+-sensitive voltage-dependent potassium channels and play a vital role in various physiological activities in the human body. The renin-angiotensin-aldosterone system is acknowledged as being vital in the body's hormone system and plays a fundamental role in the maintenance of water and electrolyte balance and blood pressure regulation. There is growing evidence that the renin-angiotensin-aldosterone system has profound influences on the expression and bioactivity of BK channels. In this review, we focus on the molecular mechanisms underlying the regulation of BK channels mediated by the renin-angiotensin-aldosterone system and its potential as a target for clinical drugs.

'Living PRA' concept for plant risk: Reliability and availability tracking

International Nuclear Information System (INIS)

Sancaktar, S.; Sharp, D.R.

1985-01-01

The 'Living PRA' (Probabilistic Risk Assessment) is based on placing a PRA plant model on an interactive computer. This model consists of fault tree analyses for plant systems, event tree analyses for abnormal events and site specific consequence analysis for public and/or financial risks, for a nuclear power plant. A living PRA allows updates and sensitivity analyses by the plant owner throughout the lifetime of a plant. Recently, event and fault trees from two major PRAs were placed in a computerized format. The BYRON PRA study and the Living PRA and Economic Risk examples for Indian Point Unit-3 enabled analysts to gain experience and insight into the problems of plant operation. The above concept is well established for the Nuclear Power Plant evaluation. It has been also used for evaluation of processing facilities. In these studies, systems modeling was carried out by using the GRAFTER system for automated fault tree construction. Presently both the tools and the experience exists to set up useful and viable living PRA models for nuclear and chemical processing plants to enhance risk management by the plant owners through in-house use of micro computer based models

Role of Nitric Oxide in the Regulation of Renin and Vasopressin Secretion

Science.gov (United States)

Reid, Ian A.

1994-01-01

Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, and anterior pituitary gland, and evidence is accumulating that it contributes to the regulation of the secretion of renin and vasopressin, hormones that play key roles in the control of sodium and water balance. Several lines of evidence have implicated nitric oxide in the control of renin secretion. The enzyme nitric oxide synthase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa, a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro, suggesting a stimulatory role for the L-arginine/nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa, and beta adrenoceptor mechanisms that regulate renin secretion. Histochemical and immunocytochemical studies have revealed the presence of nitric oxide synthase in the supraoptic and paraventricular nuclei of the hypothalamus and in the posterior pituitary gland. Colocalization of nitric oxide synthase and vasopressin has been demonstrated in some hypothalamic neurons. Nitric oxide synthase activity in the hypothalamus and pituitary is increased by maneuvers known to stimulate vasopressin secretion, including salt loading and dehydration, Administration of L-arginine and nitric

Correlations of plasma renin activity and aldosterone concentration with ambulatory blood pressure responses to nebivolol and valsartan, alone and in combination, in hypertension.

Science.gov (United States)

Giles, Thomas D; Bakris, George; Oparil, Suzanne; Weber, Michael A; Li, Huiling; Mallick, Madhuja; Bharucha, David B; Chen, ChunLin; Ferguson, William G

2015-11-01

After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial (N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%-73%) and decreased with nebivolol (51%-65%) and the combination treatment (17%-39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%-22%; nebivolol, 20%-26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan). Baseline ln(plasma renin activity) correlated with the 8-week reductions in 24-hour systolic and diastolic BP following treatments with the combination (all doses combined, P = .003 and P valsartan. Baseline ln(aldosterone) correlated with 24-hour systolic and diastolic BP reductions following combination treatment only (P < .001 and P = .005). The implications of the renin-angiotensin-aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Stimulatory effects of neuronally released norepinephrine on renin release in vitro

Energy Technology Data Exchange (ETDEWEB)

Matsumura, Yasuo; Kawazoe, Shinka; Ichihara, Toshio; Shinyama, Hiroshi; Kageyama, Masaaki; Morimoto, Shiro (Osaka Univ. of Pharmaceutical Sciences (Japan))

1988-10-01

Extracellular high potassium inhibits renin release in vitro by increasing calcium concentrations in the juxtaglomerular cells. The authors found that the decreased response of renin release from rat kidney cortical slices in high potassium solution changed to a strikingly increased one in the presence of nifedipine at doses over 10{sup {minus}6} M. They then examined the stimulatory effect of extracellular high potassium in the presence of nifedipine on renin release. The enhancement of release was significantly suppressed either by propranolol or by metoprolol but not by prazosin. High potassium plus nifedipine-induced increase in renin release was markedly attenuated by renal denervation. The enhancing effect was not observed when the slices were incubated in calcium-free medium. Divalent cations such as Cd{sup 2+}, Co{sup 2+}, and Mn{sup 2+} blocked this enhancement in a concentration-dependent manner. High potassium elicited an increase in {sup 3}H efflux from the slices preloaded with ({sup 3}H)-norepinephrine. The increasing effect was not influenced by nifedipine but was abolished by the removal of extracellular calcium or by the addition of divalent cations. These observations suggest to us that the high potassium plus nifedipine-induced increase in renin release from the slices is mediated by norepinephrine derived from renal sympathetic nerves and that this neuronally released norepinephrine stimulates renin release via activation of {beta}-adrenoceptors.

The Prenylated Rab GTPase Receptor PRA1.F4 Contributes to Protein Exit from the Golgi Apparatus.

Science.gov (United States)

Lee, Myoung Hui; Yoo, Yun-Joo; Kim, Dae Heon; Hanh, Nguyen Hong; Kwon, Yun; Hwang, Inhwan

2017-07-01

Prenylated Rab acceptor1 (PRA1) functions in the recruitment of prenylated Rab proteins to their cognate organelles. Arabidopsis ( Arabidopsis thaliana ) contains a large number of proteins belonging to the AtPRA1 family. However, their physiological roles remain largely unknown. Here, we investigated the physiological role of AtPRA1.F4, a member of the AtPRA1 family. A T-DNA insertion knockdown mutant of AtPRA1.F4 , atpra1.f4 , was smaller in stature than parent plants and possessed shorter roots, whereas transgenic plants overexpressing HA:AtPRA1.F4 showed enhanced development of secondary roots and root hairs. However, both overexpression and knockdown plants exhibited increased sensitivity to high-salt stress, lower vacuolar Na + /K + -ATPase and plasma membrane ATPase activities, lower and higher pH in the vacuole and apoplast, respectively, and highly vesiculated Golgi apparatus. HA:AtPRA1.F4 localized to the Golgi apparatus and assembled into high-molecular-weight complexes. atpra1.f4 plants displayed a defect in vacuolar trafficking, which was complemented by low but not high levels of HA : AtPRA1.F4 Overexpression of HA:AtPRA1.F4 also inhibited protein trafficking at the Golgi apparatus, albeit differentially depending on the final destination or type of protein: trafficking of vacuolar proteins, plasma membrane proteins, and trans-Golgi network (TGN)-localized SYP61 was strongly inhibited; trafficking of TGN-localized SYP51 was slightly inhibited; and trafficking of secretory proteins and TGN-localized SYP41 was negligibly or not significantly inhibited. Based on these results, we propose that Golgi-localized AtPRA1.F4 is involved in the exit of many but not all types of post-Golgi proteins from the Golgi apparatus. Additionally, an appropriate level of AtPRA1.F4 is crucial for its function at the Golgi apparatus. © 2017 American Society of Plant Biologists. All Rights Reserved.

Advances in Probabilistic Risk Assessment (PRA): a look into practitioners toolbox

International Nuclear Information System (INIS)

Mok, J.; Kaasalainen, S.; Donnelly, K.

2007-01-01

The ever-increasing emphasis on the use of Probabilistic Risk Assessment (PRA) in risk-informed decision making translates into increased expectations relating to PRA applications for the groups tasked with developing and maintaining the facility PRAs. In order to succeed in meeting the demand for PRA work, it is essential to develop methodologies and tools (or utilities) that improve the efficiency with which the PRAs are processed and manipulated to obtain a solution. Examples from the Nuclear Safety Solutions (NSS) PRA Practitioners tool box include utilities for cutting logical loops, optimizing fault trees (to decrease run-times), modularizing fault trees, and converting event trees into high level fault tree logic (an important element if the PRA study is to be used to support a risk monitor such as an Equipment Out-of-Service (EOOS) Monitor). The objective of this paper is be to briefly describe the main features of these utilities, and to illustrate the value they have in terms of improving the efficiency and effectiveness of PRA development and maintenance at NSS. (author)

The radioprotective effect of a new aminothiol (20-PRA)

International Nuclear Information System (INIS)

Dolabela, M.F.; Lopes, M.T.P.; Pereira, M.T.; Steffani, G.M.; Pilo-Veloso, D.; Salas, C.E.; Nelson, D.L.

1998-01-01

We examined the radioprotective effect of aminothiol 2-N-propylamine-cyclohexane thiol (20-PRA) on a human leukemic cell line (K562) following various radiation doses (5,7.5 and 20 Gy) using a source of 60 Co γ-rays. At 5 Gy and 1nM 20-PRA, a substantial protective effect (58%) was seen 24 h after irradiation, followed by a decrease at 48 h (11%). At the high radiation dose (20 Gy) a low protective effect was also seen (35%). In addition, the anti tumorigenic potential of 10 nM 20-PRA was shown by the inhibition of crown gall formation induced by Agrobacterium tumefaciens. The radioprotective potency of 20-PRA is 10 5- 10 6 times higher than that of the aminothiol WR-1065 (N(2-mercaptoethyl)-1,3-diamino propane) whose protective effect is in the 0.1 to 1.0 nM range. (author)

The radioprotective effect of a new aminothiol (20-PRA

Directory of Open Access Journals (Sweden)

M.F. Dolabela

1998-08-01

Full Text Available We examined the radioprotective effect of aminothiol 2-N-propylamine-cyclo-hexanethiol (20-PRA on a human leukemic cell line (K562 following various radiation doses (5, 7.5 and 20 Gy using a source of 60Co g-rays. At 5 Gy and 1 nM 20-PRA, a substantial protective effect (58% was seen 24 h after irradiation, followed by a decrease at 48 h (11%. At the high radiation dose (20 Gy a low protective effect was also seen (35%. In addition, the antitumorigenic potential of 10 nM 20-PRA was shown by the inhibition of crown gall formation induced by Agrobacterium tumefaciens. The radioprotective potency of 20-PRA is 105-106 times higher than that of the aminothiol WR-1065 (N-(2-mercaptoethyl-1,3-diaminopropane whose protective effect is in the 0.1 to 1.0 mM range.

Clinical analysis of the changes of plasma PRA, AT-II and Aid levels in patients with acute renal failure

International Nuclear Information System (INIS)

Zhang Qiuyue; Yang Yongqing

2002-01-01

Objective: To investigate the role of changes of plasma PRA, AT-II and Ald levels in the pathogenesis of acute renal failure. Methods: Plasma PRA, AT-II and Ald levels were determined with RIA in 40 normal subjects and 72 cases of acute renal failure. Results: Plasma PRA, AT-II and Ald levels in the patients were markedly increased as compared with those in normal subjects (p < 0.05, p < 0.01, p < 0.001 respectively). There were no linearity and exponential relationship between plasma PRA, AT-II, Ald levels and the 24 h urinary sodium excretion amount (within the range of 89.1 - 365.2 mEq). Conclusion: Acute renal failure could activate the RAAS function

ASSESSMENT OF DYNAMIC PRA TECHNIQUES WITH INDUSTRY AVERAGE COMPONENT PERFORMANCE DATA

Energy Technology Data Exchange (ETDEWEB)

Yadav, Vaibhav; Agarwal, Vivek; Gribok, Andrei V.; Smith, Curtis L.

2017-06-01

In the nuclear industry, risk monitors are intended to provide a point-in-time estimate of the system risk given the current plant configuration. Current risk monitors are limited in that they do not properly take into account the deteriorating states of plant equipment, which are unit-specific. Current approaches to computing risk monitors use probabilistic risk assessment (PRA) techniques, but the assessment is typically a snapshot in time. Living PRA models attempt to address limitations of traditional PRA models in a limited sense by including temporary changes in plant and system configurations. However, information on plant component health are not considered. This often leaves risk monitors using living PRA models incapable of conducting evaluations with dynamic degradation scenarios evolving over time. There is a need to develop enabling approaches to solidify risk monitors to provide time and condition-dependent risk by integrating traditional PRA models with condition monitoring and prognostic techniques. This paper presents estimation of system risk evolution over time by integrating plant risk monitoring data with dynamic PRA methods incorporating aging and degradation. Several online, non-destructive approaches have been developed for diagnosing plant component conditions in nuclear industry, i.e., condition indication index, using vibration analysis, current signatures, and operational history [1]. In this work the component performance measures at U.S. commercial nuclear power plants (NPP) [2] are incorporated within the various dynamic PRA methodologies [3] to provide better estimates of probability of failures. Aging and degradation is modeled within the Level-1 PRA framework and is applied to several failure modes of pumps and can be extended to a range of components, viz. valves, generators, batteries, and pipes.

PRA and the implementation of quantitative safety goals

International Nuclear Information System (INIS)

Okrent, D.

1983-01-01

With the adoption by the U.S. Nuclear Regulatory Commission (NRC) in January, 1983, of a Policy Statement on Safety Goals for the Operation of Nuclear Power Plants, probabilitstic risk assessment (PRA) has taken on increased importance in nuclear reactor safety. Although the Reactor Safety Study, WASH-1400, was a major pioneering effort that revolutionized thinking about reactor safety, PRA was used only on occasion by the NRC regulatory staff prior to the accident at Three Mile Island. Since then, PRA has been used more and more as an important factor in decision making, usually for specific issues. The nuclear industry has also employed PRA, sometimes to make its case on specific issues, sometimes to present a position on overall risk. The advent of the Zion and Indian Point PRAs, with their treatment of risks from fire, wind, and earthquakes, and their examination of the course of core melt accidents, has added a new dimension to the overall picture. Although the NRC has stated that during the next two year evolution period, its quantitative design objectives and PRA are not to enter directly into the licensing process, many important issues will be influenced significantly by the results of risk and reliability studies. In fact, PRA may be coming into a position of great importance before the methodology, data, and process are sufficiently mature for the task. Large gaps still exist in our understanding of phenomena and in input information; and much of the final result depends on subjective input; large differences of opinion can and should be expected to persist. Accepted standards for quality assurance, and adequacy and depth of independent, peer review remain to be formulated and achieved. This paper will summarize the recently adopted NRC safety policy and the two-year evaluation plan, and will provide, by example, some words of caution concerning a few of the difficulties which may arise. (orig.)

Characterization of the macula densa stimulus for renin secretion

DEFF Research Database (Denmark)

Lorenz, J N; Weihprecht, H; Schnermann, J

1990-01-01

These studies utilize the isolated perfused rabbit juxtaglomerular apparatus (JGA) to study the macula densa signal for renin secretion in the absence of the confounding influences of intravascular pressure and renal nerve activity. In the first experimental series, JGAs were perfused alternately...... and decreases in macula densa NaCl concentration, and these changes are rapid and largely reversible, 2) the full renin response occurs within the concentration range normally occurring at the macula densa, i.e., below 80 mM Na+ and 61 mM Cl-, and 3) RSR responds with a larger change to alterations in Na...

Free Fatty Acids Activate Renin-Angiotensin System in 3T3-L1 Adipocytes through Nuclear Factor-kappa B Pathway

Directory of Open Access Journals (Sweden)

Jia Sun

2016-01-01

Full Text Available The activity of a local renin-angiotensin system (RAS in the adipose tissue is closely associated with obesity-related diseases. However, the mechanism of RAS activation in adipose tissue is still unknown. In the current study, we found that palmitic acid (PA, one kind of free fatty acid, induced the activity of RAS in 3T3-L1 adipocytes. In the presence of fetuin A (Fet A, PA upregulated the expression of angiotensinogen (AGT and angiotensin type 1 receptor (AT1R and stimulated the secretion of angiotensin II (ANG II in 3T3-L1 adipocytes. Moreover, the activation of RAS in 3T3-L1 adipocytes was blocked when we blocked Toll-like receptor 4 (TLR4 signaling pathway using TAK242 or NF-κB signaling pathway using BAY117082. Together, our results have identified critical molecular mechanisms linking PA/TLR4/NF-κB signaling pathway to the activity of the local renin-angiotensin system in adipose tissue.

Radioimmunologic analysis of the state of the renin-angiotensin-aldosterone-system in arterial hypertension

International Nuclear Information System (INIS)

Slavnov, V.N.; Yakovlev, A.A.; Gandzha, T.I.; Yugrinov, O.G.

1985-01-01

In 110 patients suffering from various forms of arterial hypertension (hypertension, aldosteronoma, phaeochromocytoma, corticosteroma) the parameters of the system renin-angiotensin-aldosterone were measured. Basal values of aldosterone, renin activity in blood as well as their concentration in blood taken from the vena cava inferior, renal and adrenal veins during selective renography were determined. The 24-hours rhythm of the hormones in the blood, the reaction of the glomerular zone of the adrenal cortex and the juxtaglomerular renal system under acute Lasix (furosemide) stress was evaluated. It was found, that the system renin-angiotensin-aldosterone is disturbed in all patients with arterial hypertension. This is indicated by changes of aldosterone concentration, renin activity in peripheral blood and in the blood from the vena cava inferior, renal and adrenal veins, the 24-hours rhythm of their concentrations in serum and the reaction to acute Lasix stress. The radioimmunoassays of quantitative parameters of the renin-angiotensin-aldosterone system are decisive for the differential diagnosis of hypertension and adrenal gland tumors connected with a hypertension syndrome. They facilitate a rational choice of the hypertension therapy and the daily distribution of the medicaments for patients with hypertension. The radioimmunoassays can be used for checking the efficiency of medicaments and surgery. (author)

Differences in cortical and pituitary activity in response to hypoglycaemia and cognitive testing in healthy men with different basal activity of the renin-angiotensin system

DEFF Research Database (Denmark)

Bie-Olsen, Lise G; Pedersen-Bjergaard, Ulrik; Kjaer, Troels W

2010-01-01

INTRODUCTION: High renin-angiotensin system (RAS) activity has been associated with a high risk of severe hypoglycaemia in patients with type 1 diabetes and with cognitive deterioration during experimental hypoglycaemia in healthy subjects. The aim of this study was to describe possible differenc...

On the origin of urinary renin: A translational approach

NARCIS (Netherlands)

L.C.W. Roksnoer (Lodi); Heijnen, B.F.J. (Bart F.J.); Nakano, D. (Daisuke); Peti-Peterdi, J. (Janos); S.B. Walsh (Stephen); I.M. Garrelds (Ingrid); J.M. van Gool (Jeanette); R. Zietse (Bob); H.A.J. Struijker Boudier (Harry A.); E.J. Hoorn (Ewout); A.H.J. Danser (Jan)

2016-01-01

textabstractUrinary angiotensinogen excretion parallels albumin excretion, which is not the case for renin, while renin's precursor, prorenin, is undetectable in urine. We hypothesized that renin and prorenin, given their smaller size, are filtered through the glomerulus in larger amounts than

Low birth weight in response to salt restriction during pregnancy is not due to alterations in uterine-placental blood flow or the placental and peripheral renin-angiotensin system.

Science.gov (United States)

Leandro, Sandra Márcia; Furukawa, Luzia Naôko Shinohara; Shimizu, Maria Heloisa Massola; Casarini, Dulce Elena; Seguro, Antonio Carlos; Patriarca, Giuliana; Coelho, Michella Soares; Dolnikoff, Miriam Sterman; Heimann, Joel Claudio

2008-09-03

A number of studies conducted in humans and in animals have observed that events occurring early in life are associated with the development of diseases in adulthood. Salt overload and restriction during pregnancy and lactation are responsible for functional (hemodynamic and hormonal) and structural alterations in adult offspring. Our group observed that lower birth weight and insulin resistance in adulthood is associated with salt restriction during pregnancy. On the other hand, perinatal salt overload is associated with higher blood pressure and higher renal angiotensin II content in adult offspring. Therefore, we hypothesised that renin-angiotensin system (RAS) function is altered by changes in sodium intake during pregnancy. Such changes may influence fetoplacental blood flow and thereby fetal nutrient supply, with effects on growth in utero and, consequently, on birth weight. Female Wistar rats were fed low-salt (LS), normal-salt (NS), or high-salt (HS) diet, starting before conception and continuing until day 19 of pregnancy. Blood pressure, heart rate, fetuses and dams' body weight, placentae weight and litter size were measured on day 19 of pregnancy. Cardiac output, uterine and placental blood flow were also determined on day 19. Expressions of renin-angiotensin system components and of the TNF-alpha gene were evaluated in the placentae. Plasma renin activity (PRA) and plasma and tissue angiotensin-converting enzyme (ACE) activity, as well as plasma and placental levels of angiotensins I, II, and 1-7 were measured. Body weight and kidney mass were greater in HS than in NS and LS dams. Food intake did not differ among the maternal groups. Placental weight was lower in LS dams than in NS and HS dams. Fetal weight was lower in the LS group than in the NS and HS groups. The PRA was greater in LS dams than in NS and HS dams, although ACE activity (serum, cardiac, renal, and placental) was unaffected by the level of sodium intake. Placental levels of

Total renin after gonadotropin stimulation in polycystic ovarian disease.

Science.gov (United States)

Matinlauri, I; Anttila, L; Jaatinen, T A; Koskinen, P; Aalto, M; Irjala, K; Nikkanen, V

1995-02-01

To examine the influence of polycystic ovarian disease (PCOD) on the levels of total renin in plasma and follicular fluid (FF) after stimulation with hMG. Comparative study of the plasma and FF concentrations of total renin in women with and without PCOD after stimulation with hMG. In vitro fertilization-embryo transfer program at the Department of Obstetrics and Gynecology, the University Central Hospital of Turku, Finland. Thirty-six women undergoing IVF-ET for infertility with (n = 10) or without (n = 26) ultrasonographically diagnosed PCOD. Of the latter group, 15 women had tubal infertility, and the rest suffered from an anovulatory infertility and reacted with PCO-like ovarian response to stimulation. The concentrations of total renin in plasma and FF, serum E2, and protein in FF. The concentrations of plasma total renin after the gonadotropin stimulation were significantly higher in the PCOD and PCO-like groups when compared with the tubal group. The concentration of total renin in FF and the ratio of total renin per protein in FF were higher in the PCOD and PCO-like groups than in the tubal group, but the differences did not reach statistical significance. Positive correlations were found between the plasma total renin and serum E2 concentrations in the PCO-like and in the tubal group and between plasma total renin concentrations and the number of mature follicles in all groups. Follicular fluid total renin did not correlate with FF protein in any group. All findings were independent of the total hMG dosage used and the body mass index of the patients. In the present study the concentrations of total renin in plasma were enhanced markedly after gonadotropin stimulation in women with PCOD compared with women having tubal infertility. The pattern of the hormonal secretions revealed a group of infertile patients reacting biochemically like women with PCOD.

Cognitive performance, symptoms and counter-regulation during hypoglycaemia in patients with type 1 diabetes and high or low renin-angiotensin system activity

DEFF Research Database (Denmark)

Høi-Hansen, Thomas; Pedersen-Bjergaard, Ulrik; Andersen, Rikke Due

2009-01-01

INTRODUCTION: High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patient...

Mechanisms of renin release from juxtaglomerular cells

DEFF Research Database (Denmark)

Skøtt, O; Salomonsson, Max; Sellerup Persson, Anja

1991-01-01

In microdissected, nonperfused afferent arterioles changes in intravascular pressure did not affect renin secretion. On the contrary, renin release from isolated afferent arterioles perfused in a free-flow system has been reported to be sensitive to simultaneous changes in luminal pressure and fl....... Hence local blood flow may be involved in the baroreceptor control of renin release. If flow is sensed, the sensor is likely to be located near the endothelial cell layer, where ion channels have been shown to be influenced by variations in shear stress....

Vascular endothelial growth factor during hypoglycemia in patients with type 1 diabetes mellitus: relation to cognitive function and renin-angiotensin system activity

DEFF Research Database (Denmark)

Kristensen, Peter Lommer; Høi-Hansen, Thomas; Boomsma, Frans

2009-01-01

hypoglycemia. High activity in the renin-angiotensin system (RAS) is associated with an increased risk of severe hypoglycemia in patients with type 1 diabetes mellitus. Renin-angiotensin system possibly exerts its mechanism in hypoglycemia via VEGF. We studied the impact of mild hypoglycemia on plasma VEGF...... in patients with type 1 diabetes mellitus and high or low RAS activity and analyzed associations between VEGF levels and cognitive function during hypoglycemia. Eighteen patients with type 1 diabetes mellitus-9 with high and 9 with low RAS activity-underwent a single-blinded, placebo-controlled, crossover...... study with either mild hypoglycemia or stable glycemia. Cognitive function was assessed by the California Cognitive Assessment Package and the Alzheimer Quick Test. Nadir plasma glucose was 2.2 (0.3) mmol/L. During the control study, plasma VEGF did not change. During hypoglycemia, plasma VEGF increased...

The water channel aquaporin-1 contributes to renin cell recruitment during chronic stimulation of renin production

DEFF Research Database (Denmark)

Tinning, Anne Robdrup; Jensen, Boye L; Schweda, Frank

2014-01-01

Processing and release of secretory granules involve water movement across granule membranes. It was hypothesized that the water channel aquaporin-1 (AQP-1) contributes directly to recruitment of renin-positive cells in the afferent arteriole. AQP1(-/-) and (+/+) mice were fed a low NaCl diet (LS...... to baseline with no difference between genotypes. Plasma nitrite/nitrate concentration was unaffected by genotype and LS-ACEI. In AQP1(-/-) mice, the number of afferent arterioles with recruitment was significantly lower compared to (+/+) after LS-ACEI. It is concluded that aquaporin-1 is not necessary...... for acutely stimulated renin secretion in vivo and from isolated perfused kidney, whereas recruitment of renin-positive cells in response to chronic stimulation is attenuated or delayed in AQP1(-/-) mice....

Dynamic Positioning System (DPS) Risk Analysis Using Probabilistic Risk Assessment (PRA)

Science.gov (United States)

Thigpen, Eric B.; Boyer, Roger L.; Stewart, Michael A.; Fougere, Pete

2017-01-01

The National Aeronautics and Space Administration (NASA) Safety & Mission Assurance (S&MA) directorate at the Johnson Space Center (JSC) has applied its knowledge and experience with Probabilistic Risk Assessment (PRA) to projects in industries ranging from spacecraft to nuclear power plants. PRA is a comprehensive and structured process for analyzing risk in complex engineered systems and/or processes. The PRA process enables the user to identify potential risk contributors such as, hardware and software failure, human error, and external events. Recent developments in the oil and gas industry have presented opportunities for NASA to lend their PRA expertise to both ongoing and developmental projects within the industry. This paper provides an overview of the PRA process and demonstrates how this process was applied in estimating the probability that a Mobile Offshore Drilling Unit (MODU) operating in the Gulf of Mexico and equipped with a generically configured Dynamic Positioning System (DPS) loses location and needs to initiate an emergency disconnect. The PRA described in this paper is intended to be generic such that the vessel meets the general requirements of an International Maritime Organization (IMO) Maritime Safety Committee (MSC)/Circ. 645 Class 3 dynamically positioned vessel. The results of this analysis are not intended to be applied to any specific drilling vessel, although provisions were made to allow the analysis to be configured to a specific vessel if required.

Atrial distension, haemodilution, and acute control of renin release during water immersion in humans

DEFF Research Database (Denmark)

Gabrielsen, A; Pump, B; Bie, P

2002-01-01

immersion. During WI, central venous pressure (CVP) and left atrial diameter (LAD) increased (P ... is not the single pivotal stimulus for the acute suppression of renin release in response to intravascular volume expansion by water immersion in humans. Haemodilution constitutes a significant and conceivably the principal stimulus for the acute immersion-induced suppression of renin-angiotensin system activity....

Effect of furosemide and dietary sodium on kidney and plasma big and small renin

International Nuclear Information System (INIS)

Iwao, H.; Michelakis, A.M.

1981-01-01

Renin was found in mouse plasma in high-molecular-weight forms (big big renin, big renin) and a low-molecular-weight form (small renin). They were measuerd by a radioimmunoassay procedure for the direct measurement of renin. In the kidney, 89% of total renin was small renin and the rest was big big and big renin. This distribution pattern of renins was not changed when the kideny tissue was homogenized in the presence of protease inhibitors. Low-sodium or high-sodium diets changed renal renin content, but not the distribution pattern of renins in the kidney. Acute stimulation of renin release by furosemide increased small renin but not big big and big renin in plasma. However, dietary sodium depletion for 2 weeks significantly increased big big, big, and small renin in plasma of mice with or without submaxillary glands. In contrast, high-sodium intake significantly decreased big big, big, and small renin in plasma of mice with or without submaxillary glands

Graz Endocrine Causes of Hypertension (GECOH study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism

Directory of Open Access Journals (Sweden)

Dobnig Harald

2009-04-01

Full Text Available Abstract Background Primary aldosteronism (PA affects approximately 5 to 10% of all patients with arterial hypertension and is associated with an excess rate of cardiovascular complications that can be significantly reduced by a targeted treatment. There exists a general consensus that the aldosterone to renin ratio should be used as a screening tool but valid data about the accuracy of the aldosterone to renin ratio in screening for PA are sparse. In the Graz endocrine causes of hypertension (GECOH study we aim to prospectively evaluate diagnostic procedures for PA. Methods and design In this single center, diagnostic accuracy study we will enrol 400 patients that are routinely referred to our tertiary care center for screening for endocrine hypertension. We will determine the aldosterone to active renin ratio (AARR as a screening test. In addition, all study participants will have a second determination of the AARR and will undergo a saline infusion test (SIT as a confirmatory test. PA will be diagnosed in patients with at least one AARR of ≥ 5.7 ng/dL/ng/L (including an aldosterone concentration of ≥ 9 ng/dL who have an aldosterone level of ≥ 10 ng/dL after the saline infusion test. As a primary outcome we will calculate the receiver operating characteristic curve of the AARR in diagnosing PA. Secondary outcomes include the test characteristics of the saline infusion test involving a comparison with 24 hours urine aldosterone levels and the accuracy of the aldosterone to renin activity ratio in diagnosing PA. In addition we will evaluate whether the use of beta-blockers significantly alters the accuracy of the AARR and we will validate our laboratory methods for aldosterone and renin. Conclusion Screening for PA with subsequent targeted treatment is of great potential benefit for hypertensive patients. In the GECOH study we will evaluate a standardised procedure for screening and diagnosing of this disease.

Level 2 PRA for a German BWR

International Nuclear Information System (INIS)

Sassen, F.; Rapp, W.; Tietsch, W.; Roess, P.

2007-01-01

A concept for a Level 2 Probabilistic Risk Assessment (L2 PRA) for a German Boiling Water Reactor (BWR) has been developed taking into account the role of L2 PRA within the German regulatory landscape. According to this concept, a plant specific evaluation of the severe accident phenomenology as well as analyses of the accident progression for the severe accident scenarios has been performed. Furthermore a plant specific MELCOR 1.8.6 model has been developed and special MELCOR source term calculations have been performed for the different release paths. This paper will present examples from the different areas described above. (author)

Issues and insights of PRA methodology in nuclear and space applications

International Nuclear Information System (INIS)

Hsu, F.

2005-01-01

This paper presents some important issues and technical insights on the scope, conceptual framework, and essential elements of nuclear power plant Probabilistic Risk Assessments (PRAs) and that of the PRAs in general applications of the aerospace industry, such as the Space Shuttle PRA being conducted by NASA. Discussions are focused on various lessons learned in nuclear power plant PRA applications and their potential applicability to the PRAs in the aerospace and launch vehicle systems. Based on insights gained from PRA projects for nuclear power plants and from the current Space Shuttle PRA effort, the paper explores the commonalities and the differences between the conduct of the different PRAs and the key issues and risk insights derived from extensive modeling practices in both industries of nuclear and space. (author)

Association studies suggest a key role for endothelin-1 in the pathogenesis of preeclampsia and the accompanying renin-angiotensin-aldosterone system suppression.

Science.gov (United States)

Verdonk, Koen; Saleh, Langeza; Lankhorst, Stephanie; Smilde, J E Ilse; van Ingen, Manon M; Garrelds, Ingrid M; Friesema, Edith C H; Russcher, Henk; van den Meiracker, Anton H; Visser, Willy; Danser, A H Jan

2015-06-01

Women with preeclampsia display low renin-angiotensin-aldosterone system activity and a high antiangiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase (sFlt)-1 and reduced placental growth factor levels. To investigate whether renin-angiotensin-aldosterone system suppression in preeclampsia is because of this disturbed angiogenic balance, we measured mean arterial pressure, creatinine, endothelin-1 (ET-1), and renin-angiotensin-aldosterone system components in pregnant women with a high (≥85; n=38) or low (<85; n=65) soluble Fms-like tyrosine kinase-1/placental growth factor ratio. Plasma ET-1 levels were increased in women with a high ratio, whereas their plasma renin activity and plasma concentrations of renin, angiotensinogen, and aldosterone were decreased. Plasma renin activity-aldosterone relationships were identical in both the groups. Multiple regression analysis revealed that plasma renin concentration correlated independently with mean arterial pressure and plasma ET-1. Plasma ET-1 correlated positively with soluble Fms-like tyrosine kinase-1 and negatively with plasma renin concentration, and urinary protein correlated with plasma ET-1 and mean arterial pressure. Despite the lower plasma levels of renin and angiotensinogen in the high-ratio group, their urinary levels of these components were elevated. Correction for albumin revealed that this was because of increased glomerular filtration. Subcutaneous arteries obtained from patients with preeclampsia displayed an enhanced, AT2 receptor-mediated response to angiotensin II. In conclusion, a high antiangiogenic state associates with ET-1 activation, which together with the increased mean arterial pressure may underlie the parallel reductions in renin and aldosterone in preeclampsia. Because ET-1 also was a major determinant of urinary protein, our data reveal a key role for ET-1 in the pathogenesis of preeclampsia. Finally, the enhanced angiotensin responsiveness

Time course of the antiproteinuric and antihypertensive effects of direct renin inhibition in type 2 diabetes

DEFF Research Database (Denmark)

Persson, F; Rossing, P; Schjoedt, K J

2008-01-01

Inhibition of renin with an active site inhibitor, aliskiren, lowers blood pressure (BP) in diabetic patients. Here, we studied the time course of the antihypertensive and antiproteinuric effect of renin inhibition in 15 patients with type 2 diabetes and elevated urinary albumin/creatinine ratios...

Load out and offshore lifting of the PRA-1 platform modules; Embarque e icamento offshore dos modulos de PRA-1

Energy Technology Data Exchange (ETDEWEB)

Barbosa, Fernando; Raigorodsky, Jacques; Mitidieri, Jorge L.U.; Ricardi, Paulo S. [Construtora Norberto Odebrecht S.A., Rio de Janeiro, RJ (Brazil)

2008-07-01

The technology innovations are characteristics of offshore Engineering around the world. These technologies just make sense when they aim the productivity, security and costs gains compared to ordinary methods. It is in this context that the proposal of the Consorcio PRA-1 (Odebrecht e UTC) team makes sense, in the definition of basic methodology for the PRA-1 platform construction and installation. Through the innovative concept, It was defined (still in the proposal phase) the basic premise that the modules construction and assembly were onshore ending up that just few hours after the offshore installation the modules should be operational in minimal habitability conditions. This innovative method allowed the lack of Flotel, that is a platform which provide support to the offshore construction and assembly (Flotel represents a high costs to the project) and, as consequence, the contract signature by CONSORCIO PRA-1. This work aims to describe the method used for the LOUD-OUT of the PRA-1 modules and the installation of them on the jacket through a vessel provide with cranes the has performed the lifting. Theses operations became unique in Brazil due its challengers characteristics: Module 12 weight = 7203 tf and Module 35 = 5725 tf. For the accomplishment of the Load-out and offshore lifting, was performed a detailed planning and a high level of subcontract interface management. The operations mentioned above were filmed/photographed and published in the specialized media. (author)

Chinshan living PRA model using NUPRA software package

International Nuclear Information System (INIS)

Cheng, S.-K.; Lin, T.-J.

2004-01-01

A living probabilistic risk assessment (PRA) model has been established for Chinshan Nuclear Power Station (BWR-4, MARK-I) using NUPRA software package. The core damage frequency due to internal events, seismic events and typhoons are evaluated in this model. The methodology and results considering the recent implementation of the 5th emergency diesel generator and automatic boron injection function are presented. The dominant sequences of this PRA model are discussed, and some possible applications of this living model are proposed. (author)

Renin release

DEFF Research Database (Denmark)

Schweda, Frank; Friis, Ulla; Wagner, Charlotte

2007-01-01

in the walls of renal afferent arterioles at the entrance of the glomerular capillary network. It has been known for a long time that renin synthesis and secretion are stimulated by the sympathetic nerves and the prostaglandins and are inhibited in negative feedback loops by angiotensin II, high blood pressure...

A case of low renin hyperaldosteronism considered to be aldosterone-producing adrenocortical adenoma by CT image of adrenal gland

International Nuclear Information System (INIS)

Hayashi, Kozo; Tsuchihashi, Yoshihiro; Ito, Kazuro; Ozono, Noboru

1983-01-01

A case was reported in which hypertension, hypopotassemia, low plasma renin activity and hyperaldosteronemia were observed. Imaging suggested adrenocortical adenoma, leading to the diagnosis of low renin hyperaldosteronism. (Chiba, N.)

Probabilistic Risk Assessment (PRA): A Practical and Cost Effective Approach

Science.gov (United States)

Lee, Lydia L.; Ingegneri, Antonino J.; Djam, Melody

2006-01-01

The Lunar Reconnaissance Orbiter (LRO) is the first mission of the Robotic Lunar Exploration Program (RLEP), a space exploration venture to the Moon, Mars and beyond. The LRO mission includes spacecraft developed by NASA Goddard Space Flight Center (GSFC) and seven instruments built by GSFC, Russia, and contractors across the nation. LRO is defined as a measurement mission, not a science mission. It emphasizes the overall objectives of obtaining data to facilitate returning mankind safely to the Moon in preparation for an eventual manned mission to Mars. As the first mission in response to the President's commitment of the journey of exploring the solar system and beyond: returning to the Moon in the next decade, then venturing further into the solar system, ultimately sending humans to Mars and beyond, LRO has high-visibility to the public but limited resources and a tight schedule. This paper demonstrates how NASA's Lunar Reconnaissance Orbiter Mission project office incorporated reliability analyses in assessing risks and performing design tradeoffs to ensure mission success. Risk assessment is performed using NASA Procedural Requirements (NPR) 8705.5 - Probabilistic Risk Assessment (PRA) Procedures for NASA Programs and Projects to formulate probabilistic risk assessment (PRA). As required, a limited scope PRA is being performed for the LRO project. The PRA is used to optimize the mission design within mandated budget, manpower, and schedule constraints. The technique that LRO project office uses to perform PRA relies on the application of a component failure database to quantify the potential mission success risks. To ensure mission success in an efficient manner, low cost and tight schedule, the traditional reliability analyses, such as reliability predictions, Failure Modes and Effects Analysis (FMEA), and Fault Tree Analysis (FTA), are used to perform PRA for the large system of LRO with more than 14,000 piece parts and over 120 purchased or contractor

Radioimmunoassay for determination of blood aldosterone and renin in the diagnosis of some forms of arterial hypertension

International Nuclear Information System (INIS)

Khamidov, R.I.; Khalmuratova, R.A.; Sattarova, F.K.

1987-01-01

Aldosterone concentration and renin activity in the blood from the ulnar, inferior cava veins at the level of the 12th thoracic vertebra, the left and right renal veins were studied in 60 patients with arterial hypertension by means of a radioimmunoassay kits (France). The patients were divided into 4 groups: with primary and idiopathic hyperaldosteronism, renal-parenchymatous and essential arterial hypertension. The diagnosis of primary and idiopathic hyperaldosteronism was also confirmed by low blood renin activity. Renin activity in the peripheral venous blood was considerably elevated in renal-parenchymatous arterial hypertension and was normal in essential hypertension. Aldosterone concentration in the blood from the vena cava inferior and renal veins was 1.6-2-fold as high on the affected side as on the contralateral one

Aldosterone to Active Renin Ratio Is Associated With Nocturnal Blood Pressure in Obese and Treated Hypertensive Patients: The Styrian Hypertension Study

NARCIS (Netherlands)

Grubler, M.R.; Kienreich, K.; Gaksch, M.; Verheyen, N.; Fahrleitner-Pammer, A.; Schmid, J.; Grogorenz, J.; Ablasser, K.; Pieske, B.; Tomaschitz, A.; Pilz, S.

2014-01-01

High aldosterone levels are considered to play a key role in arterial hypertension. Data on the relationship between the aldosterone to active renin ratio (AARR), a quantity of aldosterone excess, and ambulatory blood pressure (BP) monitoring (ABPM) during the night are, however, sparse.

Influência do exercício aeróbio na renina de portadores de hipertensão arterial com sobrepeso Influencia del ejercicio aeróbico en la renina de portadores de hipertensión arterial con sobrepeso Effect of aerobic exercise on plasma renin in overweight patients with hypertension

Directory of Open Access Journals (Sweden)

Bruno Martinelli

2010-07-01

Full Text Available FUNDAMENTO: A atividade do sistema renina-angiotensina-aldosterona tem relação direta com sobrepeso e sedentarismo, e essas variáveis se associam à hipertensão arterial (HA. O exercício aeróbio propicia melhor controle da pressão arterial (PA por agir nos mecanismos da regulação pressórica, dentre eles, a atividade de renina plasmática (ARP. OBJETIVO: Avaliar a influência do exercício aeróbio sobre ARP em portadores de HA com sobrepeso. MÉTODOS: Foram avaliados níveis pressóricos, bioquímicos e antropométricos pré e pós-treinamento de 16 semanas, três vezes por semana, a 60%-80% da frequência cardíaca máxima. Os dados foram expressos em média ± desvio padrão ou mediana e intervalo interquartílico, e analisados pelo teste "t", Mann-Withney e ANOVA (p FUNDAMENTO: La actividad del sistema renina-angiotensina-aldosterona tiene relación directa con sobrepeso y sedentarismo, y esas variables se asocian a la hipertensión arterial (HA. El ejercicio aeróbico propicia mejor control de la presión arterial (PA por actuar en los mecanismos de la regulación presórica, entre ellos, la actividad de renina plasmática (ARP. OBJETIVO: Evaluar la influencia del ejercicio aeróbico sobre ARP en portadores de HA con sobrepeso. MÉTODOS: Fueron evaluados niveles presóricos, bioquímicos y antropométricos pre y post-entrenamiento de 16 semanas, tres veces por semana, a 60%-80% da frecuencia cardíaca máxima. Los datos fueron expresados en media ± desvío estándar o media e intervalo intercuartílico, y analizados por el teste "t", Mann-Withney y ANOVA (p BACKGROUND: The activity of the renin-angiotensin-aldosterone system (RAAS is directly related to overweight and sedentary lifestyles, both of which are associated with hypertension. Aerobic exercise helps control blood pressure (BP by acting on mechanisms of blood pressure regulation, such as plasma renin activity (PRA. OBJECTIVE: To assess the effect of aerobic exercise on

The Protective Arm of the Renin Angiotensin System (RAS)

DEFF Research Database (Denmark)

understanding of the protective side of the Renin Angiotensin System (RAS) involving angiotensin AT2 receptor, ACE2, and Ang(1-7)/Mas receptor Combines the knowledge of editors who pioneered research on the protective renin angiotensin system including; Dr. Thomas Unger, one of the founders of AT2 receptor......The Protective Arm of the Renin Angiotensin System: Functional Aspects and Therapeutic Implications is the first comprehensive publication to signal the protective role of a distinct part of the renin-angiotensin system (RAS), providing readers with early insight into a complex system which...... will become of major medical importance in the near future. Focusing on recent research, The Protective Arm of the Renin Angiotensin System presents a host of new experimental studies on specific components of the RAS, namely angiotensin AT2 receptors (AT2R), the angiotensin (1-7) peptide with its receptor...

KATP channels are not essential for pressure-dependent control of renin secretion

DEFF Research Database (Denmark)

Jensen, B L; Gambaryan, S; Scholz, H

1998-01-01

(IPRK). Cromakalim (0.1-10 muM) stimulated basal renin secretion up to threefold and caused vasorelaxation in the IPRK. Both effects of cromakalim were attenuated by glibenclamide. Cromakalim stimulated renin secretion from isolated juxtaglomerular (JG) cells and from microdissected afferent arterioles......This study aimed to investigate the functional role of ATP-sensitive K+ (KATP) channels in the control of renin secretion by renal perfusion pressure. We studied the effect of openers and blockers of KATP-channels on basal- and low-pressure-induced renin secretion from isolated perfused rat kidneys......, all of which suggests that KATP channel openers stimulate renin secretion at the level of JG cells. A decrease in the perfusion pressure from 13.3 to 9.33 kPa (100 mmHg to 70 mmHg) increased renin secretion twofold, and cromakalim further increased renin secretion. At 5.33 kPa (40 mmHg) renin...

Novel approach of fragment-based lead discovery applied to renin inhibitors.

Science.gov (United States)

Tawada, Michiko; Suzuki, Shinkichi; Imaeda, Yasuhiro; Oki, Hideyuki; Snell, Gyorgy; Behnke, Craig A; Kondo, Mitsuyo; Tarui, Naoki; Tanaka, Toshimasa; Kuroita, Takanobu; Tomimoto, Masaki

2016-11-15

A novel approach was conducted for fragment-based lead discovery and applied to renin inhibitors. The biochemical screening of a fragment library against renin provided the hit fragment which showed a characteristic interaction pattern with the target protein. The hit fragment bound only to the S1, S3, and S3 SP (S3 subpocket) sites without any interactions with the catalytic aspartate residues (Asp32 and Asp215 (pepsin numbering)). Prior to making chemical modifications to the hit fragment, we first identified its essential binding sites by utilizing the hit fragment's substructures. Second, we created a new and smaller scaffold, which better occupied the identified essential S3 and S3 SP sites, by utilizing library synthesis with high-throughput chemistry. We then revisited the S1 site and efficiently explored a good building block attaching to the scaffold with library synthesis. In the library syntheses, the binding modes of each pivotal compound were determined and confirmed by X-ray crystallography and the library was strategically designed by structure-based computational approach not only to obtain a more active compound but also to obtain informative Structure Activity Relationship (SAR). As a result, we obtained a lead compound offering synthetic accessibility as well as the improved in vitro ADMET profiles. The fragments and compounds possessing a characteristic interaction pattern provided new structural insights into renin's active site and the potential to create a new generation of renin inhibitors. In addition, we demonstrated our FBDD strategy integrating highly sensitive biochemical assay, X-ray crystallography, and high-throughput synthesis and in silico library design aimed at fragment morphing at the initial stage was effective to elucidate a pocket profile and a promising lead compound. Copyright © 2016 Elsevier Ltd. All rights reserved.

Probabilistic risk assessment (PRA): status report and guidance for regulatory application. Draft report for comment

International Nuclear Information System (INIS)

1984-02-01

This document describes the current status of the methodologies used in probabilistic risk assessment (PRA) and provides guidance for the application of the results of PRAs to the nuclear reactor regulatory process. The PRA studies that have been completed or are underway are reviewed. The levels of maturity of the methodologies used in a PRA are discussed. Insights derived from PRAs are listed. The potential uses of PRA results for regulatory purposes are discussed

Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice

NARCIS (Netherlands)

Rosendahl, Alva; Niemann, Gianina; Lange, Sascha; Ahadzadeh, Erfan; Krebs, Christian; Contrepas, Aurelie; van Goor, Harry; Wiech, Thorsten; Bader, Michael; Schwake, Michael; Peters, Judith; Stahl, Rolf; Nguyen, Genevieve; Wenzel, Ulrich

Binding of renin and prorenin to the (pro)renin receptor (PRR) increases their enzymatic activity and upregulates the expression of pro-fibrotic genes in vitro. Expression of PRR is increased in the heart and kidney of hypertensive and diabetic animals, but its causative role in organ damage is

A desktop PRA

International Nuclear Information System (INIS)

Dolan, B.J.; Weber, B.J.

1989-01-01

This paper reports that Duke Power Company has completed full-scope PRAs for each of its nuclear stations - Oconee, McGuire and Catawba. These living PRAs are being maintained using desktop personal computers. Duke's PRA group now has powerful personal computer-based tools that have both decreased direct costs (computer analysis expenses) and increased group efficiency (less time to perform analyses). The shorter turnaround time has already resulted in direct savings through analyses provided in support of justification for continued station operation. Such savings are expected to continue with similar future support

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

Energy Technology Data Exchange (ETDEWEB)

Kim, Suyeon [University of Tennessee, Knoxville (UTK); Soltani-Bejnood, Morvarid [University of Tennessee, Knoxville (UTK); Quignard-Boulange, Annie [Centre Biomedical des Cordeliers, Paris, France; Massiera, Florence [Centre de Biochimie, Nice, France; Teboul, Michele [Centre de Biochimie, Nice, France; Ailhaud, Gerard [Centre de Biochimie, Nice, France; Kim, Jung [University of Tennessee, Knoxville (UTK); Moustaid-Moussa, Naima [University of Tennessee, Knoxville (UTK); Voy, Brynn H [ORNL

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.

Renin-aldosterone-sodium profiling in hypertensive Filipinos. Pt. 2

Energy Technology Data Exchange (ETDEWEB)

Guevara, R.; Torres, J. Jr; Abundo, H.P.; Perez, A.P.; Ochoa, W.K.

1981-10-01

Plasma renin activity determination by radioimmunoassay as profiling technique is a useful guide for more rational and precise treatment of hypertension. Statistical nomograms are developed for normals, essential hypertension, diabetic hypertension, renal diseases, renal disease and dialysis, normal pregnancy, toxemic pregnancy and contraceptive pill users with and without hypertension.

Expected proton signal sizes in the PRaVDA Range Telescope for proton Computed Tomography

International Nuclear Information System (INIS)

Price, T.; Parker, D.J.; Green, S.; Esposito, M.; Waltham, C.; Allinson, N.M.; Poludniowski, G.; Evans, P.; Taylor, J.; Manolopoulos, S.; Anaxagoras, T.; Nieto-Camero, J.

2015-01-01

Proton radiotherapy has demonstrated benefits in the treatment of certain cancers. Accurate measurements of the proton stopping powers in body tissues are required in order to fully optimise the delivery of such treaments. The PRaVDA Consortium is developing a novel, fully solid state device to measure these stopping powers. The PRaVDA Range Telescope (RT), uses a stack of 24 CMOS Active Pixel Sensors (APS) to measure the residual proton energy after the patient. We present here the ability of the CMOS sensors to detect changes in the signal sizes as the proton traverses the RT, compare the results with theory, and discuss the implications of these results on the reconstruction of proton tracks

Interaction of CREDO [Centralized Reliability Data Organization] with the EBR-II [Experimental Breeder Reactor II] PRA [probabilistic risk assessment] development

International Nuclear Information System (INIS)

Smith, M.S.; Ragland, W.A.

1989-01-01

The National Academy of Sciences review of US Department of Energy (DOE) class 1 reactors recommended that the Experimental Breeder Reactor II (EBR-II), operated by Argonne National Laboratory (ANL), develop a level 1 probabilistic risk assessment (PRA) and make provisions for level 2 and level 3 PRAs based on the results of the level 1 PRA. The PRA analysis group at ANL will utilize the Centralized Reliability Data Organization (CREDO) at Oak Ridge National Laboratory to support the PRA data needs. CREDO contains many years of empirical liquid-metal reactor component data from EBR-II. CREDO is a mutual data- and cost-sharing system sponsored by DOE and the Power Reactor and Nuclear Fuels Development Corporation of Japan. CREDO is a component based data system; data are collected on components that are liquid-metal specific, associated with a liquid-metal environment, contained in systems that interface with liquid-metal environments, or are safety related for use in reliability/availability/maintainability (RAM) analyses of advanced reactors. The links between the EBR-II PRA development effort and the CREDO data collection at EBR-II extend beyond the sharing of data. The PRA provides a measure of the relative contribution to risk of the various components. This information can be used to prioritize future CREDO data collection activities at EBR-II and other sites

Effect of PTA on blood pressure, renal plasma flow and renal venous renin activity in renovascular hypertension

International Nuclear Information System (INIS)

Arlart, I.P.; Dewitz, H. von; Rosenthal, J.

1983-01-01

Percutaneous transluminal angioplasty (PTA) is more and more accepted for interventional management of renal artery stenosis in hypertensive patients. This study was carried out to assess the behaviour of arterial blood-pressure, renal plasma flow and renal venous rening activity in renovascular hypertension following catheter dilatation. Using the data the possibility is calculated to predict the effect of PTA on blood pressure preinterventionally. The results demonstrate that a successful employment of PTA depends on a normal contralateral renal plasma flow and a normalization of plasma flow of the poststenotic kidney. Determination of plasma renin activity is only of restricted value. (orig.)

Seismic PRA of a BWR plant

International Nuclear Information System (INIS)

Nishio, Masahide; Fujimoto, Haruo

2014-01-01

Since the occurrence of nuclear power plant accidents in the Fukushima Daichi nuclear power station, the regulatory framework on severe accident (SA) has been discussed in Japan. The basic concept is to typify and identify the accident sequences leading to core/primary containment vessel (PCV) damage and to implement SA measures covering internal and external events extensively. As Japan is an earthquake-prone country and earthquakes and tsunami are important natural external events for nuclear safety of nuclear power plants, JNES performed the seismic probabilistic risk assessment (PRA) on a typical nuclear power plant and evaluated the dominant accident sequences leading to core/PCV damage to discuss dominant scenarios of severe accident (SA). The analytical models and the results of level-1 seismic PRA on a 1,100 MWe BWR-5 plant are shown here. Seismic PRA was performed for a typical BWR5 plant. Initiating events with large contribution to core damage frequency are the loss of all AC powers (station blackout) and the large LOCA. The top of dominant accident sequences is the simultaneous occurrence of station blackout and large LOCA. Important components to core damage frequency are electric power supply equipment. It needs to keep in mind that the results are influenced on site geologic characteristic to a greater or lesser. In the process of analysis, issues such as conservative assumptions related to damages of building or structure and success criteria for excessive LOCA are left to be resolved. These issues will be further studied including thermal hydric analysis in the future. (authors)

Renin-aldosterone-sodium profiling in hypertensive Filipinos. Pt. 2

International Nuclear Information System (INIS)

Guevara, R.; Torres, J. Jr; Abundo, H.P.; Perez, A.P.; Ochoa, W.K.

1981-01-01

Plasma renin activity determination by radioimmunoassay as profiling technique is a useful guide for more rational and precise treatment of hypertension. Statistical nomograms are developed for normals, essential hypertension, diabetic hypertension, renal diseases, renal disease and dialysis, normal pregnancy, toxemic pregnancy and contraceptive pill users with and without hypertension. (orig.) [de

Hiperurisemia pada Pra Diabetes

Directory of Open Access Journals (Sweden)

Ellyza Nasrul

2012-09-01

Full Text Available AbstrakAsam urat (AU merupakan produk akhir dari katabolisme adenin dan guanin yang berasal dari pemecahannukleotida purin. Urat dihasilkan oleh sel yang mengandung xanthine oxidase, terutama hepar dan usus kecil.Hiperurisemia adalah keadaan kadar asam urat dalam darah lebih dari 7,0 mg/dL.Pra diabetes adalah subjek yangmempunyai kadar glukosa plasma meningkat akan tetapi peningkatannya masih belum mencapai nilai minimaluntuk kriteria diagnosis diabetes melitus (DM. Glukosa darah puasa terganggu merupakan keadaan dimanapeningkatan kadar FPG≥100 mg/dL dan <126 mg/dL. Toleransi glukosa terganggu merupakan peningkatanglukosa plasma 2 jam setelah pembebanan 75 gram glukosa oral (≥140 mg/dL dan <200mg/dL dengan FPG<126 mg/dL.Insulin juga berperan dalam meningkatkan reabsorpsi asam urat di tubuli proksimal ginjal. Sehinggapada keadaan hiperinsulinemia pada pra diabetes terjadi peningkatan reabsorpsi yang akan menyebabkanhiperurisemia. Transporter urat yang berada di membran apikal tubuli renal dikenal sebagai URAT-1 berperandalam reabsorpsi urat.Kata kunci: Hiperurisemia, Pra DiabetesAbstractUric acid (AU is the end product of the catabolism of adenine and guanine nucleotides derived from thebreakdown of purines. Veins produced by cells containing xanthine oxidase, especially the liver and small intestine.Hyperuricemia is a state in the blood uric acid levels over 7.0 mg / dL.Pre-diabetes is a subject which has a plasmaglucose level will rise but the increase is still not reached the minimum value for the diagnostic criteria for diabetesmellitus (DM. Impaired fasting blood glucose is a condition in which increased levels of FPG ≥ 100 mg / dL and<126 mg / dL. Impaired glucose tolerance is an increase in plasma glucose 2 hours after 75 gram oral glucose load(≥ 140 mg / dL and <200mg/dl with FPG <126 mg / dL.Insulin also plays a role in increasing the reabsorption ofuric acid in renal proximal tubule. So that the hyperinsulinemia in the pre

Human renin biosynthesis and secretion in normal and ischemic kidneys

International Nuclear Information System (INIS)

Pratt, R.E.; Carleton, J.E.; Richie, J.P.; Heusser, C.; Dzau, V.J.

1987-01-01

The pathway of renin biosynthesis and secretion in normal and ischemic human kidneys has been investigated by pulse-labeling experiments. The results indicate that in normal human kidney, preprorenin is rapidly processed to 47-kDa prorenin. Microradiosequencing showed that this molecule was generated by cleavage between Gly-23 and Leu-24, yielding a 43-amino acid proregion. Analysis of prorenin secreted by the kidney tissue yielded an identical sequence, indicating that prorenin is secreted without any further proteolysis. An examination of the kinetics of processing and secretion suggested that a majority of the newly synthesized prorenin is quickly secreted, while only a small fraction is processed intracellularly to the mature renin. The differences in secretion kinetics between prorenin and mature renin and the selective inhibition of prorenin secretion by monensin suggest that they are secreted independently via two pathways: a constitutive pathway probably from the Golgi or protogranules that rapidly release prorenin and a regulated pathway that secretes mature renin from the mature granules. A comparison of the kinetics of processing between normal and ischemic tissues suggests that renal ischemia leads to an overall increase in the rate of processing or prorenin to mature renin. In addition, prolonged biosynthetic labeling of renin in the ischemic kidney yielded two smaller molecular weight immunoreactive forms suggestive of renin fragments that may be degradative products. These fragments were not detected in normal kidney tissue labeled for similar lengths of time

A novel interaction between sympathetic overactivity and aberrant regulation of renin by miR-181a in BPH/2J genetically hypertensive mice.

Science.gov (United States)

Jackson, Kristy L; Marques, Francine Z; Watson, Anna M D; Palma-Rigo, Kesia; Nguyen-Huu, Thu-Phuc; Morris, Brian J; Charchar, Fadi J; Davern, Pamela J; Head, Geoffrey A

2013-10-01

Genetically hypertensive mice (BPH/2J) are hypertensive because of an exaggerated contribution of the sympathetic nervous system to blood pressure. We hypothesize that an additional contribution to elevated blood pressure is via sympathetically mediated activation of the intrarenal renin-angiotensin system. Our aim was to determine the contribution of the renin-angiotensin system and sympathetic nervous system to hypertension in BPH/2J mice. BPH/2J and normotensive BPN/3J mice were preimplanted with radiotelemetry devices to measure blood pressure. Depressor responses to ganglion blocker pentolinium (5 mg/kg i.p.) in mice pretreated with the angiotensin-converting enzyme inhibitor enalaprilat (1.5 mg/kg i.p.) revealed a 2-fold greater sympathetic contribution to blood pressure in BPH/2J mice during the active and inactive period. However, the depressor response to enalaprilat was 4-fold greater in BPH/2J compared with BPN/3J mice, but only during the active period (P=0.01). This was associated with 1.6-fold higher renal renin messenger RNA (mRNA; P=0.02) and 0.8-fold lower abundance of micro-RNA-181a (P=0.03), identified previously as regulating human renin mRNA. Renin mRNA levels correlated positively with depressor responses to pentolinium (r=0.99; P=0.001), and BPH/2J mice had greater renal sympathetic innervation density as identified by tyrosine hydroxylase staining of cortical tubules. Although there is a major sympathetic contribution to hypertension in BPH/2J mice, the renin-angiotensin system also contributes, doing so to a greater extent during the active period and less during the inactive period. This is the opposite of the normal renin-angiotensin system circadian pattern. We suggest that renal hyperinnervation and enhanced sympathetically induced renin synthesis mediated by lower micro-RNA-181a contributes to hypertension in BPH/2J mice.

Percutaneous transluminal angioplasty in the region of the renal artery: indications, technique and results

Energy Technology Data Exchange (ETDEWEB)

Olbert, F; Ogris, E; Muzika, N; Schlegl, A; Vacariu, O; Diez, W

1985-01-01

The paper reports the results obtained by percutaneous transluminal angioplasty (PTA) in the treatment of renal artery stenosis in 25 patients with secondary hypertension and discusses indications and the technique used. The follow-up period ranged from 0.5 to 12 months. All interventions were performed with the Olbert catheter system. Following PTA a significant decrease in systolic, diastolic and mean arterial pressure was observed in nearly all patients. The response of the plasma renin activity (PRA) to orthostatic stimulation and pharmacological stimulation by furosemide was determined in a subset of 15 patients before and after PTA. A significant decrease in both basal and stimulated PRA values was observed subsequent to PTA. The decrease in PRA values after successful PTA did not, however, correlate with the extent of the blood pressure changes. (Author).

Percutaneous transluminal angioplasty in the region of the renal artery: indications, technique and results

International Nuclear Information System (INIS)

Olbert, F.; Ogris, E.; Muzika, N.; Schlegl, A.; Vacariu, O.; Diez, W.

1985-01-01

The paper reports the results obtained by percutaneous transluminal angioplasty (PTA) in the treatment of renal artery stenosis in 25 patients with secondary hypertension and discusses indications and the technique used. The follow-up period ranged from 0.5 to 12 months. All interventions were performed with the Olbert catheter system. Following PTA a significant decrease in systolic, diastolic and mean arterial pressure was observed in nearly all patients. The response of the plasma renin activity (PRA) to orthostatic stimulation and pharmacological stimulation by furosemide was determined in a subset of 15 patients before and after PTA. A significant decrease in both basal and stimulated PRA values was observed subsequent to PTA. The decrease in PRA values after successful PTA did not, however, correlate with the extent of the blood pressure changes. (Author)

Renin-aldosterone-sodium profiling in normal Filipinos. Pt. 1

International Nuclear Information System (INIS)

Guevara, R.; Torres, J. Jr.; Abundo, H.P.; Perez, A.P.; Ochoa, W.K.

1981-01-01

Plasma renin activity determination by radioimmunoassay is feasible, accurate, reproducible and reliable. This profiling technic is a very useful guide for more rational and precise treatment of the hypertensive state, but even when profiling cannot be done, statistical nomograms can be useful, just as well, as a guide in the treatment of hypertewnsion. (orig.) [de

Intracellular renin disrupts chemical communication between heart cells. Pathophysiological implications

Directory of Open Access Journals (Sweden)

Walmor eDe Mello

2015-01-01

Full Text Available The influence of intracellular renin on the process of chemical communication between cardiac cells was investigated in cell pairs isolated from the left ventricle of adult Wistar Kyoto rats. The enzyme together with Lucifer yellow CH was dialyzed into one cell of the pair using the whole cell clamp technique. The diffusion of the dye in the dialyzed and in non-dialyzed cell was followed by measuring the intensity of fluorescence in both cells as a function of time. The results indicated that; 1 under normal conditions, Lucifer Yellow flows from cell-to-cell through gap junctions; 2 the intracellular dialysis of renin (100nM disrupts chemical communication-an effect enhanced by simultaneous administration of angiotensinogen (100nM; 3 enalaprilat (10-9M administered to the cytosol together with renin reduced drastically the uncoupling action of the enzyme; 4 aliskiren (10-8M inhibited the effect of renin on chemical communication;5 the possible role of intracellular renin independently of angiotensin II (Ang II was evaluated including the increase of the inward calcium current elicited by the enzyme and the possible role of oxidative stress on the disruption of cell communication; 6 the possible harmful versus the beneficial effect of intracellular renin during myocardial infarction was discussed;7 the present results indicate that intracellular renin due to internalization or in situ synthesis, causes a severe impairment of chemical communication in the heart resulting in derangement of metabolic cooperation with serious consequences for heart function.

Prediction of response to medical therapy by serum soluble (pro)renin receptor levels in Graves' disease.

Science.gov (United States)

Mizuguchi, Yuki; Morimoto, Satoshi; Kimura, Shihori; Takano, Noriyoshi; Yamashita, Kaoru; Seki, Yasufumi; Bokuda, Kanako; Yatabe, Midori; Yatabe, Junichi; Watanabe, Daisuke; Ando, Takashi; Ichihara, Atsuhiro

2018-01-01

Antithyroid drugs are generally selected as the first-line treatment for Graves' Disease (GD); however, the existence of patients showing resistance or severe side effects to these drugs is an important issue to be solved. The (pro)renin receptor [(P)RR] is a multi-functional protein that activates the tissue renin-angiotensin system and is an essential constituent of vacuolar H+-ATPase, necessary for the autophagy-lysosome pathway. (P)RR is cleaved to soluble (s)(P)RR, which reflects the status of (P)RR expression. In this retrospective study, we aimed to investigate whether serum s(P)RR concentration can be used as a biomarker to predict the outcome of antithyroid drug treatment in GD patients. Serum s(P)RR levels were measured in 54 untreated GD patients and 47 control participants. Effects of medical treatment with antithyroid drugs on these levels were investigated in GD patients. Serum s(P)RR levels were significantly higher in patients with Graves' disease than in control subjects (PGraves' disease. High serum s(P)RR levels were associated with resistance to antithyroid drug treatment, suggesting that serum s(P)RR concentration can be used as a useful biomarker to predict the outcome of antithyroid drug treatment in these patients. Patients with Graves' disease with low body mass index showed higher levels of serum soluble (pro)renin receptor levels than those with high body mass index. In addition, in patients with Graves' disease, serum triglyceride levels were negatively correlated with serum soluble (pro)renin receptor levels. All these data indicated an association between low nutrient condition due to hyperthyroidism and increased (pro)renin receptor expression in these patients, suggesting that (pro)renin receptor expression could be increased in the process of stimulating intracellular energy production via activating autophagy function to compensate energy loss.

Prediction of response to medical therapy by serum soluble (pro)renin receptor levels in Graves’ disease

Science.gov (United States)

Kimura, Shihori; Takano, Noriyoshi; Yamashita, Kaoru; Seki, Yasufumi; Bokuda, Kanako; Yatabe, Midori; Yatabe, Junichi; Watanabe, Daisuke; Ando, Takashi

2018-01-01

Antithyroid drugs are generally selected as the first-line treatment for Graves’ Disease (GD); however, the existence of patients showing resistance or severe side effects to these drugs is an important issue to be solved. The (pro)renin receptor [(P)RR] is a multi-functional protein that activates the tissue renin-angiotensin system and is an essential constituent of vacuolar H+-ATPase, necessary for the autophagy-lysosome pathway. (P)RR is cleaved to soluble (s)(P)RR, which reflects the status of (P)RR expression. In this retrospective study, we aimed to investigate whether serum s(P)RR concentration can be used as a biomarker to predict the outcome of antithyroid drug treatment in GD patients. Serum s(P)RR levels were measured in 54 untreated GD patients and 47 control participants. Effects of medical treatment with antithyroid drugs on these levels were investigated in GD patients. Serum s(P)RR levels were significantly higher in patients with Graves’ disease than in control subjects (Pantithyroid drug treatment, suggesting that serum s(P)RR concentration can be used as a useful biomarker to predict the outcome of antithyroid drug treatment in these patients. Patients with Graves’ disease with low body mass index showed higher levels of serum soluble (pro)renin receptor levels than those with high body mass index. In addition, in patients with Graves’ disease, serum triglyceride levels were negatively correlated with serum soluble (pro)renin receptor levels. All these data indicated an association between low nutrient condition due to hyperthyroidism and increased (pro)renin receptor expression in these patients, suggesting that (pro)renin receptor expression could be increased in the process of stimulating intracellular energy production via activating autophagy function to compensate energy loss. PMID:29621332

A model for assessing human cognitive reliability in PRA studies

International Nuclear Information System (INIS)

Hannaman, G.W.; Spurgin, A.J.; Lukic, Y.

1985-01-01

This paper summarizes the status of a research project sponsored by EPRI as part of the Probabilistic Risk Assessment (PRA) technology improvement program and conducted by NUS Corporation to develop a model of Human Cognitive Reliability (HCR). The model was synthesized from features identified in a review of existing models. The model development was based on the hypothesis that the key factors affecting crew response times are separable. The inputs to the model consist of key parameters the values of which can be determined by PRA analysts for each accident situation being assessed. The output is a set of curves which represent the probability of control room crew non-response as a function of time for different conditions affecting their performance. The non-response probability is then a contributor to the overall non-success of operating crews to achieve a functional objective identified in the PRA study. Simulator data and some small scale tests were utilized to illustrate the calibration of interim HCR model coefficients for different types of cognitive processing since the data were sparse. The model can potentially help PRA analysts make human reliability assessments more explicit. The model incorporates concepts from psychological models of human cognitive behavior, information from current collections of human reliability data sources and crew response time data from simulator training exercises

Influence of bicarbonate on the sensitivity of renin release to sodium chloride

DEFF Research Database (Denmark)

Skøtt, O; Jensen, B L

1989-01-01

glomeruli treated with bicarbonate/chloride exchange inhibitor (DNDS), NaCl/KCl cotransport inhibitor (bumetanide), or Na+/H+ antiport inhibitor (amiloride) in the presence or absence of bicarbonate. In addition, the sensitivity to increases in osmolality by addition of sucrose was tested in the presence...... or absence of bicarbonate. Renin release from time controls superfused with a bicarbonate-free Ringer was identical to release from glomeruli superfused with a bicarbonate Ringer. DNDS (0.11 or 1.1 mM) had no effect on renin release in a bicarbonate Ringer. 30 mM sucrose inhibited renin release independently...... of bicarbonate. 15 mM NaCl stimulated renin release when bicarbonate was absent, while it caused an inhibition in the presence of bicarbonate. When bicarbonate/chloride exchange was inhibited, addition of NaCl stimulated renin release even when bicarbonate was present. The effect of NaCl on renin release...

Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal renin-angiotensin system.

Science.gov (United States)

Wang, Lei; Zhu, Qing; Lu, Aihua; Liu, Xiaofen; Zhang, Linlin; Xu, Chuanming; Liu, Xiyang; Li, Haobo; Yang, Tianxin

2017-09-01

Butyrate, a short-chain fatty acid, is the end product of the fermentation of complex carbohydrates by the gut microbiota. Recently, sodium butyrate (NaBu) has been found to play a protective role in a number of chronic diseases. However, it is still unclear whether NaBu has a therapeutic potential in hypertension. The present study was aimed to investigate the role of NaBu in angiotensin II (Ang II)-induced hypertension and to further explore the underlying mechanism. Ang II was infused into uninephrectomized Sprague-Dawley rats with or without intramedullary infusion of NaBu for 14 days. Mean arterial blood pressure was recorded by the telemetry system. Renal tissues, serum samples, and 24-h urine samples were collected to examine renal injury and the regulation of the (pro)renin receptor (PRR) and renin. Intramedullary infusion of NaBu in Sprague-Dawley rats lowered the Ang II-induced mean arterial pressure from 129 ± 6 mmHg to 108 ± 4 mmHg (P renal injury, including urinary albumin, glomerulosclerosis, and renal fibrosis, as well as the expression of inflammatory mediators tumor necrosis factor α, interleukin 6. The renal expression of PRR, angiotensinogen, angiotensin I-converting enzyme and the urinary excretion of soluble PRR, renin, and angiotensinogen were all increased by Ang II infusion but decreased by NaBu treatment. In cultured innermedullary collecting duct cells, NaBu treatment attenuated Ang II-induced expression of PRR and renin. These results demonstrate that NaBu exerts an antihypertensive action, likely by suppressing the PRR-mediated intrarenal renin-angiotensin system.

Probabilistic risk assessment (PRA) update in light of the accident at Fukushima Daiichi Nuclear Power Station - 15461

International Nuclear Information System (INIS)

Maeda, K.; Abe, H.; Hirokawa, N.; Satou, C.

2015-01-01

We have performed internal and external event probabilistic risk assessments (PRA) for boiling water reactor power nuclear plants to identify the important accident sequence groups and to evaluate the effectiveness of the additional severe accident measures, regarding to the new regulatory requirements implemented after the accident at Fukushima Daiichi Nuclear Power Station in Japan in 2011. In addition, we will further update our PRA by extracting problems and improvements from the current PRA, by catching up the state-of-the-art knowledge, modern PRA methodologies in order to contribute voluntarily to safety improvement as well as to comply with regulations. In this document, prior to the extensive PRA updates, we would describe technical contents and qualitative results about PRA updates that have been performed preliminary so far, especially about the external event (seismic) PRA and how to model the additionally deployed severe accident measures (e.g. power supply car, fire engine) so that they can be function external hazards, such as component failure rate of equipment, human reliability 'out of control room', and mission time extension. (authors)

Comparison of SKIFS 2004:1 and Tillsynshandbok PSA against the ASME PRA Standard and European requirements on PSA

International Nuclear Information System (INIS)

Hellstroem, Per

2005-04-01

Requirements on PSA for risk informed applications are expressed in different international documents. The ASME PRA standard published in spring 2002 is one such document, PSA requirements are also expressed in the European Utility Requirements (EUR) for new reactors. The Swedish PSA requirements are provided in the Swedish regulators (SKI) statutes SKIFS 2004:1. SKI also has a review handbook for PSA activities (SKI report 2003:48). The review handbook is a support during review of the utilities PSA activities and the PSAs themselves. The review handbook expresses SKIs expectations by providing so called important aspects for both the PSA work and the PSAs, A comparison of SKIFS requirements and the important aspects in the Review handbook, on one side, and the requirements on PSA in EUR and ASME on the other side, is presented. The comparison shows a large difference in the level of detail in the different documents, where ASME is most detailed and specific. This is expected since the SKI review handbook not is a 'PSA guide' in the same way as the ASME PRA standard. A direct comparison of the ASME PRA standard requirements with the important aspects in the review handbook cannot answer the question which ASME capacity level that is achieved by a PSA meeting all important aspects. The conclusion is that it is not likely to achieve capacity level 2 and 3, since very few ASME level 3 attributes are explicitly expressed as important aspects, though many are expressed in general terms. The review handbook important aspects that are most similar to the ASME capacity level 1 attributes are initiating events, sequence analysis, and system analysis while less similarity is found for analysis of operator actions data analysis, quantification and containment analysis (level 2). Less similarity is found for capacity level 2 and 3. However, the number of additional ASME attributes on capacity level 2 and 3 are few. There are also important aspects in the review handbook that

Renin-sodium profile and renal prostaglandins in the pathogenesis ...

African Journals Online (AJOL)

the patients having normal-renin hypertension. At basal level the ... finding was in keeping with their low-renin hypertension. ... pathological factor in the development of hypertension in blacks. ... Subjects and methods .... zero sphygmomanometer. ..... Part 11. Biochemistry and endocrine. Hypertension 1990; 15(6): 681-685.

Medical Updates Number 5 to the International Space Station Probability Risk Assessment (PRA) Model Using the Integrated Medical Model

Science.gov (United States)

Butler, Doug; Bauman, David; Johnson-Throop, Kathy

2011-01-01

The Integrated Medical Model (IMM) Project has been developing a probabilistic risk assessment tool, the IMM, to help evaluate in-flight crew health needs and impacts to the mission due to medical events. This package is a follow-up to a data package provided in June 2009. The IMM currently represents 83 medical conditions and associated ISS resources required to mitigate medical events. IMM end state forecasts relevant to the ISS PRA model include evacuation (EVAC) and loss of crew life (LOCL). The current version of the IMM provides the basis for the operational version of IMM expected in the January 2011 timeframe. The objectives of this data package are: 1. To provide a preliminary understanding of medical risk data used to update the ISS PRA Model. The IMM has had limited validation and an initial characterization of maturity has been completed using NASA STD 7009 Standard for Models and Simulation. The IMM has been internally validated by IMM personnel but has not been validated by an independent body external to the IMM Project. 2. To support a continued dialogue between the ISS PRA and IMM teams. To ensure accurate data interpretation, and that IMM output format and content meets the needs of the ISS Risk Management Office and ISS PRA Model, periodic discussions are anticipated between the risk teams. 3. To help assess the differences between the current ISS PRA and IMM medical risk forecasts of EVAC and LOCL. Follow-on activities are anticipated based on the differences between the current ISS PRA medical risk data and the latest medical risk data produced by IMM.

Effects of adenosine on renin release from isolated rat glomeruli and kidney slices

DEFF Research Database (Denmark)

Skøtt, O; Baumbach, L

1985-01-01

was used. The specificity of the renin release process was validated by measuring adenylate kinase as a marker for cytoplasmatic leak. Adenosine (10 micrograms/ml) halved basal renin release from incubated KS as compared to controls (P less than 0.001, n = 8, 8). Renin release from LAG stimulated...... by calcium depletion was also inhibited (P less than 0.05, n = 8, 9) whereas basal release was not affected (n = 6, 12). No effect was detected neither on basal nor on calcium stimulated renin release from SAG. We conclude that adenosine inhibits renin release in vitro by a mechanism independent...

Prediction of renovascualar hypertension by captopril-stimulated renal vein renin ratios

International Nuclear Information System (INIS)

Roubidoux, M.A.; Dunnick, N.R.; Svetkey, L.; Newmann, G.E.; Cohan, R.H.; Kadir, S.; Klotman, P.

1989-01-01

The authors have prospectively studied 114 patients with suspected renovascular hypertension to determine whether captopril-stimulated, selective, renal vein renin ratios could be used to predict renovascular hypertension. As judged by the response to correction of renal artery lesions, 14 patients had renovascular hypertension, and renal vein renin ratios were significant in eight (sensitivity 57%). Overall, the positive predictive value of renal vein renin ratios was 33%, and the negative predictive value was 89%. The authors concluded that, in patients with renal artery stenosis, renal vein renin ratios predict neither the need for conventional arteriography nor potential benefit from the correction of vascular insufficiency

Current and future applications of PRA in regulatory activities

Energy Technology Data Exchange (ETDEWEB)

Speis, T.P.; Murphy, J.A.; Cunningham, M.A. [Nuclear Regulatory Commission, Washington, DC (United States)] [and others

1995-04-01

Probabilistic Risk Assessments (PRAs) have proven valuable in providing the regulators, the nuclear plant operators, and the reactor designers insights into plant safety, reliability, design and operation. Both the NRC Commissioners and the staff have grown to appreciate the valuable contributions PRAs can have in the regulatory arena, though I will admit the existence of some tendencies for strict adherence to the deterministic approach within the agency and the public at large. Any call for change, particularly one involving a major adjustment in approach to the regulation of nuclear power, will meet with a certain degree of resistance and retrenchment. Change can appear threatening and can cause some to question whether the safety mission is being fulfilled. This skepticism is completely appropriate and is, in fact, essential to a proper transition towards risk and performance-based approaches. Our task in the Office of Nuclear Regulatory Research is to increase the PRA knowledge base within the agency and develop appropriate guidance and methods needed to support the transitioning process.

PRA and Conceptual Design

Science.gov (United States)

DeMott, Diana; Fuqua, Bryan; Wilson, Paul

2013-01-01

Once a project obtains approval, decision makers have to consider a variety of alternative paths for completing the project and meeting the project objectives. How decisions are made involves a variety of elements including: cost, experience, current technology, ideologies, politics, future needs and desires, capabilities, manpower, timing, available information, and for many ventures management needs to assess the elements of risk versus reward. The use of high level Probabilistic Risk Assessment (PRA) Models during conceptual design phases provides management with additional information during the decision making process regarding the risk potential for proposed operations and design prototypes. The methodology can be used as a tool to: 1) allow trade studies to compare alternatives based on risk, 2) determine which elements (equipment, process or operational parameters) drives the risk, and 3) provide information to mitigate or eliminate risks early in the conceptual design to lower costs. Creating system models using conceptual design proposals and generic key systems based on what is known today can provide an understanding of the magnitudes of proposed systems and operational risks and facilitates trade study comparisons early in the decision making process. Identifying the "best" way to achieve the desired results is difficult, and generally occurs based on limited information. PRA provides a tool for decision makers to explore how some decisions will affect risk before the project is committed to that path, which can ultimately save time and money.

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

Science.gov (United States)

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.

System 80+TM PRA insights on severe accident prevention and mitigation

International Nuclear Information System (INIS)

Finnicum, D.J.; Jacob, M.C.; Schneider, R.E.; Weston, R.A.

2004-01-01

The System 80 + design is ABB-CE's standardized evolutionary Advanced Light Water Reactor (ALWR) design. It incorporates design enhancements based on Probabilistic Risk Assessment (PRA) insights, guidance from the ALWR Utility Requirements Document (URD), and US NRC's Severe Accident Policy. Major severe accident prevention and mitigation design features of the System 80 + design are described. The results of the System 80 + PRA are presented and the insights gained from the PRA sensitivity analyses are discussed. ABB-CE considered defense-in-depth for accident prevention and mitigation early in the design process and used robust design features to ensure that the System 80 + design achieved a low core damage frequency, low containment conditional failure probability, and excellent deterministic containment performance under severe accident conditions and to ensure that the risk was properly allocated among design features and between prevention and mitigation. (author)

The Evaluation of the Adequacy of PRA Results for Risk-informed Decision Makings With Respect to Incompleteness

International Nuclear Information System (INIS)

Kang, Kyungmin; Jae, Moosung

2007-01-01

PRA(Probabilistic Risk Assessment), as a quantitative tool, has many strengths as well as weaknesses. There are several limitations on the use of PRA techniques for risk modeling and analysis. First, the true values of most model inputs are unknown. Ideally, probability distribution models are well developed and assigned to the unknown input parameters to reflect the analyst's state of knowledge of the values of this input parameter. The problem of overconfidence and lack of confidence in the values of certain model input parameters can lead to inaccurate PRA results. Secondly, the analyst's lack of knowledge of a system's practical application as opposed to its theoretical operation can lead to modeling errors. The quality of PRAs has been addressed by a number of regulatory and industry organizations Some have argued that a good PRA should be a complete, full scope, three level PRA, while others have claimed that the quality of a PRA should be measured with respect to the application and decision supported. we show by way of an example that the adequacy of a PRA results is important to risk-informed decision making process and should be measured with respect to the application and decision supported

Reliability design of a critical facility: An application of PRA methods

International Nuclear Information System (INIS)

Souza Vieira Neto, A.; Souza Borges, W. de

1987-01-01

Although a general agreement concerning the enforcement of reliability (probabilistic) design criteria for nuclear utilities is yet to be achieved. PRA methodology can still be used successfully as a project design and review tool, aimed at improving system's prospective performance or minimizing expected accident consequences. In this paper, the potential of such an application of PRA methods is examined in the special case of a critical design project currently being developed in Brazil. (orig.)

Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by regulating skeletal renin-angiotensin system and kallikrein-kinin system in ovariectomized mice.

Science.gov (United States)

Zhang, Y; Wang, L; Song, Y; Zhao, X; Wong, M S; Zhang, W

2016-03-01

The skeletal renin-angiotensin system contributes to the development of osteoporosis. The renin inhibitor aliskiren exhibited beneficial effects on trabecular bone of osteoporotic mice, and this action might be mediated through angiotensin and bradykinin receptor pathways. This study implies the potential application of renin inhibitor in the management for postmenopausal osteoporosis. The skeletal renin-angiotensin system plays key role in the pathological process of osteoporosis. The present study is designed to elucidate the effect of renin inhibitor aliskiren on trabecular bone and its potential action mechanism in ovariectomized (OVX) mice. The OVX mice were treated with low dose (5 mg/kg) or high dose (25 mg/kg) of aliskiren or its vehicle for 8 weeks. The bone turnover markers were measured by ELISA. The structural parameters of trabecular bone at lumbar vertebra (LV) and distal femoral metaphysis were measured by micro-CT. The expression of messenger RNA (mRNA) and protein was studied by RT-PCR and immunoblotting, respectively. Aliskiren treatment reduced urinary excretion of calcium and serum level of tartrate-resistant acid phosphatase in OVX mice. The treatment with aliskiren significantly increased bone volume (BV/TV) and connectivity density (Conn.D) of trabecular bone at LV-2 and LV-5 as well as dramatically enhanced BV/TV, Conn.D, bone mineral density (BMD/BV) and decreased bone surface (BS/BV) at the distal femoral end. Aliskiren significantly down-regulated the expression of angiotensinogen, angiotensin II (Ang II), Ang II type 1 receptor, bradykinin receptor (BR)-1, and osteocytic-specific gene sclerostin as well as the osteoclast-specific genes, including carbonic anhydrase II, matrix metalloproteinase-9, and cathepsin K. This study revealed that renin inhibitor aliskiren exhibited the beneficial effects on trabecular bone of ovariectomy-induced osteoporotic mice, and the underlying mechanism for this action might be mediated through Ang II and

Normotensive sodium loading in normal man: Regulation of renin secretion during beta-receptor blockade

DEFF Research Database (Denmark)

Mølstrøm, Simon; Larsen, Nils Heden; Simonsen, Jane Angel

2008-01-01

and renal excretion during slow saline loading at constant plasma sodium con-centration (Na-loading: 12 micromol Na(+) kg(-1) min(-1) for 4 h). Normal subjects were studied on low-sodium intake with and without beta1-adrenergic blockade by metoprolol. Metoprolol per se reduced RAAS activity as expected. Na......Saline administration may change renin system (RAAS) activity and sodium excretion at constant mean arterial pressure (MAP). We hypothesized that such responses are elicited mainly by renal sympathetic nerve activity by beta1-receptors (beta1-RSNA), and tested the hypothesis by studying RAAS......-loading decreased plasma renin (PRC) by 1/3, AngII by 1/2, and aldosterone (pAldo) by 2/3, (all psodium excretion increased indistinguishably with and without metoprolol (16+/-2 to 71...

Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport

DEFF Research Database (Denmark)

Lorenz, J N; Weihprecht, H; Schnermann, J

1991-01-01

salts to inhibit renin secretion, starting from a stimulated value produced by low-NaCl perfusion. Perfusion with a high-NaCl solution decreased renin secretion from 58.9 to 14.8 nGU/min, which served as a positive control. Addition of choline chloride decreased renin secretion from 42.7 to 16.6 n...

40 CFR 180.1200 - Pseudomonas fluorescens strain PRA-25; temporary exemption from the requirement of a tolerance.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Pseudomonas fluorescens strain PRA-25... RESIDUES IN FOOD Exemptions From Tolerances § 180.1200 Pseudomonas fluorescens strain PRA-25; temporary... established for residues of the microbial pesticide, pseudomonas fluorescens strain PRA-25 when used on peas...

Renin secretion from permeabilized juxtaglomerular cells requires a permeant cation

DEFF Research Database (Denmark)

Jensen, B L; Ellekvist, Peter; Skøtt, O

1999-01-01

The cytosolic concentration of chloride correlates directly with renin secretion from renal juxtaglomerular granular (JG) cells. In the present study, the mechanism by which chloride stimulates renin release was investigated in a preparation of permeabilized rat glomeruli with attached JG cells....... An isosmotic increase in the concentration of chloride by 129 mM stimulated renin release 16- to 20-fold. Substitution of K+ by the impermeant cation N-methyl-d-glucamine (NMDG) abolished this response, while substitution with Na+ caused marginal inhibition. Substitution with Cs+ had no effect. Addition...... of sucrose, which permeates the secretory granules poorly, also abolished the stimulation of renin secretion by KCl. The response to KCl was not affected by K+-channel antagonists or by agonists of K+ channels. Chloride channel blockers were also without effect on the secretory response to KCl. When the ATP...

Selecting the seismic HRA approach for Savannah River Plant PRA revision 1

International Nuclear Information System (INIS)

Papouchado, K.; Salaymeh, J.

1993-10-01

The Westinghouse Savannah River Company (WSRC) has prepared a level I probabilistic risk assessment (PRA), Rev. 0 of reactor operations for externally-initiated events including seismic events. The SRS PRA, Rev. 0 Seismic HRA received a critical review that expressed skepticism with the approach used for human reliability analysis because it had not been previously used and accepted in other published PRAs. This report provides a review of published probabilistic risk assessments (PRAs), the associated methodology guidance documents, and the psychological literature to identify parameters important to seismic human reliability analysis (HRA). It also describes a recommended approach for use in the Savannah River Site (SRS) PRA. The SRS seismic event PRA performs HRA to account for the contribution of human errors in the accident sequences. The HRA of human actions during and after a seismic event is an area subject to many uncertainties and involves significant analyst judgment. The approach recommended by this report is based on seismic HRA methods and associated issues and concerns identified from the review of these referenced documents that represent the current state-of-the- art knowledge and acceptance in the seismic HRA field

An evaluation of the reliability and usefulness of external-initiator PRA (probabilistic risk analysis) methodologies

Energy Technology Data Exchange (ETDEWEB)

Budnitz, R.J.; Lambert, H.E. (Future Resources Associates, Inc., Berkeley, CA (USA))

1990-01-01

The discipline of probabilistic risk analysis (PRA) has become so mature in recent years that it is now being used routinely to assist decision-making throughout the nuclear industry. This includes decision-making that affects design, construction, operation, maintenance, and regulation. Unfortunately, not all sub-areas within the larger discipline of PRA are equally mature,'' and therefore the many different types of engineering insights from PRA are not all equally reliable. 93 refs., 4 figs., 1 tab.

An evaluation of the reliability and usefulness of external-initiator PRA [probabilistic risk analysis] methodologies

International Nuclear Information System (INIS)

Budnitz, R.J.; Lambert, H.E.

1990-01-01

The discipline of probabilistic risk analysis (PRA) has become so mature in recent years that it is now being used routinely to assist decision-making throughout the nuclear industry. This includes decision-making that affects design, construction, operation, maintenance, and regulation. Unfortunately, not all sub-areas within the larger discipline of PRA are equally ''mature,'' and therefore the many different types of engineering insights from PRA are not all equally reliable. 93 refs., 4 figs., 1 tab

Use of plant-specific PRA in an EOP scope audit

International Nuclear Information System (INIS)

O'Brien, J.J.

1991-01-01

Traditionally, decisions on which accident scenarios to proceduralize as emergency operating procedures (EOPs) have been based on existing design basis analyses, engineering judgment, and probabilistic risk assessments (PRAs) on generic plants. This approach has important strengths and limits. The major limitation of generic PRAs is their inability to account for plant-specific features. Use of plant-specific PRA to determine the impact of proceduralizing, or not proceduralizing, responses to scenarios considers plant-specific features. This helps to eliminate unnecessary EOPs, thus allowing resources to be concentrated on scenarios that are more important for a particular plant. In preparation for a US Nuclear Regulatory Commission audit, a plant-specific PRA was used to assess and quantify the plant's previous decision not to implement six reference emergency response guidelines (ERGs) as procedures. The original justification for nonimplementation of the ERGs was based on engineering judgment. The PRA provided a quantitative justification for implementation/nonimplementation of each guidelines. This analysis accounted for plant-specific design features not common to all reference plants

Task analysis: How far are we from usable PRA input

International Nuclear Information System (INIS)

Gertman, D.I.; Blackman, H.S.; Hinton, M.F.

1984-01-01

This chapter reviews data collected at the Idaho National Engineering Laboratory for three DOE-owned reactors (the Advanced Test Reactor, the Power Burst Facility, and the Loss of Fluids Test Reactor) in order to identify usable Probabilistic Risk Assessment (PRA) input. Task analytic procedures involve the determination of manning and skill levels as a means of determining communication requirements, in assessing job performance aids, and in assessing the accuracy and completeness of emergency and maintenance procedures. The least understood aspect in PRA and plant reliability models is the human factor. A number of examples from the data base are discussed and offered as a means of providing more meaningful data than has been available to PRA analysts in the past. It is concluded that the plant hardware-procedures-personnel interfaces are essential to safe and efficient plant operations and that task analysis is a reasonably sound way of achieving a qualitative method for identifying those tasks most strongly associated with task difficulty, severity of consequence, and error probability

Role of (Pro)Renin Receptor in Albumin Overload-Induced Nephropathy in Rats.

Science.gov (United States)

Fang, Hui; Deng, Mokan; Zhang, Linlin; Lu, Aihua; Su, Jiahui; Xu, Chuanming; Zhou, Li; Wang, Lei; Ou, Jing-Song; Wang, Weidong; Yang, Tianxin

2018-05-30

Proteinuria is not only a common feature of chronic kidney diseases (CKD) but also an independent risk factor promoting CKD progression to end-stage renal failure. However, the underlying molecular mechanisms for protein overload-induced renal injury remain elusive. The present study examined the role of (pro)renin receptor (PRR) in pathogenesis of albumin overload (AO)-induced nephropathy and activation of intrarenal renin-angiotensin system (RAS) in rats. Wistar rats underwent unilateral nephrectomy and were treated for 7 weeks with vehicle, bovine serum albumin (5 g/kg/d via a single i.p. injection) alone or in conjunction with a PRR decoy inhibitor PRO20 (500 μg/kg/d via 3 s.c. injections). The AO rat model exhibited severe proteinuria, tubular necrosis, and interstitial fibrosis, oxidative stress, inflammation, accompanied by elevated urinary N-acetyl-beta-D-glucosaminidase activity and urinary β2-microglobulin secretion, all of which were significantly attenuated by PRO20. Urinary and renal levels of renin, angiotensinogen (AGT), and Ang II were elevated by AO and suppressed by PRO20, contrasting to largely unaltered plasma levels of the RAS parameters. The AO model also showed increased renal expression of full-length PRR and soluble PRR (sPRR) and urinary excretion of sPRR. Taken together, we conclude that PRR antagonism with PRO20 alleviates AO-induced nephropathy via inhibition of intrarenal RAS.

Certification plan for safety and PRA codes

International Nuclear Information System (INIS)

Toffer, H.; Crowe, R.D.; Ades, M.J.

1990-05-01

A certification plan for computer codes used in Safety Analyses and Probabilistic Risk Assessment (PRA) for the operation of the Savannah River Site (SRS) reactors has been prepared. An action matrix, checklists, and a time schedule have been included in the plan. These items identify what is required to achieve certification of the codes. A list of Safety Analysis and Probabilistic Risk Assessment (SA ampersand PRA) computer codes covered by the certification plan has been assembled. A description of each of the codes was provided in Reference 4. The action matrix for the configuration control plan identifies code specific requirements that need to be met to achieve the certification plan's objectives. The checklist covers the specific procedures that are required to support the configuration control effort and supplement the software life cycle procedures based on QAP 20-1 (Reference 7). A qualification checklist for users establishes the minimum prerequisites and training for achieving levels of proficiency in using configuration controlled codes for critical parameter calculations

PRA: a powerful engineering decision tool

International Nuclear Information System (INIS)

Carvalho, H.G. de.

1988-03-01

The probabilistic risk analysis (PRA) is studied and its historical development is briefly presented. Human factors, sofware and guides, improvement of utility management of nuclear power operations are discussed. The development of a standardized LWR design, optimized for safety, reliability and economy is studied. The impact of risk assessments in public acceptance of nuclear power is discussed. (M.A.C.) [pt

Mutation of praR in Rhizobium leguminosarum enhances root biofilms, improving nodulation competitiveness by increased expression of attachment proteins.

Science.gov (United States)

Frederix, Marijke; Edwards, Anne; Swiderska, Anna; Stanger, Andrew; Karunakaran, Ramakrishnan; Williams, Alan; Abbruscato, Pamela; Sanchez-Contreras, Maria; Poole, Philip S; Downie, J Allan

2014-08-01

In Rhizobium leguminosarum bv. viciae, quorum-sensing is regulated by CinR, which induces the cinIS operon. CinI synthesizes an AHL, whereas CinS inactivates PraR, a repressor. Mutation of praR enhanced biofilms in vitro. We developed a light (lux)-dependent assay of rhizobial attachment to roots and demonstrated that mutation of praR increased biofilms on pea roots. The praR mutant out-competed wild-type for infection of pea nodules in mixed inoculations. Analysis of gene expression by microarrays and promoter fusions revealed that PraR represses its own transcription and mutation of praR increased expression of several genes including those encoding secreted proteins (the adhesins RapA2, RapB and RapC, two cadherins and the glycanase PlyB), the polysaccharide regulator RosR, and another protein similar to PraR. PraR bound to the promoters of several of these genes indicating direct repression. Mutations in rapA2, rapB, rapC, plyB, the cadherins or rosR did not affect the enhanced root attachment or nodule competitiveness of the praR mutant. However combinations of mutations in rapA, rapB and rapC abolished the enhanced attachment and nodule competitiveness. We conclude that relief of PraR-mediated repression determines a lifestyle switch allowing the expression of genes that are important for biofilm formation on roots and the subsequent initiation of infection of legume roots. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

MAAP4.0.7 analysis and justification for PRA level 1 mission success criteria

International Nuclear Information System (INIS)

Butler, J.S.; Kapitz, D.; Martin, R.P.; Seifaee, F.; Sundaram, R.K.

2008-01-01

The U.S. EPR is a 4590 MWth evolutionary pressurized water reactor that incorporates proven technology with innovative system architecture to provide an unprecedented level of safety. One of the measures of safety is provided by Probability Risk Assessment (PRA). PRA Level 1 concerns the evaluation of core damage frequency based on various initiating events and the success or failure of various plant event mitigation features. Determination of this measure requires mission success criteria, which are used to build the logic that makes up the fault trees and event trees of the Level 1 PRA. Developing mission success criteria for the wide variety of accident sequences modeled in the PRA Level 1 model requires a large number of thermal hydraulic calculations. The MAAP4 code, developed by Fauske and Associates, Inc. and distributed by EPRI, was chosen to perform these calculations because of its fast computation times relative to more sophisticated thermal-hydraulics codes This is a unique application of MAAP4, which was developed specifically for severe accident and PRA Level 2 analysis. As such, a study was performed to assess MAAP4 's thermal-hydraulic response capabilities against AREVA 's S-RELAP5 best-estimate integral systems thermal-hydraulic analysis code. (authors)

PRA quality and use

International Nuclear Information System (INIS)

Okrent, D.; Apostolakis, G.; Whitley, R.; Garrick, B.J.

1982-10-01

This report deals with several inter-related aspects of probabilistic risk assessment. Some prior opinion regarding quality assurance, methodology and questions of peer review are reviewed, followed by comments by the authors on these and related subjects. Problems arising in decision-making by different groups concerning the meaning and validity of a PRA are examined, and the role of performance criteria in helping to achieve consensus is treated. Finally, a general approach to the development of performance criteria for systems and functions by the retrospective comparison of existing PRAs is proposed and examined in a preliminary fashion

Influence of chronic renal failure on captopril pharmacokinetics and clinical and biological effects in hypertensive patients.

OpenAIRE

Giudicelli, J F; Chaignon, M; Richer, C; Giroux, B; Guedon, J

1984-01-01

The pharmacokinetic parameters of unchanged plasma captopril and the kinetics of the drug effects on plasma converting enzyme activity (PCEA), plasma renin activity (PRA), plasma aldosterone (PA) and mean blood pressure (MBP) were studied over 24 h after oral administration in three groups of hypertensive patients: with normal renal function (group 1, plasma creatinine less than 110 mumol/l, n = 10), with moderate chronic renal failure (group 2, 135 less than plasma creatinine less than 450 m...

PRA: an evaluation of state-of-the-art

International Nuclear Information System (INIS)

Joksimovich, V.

1985-01-01

Some elements of the probabilistic risk assessment (PRA) methodology can be characterized as mature and are even ready for some kind of a standardization effort. Other elements are still, however, in a rapid state of evolution. Questions are continuously being asked regarding maturity of PRA techniques vis-a-vis a regulatory decision-making process. Establishing a framework for evaluating state-of-the-art in any technological field is a challenging task. An implementation of a selected framework to a satisfactory conclusion is a monumental task. Of course, these types of issues can be discussed meaningfully only if they are tied to a particular application. The author's participation in the NSF-sponsored risk assessment project is discussed in the paper. The evaluation employed here makes use of the following five evaluation criteria: logical soundness, completeness, accuracy, acceptability, and practicality

Manutenção de brinquedo em praças públicas

Directory of Open Access Journals (Sweden)

Fabio Namiki

2007-12-01

Full Text Available O artigo apresenta o jacaré, um dos brinquedos executados no âmbito do Programa Centros de Bairro, que foi responsável pela implantação de cerca de 50 praças na cidade de São Paulo entre 2002 e 2004. O conjunto dos brinquedos deste programa foi apresentado e analisado no mestrado “Manutenção de praças na cidade de São Paulo. Estudo de caso: brinquedos do programa Centros de Bairro”, segundo metodologia que pode ser também aplicada para outros componentes de uma praça e mesmo para a praça em si. Espera-se que esta metodologia sirva como instrumento para o planejamento das ações de manutenção de praças e de mobiliários urbanos de modo geral. Neste texto, são apresentadas informações (da mesma forma que seriam em um manual de uso, operação e manutenção do projeto do brinquedo, obtidas junto aos responsáveis pelo programa, em entrevista com o executor dos brinquedos e através dos desenhos e documentos produzidos para a licitação e execução das peças. São também apresentadas as informações obtidas a partir das inspeções a campo e estimativas do custo de manutenção preventiva. Frente ao custo de reposição de um brinquedo novo, os valores da manutenção nos provam a importância econômica de tais ações.

Effects of gender on screening value of aldosterone-renin ratio for primary aldosteronism

Directory of Open Access Journals (Sweden)

Ye-qiong SONG

2017-02-01

Full Text Available Objective　To explore the potential influence of gender on screening value of aldosterone-renin ratio (ARR for primary aldosteronism (PA. Methods　The biochemical parameters were collected of 451 PA patients and 300 essential hypertension (EH patients who were diagnosed in the General Hospital of PLA from 1992 to 2014. Each group was then divided into two groups by gender. The clinical characteristics were compared and then the receiver operating characteristic curve (ROC was conducted to evaluate the best cut-off value. Results　The plasma aldosterone concentration (PAC, serum sodium and ARR were much higher, but the plasma rennin activity (PRA, serum potassium and BMI were much lower in PA patients than in EH patients (P0.05. The best cut-off value of ARR in male PA patients was 19.11, the relevant area under the curve (AUC was 0.968, the sensitivity and specificity was 92.44% and 93.08%, and the Youden index (YI was 0.86. The best cut-off value of ARR in female PA patients was 27.26, with AUC 0.956, sensitivity 92.07%, specificity 90.00% and YI 0.82, respectively. If the cut-off value was set at 27.26 in males, the specificity would rise a little, but the sensitivity and YI would sharply decrease. Similarly, the sensitivity would increase a little but the specificity and YI would fall substantially if the cut-off value in females was set at 19.11. The best cut-off value of ARR in men was smaller than the official value recommended by guidelines. Conclusion　Gender is an important factor should be considered while ARR is used in PA screening, and the cut-off value of ARR in screening female PA patients should be setting higher. DOI: 10.11855/j.issn.0577-7402.2017.01.10

Using level-I PRA for enhanced safety of the advanced neutron source reactor

International Nuclear Information System (INIS)

Ramsey, C.T.; Linn, M.A.

1995-01-01

The phase-1, level-I probabilistic risk assessment (PRA) of the Advanced Neutron Source (ANS) reactor has been completed as part of the conceptual design phase of this proposed research facility. Since project inception, PRA and reliability concepts have been an integral part of the design evolutions contributing to many of the safety features in the current design. The level-I PRA has been used to evaluate the internal events core damage frequency against project goals and to identify systems important to safety and availability, and it will continue to guide and provide support to accident analysis, both severe and nonsevere. The results also reflect the risk value of defense-in-depth safety features in reducing the likelihood of core damage

Investigating the association of vitamin D with blood pressure and the renin-angiotensin-aldosterone system in hypertensive subjects: a cross-sectional prospective study.

Science.gov (United States)

Cremer, Antoine; Tambosco, Chloé; Corcuff, Jean-Benoît; Boulestreau, Romain; Gaillard, Prune; Lainé, Marion; Papaioannou, Georgios; Gosse, Philippe

2018-02-01

The hypothesis that vitamin D (25(OH)D) insufficiency plays a role in occurring of various disease has led to a rise in requests of dosages and to an increase of health-care costs. 25(OH)D insufficiency is associated with increased risk of cardiovascular disease and hypertension in many studies. Animal studies demonstrated that 25(OH)D insufficiency activates renin angiotensin system but corresponding humans data are limited. The aim of the study was to document relationship between 25(OH)D, blood pressure, and renin angiotensin system in hypertensive subjects. In all, 248 hypertensive individuals, 46.8 years (±14), were hospitalized for an etiological assessment of hypertension in this cross-sectional study over two calendar years. 25(OH)D, plasma renin activity, and aldosterone were determined in stringent conditions and blood pressure was measure. Statistical analyses were carried out to analyze the association between 25(OH)D, blood pressure, and renin angiotensin system using linear and logistic regressions with adjustments on relevant variables. In all, 80% of the studied population had a 25(OH)D insufficiency. There were no significant association between 25(OH)D and levels of systolic or diastolic blood pressure, plasma renin activity, and aldosterone whatever the statiscal method used after adjustment. 25(OH)D is not associated with blood pressure and renin angiontensin component in hypertensive subjects. These results corroborate the interventional studies which are for a large majority negatives. A new definition of the 25(OH)D insufficiency in general population is necessary.

Recombinant erythropoietin acutely decreases renal perfusion and decouples the renin-angiotensin-aldosterone system

DEFF Research Database (Denmark)

Aachmann-Andersen, Niels J.; Christensen, Soren J.; Lisbjerg, Kristian

2018-01-01

The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt...... that seems to decouple the activity of the renin-angiotensin-aldosterone system from changes in renal hemodynamics. This may serve as a negative feed-back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect...... of rhEPO on renal hemodynamics and a decoupling of the renin-angiotensin-aldosterone system....

Radioimmunologic analysis of the state of the renin-angiotensin-aldosterone system in arterial hypertension

International Nuclear Information System (INIS)

Slavnov, V.N.; Yakovlev, A.A.; Gandzha, T.I.; Yugrinov, O.G.

1986-01-01

For 110 patients having various forms of arterial hypertension (hypertension, aldersteronoma, phaeochromocytoma, corticosteroma) the parameters of the system renin-angiotensin-aldosterone (RAA) were measured. Basal values of aldosterone and renin activity in blood were determined as well as their concentration in blood taken from the vena cava inferior, renal and adrenal veins during selective renography. The 24-hours rhythm of the hormones in the blood, the reaction of the glomerular zone of the adrenal cortex and the juxtaglomerular renal system under acute lasix stress was evaluated. It was found, that the system RAA is disturbed in all patients with arterial hypertension. This is indicated by changes of aldosterone concentration, renin activity in peripheral blood and in the blood from the vena cava inferior, renal and adrenal veins, the 24-hour rhythm of their concentrations in serum and the reaction to acute lasix stress. The radioimmunoassays of quantitative parameters of the RAA system are decisive for the differential diagnostics of hypertension and suprarenomas connected with a hypertension syndrome. They facilitate a rational choice of the hypertension therapy and the daily distribution of the medicaments for patients with hypertension. The radioimmunoassays can be used for checking the efficiency of medicaments and surgery. (author)

Preliminary ATWS analysis for the IRIS PRA

International Nuclear Information System (INIS)

Maddalena Barra; Marco S Ghisu; David J Finnicum; Luca Oriani

2005-01-01

Full text of publication follows: The pressurized light water cooled, medium power (1000 MWt) IRIS (International Reactor Innovative and Secure) has been under development for four years by an international consortium of over 21 organizations from ten countries. The plant conceptual design was completed in 2001 and the preliminary design is nearing completion. The pre-application licensing process with NRC started in October, 2002. IRIS has been primarily focused on establishing a design with innovative safety characteristics. The first line of defense in IRIS is to eliminate event initiators that could potentially lead to core damage. In IRIS, this concept is implemented through the 'safety by design' approach, which allows to minimize the number and complexity of the safety systems and required operator actions. The end result is a design with significantly reduced complexity and improved operability, and extensive plant simplifications to enhance construction. To support the optimization of the plant design and confirm the effectiveness of the safety by design approach in mitigating or eliminating events and thus providing a significant reduction in the probability of severe accidents, the PRA is being used as an integral part of the design process. A preliminary but extensive Level 1 PRA model has been developed to support the pre-application licensing of the IRIS design. As a result of the Preliminary IRIS PRA, an optimization of the design from a reliability point of view was completed, and an extremely low (about 1.2 E -8 ) core damage frequency (CDF) was assessed to confirm the impact of the safety by design approach. This first assessment is a result of a PRA model including internal initiating events. During this assessment, several assumptions were necessary to complete the CDF evaluation. In particular Anticipated Transients Without Scram (ATWS) were not included in this initial assessment, because their contribution to core damage frequency was assumed

Differences in cortical and pituitary activity in response to hypoglycaemia and cognitive testing in healthy men with different basal activity of the renin-angiotensin system

DEFF Research Database (Denmark)

Bie-Olsen, Lise G; Pedersen-Bjergaard, Ulrik; Kjaer, Troels W

2010-01-01

in cerebral activity during hypoglycaemia and cognitive testing in two groups of healthy men with different basal RAS activity. METHODS: Ten healthy men with high RAS activity and 10 with low activity underwent six oxygen-15-labelled water positron emission tomography scans: twice during normoglycaemia, twice......INTRODUCTION: High renin-angiotensin system (RAS) activity has been associated with a high risk of severe hypoglycaemia in patients with type 1 diabetes and with cognitive deterioration during experimental hypoglycaemia in healthy subjects. The aim of this study was to describe possible differences...... during insulin-induced hypoglycaemia and twice during post-hypoglycaemia. During the scans, the subjects performed a computer-based reaction time test. RESULTS: Occipital areas were consistently more activated in the low RAS group than in the high RAS group throughout all three conditions. During...

Dietary sodium modulation of aldosterone activation and renal function during the progression of experimental heart failure.

Science.gov (United States)

Miller, Wayne L; Borgeson, Daniel D; Grantham, J Aaron; Luchner, Andreas; Redfield, Margaret M; Burnett, John C

2015-02-01

Aldosterone activation is central to the sodium–fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: (i) high sodium [250 mEq (5.8 g) per day, n =6]; (ii) standard sodium [58 mEq (1.3 g) per day, n =6]; and (iii) sodium restriction [11 mEq (0.25 g) per day, n =6]. During the 38-day study, haemodynamics, renal function, plasma renin activity (PRA), and aldosterone were measured. Changes in haemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups; however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression.

Intramuscular renin-angiotensin system is activated in human muscular dystrophy.

Science.gov (United States)

Sun, Guilian; Haginoya, Kazuhiro; Dai, Hongmei; Chiba, Yoko; Uematsu, Mitsugu; Hino-Fukuyo, Naomi; Onuma, Akira; Iinuma, Kazuie; Tsuchiya, Shigeru

2009-05-15

To investigate the role of the muscular renin-angiotensin system (RAS) in human muscular dystrophy, we used immunohistochemistry and Western blotting to examine the cellular localization of angiotensin-converting enzyme (ACE), the angiotensin II type 1 receptor (AT1) and the angiotensin II type 2 receptor (AT2) in muscle biopsies from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and congenital muscular dystrophy (CMD). In normal muscle, ACE was expressed in vascular endothelial cells and neuromuscular junctions (NMJs), whereas AT1 was immunolocalized to the smooth muscle cells of blood vessels and intramuscular nerve twigs. AT2 was immunolocalized in the smooth muscle cells of blood vessels. These findings suggest that the RAS has a functional role in peripheral nerves and NMJs. ACE and AT1, but AT2 immunoreactivity were increased markedly in dystrophic muscle as compared to controls. ACE and the AT1 were strongly expressed in the cytoplasm and nuclei of regenerating muscle fibers, fibroblasts, and in macrophages infiltrating necrotic fibers. Double immunolabeling revealed that activated fibroblasts in the endomysium and perimysium of DMD and CMD muscle were positive for ACE and AT1. Triple immunolabeling demonstrated that transforming growth factor-beta1 (TGF-beta1) and ACE were colocalized on the cytoplasm of activated fibroblasts in dystrophic muscle. Furthermore, Western blotting showed increases in the expression of AT1 and TGF-beta1 protein in dystrophic muscle, which coincided with our immunohistochemical results. The overexpression of ACE and AT1 in dystrophic muscle would likely result in the increased production of Ang II, which may act on these cells in an autocrine manner via AT1. The activation of AT1 may induce fibrous tissue formation through overexpression of TGF-beta1, which potently activates fibrogenesis and suppresses regeneration. In conclusion, our results imply that the intramuscular RAS-TGF-beta1 pathway

Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone study

Directory of Open Access Journals (Sweden)

McInnes Gordon T

2007-05-01

Full Text Available Abstract Background High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT1study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study. The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting. Methods/design The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios. Primary Objective – To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios. Secondary Objectives – To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement

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

DEFF Research Database (Denmark)

Pedersen-Bjergaard, Ulrik

2009-01-01

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...... targets and thereby open for prevention of severe hypoglycaemia. Furthermore, subjects with elevated renin-angiotensin system activity and a high rate of severe hypoglycaemia might benefit from pharmacological blockade of the renin-angiotensin system by ACE inhibitors or angiotensin II receptor blockers...

Effect of hypothermic renal ischaemia on renin secretion rate in man

DEFF Research Database (Denmark)

Henriksen, Jens Henrik Sahl; Petersen, H K; Giese, J

1985-01-01

Plasma renin concentration (PRC), renal blood flow (RBF) and renin secretion rate (RSR = renal veno-arterial PRC difference multiplied by renal plasma flow) were measured before and after a period of hypothermic renal ischaemia in seven patients undergoing surgery for renal calculi. After...

The renin-angiotensin system and aging in the kidney

OpenAIRE

Yoon, Hye Eun; Choi, Bum Soon

2014-01-01

Aging is associated with progressive functional deterioration and structural changes in the kidney. Changes in the activity or responsiveness of the renin-angiotensin system (RAS) occur with aging. RAS changes predispose the elderly to various fluid and electrolyte imbalances as well as acute kidney injury and chronic kidney disease. Among the multiple pathways involved in renal aging, the RAS plays a central role. This review summarizes the association of the RAS with structural and function...

Calculation of Fire Severity Factors and Fire Non-Suppression Probabilities For A DOE Facility Fire PRA

International Nuclear Information System (INIS)

Elicson, Tom; Harwood, Bentley; Lucek, Heather; Bouchard, Jim

2011-01-01

Over a 12 month period, a fire PRA was developed for a DOE facility using the NUREG/CR-6850 EPRI/NRC fire PRA methodology. The fire PRA modeling included calculation of fire severity factors (SFs) and fire non-suppression probabilities (PNS) for each safe shutdown (SSD) component considered in the fire PRA model. The SFs were developed by performing detailed fire modeling through a combination of CFAST fire zone model calculations and Latin Hypercube Sampling (LHS). Component damage times and automatic fire suppression system actuation times calculated in the CFAST LHS analyses were then input to a time-dependent model of fire non-suppression probability. The fire non-suppression probability model is based on the modeling approach outlined in NUREG/CR-6850 and is supplemented with plant specific data. This paper presents the methodology used in the DOE facility fire PRA for modeling fire-induced SSD component failures and includes discussions of modeling techniques for: Development of time-dependent fire heat release rate profiles (required as input to CFAST), Calculation of fire severity factors based on CFAST detailed fire modeling, and Calculation of fire non-suppression probabilities.

Human renin 5'-flanking DNA to nucleotide-2750.

Science.gov (United States)

Smith, D L; Jeyapalan, S; Lang, J A; Guo, X H; Sigmund, C D; Morris, B J

1995-01-01

Renin is one of the most important factors in blood pressure and electrolyte regulation in mammals and the renin locus has been implicated in hypertension. To assist studies of promoter control we therefore determined the 5'-flanking sequence of the human gene (REN) to residue -2750 relative to the transcription start site (+1). Sites of homology to consensus sequences for binding of trans-acting factors involved in transcriptional control of other genes were identified, and functionality for two of these (a CRE and Pit-1 site) have so far been demonstrated.

Development of a methodology for conducting an integrated HRA/PRA --

Energy Technology Data Exchange (ETDEWEB)

Luckas, W.J.; Barriere, M.T.; Brown, W.S. (Brookhaven National Lab., Upton, NY (United States)); Wreathall, J. (Wreathall (John) and Co., Dublin, OH (United States)); Cooper, S.E. (Science Applications International Corp., McLean, VA (United States))

1993-01-01

During Low Power and Shutdown (LP S) conditions in a nuclear power plant (i.e., when the reactor is subcritical or at less than 10--15% power), human interactions with the plant's systems will be more frequent and more direct. Control is typically not mediated by automation, and there are fewer protective systems available. Therefore, an assessment of LP S related risk should include a greater emphasis on human reliability than such an assessment made for power operation conditions. In order to properly account for the increase in human interaction and thus be able to perform a probabilistic risk assessment (PRA) applicable to operations during LP S, it is important that a comprehensive human reliability assessment (HRA) methodology be developed and integrated into the LP S PRA. The tasks comprising the comprehensive HRA methodology development are as follows: (1) identification of the human reliability related influences and associated human actions during LP S, (2) identification of potentially important LP S related human actions and appropriate HRA framework and quantification methods, and (3) incorporation and coordination of methodology development with other integrated PRA/HRA efforts. This paper describes the first task, i.e., the assessment of human reliability influences and any associated human actions during LP S conditions for a pressurized water reactor (PWR).

Screening for primary aldosteronism in an argentinian population: a multicenter prospective study.

Science.gov (United States)

Leal Reyna, Mariela; Gómez, Reynaldo M; Lupi, Susana N; Belli, Susana H; Fenili, Cecilia A; Martínez, Marcela S; Ruibal, Gabriela F; Rossi, María A; Chervin, Raúl A; Cornaló, Dora; Contreras, Liliana N; Costa, Liliana; Nofal, María T; Damilano, Sergio A; Pardes, Ester M

2015-10-01

Primary aldosteronism (PA) is characterized by the autonomous overproduction of aldosterone. Its prevalence has increased since the use of the aldosterone (ALD)/plasma renin activity (PRA) ratio (ARR). The objective of this study is to determine ARR and ARC (ALD/plasma renin concentration ratio) cut-off values (COV) and their diagnostic concordance (DC%) in the screening for PA in an Argentinian population.Design multicenter prospective study. We studied 353 subjects (104 controls and 249 hypertensive patients). Serum aldosterone, PRA and ARR were determined. In 220 randomly selected subjects, 160 hypertensive patients and 60 controls, plasma renin concentration (PRC) was simultaneously measured and ARC was determined. According to the 95th percentile of controls, we determined a COV of 36 for ARR and 2.39 for ARC, with ALD ≥ 15 ng/dL. In 31/249 hypertensive patients, ARR was ≥ 36. PA diagnosis was established in 8/31 patients (23/31 patients did not complete confirmatory tests). DC% between ARR and ARC was calculated. A significant correlation between ARR and ARC (r = 0.742; p 0.3 ng/mL/h and PRC > 5 pg/mL. DC% for ARR and ARC above or below 36 and 2.39 was 79.1%, respectively. This first Argentinian multicenter study determined a COV of 36 for ARR and 2.39 for ARC. Applying an ARR ≥ 36 in the hypertensive group, we confirmed PA in a higher percentage of patients than the previously reported one in our population. As for ARC, further studies are needed for its clinical application, since DC% is acceptable only for medium range renin values.

Pemikiran Suksesi Dalam Politik Islam Masa Pra Modern

Directory of Open Access Journals (Sweden)

Mazro'atus Sa'adah

2016-12-01

Abstrak: Pemikiran politik Islam muncul setelah Islam melalui Nabi Muhammad SAW berhasil membentuk sebuah ummat baru, dari peralihan kekuasaan kerajaan/kesukuan kepada Nabi yang kemudian kepada umat. Nabi Muhammad dinilai berhasil dalam mengatur komunitas barunya yang dikendalikan oleh ajarannya dalam seluruh lini kehidupan. Persoalan muncul kemudian setelah beliau wafat, yang akhirnya memunculkan pemikiran tentang suksesi. Artikel ini akan membahas tentang mengapa terjadi suksesi setelah Nabi Muhammad SAW wafat, bagaimana pemikiran para tokoh politik Islam masa pra modern terkait dengan suksesi, dan apa kontribusi pemikiran suksesi ini terhadap politik Islam di Indonesia. Dengan menggunakan pendekatan sejarah, ditemukan bahwa Nabi Muhammad tidak menetapkan siapa yang akan menggantikannya, dan ketika beliau wafat (632 M, para sahabat memilih seorang pemimpin (imam/khalifah. Masa pemerintahan Abu Bakar, Umar dan Usman banyak terjadi perselisihan yang awalnya terkait kepentingan agama namun berkembang menjadi kepentingan politik. Ketika Ali bin Abi Talib diangkat sebagai khalifah, konflik politik berkepanjangan berkaitan dengan pembunuhan Usman, menjadikan timbulnya perang jamal antara Aisyah dan Ali. Pada masa ini perbedaan kepentingan aqidah dipolitisir lebih jauh menjadi sebuah kepentingan politik. Dinamika politik ini kemudian melahirkan mazhab politik Islam klasik yang terbagi dalam tiga mazhab besar yaitu Sunni, Syi'ah dan Khawarij, yang darinya muncul istilah-istilah khilafah, imamah, ahlul halli wal aqdi, bay’ah, walayah dan lain-lain. Dari ketiga mazhab politik ini, kemudian muncul ide pemikiran politik Islam yang sangat kompleks dan berkepanjangan dari para tokoh politik Islam pra modern yang banyak dipengaruhi oleh filosof Yunani. Di Indonesia, pemikiran suksesi dalam politik Islam masa pra modern ini pernah diwacanakan. Namun untuk pemilihan kepala Negara belum terealisasi mengingat Indonesia bukan Negara Islam.

Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome

Directory of Open Access Journals (Sweden)

V Raghunathan

2017-01-01

Full Text Available Hypertension is common in hemolytic uremic syndrome (HUS and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency.

The Renal Renin-Angiotensin System

Science.gov (United States)

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…

Urgensi Pemeriksaan Psikis Pra-Nikah (Studi Pandangan Kepala KUA dan Psikolog Kota Malang

Directory of Open Access Journals (Sweden)

Ika Kurnia Fitriani

2015-06-01

Full Text Available Beberapa negara muslim memberikan perhatian terhadap pemeriksaan psikis pra-nikah bagi calon mempelai, sebagai upaya menanggulangi masalah rumah tangga akibat gangguan kejiwaan di masa yang akan datang. Penelitian ini bertujuan menggali informasi dari Kepala KUA dan Psikolog di Kota Malang tentang pemeriksaan psikis pra-nikah dan urgensinya bagi calon mempelai. Penelitian ini termasuk dalam penelitian lapangan (field reasearch, dengan menggunakan pendekatan kualitatif.  Alanisis data dilakukan melalui tiga tahapan yaitu reduksi data, penyajian data, dan menarik kesimpulan. Pengecekan keabsahan data menggunakan triangulasi sumber yang membandingkan hasil wawancara dengan data sekunder, dan triangulasi teori. Hasil dari penelitian ini menunjukkan bahwa Kepala KUA dan Psikolog di kota Malang menyetujui diadakan pemeriksaan psikis pranikah akan tetapi harus ada aturan hukumnya dan dilakukan sosialisasi agar program menjadi efektif. Selain itu, pemeriksaan psikis pra-nikah tidak bertentangan dengan konsep maqashid al-syari’ah dan konsep sadz al-dzari’ah dalam hukum Islam.

Fire PRA requantification studies. Final report

International Nuclear Information System (INIS)

Parkinson, W.

1993-03-01

This report describes the requantification of two existing fire probabilistic risk assessments (PRAs) using a fire PRA method and data that are being developed by the Electric Power Research Institute (EPRI). The two existing studies are the Seabrook Station Probabilistic Safety Assessment that was made in 1983 and the 1989 NUREG-1150 analysis of the Peach Bottom Plant. Except for the fire methods and data, the original assumptions were used. The results from the requantification show that there were excessive conservatisms in the original studies. The principal reason for a hundredfold reduction in the Peach Bottom core- damage frequency is the determination that no electrical cabinet fire in a switchgear room would damage both offsite power feeds. Past studies often overestimated the heat release from electrical cabinet fires. EPRI's electrical cabinet heat release rates are based on tests that were conducted for Sandia's fire research program. The rates are supported by the experience in the EPRI Fire Events Database for U.S. nuclear plants. Test data and fire event experience also removed excessive conservatisms in the Peach Bottom control and cable spreading rooms, and the Seabrook primary component cooling pump, turbine building relay and cable spreading rooms. The EPRI fire PRA method and data will show that there are excessive conservatisms in studies that were made for many plants and can benefit them accordingly

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

Science.gov (United States)

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

Elevated renin levels in patients with liver cirrhosis and hepatocellular carcinoma.

Science.gov (United States)

Lotfy, Mahmoud; El-Kenawy, Ayman El-Meghawry; Abdel-Aziz, Mohamed M; El-Kady, Ibrahim; Talaat, Ayman

2010-01-01

Liver fibrosis is the common consequence of chronic liver injury of any etiology, disrupting the normal architecture,and causing hepatocellular dysfunction and portal hypertension. Since the renin-angiotensin system (RAS) may be involved in chronic liver diseases, in the present study we assayed renin levels using ELISA in groups of Egyptian patients with liver cirrhosis (N=32) and hepatocellular carcinoma (HCC) (N=67), for comparison with twenty five healthy controls. The results showed significant differences between the control and liver cirrhosis patients (P<0.001) and also the controls and HCC patients (P<0.001), without significant variation between the patient groups. Furthermore, in HCC patients, it was found that the renin levels negatively correlated with serum albumin and prothrombin time (P=0.003 for each) and positively with α-fetoprotein (P=0.04). Thus, it is concluded that renin levels are elevated in patients with liver cirrhosis and HCC and suitable medical intervention should be placed for management of such alteration. Moreover, further studies are warranted to explore its prognostic significance.

Development of a methodology for conducting an integrated HRA/PRA --

International Nuclear Information System (INIS)

Luckas, W.J.; Barriere, M.T.; Brown, W.S.; Wreathall, J.; Cooper, S.E.

1993-01-01

During Low Power and Shutdown (LP ampersand S) conditions in a nuclear power plant (i.e., when the reactor is subcritical or at less than 10--15% power), human interactions with the plant's systems will be more frequent and more direct. Control is typically not mediated by automation, and there are fewer protective systems available. Therefore, an assessment of LP ampersand S related risk should include a greater emphasis on human reliability than such an assessment made for power operation conditions. In order to properly account for the increase in human interaction and thus be able to perform a probabilistic risk assessment (PRA) applicable to operations during LP ampersand S, it is important that a comprehensive human reliability assessment (HRA) methodology be developed and integrated into the LP ampersand S PRA. The tasks comprising the comprehensive HRA methodology development are as follows: (1) identification of the human reliability related influences and associated human actions during LP ampersand S, (2) identification of potentially important LP ampersand S related human actions and appropriate HRA framework and quantification methods, and (3) incorporation and coordination of methodology development with other integrated PRA/HRA efforts. This paper describes the first task, i.e., the assessment of human reliability influences and any associated human actions during LP ampersand S conditions for a pressurized water reactor (PWR)

The role of PRA in the safety assessment of VVER Nuclear Power Plants in Ukraine

International Nuclear Information System (INIS)

Kot, C.

1999-01-01

Ukraine operates thirteen (13) Soviet-designed pressurized water reactors, VVERS. All Ukrainian plants are currently operating with annually renewable permits until they update their safety analysis reports (SARs), in accordance with new SAR content requirements issued in September 1995, by the Nuclear Regulatory Authority and the Government Nuclear Power Coordinating Committee of Ukraine. The requirements are in three major areas: design basis accident (DBA) analysis, probabilistic risk assessment (PRA), and beyond design-basis accident (BDBA) analysis. The last two requirements, on PRA and BDBA, are new, and the DBA requirements are an expanded version of the older SAR requirements. The US Department of Energy (USDOE), as part of its Soviet-Designed Reactor Safety activities, is providing assistance and technology transfer to Ukraine to support their nuclear power plants (NPPs) in developing a Western-type technical basis for the new SARs. USDOE sponsored In-Depth Safety Assessments (ISAs) are in progress at three pilot nuclear reactor units in Ukraine, South Ukraine Unit 1, Zaporizhzhya Unit 5, and Rivne Unit 1, and a follow-on study has been initiated at Khmenytskyy Unit 1. The ISA projects encompass most areas of plant safety evaluation, but the initial emphasis is on performing a detailed, plant-specific Level 1 Internal Events PRA. This allows the early definition of the plant risk profile, the identification of risk significant accident sequences and plant vulnerabilities and provides guidance for the remainder of the safety assessments

Application of the NUREG/CR-6850 EPRI/NRC Fire PRA Methodology to a DOE Facility

International Nuclear Information System (INIS)

Elicson, Tom; Harwood, Bentley; Yorg, Richard; Lucek, Heather; Bouchard, Jim; Jukkola, Ray; Phan, Duan

2011-01-01

The application NUREG/CR-6850 EPRI/NRC fire PRA methodology to DOE facility presented several challenges. This paper documents the process and discusses several insights gained during development of the fire PRA. A brief review of the tasks performed is provided with particular focus on the following: Tasks 5 and 14: Fire-induced risk model and fire risk quantification. A key lesson learned was to begin model development and quantification as early as possible in the project using screening values and simplified modeling if necessary. Tasks 3 and 9: Fire PRA cable selection and detailed circuit failure analysis. In retrospect, it would have been beneficial to perform the model development and quantification in 2 phases with detailed circuit analysis applied during phase 2. This would have allowed for development of a robust model and quantification earlier in the project and would have provided insights into where to focus the detailed circuit analysis efforts. Tasks 8 and 11: Scoping fire modeling and detailed fire modeling. More focus should be placed on detailed fire modeling and less focus on scoping fire modeling. This was the approach taken for the fire PRA. Task 14: Fire risk quantification. Typically, multiple safe shutdown (SSD) components fail during a given fire scenario. Therefore dependent failure analysis is critical to obtaining a meaningful fire risk quantification. Dependent failure analysis for the fire PRA presented several challenges which will be discussed in the full paper.

Impact of glycaemic control on the effect of direct renin inhibition in the AVOID study

DEFF Research Database (Denmark)

Persson, Frederik; Lewis, Julia B; Lewis, Edmund J

2012-01-01

Hyperglycaemia induces development and progression of microvascular complications in diabetes. A direct link between high glucose levels and intrarenal renin-angiotensin activation has been demonstrated. This post-hoc analysis assessed the influence of baseline glycaemic control on the reduction ...

EPRI/NRC-RES fire PRA guide for nuclear power facilities. Volume 1, summary and overview

International Nuclear Information System (INIS)

2004-01-01

This report documents state-of-the-art methods, tools, and data for the conduct of a fire Probabilistic Risk Assessment (PRA) for a commercial nuclear power plant (NPP) application. The methods have been developed under the Fire Risk Re-quantification Study. This study was conducted as a joint activity between EPRI and the U. S. NRC Office of Nuclear Regulatory Research (RES) under the terms of an EPRI/RES Memorandum of Understanding (RS.1) and an accompanying Fire Research Addendum (RS.2). Industry participants supported demonstration analyses and provided peer review of this methodology. The documented methods are intended to support future applications of Fire PRA, including risk-informed regulatory applications. The documented method reflects state-of-the-art fire risk analysis approaches. The primary objective of the Fire Risk Study was to consolidate recent research and development activities into a single state-of-the-art fire PRA analysis methodology. Methodological issues raised in past fire risk analyses, including the Individual Plant Examination of External Events (IPEEE) fire analyses, have been addressed to the extent allowed by the current state-of-the-art and the overall project scope. Methodological debates were resolved through a consensus process between experts representing both EPRI and RES. The consensus process included a provision whereby each major party (EPRI and RES) could maintain differing technical positions if consensus could not be reached. No cases were encountered where this provision was invoked. While the primary objective of the project was to consolidate existing state-of-the-art methods, in many areas, the newly documented methods represent a significant advancement over previously documented methods. In several areas, this project has, in fact, developed new methods and approaches. Such advances typically relate to areas of past methodological debate.

Emerging drugs which target the renin-angiotensin-aldosterone system.

Science.gov (United States)

Steckelings, Ulrike Muscha; Paulis, Ludovit; Unger, Thomas; Bader, Michael

2011-12-01

The renin-angiotensin-aldosterone system (RAAS) is already the most important target for drugs in the cardiovascular system. However, still new developments are underway to interfere with the system on different levels. The novel strategies to interfere with RAAS aim to reduce the synthesis of the two major RAAS effector hormones, angiotensin (Ang) II and aldosterone, or interfere with their receptors, AT1 and mineralocorticoid receptor, respectively. Moreover, novel targets have been identified in RAAS, such as the (pro)renin receptor, and molecules, which counteract the classical actions of Ang II and are therefore beneficial in cardiovascular diseases. These include the AT2 receptor and the ACE2/Ang-(1-7)/Mas axis. The search for drugs activating these tissue-protective arms of RAAS is therefore the most innovative field in RAAS pharmacology. Most of the novel pharmacological strategies to inhibit the classical RAAS need to prove their superiority above the existing treatment in clinical trials and then have to compete against these now quite cheap drugs in a competitive market. The newly discovered targets have functions beyond the cardiovascular system opening up novel therapeutic areas for drugs interfering with RAAS components.

Sequence variations and protein expression levels of the two immune evasion proteins Gpm1 and Pra1 influence virulence of clinical Candida albicans isolates.

Science.gov (United States)

Luo, Shanshan; Hipler, Uta-Christina; Münzberg, Christin; Skerka, Christine; Zipfel, Peter F

2015-01-01

Candida albicans, the important human fungal pathogen uses multiple evasion strategies to control, modulate and inhibit host complement and innate immune attack. Clinical C. albicans strains vary in pathogenicity and in serum resistance, in this work we analyzed sequence polymorphisms and variations in the expression levels of two central fungal complement evasion proteins, Gpm1 (phosphoglycerate mutase 1) and Pra1 (pH-regulated antigen 1) in thirteen clinical C. albicans isolates. Four nucleotide (nt) exchanges, all representing synonymous exchanges, were identified within the 747-nt long GPM1 gene. For the 900-nt long PRA1 gene, sixteen nucleotide exchanges were identified, which represented synonymous, as well as non-synonymous exchanges. All thirteen clinical isolates had a homozygous exchange (A to G) at position 73 of the PRA1 gene. Surface levels of Gpm1 varied by 8.2, and Pra1 levels by 3.3 fold in thirteen tested isolates and these differences influenced fungal immune fitness. The high Gpm1/Pra1 expressing candida strains bound the three human immune regulators more efficiently, than the low expression strains. The difference was 44% for Factor H binding, 51% for C4BP binding and 23% for plasminogen binding. This higher Gpm1/Pra1 expressing strains result in enhanced survival upon challenge with complement active, Factor H depleted human serum (difference 40%). In addition adhesion to and infection of human endothelial cells was increased (difference 60%), and C3b surface deposition was less effective (difference 27%). Thus, variable expression levels of central immune evasion protein influences immune fitness of the human fungal pathogen C. albicans and thus contribute to fungal virulence.

Effect of Uric Acid Lowering on Renin-Angiotensin-System Activation and Ambulatory BP: A Randomized Controlled Trial.

Science.gov (United States)

McMullan, Ciaran J; Borgi, Lea; Fisher, Naomi; Curhan, Gary; Forman, John

2017-05-08

Higher serum uric acid levels, even within the reference range, are strongly associated with increased activity of the renin-angiotensin system (RAS) and risk of incident hypertension. However, the effect of lowering serum uric acid on RAS activity in humans is unknown, although the data that lowering serum uric acid can reduce BP are conflicting. In a double-blind placebo-controlled trial conducted from 2011 to 2015, we randomly assigned 149 overweight or obese adults with serum uric acid ≥5.0 mg/dl to uric acid lowering with either probenecid or allopurinol, or to placebo. The primary endpoints were kidney-specific and systemic RAS activity. Secondary endpoints included mean 24-hour systolic BP, mean awake and asleep BP, and nocturnal dipping. Allopurinol and probenecid markedly lowered serum uric acid after 4 and 8 weeks compared with placebo (mean serum uric acid in allopurinol, probenecid, and placebo at 8 weeks was 2.9, 3.5, and 5.6 mg/dl, respectively). The change in kidney-specific RAS activity, measured as change in the median (interquartile range) renal plasma flow response to captopril (in ml/min per 1.73 m 2 ) from baseline to 8 weeks, was -4 (-25 to 32) in the probenecid group ( P =0.83), -4 (-16 to 9) in the allopurinol group ( P =0.32), and 1 (-21 to 17) in the placebo group ( P =0.96), with no significant treatment effect ( P =0.77). Similarly, plasma renin activity and plasma angiotensin II levels did not significantly change with treatment. The change in mean (±SD) 24-hour systolic BPs from baseline to 8 weeks was -1.6±10.1 with probenecid ( P =0.43), -0.4±6.1 with allopurinol ( P =0.76), and 0.5±6.0 with placebo ( P =0.65); there was no significant treatment effect ( P =0.58). Adverse events occurred in 9%, 12%, and 2% of those given probenecid, allopurinol, or placebo, respectively. In contrast to animal experiments and observational studies, this randomized, placebo-controlled trial found that uric acid lowering had no effect on kidney

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

Directory of Open Access Journals (Sweden)

Smita I. Negi

2015-01-01

Full Text Available 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.

Evaluation of hsp65 Nested PCR-Restriction Analysis (PRA) for Diagnosing Tuberculosis in a High Burden Country

Science.gov (United States)

Macente, Sara; Fujimura Leite, Clarice Queico; Santos, Adolfo Carlos Barreto; Siqueira, Vera Lúcia Dias; Machado, Luzia Neri Cosmo; Marcondes, Nadir Rodrigues; Hirata, Mario Hiroyuki; Hirata, Rosário Dominguez Crespo

2013-01-01

Current study evaluated the hsp65 Nested PCR Restriction Fragment Length Polymorphism Analysis (hsp65 Nested PCR-PRA) to detect and identify Mycobacterium tuberculosis complex directly in clinical samples for a rapid and specific diagnosis of tuberculosis (TB). hsp65 Nested PCR-PRA was applied directly to 218 clinical samples obtained from 127 patients suspected of TB or another mycobacterial infection from July 2009 to July 2010. The hsp65 Nested PCR-PRA showed 100% sensitivity and 95.0 and 93.1% specificity in comparison with culture and microscopy (acid fast bacillus smear), respectively. hsp65 Nested PCR-PRA was shown to be a fast and reliable assay for diagnosing TB, which may contribute towards a fast diagnosis that could help the selection of appropriate chemotherapeutic and early epidemiological management of the cases which are of paramount importance in a high TB burden country. PMID:24260739

Bovine ovarian cells have (pro)renin receptors and prorenin induces resumption of meiosis in vitro.

Science.gov (United States)

Dau, Andressa Minussi Pereira; da Silva, Eduardo Pradebon; da Rosa, Paulo Roberto Antunes; Bastiani, Felipe Tusi; Gutierrez, Karina; Ilha, Gustavo Freitas; Comim, Fabio Vasconcellos; Gonçalves, Paulo Bayard Dias

2016-07-01

The discovery of a receptor that binds prorenin and renin in human endothelial and mesangial cells highlights the possible effect of renin-independent prorenin in the resumption of meiosis in oocytes that was postulated in the 1980s.This study aimed to identify the (pro)renin receptor in the ovary and to assess the effect of prorenin on meiotic resumption. The (pro)renin receptor protein was detected in bovine cumulus-oocyte complexes, theca cells, granulosa cells, and in the corpus luteum. Abundant (pro)renin receptor messenger ribonucleic acid (mRNA) was detected in the oocytes and cumulus cells, while prorenin mRNA was identified in the cumulus cells only. Prorenin at concentrations of 10(-10), 10(-9), and 10(-8)M incubated with oocytes co-cultured with follicular hemisections for 15h caused the resumption of oocyte meiosis. Aliskiren, which inhibits free renin and receptor-bound renin/prorenin, at concentrations of 10(-7), 10(-5), and 10(-3)M blocked this effect (Pmeiosis resumption, cumulus-oocyte complexes and follicular hemisections were treated with prorenin and with angiotensin II or saralasin (angiotensin II antagonist). Prorenin induced the resumption of meiosis independently of angiotensin II. Furthermore, cumulus-oocyte complexes cultured with forskolin (200μM) and treated with prorenin and aliskiren did not exhibit a prorenin-induced resumption of meiosis (Pmeiosis in cattle. Copyright © 2016 Elsevier Inc. All rights reserved.

Dietary Sodium Modulation of Aldosterone Activation and Renal Function During the Progression of Experimental Heart Failure Miller: Dietary Sodium and Early Heart Failure

Science.gov (United States)

Miller, Wayne L.; Borgeson, Daniel D.; Grantham, J. Aaron; Luchner, Andreas; Redfield, Margaret M.; Burnett, John C.

2015-01-01

Aims Aldosterone activation is central to the sodium-fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Methods and Results Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: 1) high sodium [250 mEq (5.8 grams) per day, n=6]; 2) standard sodium [58 mEq (1.3 grams) per day, n=6]; and 3) sodium restriction [11 mEq (0.25 grams) per day, n=6]. During the 38 day study hemodynamics, renal function, renin activity (PRA), and aldosterone were measured. Changes in hemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups, however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Conclusions Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression. PMID:25823360

An integrated PRA module for fast determination of risk significance and improvement effectiveness

International Nuclear Information System (INIS)

Chao, Chun-Chang; Lin, Jyh-Der

2004-01-01

With the widely use of PRA technology in risk-informed applications, to predict the changes of CDF and LERF becomes a standard process for risk-informed applications. This paper describes an integrated PRA module prepared for risk-informed applications. The module contains a super risk engine, a super fault tree engine, an advanced PRA model and a tool for data base maintenance. The individual element of the module also works well for purpose other than risk-informed applications. The module has been verified and validated through a series of scrupulous benchmark tests with similar software. The results of the benchmark tests showed that the module has remarkable accuracy and speed even for an extremely large-size top-logic fault tree as well as for the case in which large amount of MCSs may be generated. The risk monitor for nuclear power plants in Taiwan is the first application to adopt the module. The results predicted by the risk monitor are now accepted by the regulatory agency. A tool to determine the risk significance according to the inspection findings will be the next application to adopt the module in the near future. This tool classified the risk significance into four different color codes according to the level of increase on CDF. Experience of application showed that the flexibility, the accuracy and speed of the module make it useful in any risk-informed applications when risk indexes must be determined by resolving a PRA model. (author)

(Pro)renin receptor: Involvement in diabetic retinopathy and development of molecular targeted therapy.

Science.gov (United States)

Kanda, Atsuhiro; Ishida, Susumu

2018-03-25

The renin-angiotensin system (RAS), a crucial regulator of systemic blood pressure (circulatory RAS), plays distinct roles in pathological angiogenesis and inflammation in various organs (tissue RAS), such as diabetic microvascular complications. Using ocular clinical samples and animal disease models, we elucidated molecular mechanisms in which tissue RAS excites the expression of vascular endothelial growth factor (VEGF)-A responsible for retinal inflammation and angiogenesis, the two major pathological events in diabetic retinopathy (DR). Furthermore, we showed the involvement of (pro)renin receptor [(P)RR] in retinal RAS activation and its concurrent intracellular signal transduction (e.g., extracellular signal-regulated kinase); namely, the (P)RR-induced dual pathogenic bioactivity referred to as the receptor-associated prorenin system. Indeed, neovascular endothelial cells in the fibrovascular tissue collected from eyes with proliferative DR were immunoreactive for the receptor-associated prorenin system components including prorenin, (P)RR, phosphorylated extracellular signal-regulated kinase and VEGF-A. Protein levels of soluble (P)RR increased with its positive correlations with prorenin, renin enzymatic activity and VEGF in the vitreous of proliferative DR eyes, suggesting a close link between (P)RR and VEGF-A-driven angiogenic activity. Furthermore, we revealed an unsuspected, PAPS-independent role of (P)RR in glucose-induced oxidative stress. Recently, we developed an innovative single-strand ribonucleic acid interference molecule selectively targeting human and mouse (P)RR, and confirmed its efficacy in suppressing diabetes-induced retinal inflammation in mice. Our data using clinical samples and animal models suggested the significant implication of (P)RR in the pathogenesis of DR, and the potential usefulness of the ribonucleic acid interference molecule as a therapeutic agent to attenuate ocular inflammation and angiogenesis. © 2018 The Authors

Loss of coolant accident (LOCA) analysis for McMaster Nuclear Reactor through probabilistic risk assessment (PRA)

Energy Technology Data Exchange (ETDEWEB)

Ha, T.; Garland, W.J. [McMaster Univ., Dept. of Engineering Physics, Hamilton, Ontario (Canada)]. E-mail: hats@mcmaster.ca

2006-07-01

A probabilistic risk assessment (PRA) was conducted for the loss of coolant accident (LOCA) sequence in the McMaster Nuclear Reactor (MNR). A level 1 PRA was completed including event sequence modeling, system modeling, and quantification. To support the quantification of the accident sequence identified, data analysis using the Bayesian method and human reliability analysis (HRA) using the ASEP approach were performed. Since human performance in research reactors is significantly different from that in power reactors, a different time-oriented HRA model was proposed and applied for the estimation of the human error probability (HEP) of core relocation. This HEP estimate was less than that by the ASEP approach by a factor of about 2. These two HEP estimates were used for sensitivity analysis, and modeling uncertainty in the PRA models was quantified. This showed the necessity of appropriate human reliability models in PRA for research reactors. This method could be implemented for the operators' actions which require extensive manual execution with little cognitive load, as might be the case for some maintenance operations in power reactors. (author)

Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction

DEFF Research Database (Denmark)

Solomon, Scott D; Shin, Sung Hee; Shah, Amil

2011-01-01

Direct renin inhibitors provide an alternative approach to inhibiting the renin-angiotensin-aldosterone system (RAAS) at the most proximal, specific, and rate-limiting step. We tested the hypothesis that direct renin inhibition would attenuate left ventricular remodelling in patients following...

Survey of seismic fragilities used in PRA studies of nuclear power plants

International Nuclear Information System (INIS)

Park, Y.J.; Hofmayer, C.H.; Chokshi, N.C.

1998-01-01

In recent years, seismic PRA studies have been performed on a large number of nuclear power plants in the USA. This paper presents a summary of a survey on fragility databases and the range of evaluated fragility values of various equipment categories based on past PRAs. The survey includes the use of experience data, the interpretations of available test data, and the quantification of uncertainties. The surveyed fragility databases are limited to data available in the public domain such as NUREG reports, conference proceedings and other publicly available reports. The extent of the availability of data as well as limitations are studied and tabulated for various equipment categories. The survey of the fragility values in past PRA studies includes not only the best estimate values, but also the dominant failure modes and the estimated uncertainty levels for each equipment category. The engineering judgments employed in estimating the uncertainty in the fragility values are also studied. This paper provides a perspective on the seismic fragility evaluation procedures for equipment in order to clearly identify the engineering analysis and judgment used in past seismic PRA studies

Applicability of PRA methods and data to the financial risk assessment of nuclear power plants

International Nuclear Information System (INIS)

El-Sheik, K.A.

1985-01-01

Financial risk assessment, where the probability and severity of financial consequences are estimated, offers a logical framework for organizing and evaluating data pertinent to nuclear power plant accidents. Under the sponsorship of the Electric Power Research Institute, General Electric investigated the feasibility of financial risk assessment of nuclear power plants and of applying PRA methods and data in such an assessment. This paper summarizes the main findings of this investigation. Specifically, the paper discussed the following topics: definition of financial consequences and financial risk; overall approach for financial risk assessment and how it compares with the approach for PRA used in the Reactor Safety Study; and specific financial risk assessment procedures for defining initiating events, plant response sequences, institutional scenarios, and financial consequences and how they compare to analogous procedures for PRA

[Changes in the renin-angiotensin-aldosterone system and water-salt exchange in mining workers in coal mines].

Science.gov (United States)

Rebrov, B A

1996-01-01

Blood and urine content of electrolytes and creatinine was determined in 76 essentially healthy miners before and after work shift, as was activity of plasma renin, blood plasma level of aldosterone and its urinary excretion, with the aid of radioimmunoassay. The greatest activity of the renin-angiotensine-aldosterone system (RAAS) occurred in those individuals engaged in hard physical labour under most harsh conditions of underground workings, this being recordable not only is response to the load but also from the very start. Controls and miners doing jobs of medium-level strenuousness demonstrated changes in the correlations between RAAS and water-salt balance after the work shift as compared with those before the work shift, while in those miners engaged in hard work correlations RAAS-water-salt exchange remained practically the same throughout the study.

MboI RFLP at the human renin (ren) gene locus

Energy Technology Data Exchange (ETDEWEB)

Masharani, U; Frossard, P M

1988-03-25

1.5kb full length human renin cDNA was isolated from a human kidney cDNA library and subcloned into pUC9. MboI (GATC) detects a single two allele polymorphism with fragments at either 1.4kb or 1.0kb. The frequency was studied in 80 unrelated North American. The human renin gene was assigned to chromosome 1 by southern blot analysis of DNA from human-rodent somatic cell hybrids. Codominant segregation was observed in 1 family (7 individuals).

Effect of adenosine1-receptor blockade on renin release from rabbit isolated perfused juxtaglomerular apparatus

DEFF Research Database (Denmark)

Weihprecht, H; Lorenz, J N; Schnermann, J

1990-01-01

Adenosine has been proposed to act within the juxtaglomerular apparatus (JGA) as a mediator of the inhibition of renin secretion produced by a high NaCl concentration at the macula densa. To test this hypothesis, we studied the effects of the adenosine1 (A1)-receptor blocker 8-cyclopentyl-1......,3-dipropylxanthine (CPX) on renin release from single isolated rabbit JGAs with macula densa perfused. The A1-receptor agonist, N6-cyclohexyladenosine (CHA), applied in the bathing solution at 10(-7) M, was found to inhibit renin secretion, an effect that was completely blocked by adding CPX (10(-5) M) to the bath....... Applied to the lumen, 10(-5) M CPX produced a modest stimulation of renin secretion rates suppressed by a high NaCl concentration at the macula densa (P less than 0.05). The effect of changing luminal NaCl concentration on renin secretion rate was examined in the presence of CPX (10(-7) and 10(-5) M...

PRA-1 offshore platform start-up within seven days; Operacionalizacao da plataforma offshore PRA-1 em sete dias

Energy Technology Data Exchange (ETDEWEB)

Barbosa, Fernando; Mitidieri, Jorge; Faria, Jose Luis Coutinho de; Ribeiro, Juan Carlos; Moura, Mario Arthur [Construtora Norberto Oderbrecht S.A., Rio de Janeiro, RJ (Brazil)

2008-07-01

The technologic innovations are very hard features with regards to Offshore Engineering and Construction over the worldwide. The innovations only make sense since they are focus on the high productivity, safe job and cost reduction compared with the current technologies. Inside the scenario mentioned above is Construtora Norberto Odebrecht S.A. concept for the PRA-1 platform Engineering and Construction. Through a very advanced and innovation concept, it was defined as the Main Strategic Planning of the undertaking not use a temporary platform support (named in Brazil as 'Flotel') during the 'Hook-up', commissioning and star-up offshore phase. The success of the strategic made possible through the implementation of new engineering tools, and, besides this, through a very careful offshore planning focused on minimizing and make easier as much as possible the offshore activities. The planning can be basically spitted on the following parts: A- Onshore preparations (Assembly, Integration and Commissioning of the Utilities and Accommodation Modules) B- Offshore detailed planning of the critical activities concerning the start-up of the systems responsible for leaving the platform ready for 'live'. This operation was defined as 'seven days of platform live support' (main target of this paper). (author)

The evolution of renin-angiotensin blockade: angiotensin-converting enzyme inhibitors as the starting point.

Science.gov (United States)

Sica, Domenic A

2010-04-01

The renin-angiotensin system has been a target in the treatment of hypertension for close to three decades. Several medication classes that block specific aspects of this system have emerged as useful therapies, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and, most recently, direct renin inhibitors. There has been a natural history to the development of each of these three drug classes, starting with their use as antihypertensive agents; thereafter, in each case they have been employed as end-organ protective agents. To date, there has been scant evidence to favor angiotensin receptor blockers or direct renin inhibitors over angiotensin-converting enzyme inhibitors in treating hypertension or in affording end-organ protection; thus, angiotensin-converting enzyme inhibitors remain the standard of care when renin-angiotensin system blockade is warranted.

Evaluation of allowed outage time using PRA results

International Nuclear Information System (INIS)

Johanson, G.

1985-01-01

In a probabilistic risk assessment (PRA) different measures of risk importance can be established. These measures can be used as a basis for further evaluation and determination of allowed outage time for specific components, within safety systems of a nuclear power plant. In order to optimize the allowed outage time (AOT) stipulated in the plant's Technical Specification it is necessary to create a methodology which could incorporate existing PRA data into a quantitative extrapolation. In order to evaluate the plant risk status due to AOT in a quantitative manner, the risk achievement worth is utilized. Risk achievement worth is defined as follows: to measure the worth of a feature, in achieving the present risk, one approach is to remove the feature and then determine how much the risk has increased. Thus, the risk achievement worth is formally defined to be the increase in risk if the feature were assumed not be there or to be failed. Another parameter of interest for this analysis is the shutdown risk increase. The shutdown risk achievement worth must be incorporated into the accident sequence risk achievement worth to arrive at an optimal set of plant specific AOTs

High-salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system.

Science.gov (United States)

Mao, Caiping; Liu, Rong; Bo, Le; Chen, Ningjing; Li, Shigang; Xia, Shuixiu; Chen, Jie; Li, Dawei; Zhang, Lubo; Xu, Zhice

2013-07-01

Intrauterine environments are related to fetal renal development and postnatal health. Influence of salty diets during pregnancy on renal functions and renin-angiotensin system (RAS) was determined in the ovine fetuses and offspring. Pregnant ewes were fed high-salt diet (HSD) or normal-salt diet (NSD) for 2 months during middle-to-late gestation. Fetal renal functions, plasma hormones, and mRNA and protein expressions of the key elements of renal RAS were measured in the fetuses and offspring. Fetal renal excretion of sodium was increased while urine volume decreased in the HSD group. Fetal blood urea nitrogen was increased, while kidney weight:body weight ratio decreased in the HSD group. The altered ratio was also observed in the offspring aged 15 and 90 days. Maternal and fetal plasma antidiuretic hormone was elevated without changes in plasma renin activity and Ang I levels, while plasma Ang II was decreased. The key elements of local renal RAS, including angiotensinogen, angiotensin converting enzyme (ACE), ACE2, AT1, and AT2 receptor expression in both mRNA and protein, except renin, were altered following maternal high salt intake. The results suggest that high intake of salt during pregnancy affected fetal renal development associated with an altered expression of the renal key elements of RAS, some alterations of fetal origins remained after birth as possible risks in developing renal or cardiovascular diseases.

Direct renin inhibitor ameliorates insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice.

Science.gov (United States)

Fukushima, Arata; Kinugawa, Shintaro; Takada, Shingo; Matsumoto, Junichi; Furihata, Takaaki; Mizushima, Wataru; Tsuda, Masaya; Yokota, Takashi; Matsushima, Shouji; Okita, Koichi; Tsutsui, Hiroyuki

2016-05-15

Insulin resistance can occur as a consequence of heart failure (HF). Activation of the renin-angiotensin system (RAS) may play a crucial role in this phenomenon. We thus investigated the effect of a direct renin inhibitor, aliskiren, on insulin resistance in HF after myocardial infarction (MI). MI and sham operation were performed in male C57BL/6J mice. The mice were divided into 4 groups and treated with sham-operation (Sham, n=10), sham-operation and aliskiren (Sham+Aliskiren; 10mg/kg/day, n=10), MI (n=11), or MI and aliskiren (MI+Aliskiren, n=11). After 4 weeks, MI mice showed left ventricular dilation and dysfunction, which were not affected by aliskiren. The percent decrease of blood glucose after insulin load was significantly smaller in MI than in Sham (14±5% vs. 36±2%), and was ameliorated in MI+Aliskiren (34±5%) mice. Insulin-stimulated serine-phosphorylation of Akt and glucose transporter 4 translocation were decreased in the skeletal muscle of MI compared to Sham by 57% and 69%, and both changes were ameliorated in the MI+Aliskiren group (91% and 94%). Aliskiren administration in MI mice significantly inhibited plasma renin activity and angiotensin II (Ang II) levels. Moreover, (pro)renin receptor expression and local Ang II production were upregulated in skeletal muscle from MI and were attenuated in MI+Aliskiren mice, in tandem with a decrease in superoxide production and NAD(P)H oxidase activities. In conclusion, aliskiren ameliorated insulin resistance in HF by improving insulin signaling in the skeletal muscle, at least partly by inhibiting systemic and (pro)renin receptor-mediated local RAS activation, and subsequent NAD(P)H oxidase-induced oxidative stress. Copyright © 2016 Elsevier B.V. All rights reserved.

Some Aspects of the Renin-Angiotensin-System in Hemodialysis Patients

Directory of Open Access Journals (Sweden)

Umar Malik

2015-11-01

Full Text Available Understanding of the renin-angiotensin system (RAS has changed remarkably over the past decade. Renin, angiotensin converting enzyme (ACE, angiotensin II (Ang II, and Ang II receptors are the main components of the RAS. Recent studies identified the ACE2/Ang 1-7/Mas receptor axis, which counter-regulates the classical RAS. Many studies have examined the effects of the RAS on the progression of cardiovascular disease and chronic kidney disease (CKD. In addition, many studies have documented increased levels of ACE in hemodialysis (HD patients, raising concerns about the negative effects of RAS activation on the progression of renal disease. Elevated ACE increases the level of Ang II, leading to vasoconstriction and cell proliferation. Ang II stimulation of the sympathetic system leads to renal and cardiovascular complications that are secondary to uncontrolled hypertension. This review provides an overview of the RAS, evaluates new research on the role of ACE2 in dialysis, and reviews the evidence for potentially better treatments for patients undergoing HD. Further understanding of the role of ACE and ACE2 in HD patients may aid the development of targeted therapies that slow the progression of CKD and cardiovascular disease.

Emergence of Participatory Rural Appraisal (PRA Technique as a Strategy towards Sustainable Development: A Sri Lankan Experience

Directory of Open Access Journals (Sweden)

D. N. Koralagama

2007-10-01

Full Text Available In this millennium all the development activities are mostly focused on sustainable development, i.e. the development which fulfils the requirements of the present without disturbing the utilization of future generation. Basically, the sustainable development deals with environmental, social, and economical initiations. In relation to these three objectives, community participation plays a key role as an effective strategy for sustainable development. Among the numerous types of participation, Participatory Rural Appraisal (PRA technique is the most relevant effective method to receive the participation. Because, it has been strengthen by bottom up approach, well defined objectives, practicable solutions, and remedies. Hence, the out come of such an event is most productive rather than a top bottom approach techniques. In fact, a PRA was practiced to develop a strategic plan for tsunami affected village – Bambaranda east, in southern province of Sri Lanka. PRA sessions were carried out during February, 2007 by the Department of Agric. Economics of Ruhuna University, Sri Lanka in collaboration with Japanese Green Resource Agency, Japan.Participatory mapping, venn diagram, matrix ranking, preference ranking, and pair - wise ranking were demonstrated to gather information from the community. The tsunami affected area, including the paddy fields, four irrigation canals were shown by the group with the help of the participatory map. Preference ranking was resulted the reconstruction of irrigation canals as the most important rehabilitation activity to recover the livelihood of villagers. Intrusion of sea water into the paddy fields was the main limitation revealed by the pair - wise ranking. The second limitation marked as unavailability of enough fertilizer and the dilapidated irrigation canals was the third that has to be solved. Matrix ranking was employed to identify the most facilitated sectors by the government and other institutes in order

The Low-Renin Hypertension Phenotype: Genetics and the Role of the Mineralocorticoid Receptor

Directory of Open Access Journals (Sweden)

Rene Baudrand

2018-02-01

Full Text Available A substantial proportion of patients with hypertension have a low or suppressed renin. This phenotype of low-renin hypertension (LRH may be the manifestation of inherited genetic syndromes, acquired somatic mutations, or environmental exposures. Activation of the mineralocorticoid receptor is a common final mechanism for the development of LRH. Classically, the individual causes of LRH have been considered to be rare diseases; however, recent advances suggest that there are milder and “non-classical” variants of many LRH-inducing conditions. In this regard, our understanding of the underlying genetics and mechanisms accounting for LRH, and therefore, potentially the pathogenesis of a large subset of essential hypertension, is evolving. This review will discuss the potential causes of LRH, with a focus on implicated genetic mechanisms, the expanding recognition of non-classical variants of conditions that induce LRH, and the role of the mineralocorticoid receptor in determining this phenotype.

Pharmacokinetic/Pharmacodynamic Modeling of Renin-Angiotensin Aldosterone Biomarkers Following Angiotensin-Converting Enzyme (ACE) Inhibition Therapy with Benazepril in Dogs.

Science.gov (United States)

Mochel, Jonathan P; Fink, Martin; Peyrou, Mathieu; Soubret, Antoine; Giraudel, Jérôme M; Danhof, Meindert

2015-06-01

The objective of this research was to provide a comprehensive description of the effect of benazepril on the dynamics of the renin-angiotensin aldosterone system (RAAS) in dogs. Blood specimens for renin activity (RA), angiotensin II (AII), and aldosterone (ALD) quantitation in plasma were drawn from 12 healthy adult beagle dogs randomly allocated to 2 treatment groups: (i) benazepril 5 mg PO, q24 h (n: 6) and (ii) placebo (n: 6), in a cross-over design. A mechanism-based pharmacokinetic/pharmacodynamic model, which includes the periodic nature of RA, AII, and ALD during placebo treatment and the subsequent changes in dynamics following repeated dosing with benazepril, was developed. The disposition kinetics of benazepril active metabolite, benazeprilat, was characterized using a saturable binding model to the angiotensin converting enzyme. The modulatory effect of benazeprilat on the RAAS was described using a combination of immediate response models. Our data show that benazepril noticeably influences the dynamics of the renin cascade, resulting in a substantial decrease in AII and ALD, while increasing RA throughout the observation span. The model provides a quantitative framework for better understanding the effect of ACE inhibition on the dynamics of the systemic RAAS in dogs.

Aldosterone breakthrough with benazepril in furosemide-activated renin-angiotensin-aldosterone system in normal dogs.

Science.gov (United States)

Lantis, A C; Ames, M K; Atkins, C E; DeFrancesco, T C; Keene, B W; Werre, S R

2015-02-01

Pilot studies in our laboratory revealed that furosemide-induced renin-angiotensin-aldosterone system (RAAS) activation was not attenuated by the subsequent co-administration of benazepril. This study was designed to evaluate the effect of benazepril on angiotensin-converting enzyme (ACE) activity and furosemide-induced circulating RAAS activation. Our hypothesis was that benazepril suppression of ACE activity would not suppress furosemide-induced circulating RAAS activation, indicated by urinary aldosterone concentration. Ten healthy hound dogs were used in this study. The effect of furosemide (2 mg/kg p.o., q12h; Group F; n = 5) and furosemide plus benazepril (1 mg/kg p.o., q24h; Group FB; n = 5) on circulating RAAS was determined by plasma ACE activity, 4-6 h posttreatment, and urinary aldosterone to creatinine ratio (UAldo:C) on days -1, -2, 1, 3, and 7. There was a significant increase in the average UAldo:C (μg/g) after the administration of furosemide (Group F baseline [average of days -1 and -2] UAldo:C = 0.41, SD 0.15; day 1 UAldo:C = 1.1, SD 0.56; day 3 UAldo:C = 0.85, SD 0.50; day 7 UAldo:C = 1.1, SD 0.80, P Benazepril suppressed ACE activity (U/L) in Group FB (Group FB baseline ACE = 16.4, SD 4.2; day 1 ACE = 3.5, SD 1.4; day 3 ACE = 1.6, SD 1.3; day 7 ACE = 1.4, SD 1.4, P Benazepril decreased plasma ACE activity but did not prevent furosemide-induced RAAS activation, indicating aldosterone breakthrough (escape). This is particularly noteworthy in that breakthrough is observed at the time of initiation of RAAS suppression, as opposed to developing after months of therapy. © 2014 John Wiley & Sons Ltd.

The role of renin angiotensin system intervention in stage B heart failure.

LENUS (Irish Health Repository)

Collier, Patrick

2012-04-01

This article outlines the link between the renin angiotensin aldosterone system (RAAS) and various forms of cardiomyopathy, and also reviews the understanding of the effectiveness of RAAS intervention in this phase of ventricular dysfunction. The authors focus their discussion predominantly on patients who have had previous myocardial infarction or those who have left ventricular hypertrophy and also briefly discuss the role of RAAS activation and intervention in patients with alcoholic cardiomyopathy.

Impact of Gold mining activities on the water quality of the lower pra river

International Nuclear Information System (INIS)

Dwamena, Offei Samuel K.

2013-07-01

This study was conducted to assess the extent of Mercury (THg) contamination at four locations within the Shama-Mporhor Wassa catchment area of the Lower Pra River. Water, fish and sediment samples were taken twice with the longitudinal transect method at Daboase, Beposo, Bokorkope and Shama during the minor rainy season in October and at the apex of the dry season in March. Careful investigation of the Shama-Mporhor Wassa catchment area revealed that two of the locations Daboase and Beposo had been continuously impacted by the activities of Artisanal Gold miners (AGM). From the study, Total Mercury (THg) levels were found to have persisted in River water several kilometers downstream the second Artisanal Gold mining (AGM) location at Shama estuary for both seasons. Ten trace elements Mercury (Hg), Selenium (Se), Copper (Cu), Chromium (Cr), Lead (Pb), Iron (Fe), Manganese (Mn), Nickel (Ni), Zinc (Zn) and Cadmium (Cd) were determined in water, fish and sediment samples using the Atomic Absorption Spectroscopy (AAS) equipped with both Hydride Generation (HGAAS) for Selenium (Se) and Cold Vapour (CVAAS) for Total Mercury (THg). The levels of Total Mercury (THg) were largely above the WHO and USEPA guidelines for drinking water (1μg/L) and sediments (200 μg/Kg) respectively for the four locations investigated. Total Mercury (THg) exceeded the WHO, 2011 guideline value of 0.5 mg/Kg for fish species Clarias submarginatus but was below the guideline value for Xenomystus nigri. Mean concentration of Cd and Fe exceeded the WHO, 2011 guideline values for drinking water for the wet season. The other trace elements Zn, Ni, Cu, Cr, Se, Mn, and Pb had their mean concentration below the WHO, 2011 guideline values for drinking water. Apart from the mean concentration of Cd that exceeded the Canadian Interim Sediment Quality (ISQG) guideline value of 0.6 mg/Kg for the wet season, Cr, Cu, Zn, Ni and Pb were below their respective guideline values for both seasons. Statistical

Applications of Living Fire PRA models to Fire Protection Significance Determination Process in Taiwan

International Nuclear Information System (INIS)

De-Cheng, Chen; Chung-Kung, Lo; Tsu-Jen, Lin; Ching-Hui, Wu; Lin, James C.

2004-01-01

The living fire probabilistic risk assessment (PRA) models for all three operating nuclear power plants (NPPs) in Taiwan had been established in December 2000. In that study, a scenario-based PRA approach was adopted to systematically evaluate the fire and smoke hazards and associated risks. Using these fire PRA models developed, a risk-informed application project had also been completed in December 2002 for the evaluation of cable-tray fire-barrier wrapping exemption. This paper presents a new application of the fire PRA models to fire protection issues using the fire protection significance determination process (FP SDP). The fire protection issues studied may involve the selection of appropriate compensatory measures during the period when an automatic fire detection or suppression system in a safety-related fire zone becomes inoperable. The compensatory measure can either be a 24-hour fire watch or an hourly fire patrol. The living fire PRA models were used to estimate the increase in risk associated with the fire protection issue in terms of changes in core damage frequency (CDF) and large early release frequency (LERF). In compliance with SDP at-power and the acceptance guidelines specified in RG 1.174, the fire protection issues in question can be grouped into four categories; red, yellow, white and green, in accordance with the guidelines developed for FD SDP. A 24-hour fire watch is suggested only required for the yellow condition, while an hourly fire patrol may be adopted for the white condition. More limiting requirement is suggested for the red condition, but no special consideration is needed for the green condition. For the calculation of risk measures, risk impacts from any additional fire scenarios that may have been introduced, as well as more severe initiating events and fire damages that may accompany the fire protection issue should be considered carefully. Examples are presented in this paper to illustrate the evaluation process. (authors)

SHARP - a framework for incorporating human interactions into PRA studies

International Nuclear Information System (INIS)

Hannaman, G.W.; Joksimovich, V.; Spurgin, A.J.; Worledge, D.H.

1985-01-01

Recently, increased attention has been given to understanding the role of humans in the safe operation of nuclear power plants. By virtue of the ability to combine equipment reliability with human reliability probabilistic risk assessment (PRA) technology was deemed capable of providing significant insights about the contributions of human interations in accident scenarios. EPRI recognized the need to strengthen the methodology for incorporating human interactions into PRAs as one element of their broad research program to improve the credibility of PRAs. This research project lead to the development and detailed description of SHARP (Systematic Human Application Reliability Procedure) in EPRI NP-3583. The objective of this paper is to illustrate the SHARP framework. This should help PRA analysts state more clearly their assumptions and approach no matter which human reliability assessment technique is used. SHARP includes a structure of seven analysis steps which can be formally or informally performed during PRAs. The seven steps are termed definition, screening, breakdown, representation, impact assessment, quantification, and documentation

Prevention of atrial fibrillation by Renin-Angiotensin system inhibition a meta-analysis

DEFF Research Database (Denmark)

Schneider, Markus; Hua, Tsushung A; Böhm, Michael

2010-01-01

The authors reviewed published clinical trial data on the effects of renin-angiotensin system (RAS) inhibition for the prevention of atrial fibrillation (AF), aiming to define when RAS inhibition is most effective.......The authors reviewed published clinical trial data on the effects of renin-angiotensin system (RAS) inhibition for the prevention of atrial fibrillation (AF), aiming to define when RAS inhibition is most effective....

Changes of RAAS in maternal and placental blood during caesarean operation

International Nuclear Information System (INIS)

Huang Daihua; Cui Bangping; Hu Wei; Zhou Wei

2006-01-01

To study changes of renin-angiotensin-aldosterone system (RAAS) and influence of anesthetic effect on it during caesarean operation, PRA, AT II and ALD in maternal and placental blood were determined by RIA for 30 healthy women scheduled for caesarean operation. Blood was taken before anesthesia(T 0 group) and just at the end of surgery (T 1 group) for comparison. Results showed that there were significant differences in PRA(P 0 and T 1 group, but there were no significant differences in ALD, PRA and AT II between placental blood, umbilical arteria and vein blood. The data suggest that there was obvious relationship between anesthetic effect and the secretion of RAAS. The levels of AT II, ALD and PRA in patients of partial block anesthesia were significantly than those in patients of complete block anesthesia. (authors)

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

DEFF Research Database (Denmark)

Pedersen-Bjergaard, Ulrik

2009-01-01

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 n......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...... 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 system activity to maintain cognitive function during hypoglycaemia. The clinical implications of this finding...... which, however, must await additional independent confirmation, include prediction and possibly some prevention of severe hypoglycaemia. An evaluation of renin-angiotensin system activity may - together with assessment of other risk factors - contribute to rational individualized setting of glycaemic...

New Frontiers in the Intrarenal Renin-Angiotensin System: A Critical Review of Classical and New Paradigms

Science.gov (United States)

Zhuo, Jia L.; Ferrao, Fernanda M.; Zheng, Yun; Li, Xiao C.

2013-01-01

The renin-angiotensin system (RAS) is well-recognized as one of the oldest and most important regulators of arterial blood pressure, cardiovascular, and renal function. New frontiers have recently emerged in the RAS research well beyond its classic paradigm as a potent vasoconstrictor, an aldosterone release stimulator, or a sodium-retaining hormone. First, two new members of the RAS have been uncovered, which include the renin/(Pro)renin receptor (PRR) and angiotensin-converting enzyme 2 (ACE2). Recent studies suggest that prorenin may act on the PRR independent of the classical ACE/ANG II/AT1 receptor axis, whereas ACE2 may degrade ANG II to generate ANG (1–7), which activates the Mas receptor. Second, there is increasing evidence that ANG II may function as an intracellular peptide to activate intracellular and/or nuclear receptors. Third, currently there is a debate on the relative contribution of systemic versus intrarenal RAS to the physiological regulation of blood pressure and the development of hypertension. The objectives of this article are to review and discuss the new insights and perspectives derived from recent studies using novel transgenic mice that either overexpress or are deficient of one key enzyme, ANG peptide, or receptor of the RAS. This information may help us better understand how ANG II acts, both independently or through interactions with other members of the system, to regulate the kidney function and blood pressure in health and disease. PMID:24273531

Inhibition of calcineurin phosphatase promotes exocytosis of renin from juxtaglomerular cells

DEFF Research Database (Denmark)

Madsen, Kirsten; Friis, Ulla Glenert; Gooch, Jennifer L

2010-01-01

. Simultaneous exposure to EGTA and CsA had no additive effect. The protein kinase A (PKA) blocker RpcAMPs had no effect on the CsA-induced increase in membrane capacitance. Intra- and extracellular application of tacrolimus did not alter membrane capacitance. A calmodulin antagonist (calmidazolium) and Cs...... after CsA treatment of the A-alpha knockout, while renin mRNA was suppressed. We conclude that calcineurin and calcium/calmodulin suppress exocytosis of renin from juxtaglomerular cells independent of PKA....

Dexamethasone-responsive hypertension in young women with suppressed renin and aldosterone

International Nuclear Information System (INIS)

Hoefnagels, W.H.L.; Hofman, J.A.; Smals, A.G.H.; Drayer, J.I.M.; Kloppenborg, P.W.C.; Benraad, T.J.

1978-01-01

Pronounced hypoaldosteronism was found in three young women with hypertension and symptoms of mineralocorticoid overproduction - i.e., hyporeninaemia, hypokalaemia, and a fall in blood-pressure after diuretic therapy. Plasma 11-deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone concentrations were normal. Treatment with dexamethasone induced a return to normal of blood-pressure and plasma-potassium and an increase in plasma-renin activity and urinary aldosterone excretion. The data suggest that hypertension in these patients is maintained by overproduction of an unknown adrenocorticotropin-dependent mineralocortocoid. (author)

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

DEFF Research Database (Denmark)

Pöschke, Antje; Kern, Niklas; Maruyama, Takayuki

2012-01-01

, 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....

The role of the renin-angiotensin system in the development of insulin resistance in skeletal muscle.

Science.gov (United States)

Henriksen, Erik J; Prasannarong, Mujalin

2013-09-25

The canonical renin-angiotensin system (RAS) involves the initial action of renin to cleave angiotensinogen to angiotensin I (ANG I), which is then converted to ANG II by the angiotensin converting enzyme (ACE). ANG II plays a critical role in numerous physiological functions, and RAS overactivity underlies many conditions of cardiovascular dysregulation. In addition, ANG II, by acting on both endothelial and myocellular AT1 receptors, can induce insulin resistance by increasing cellular oxidative stress, leading to impaired insulin signaling and insulin-stimulated glucose transport activity. This insulin resistance associated with RAS overactivity, when coupled with progressive ß-cell dysfunction, eventually leads to the development of type 2 diabetes. Interventions that target RAS overactivity, including ACE inhibitors, ANG II receptor blockers, and, most recently, renin inhibitors, are effective both in reducing hypertension and in improving whole-body and skeletal muscle insulin action, due at least in part to enhanced Akt-dependent insulin signaling and insulin-dependent glucose transport activity. ANG-(1-7), which is produced from ANG II by the action of ACE2 and acts via Mas receptors, can counterbalance the deleterious actions of the ACE/ANG II/AT1 receptor axis on the insulin-dependent glucose transport system in skeletal muscle. This beneficial effect of the ACE2/ANG-(1-7)/Mas receptor axis appears to depend on the activation of Akt. Collectively, these findings underscore the importance of RAS overactivity in the multifactorial etiology of insulin resistance in skeletal muscle, and provide support for interventions that target the RAS to ameliorate both cardiovascular dysfunctions and insulin resistance in skeletal muscle tissue. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Antihypertensive effect of eicosapentaenoic acid (EPA) on spontaneously hypertensive rats (SHR)

International Nuclear Information System (INIS)

Lam, B.K.; Quilley, J.; Hirai, A.; Yoshida, S.; Tamura, Y.; Wong, P.Y.K.

1986-01-01

EPA ethyl ester (99.8% pure) was administered orally (300 mg/kg/d) to adult (25-wk-old) and young (11 1/2-wk-old) SHR rats for 2 weeks at which time systolic blood pressure (BP), platelet aggregation, glomerular leukotriene (LT)A 4 hydrolase activity, plasma renin activity (PRA), urinary levels of TxB 2 and 6-keto-PGF/sub 1α/ and aortic conversion of [ 14 C]-AA to [ 14 C]-6-keto-PGF/sub 1α/ were measured. EPA treatment decreased BP of adult SHR with established hypertension from 238.7 +/- 2 to 217 +/- 4 mmHg (M +/- SD, P 4 hydrolase activity was inhibited. PRA and urinary levels of TxB 2 and 6-keto-PGF/sub 1α/ were not changed. Similarly, there was no change in aortic conversion of [ 14 C]-AA to [ 14 C]-6-keto-PGF/sub 1α/ indicating that EPA treatment does not alter vascular cyclo-oxygenase activity. These results indicate that EPA treatment affects eicosanoid metabolism and cardiovascular function

How Can You Support RIDM/CRM/RM Through the Use of PRA

Science.gov (United States)

DoVemto. Tpmu

2011-01-01

Probabilistic Risk Assessment (PRA) is one of key Risk Informed Decision Making (RIDM) tools. It is a scenario-based methodology aimed at identifying and assessing Safety and Technical Performance risks in complex technological systems.

A case of posterior reversible encephalopathy syndrome in the setting of post-partum preeclampsia with suppressed plasma aldosterone levels and plasma renin activity

Directory of Open Access Journals (Sweden)

Aurelio Negro

2013-12-01

Full Text Available Posterior reversible encephalopathy syndrome (PRES is characterized by headache, altered mental status, visual loss, and seizures. PRES is associated with neuroradiological findings: white matter abnormalities, predominantly in the parieto-occipital regions of the brain. PRES has been described in association with hypertensive encephalopathy, eclampsia, renal failure, or following immunosuppressive or anticancer therapy. We report a case of PRES in a severe preeclampsia occurring in the late postpartum period, with suppressed plasma aldosterone levels and plasma renin activity. These laboratory abnormalities may be due to an apparent mineralocorticoid excess syndrome.

The renin-angiotensin system and its blockers

Directory of Open Access Journals (Sweden)

Igić Rajko

2014-01-01

Full Text Available Research on the renin-angiotensin system (RAS has contributed significantly to advances in understanding cardiovascular and renal homeostasis and to the treatment of cardiovascular diseases. This review offers a brief history of the RAS with an overview of its major components and their functions, as well as blockers of the RAS, their clinical usage and current research that targets various components of the RAS. Because angiotensin-converting enzyme (ACE metabolizes two biologically active peptides, one in the kallikrein-kinin system (KKS and one in the RAS, it is the essential connection between the two systems. ACE releases very powerful hypertensive agent, angiotensin II and also inactivates strong hypotensive peptide, bradykinin. Inhibition of ACE thus has a dual effect, resulting in decreased angiotensin II and increased bradykinin. We described the KKS as well.

Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction).

Science.gov (United States)

Schroten, Nicolas F; Damman, Kevin; Hemmelder, Marc H; Voors, Adriaan A; Navis, Gerjan; Gaillard, Carlo A J M; van Veldhuisen, Dirk J; Van Gilst, Wiek H; Hillege, Hans L

2015-05-01

We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated with increased mortality. Aliskiren can provide additional renin-angiotensin-aldosterone system inhibition and increases RBF in healthy individuals. Patients with left ventricular ejection fraction ≤45% and estimated GFR 30 to 75 mL/min per 1.73 m(2) on optimal medical therapy were randomized 2:1 to receive aliskiren 300 mg once daily or placebo. Renal blood flow and GFR were measured using radioactive-labeled (125)I-iothalamate and (131)I-hippuran at baseline and 26 weeks. After 41 patients were included, the trial was halted based on an interim safety analysis showing futility. Mean age was 68 ± 9 years, 82% male, GFR (49 ± 16 mL/min per 1.73 m(2)), RBF (294 ± 77 mL/min per 1.73 m(2)), and NT-proBNP 999 (435-2040) pg/mL. There was a nonsignificant change in RBF after 26 weeks in the aliskiren group compared with placebo (-7.1 ± 30 vs +14 ± 54 mL/min per 1.73 m(2); P = .16). However, GFR decreased significantly in the aliskiren group compared with placebo (-2.8 ± 6.0 vs +4.4 ± 9.6 mL/min per 1.73 m(2); P = .01) as did filtration fraction (-2.2 ± 3.3 vs +1.1 ± 3.1%; P = .01). There were no significant differences in plasma aldosterone, NT-proBNP, urinary tubular markers, or adverse events. Plasma renin activity was markedly reduced in the aliskiren group versus placebo throughout the treatment phase (P = .007). Adding aliskiren on top of optimal HFREF medical therapy did not improve RBF and was associated with a reduction of GFR and filtration fraction. Copyright © 2015 Mosby, Inc. All rights reserved.

Epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels

NARCIS (Netherlands)

Asselbergs, Folkert W.; Williams, Scott M.; Hebert, Patricia R.; Coffey, Christopher S.; Hillege, Hans L.; Navis, Gerjan; Vaughan, Douglas E.; van Gilst, Wiek H.; Moore, Jason H.

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) directly influence thrombus formation and degradation and thereby risk for arterial thrombosis. Activation of the renin-angiotensin system has been linked to the production of PAI-1 expression via the angiotensin II

Results of the Level 1 probabilistic risk assessment (PRA) of internal events for heavy water production reactors

International Nuclear Information System (INIS)

Tinnes, S.P.; Cramer, D.S.; Logan, V.E.; Topp, S.V.; Smith, J.A.; Brandyberry, M.D.

1990-01-01

A full-scope probabilistic risk assessment (PRA) is being performed for the Savannah River site (SRS) production reactors. The Level 1 PRA for the K Reactor has been completed and includes the assessment of reactor systems response to accidents and estimates of the severe core melt frequency (SCMF). The internal events spectrum includes those events related directly to plant systems and safety functions for which transients or failures may initiate an accident. The SRS PRA has three principal objectives: improved understanding of SRS reactor safety issues through discovery and understanding of the mechanisms involved. Improved risk management capability through tools for assessing the safety impact of both current standard operations and proposed revisions. A quantitative measure of the risks posed by SRS reactor operation to employees and the general public, to allow comparison with declared goals and other societal risks

Organizational extension of PRA models and NASA application

International Nuclear Information System (INIS)

Pate-Cornell, E.

1989-01-01

This paper describes a probabilistic method which extends classical PRA to include some characteristics of the organization that processes or manages an engineering system. Ataxonomy of errors is presented and their organizational roots are examined. An assembly model is proposed for the analysis of the resulting spectrum of capacities of the system. The management of the Thermal Protection system of the Space Shuttle is used as an illustration. The model allows assessment of the benefits of organizational improvements of the orbiter's processing

Anthology of the renin-angiotensin system: a one hundred reference approach to angiotensin II antagonists.

Science.gov (United States)

Ménard, J

1993-04-01

To provide a historical overview of the renin-angiotensin system as a guide to the introduction of a new therapeutic pathway, non-peptide inhibition of a angiotensin II. One hundred references were selected as a personal preference, for their originality or for their potential impact on medicine. This review raises the following questions for future research. (1) Will the long-term cardiovascular effects of angiotensin converting enzyme (ACE) inhibition, angiotensin II antagonism and renin inhibition be similar or not, and dependent or independent of blood pressure levels? (2) What are the local-regional interactions between vasoconstrictor and vasodilator systems, and does the renin-angiotensin system synchronize these regional hemodynamic regulatory mechanisms? (3) If hypertension is the result of an interaction between genetic and environmental factors, do proteins secreted through constitutive pathways contribute to the genetic abnormality (prorenin, angiotensinogen, ACE) while regulated secretion (renin) and other regulatory mechanisms (angiotensin II receptors) provide biological support for the environmental effects?

Advanced Small Modular Reactor (SMR) Probabilistic Risk Assessment (PRA) Technical Exchange Meeting

Energy Technology Data Exchange (ETDEWEB)

Smith, Curtis [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2013-09-01

During FY13, the INL developed an advanced SMR PRA framework which has been described in the report Small Modular Reactor (SMR) Probabilistic Risk Assessment (PRA) Detailed Technical Framework Specification, INL/EXT-13-28974 (April 2013). In this framework, the various areas are considered: Probabilistic models to provide information specific to advanced SMRs Representation of specific SMR design issues such as having co-located modules and passive safety features Use of modern open-source and readily available analysis methods Internal and external events resulting in impacts to safety All-hazards considerations Methods to support the identification of design vulnerabilities Mechanistic and probabilistic data needs to support modeling and tools In order to describe this framework more fully and obtain feedback on the proposed approaches, the INL hosted a technical exchange meeting during August 2013. This report describes the outcomes of that meeting.

Improved interpretation of renal-vein-renin-ratio by simultaneous determination of renal 131I-hippuric-acid-clearance-ratio in patients with renovascular hypertension

International Nuclear Information System (INIS)

Helber, A.; Boenner, G.; Hummerich, W.; Wambach, G.; Meurer, K.A.; Dvorak, K.; Lent, V.; Zehle, A.; Kaufmann, W.; Koeln Univ.; Staedtisches Krankenhaus Koeln-Merheim; Staedtisches Krankenhaus Koeln-Merheim; Koeln Univ.

1979-01-01

In patients with unilateral vascular kidney disease and hypertension, ratio of renal-vein-renin was compared with 131 I-Hippuric-acid clearance and change in blood pressure during Saralasininfusion. The ratio of renal-vein-renin was positively correlated with the ratio in renal plasma flow between the kidneys in all patients studied. The ratio of renins therefore is a result of two factors: The difference in renin secretion and the difference in blood flow in the two kidneys. In patients with angiotensin independent hypertension renin-ratios up to 2.0 were found without relevance to elevated blood pressure. When the difference in renal blood flow between both kidneys was small, even a slight difference in renal vein renin indicated hypertension related to increased renin secretion. (orig./AJ) [de

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

Science.gov (United States)

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.

Direct demonstration of macula densa-mediated renin secretion

DEFF Research Database (Denmark)

Skøtt, O; Briggs, J P

1987-01-01

An in vitro method has been used to examine whether secretion of renin from the juxtaglomerular apparatus is affected by changes in the sodium chloride concentration of the tubular fluid at the macula densa. Single juxtaglomerular apparatuses were microdissected from rabbits and the tubule segmen...

Osmotically sensitive renin release from permeabilized juxtaglomerular cells

DEFF Research Database (Denmark)

Jensen, B L; Skøtt, O

1993-01-01

Renin secretion from juxtaglomerular (JG) cells is sensitive to external osmolality in a way that has been suggested to depend either on cellular volume or on effects on secretory granules. To distinguish between these possibilities, a technique for permeabilization of JG cell membranes was devel...

NP-59 SPECT/CT Imaging in Stage 1 Hypertensive and Atypical Primary Aldosteronism: A 5-Year Retrospective Analysis of Clinicolaboratory and Imaging Features

Directory of Open Access Journals (Sweden)

Yi-Chun Chen

2013-01-01

Full Text Available Objective. We retrospectively analyzed all primary aldosteronism (PA patients undergoing NP-59 SPECT/CT imaging with regard to their clinicolaboratory and imaging features, investigation, and outcomes. Material and Methods. 11 PA patients who presented to our hospital for NP-59 SPECT/CT imaging between April 2007 and March 2012 and managed here were analyzed. Results. Among 11 PA patients, eight (73% had stage 1 hypertension, three (27% stage 2 hypertension, four (36% normal plasma aldosterone concentration, nine (82% nonsuppressed plasma renin activity (PRA, six (55% normal aldosterone-renin-ratio (ARR, eight (73% serum potassium ≧3 mEq/L, seven (64% subclinical presentation, seven (64% negative confirmatory testing, and four (36% inconclusive results on CT scan and seven (64% on planar NP-59 scan. All 11 (100% patients had positive results on NP-59 SPECT/CT scan. Two (18% met typical triad and nine (82% atypical triad. Among nine atypical PA patients, three (33% had clinical presentation, six (67% subclinical presentation, six (67% negative confirmatory testing, and four (44% inconclusive results on CT scan and six (67% on planar NP-59 scan. All patients had improved outcomes. Significant differences between typical and atypical PA existed in PRA and ARR. Conclusions. NP-59 SPECT/CT may provide diagnostic potential in stage 1 hypertensive and atypical PA.

Spatially Informed Plant PRA Models for Security Assessment

International Nuclear Information System (INIS)

Wheeler, Timothy A.; Thomas, Willard; Thornsbury, Eric

2006-01-01

Traditional risk models can be adapted to evaluate plant response for situations where plant systems and structures are intentionally damaged, such as from sabotage or terrorism. This paper describes a process by which traditional risk models can be spatially informed to analyze the effects of compound and widespread harsh environments through the use of 'damage footprints'. A 'damage footprint' is a spatial map of regions of the plant (zones) where equipment could be physically destroyed or disabled as a direct consequence of an intentional act. The use of 'damage footprints' requires that the basic events from the traditional probabilistic risk assessment (PRA) be spatially transformed so that the failure of individual components can be linked to the destruction of or damage to specific spatial zones within the plant. Given the nature of intentional acts, extensive modifications must be made to the risk models to account for the special nature of the 'initiating events' associated with deliberate adversary actions. Intentional acts might produce harsh environments that in turn could subject components and structures to one or more insults, such as structural, fire, flood, and/or vibration and shock damage. Furthermore, the potential for widespread damage from some of these insults requires an approach that addresses the impacts of these potentially severe insults even when they occur in locations distant from the actual physical location of a component or structure modeled in the traditional PRA. (authors)

Role of the renin-angiotensin system, renal sympathetic nerve system, and oxidative stress in chronic foot shock-induced hypertension in rats.

Science.gov (United States)

Dong, Tao; Chen, Jing-Wei; Tian, Li-Li; Wang, Lin-Hui; Jiang, Ren-Di; Zhang, Zhe; Xu, Jian-Bing; Zhao, Xiao-Dong; Zhu, Wei; Wang, Guo-Qing; Sun, Wan-Ping; Zhang, Guo-Xing

2015-01-01

The renin-angiotensin system (RAS) and renal sympathetic nerve system (RSNS) are involved in the development of hypertension. The present study is designed to explore the possible roles of the RAS and the RSNS in foot shock-induced hypertension. Male Sprague-Dawley rats were divided into six groups: control, foot shock, RSNS denervation, denervation plus foot shock, Captopril (angiotensin I converting enzyme inhibitor, ACE inhibitor) plus foot shock, and Tempol (superoxide dismutase mimetic) plus foot shock. Rats received foot shock for 14 days. We measured the quantity of thiobarbituric acid reactive substances (TBARS), corticosterone, renin, and angiotensin II (Ang II) in plasma, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and renal noradrenaline content. RAS component mRNA and protein levels were quantified in the cerebral cortex and hypothalamus. The two week foot shock treatment significantly increased systolic blood pressure, which was accompanied by an increase in angiotensinogen, renin, ACE1, and AT1a mRNA and protein expression in the cerebral cortex and hypothalamus, an increase of the plasma concentrations of renin, Ang II, corticosterone, and TBARS, as well as a decrease in plasma SOD and GSH-Px activities. Systolic blood pressure increase was suppressed by denervation of the RSNS or treatment with Captopril or Tempol. Interestingly, denervation or Tempol treatment both decreased main RAS components not only in the circulatory system, but also in the central nervous system. In addition, decreased antioxidant levels and increased TBARS and corticosterone levels were also partially restored by denervation or treatment with Tempol or Captopril. RAS, RSNS and oxidative stress reciprocally potentiate to play important roles in the development of foot shock-induced hypertension.

Recombinant erythropoietin acutely decreases renal perfusion and decouples the renin-angiotensin-aldosterone system.

Science.gov (United States)

Aachmann-Andersen, Niels J; Christensen, Soren J; Lisbjerg, Kristian; Oturai, Peter; Johansson, Pär I; Holstein-Rathlou, Niels-Henrik; Olsen, Niels V

2018-03-01

The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance). rhEPO increased arterial blood pressure, total peripheral resistance, and renal vascular resistance, and decreased renal plasma flow in the high-dose rhEPO intervention and tended to decrease GFR. In spite of the decrease in renal perfusion, rhEPO tended to decrease reabsorption of sodium and water in the proximal tubule and induced a prompt decrease in circulating levels of renin and aldosterone, independent of changes in red blood cell mass, blood volumes, and blood pressure. We also found changes in biomarkers showing evidence that rhEPO induced a prothrombotic state. Our results suggest that rhEPO causes a direct downregulation in proximal tubular reabsorption that seems to decouple the activity of the renin-angiotensin-aldosterone system from changes in renal hemodynamics. This may serve as a negative feed-back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect of rhEPO on renal hemodynamics and a decoupling of the renin-angiotensin-aldosterone system. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Results of the Level 1 probabilistic risk assessment (PRA) of internal events for heavy water production reactors (U)

International Nuclear Information System (INIS)

Tinnes, S.P.; Cramer, D.S.; Logan, V.E.; Topp, S.V.; Smith, J.A.; Brandyberry, M.D.

1990-01-01

This paper reports on a full-scope probabilistic risk assessment (PRA) performed for the Savannah River Site (SRS) production reactors. The Level 1 PRA for the K Reactor has been completed and includes the assessment of reactor systems response to accidents and estimates of the severe core melt frequency (SCMF). The internal events spectrum includes those events related directly to plant systems and safety functions for which transients or failures may initiate an accident

Negative captopril renography on patients with renin mediated hypertension due to page kidney and reninoma

International Nuclear Information System (INIS)

Yung, B.C.K.; Wong, K.W.; Fan, W.C.; Chan, J.C.S.; Lo, S.S.S.

1999-01-01

Through a mechanism similar to renal artery stenosis, patients with reninoma and page kidney also suffered from renin mediated hypertension. Captopril renograms performed on our patients with the latter two conditions, however, did not yield diagnostic findings. Therefore, equivocal or negative captopril renography cannot serve to rule out conditions with elevated renin other than renal artery stenosis

Heart-specific overexpression of (pro)renin receptor induces atrial fibrillation in mice.

Science.gov (United States)

Lian, Hong; Wang, Xiaojian; Wang, Juan; Liu, Ning; Zhang, Li; Lu, Yingdong; Yang, Yanmin; Zhang, Lianfeng

2015-04-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia, causing substantial cardiovascular morbidity and mortality. The renin-angiotensin system (RAS) has been shown to be involved in the pathophysiology of AF. The (pro)renin receptor [(p)RR] is the last identified member of RAS. However, the role of (p)RR in AF is still unknown. Circulating levels of (p)RR were determined using an immunosorbent assay in 22 patients with AF (paroxysmal or persistent) and 22 healthy individuals. The plasma levels of (p)RR increased 3.6-fold in AF patients (Patrial flutter since 2 months, then spontaneously converted to atrial fibrillation by 10 months. The atria of the transgenic mice demonstrated significant dilation and fibrosis, and exhibited a high incidence of sudden death. Additionally, the genes of SERCA and HCN4, which are involved in the electrophysiology of AF, were significantly down-regulated and up-regulated respectively in transgenic mice atria. The phosphorylation of Erk1/2 significantly increased in the atria of the transgenic mice, and the activated Erk1/2 was found predominantly in cardiac fibroblasts, suggesting that the transgenic (p)RR gene may induce atrial fibrillation by activation of Erk1/2 in the cardiac fibroblasts of the atria. (p)RR promotes atrial structural and electrical remodeling in vivo, which indicates that (p)RR plays an important role in the pathological development of AF. Copyright © 2015. Published by Elsevier Ireland Ltd.

Development of extreme rainfall PRA methodology for sodium-cooled fast reactor

International Nuclear Information System (INIS)

Nishino, Hiroyuki; Kurisaka, Kenichi; Yamano, Hidemasa

2016-01-01

The objective of this study is to develop a probabilistic risk assessment (PRA) methodology for extreme rainfall with focusing on decay heat removal system of a sodium-cooled fast reactor. For the extreme rainfall, annual excess probability depending on the hazard intensity was statistically estimated based on meteorological data. To identify core damage sequence, event trees were developed by assuming scenarios that structures, systems and components (SSCs) important to safety are flooded with rainwater coming into the buildings through gaps in the doors and the SSCs fail when the level of rainwater on the ground or on the roof of the building becomes higher than thresholds of doors on first floor or on the roof during the rainfall. To estimate the failure probability of the SSCs, the level of water rise was estimated by comparing the difference between precipitation and drainage capacity. By combining annual excess probability and the failure probability of SSCs, the event trees led to quantification of core damage frequency, and therefore the PRA methodology for rainfall was developed. (author)

Chronic activation of plasma renin is log-linearly related to dietary sodium and eliminates natriuresis in response to a pulse change in total body sodium

DEFF Research Database (Denmark)

Kjolby, Mads; Bie, Peter

2008-01-01

rate, urine flow, plasma potassium, and plasma renin activity did not change. The results indicate that sodium excretion is controlled by neurohumoral mechanisms that are quite resistant to acute changes in plasma volume and colloid osmotic pressure and are not down-regulated within 2 h. With previous......Cl administration increased PV (+6.3-8.9%) and plasma sodium concentration (~2%) and decreased plasma protein concentration (-6.4-8.1%). Plasma ANG II and aldosterone concentrations decreased transiently. Potassium excretion increased substantially. Sodium excretion, arterial blood pressure, glomerular filtration...

Associations of aldosterone and renin concentrations with inflammation-the Study of Health in Pomerania and the German Conn's Registry.

Science.gov (United States)

Grotevendt, A; Wallaschofski, H; Reincke, M; Adolf, C; Quinkler, M; Nauck, M; Hoffmann, W; Rettig, R; Hannemann, A

2017-08-01

Chronic inflammation is an age-independent and body mass index-independent contributor to the development of multi-morbidity. Alterations of the renin-angiotensin-aldosterone system are observed within the context of proinflammatory states. We assessed circulating aldosterone, renin, and inflammatory biomarker concentrations in healthy, normotensive subjects and patients with primary aldosteronism. We included 1177 normotensive individuals from the population-based Study of Health in Pomerania (first follow-up, Study of Health in Pomerania-1) and 103 primary aldosteronism patients from the German Conn's Registry. A 1:1 matching for sex, age, body mass index, smoking status, diabetes mellitus, and the estimated glomerular filtration rate was performed to determine whether primary aldosteronism patients exhibit higher inflammatory biomarker concentrations than normotensive controls. The associations of plasma aldosterone concentration or plasma renin concentration with circulating fibrinogen concentrations, white blood cell count, and high sensitive C-reactive protein concentrations in the normotensive sample were determined with multivariable linear and logistic regression analyses. 1:1 matched primary aldosteronism patients demonstrated significantly (p < 0.01) higher plasma aldosterone concentration (198 vs. 47 ng/l), lower plasma renin concentration (3.1 vs. 7.7 ng/l) and higher high sensitive C-reactive protein concentrations (1.5 vs. 1.0 mg/l) than normotensive controls. Within the normotensive cohort, plasma renin concentration but not plasma aldosterone concentration was positively associated with fibrinogen concentrations and white blood cell count. Further, a J-shaped association between plasma renin concentration and high sensitive C-reactive protein concentrations was detected. High plasma aldosterone concentration in a primary aldosteronism cohort and high plasma renin concentration in normotensive subjects are associated with increased

The renin-angiotensin-aldosterone system (RAAS – physiology and molecular mechanisms of functioning

Directory of Open Access Journals (Sweden)

Monika Chaszczewska-Markowska

2016-09-01

Full Text Available Secretion of renin juxtaglomerular cells into bloodstream initiates activation of an enzymatic-hormonal cascade known as the RAAS (renin – angiotensin – aldosterone system. As a result, blood pressure is increased by the means several interrelated mechanisms. Mechanism of Zjednoczoaction of this system has been known for decades, but a few previously unknown components were recently added, such as ACE-2 and Ang(1-7, and their role often seems to be opposite to that of the conventional components. Local tissue systems also have important biological functions. They operate largely independently of the systemic activity, and their activity is observed primarily in the kidney, heart, in blood vessels, adrenal gland and nervous system. Angiotensin-2 (Ang-2, the main RAAS effector, has a wide scope of action, and thus abnormalities in its functioning have many consequences. Excessive activation is accompanied by chronic inflammation, as Ang-2 stimulates inflammatory mediators. As a result, degenerative processes and atherosclerosis are initiated. RAAS imbalance is associated with the most common diseases of civilization, such as cardio-vascular diseases, diabetes, kidney diseases, preeclampsia, osteoporosis and even neurodegenerative diseases. Many of these pathological processes are attributed to the excessive activation of tissue RA system. Therapeutic strategies based on inhibition of the RAAS are commonly used mainly in the treatment of hypertension and other cardiovascular disorders. The benefits of this class of drugs is primarily a decrease in blood pressure, but also the suppression of inflammatory processes and other pathological phenomena resulting from excessive activation of the RAAS. For that reason, some consider to use RAAS inhibitors in other diseases, e.g. Parkinson’s disease. Further studies give hope for the improvement of RAAS inhibitor therapy and the development of new therapeutic strategies

Altered renal expression of angiotensin II receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats.

Science.gov (United States)

Schulman, Ivonne Hernandez; Zhou, Ming-Sheng; Treuer, Adriana V; Chadipiralla, Kiranmai; Hare, Joshua M; Raij, Leopoldo

2010-01-01

The susceptibility to fibrosis and progression of renal disease is mitigated by inhibition of the renin-angiotensin system (RAS). We hypothesized that activation of the intrarenal RAS predisposes to renal fibrosis in aging. Intrarenal expression of angiotensin II type 1 (AT(1)R), type 2 (AT(2)R), and (pro)renin receptors, ACE and ACE-2, as well as pro- and antioxidant enzymes were measured in 3-month-old (young), 14-month-old (middle-aged), and 24-month-old (old) male Sprague-Dawley rats. Old rats manifested glomerulosclerosis and severe tubulointerstitial fibrosis with increased fibronectin and TGF-β expression (7-fold). AT(1)R /AT(2)R ratios were increased in middle-aged (cortical 1.6-fold, medullary 5-fold) and old rats (cortical 2-fold, medullary 4-fold). Similarly, (pro)renin receptor expression was increased in middle-aged (cortical 2-fold, medullary 3-fold) and old (cortical 5-fold, medullary 3-fold) rats. Cortical ACE was increased (+35%) in old rats, whereas ACE-2 was decreased (-50%) in middle-aged and old rats. NADPH oxidase activity was increased (2-fold), whereas antioxidant capacity and expression of the mitochondrial enzyme manganese superoxide dismutase (cortical -40%, medullary -53%) and medullary endothelial nitric oxide synthase (-48%) were decreased in old rats. Age-related intrarenal activation of the RAS preceded the development of severe renal fibrosis, suggesting that it contributes to the increased susceptibility to renal injury observed in the elderly. Copyright © 2010 S. Karger AG, Basel.

Uncertainty and sensitivity studies supporting the interpretation of the results of TVO I/II PRA

International Nuclear Information System (INIS)

Holmberg, J.

1992-01-01

A comprehensive Level 1 probabilistic risk assessment (PRA) has been performed for the TVO I/II nuclear power units. As a part of the PRA project, uncertainties of risk models and methods were systematically studied in order to describe them and to demonstrate their impact by way of results. The uncertainty study was divided into two phases: a qualitative and a quantitative study. The qualitative study contained identification of uncertainties and qualitative assessments of their importance. The PRA was introduced, and identified assumptions and uncertainties behind the models were documented. The most significant uncertainties were selected by importance measures or other judgements for further quantitative studies. The quantitative study included sensitivity studies and propagation of uncertainty ranges. In the sensitivity studies uncertain assumptions or parameters were varied in order to illustrate the sensitivity of the models. The propagation of the uncertainty ranges demonstrated the impact of the statistical uncertainties of the parameter values. The Monte Carlo method was used as a propagation method. The most significant uncertainties were those involved in modelling human interactions, dependences and common cause failures (CCFs), loss of coolant accident (LOCA) frequencies and pressure suppression. The qualitative mapping out of the uncertainty factors turned out to be useful in planning quantitative studies. It also served as internal review of the assumptions made in the PRA. The sensitivity studies were perhaps the most advantageous part of the quantitative study because they allowed individual analyses of the significance of uncertainty sources identified. The uncertainty study was found reasonable in systematically and critically assessing uncertainties in a risk analysis. The usefulness of this study depends on the decision maker (power company) since uncertainty studies are primarily carried out to support decision making when uncertainties are

Effect of Dual Blockade of Renin-Angiotensin Aldosterone System ...

African Journals Online (AJOL)

Methods: Patients with diabetes of > 5 years duration, proteinuria at a ... nephropathy, Azotemia, Proteinuria, Aldosterone, Renin, Blood pressure ... Hypertension is a risk factor that exacerbates all ... Arterial tension values of the patients were measured with an. ERKA sleeve .... receiving treatment remained within normal.

Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

Directory of Open Access Journals (Sweden)

E.P. Velloso

2007-04-01

Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

Directory of Open Access Journals (Sweden)

E.P. Velloso

Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

The renin-angiotensin system and aging in the kidney.

Science.gov (United States)

Yoon, Hye Eun; Choi, Bum Soon

2014-05-01

Aging is associated with progressive functional deterioration and structural changes in the kidney. Changes in the activity or responsiveness of the renin-angiotensin system (RAS) occur with aging. RAS changes predispose the elderly to various fluid and electrolyte imbalances as well as acute kidney injury and chronic kidney disease. Among the multiple pathways involved in renal aging, the RAS plays a central role. This review summarizes the association of the RAS with structural and functional changes in the aging kidney and age-related renal injury, and describes the underlying mechanisms of RAS-related renal aging. An improved understanding of the renal aging process may lead to better individualized care of the elderly and improved renal survival in age-related diseases.

The renin-angiotensin system; development and differentiation of the renal medulla

DEFF Research Database (Denmark)

Madsen, Kirsten; Robdrup Tinning, Anne; Marcussen, Niels

2013-01-01

on mechanisms of postnatal development the renal medulla and putting medullary developmental lesions into perspective with regard to the programming effect. Moreover, the renin-angiotensin system is critically involved in mammalian kidney development and signaling disorders give rise to developmental renal...... disturbances reaching into adulthood. A review of current knowledge of the role of the renin-angiotensin system for renal medullary development will be given. Acta Physiologica © 2013 Scandinavian Physiological Society....... lesions that has been associated with hypertension later in life. A consistent finding in both experimental animal models and in human case reports is atrophy of the renal medulla with developmental lesions to both medullary nephron segments and vascular development with concomitant functional...

Prolonged fasting does not increase oxidative damage or inflammation in postweaned northern elephant seal pups.

Science.gov (United States)

Vázquez-Medina, José Pablo; Crocker, Daniel E; Forman, Henry Jay; Ortiz, Rudy M

2010-07-15

Elephant seals are naturally adapted to survive up to three months of absolute food and water deprivation (fasting). Prolonged food deprivation in terrestrial mammals increases reactive oxygen species (ROS) production, oxidative damage and inflammation that can be induced by an increase in the renin-angiotensin system (RAS). To test the hypothesis that prolonged fasting in elephant seals is not associated with increased oxidative stress or inflammation, blood samples and muscle biopsies were collected from early (2-3 weeks post-weaning) and late (7-8 weeks post-weaning) fasted seals. Plasma levels of oxidative damage, inflammatory markers and plasma renin activity (PRA), along with muscle levels of lipid and protein oxidation, were compared between early and late fasting periods. Protein expression of angiotensin receptor 1 (AT(1)), pro-oxidant (Nox4) and antioxidant enzymes (CuZn- and Mn-superoxide dismutases, glutathione peroxidase and catalase) was analyzed in muscle. Fasting induced a 2.5-fold increase in PRA, a 50% increase in AT(1), a twofold increase in Nox4 and a 70% increase in NADPH oxidase activity. By contrast, neither tissue nor systemic indices of oxidative damage or inflammation increased with fasting. Furthermore, muscle antioxidant enzymes increased 40-60% with fasting in parallel with an increase in muscle and red blood cell antioxidant enzyme activities. These data suggest that, despite the observed increases in RAS and Nox4, an increase in antioxidant enzymes appears to be sufficient to suppress systemic and tissue indices of oxidative damage and inflammation in seals that have fasted for a prolonged period. The present study highlights the importance of antioxidant capacity in mammals during chronic periods of stress to help avoid deleterious systemic consequences.

Treatment of system dependencies and human interactions in PRA studies: a review and sensitivity study

International Nuclear Information System (INIS)

Orvis, D.D.; Joksimovich, V.; Worledge, D.H.

1985-01-01

The Electric Power Research Institute sponsored the review and comparison of five PRA studies: Arkansas Nuclear One - Unit 1, Big Rock Point, Grand Gulf, Limerick, and Zion - Unit 1. The review has been conducted in two phases. The Phase I review may be characterized as a qualitative look into many aspects of a PRA study. The Phase II review was performed to quantify the extent that differences in analytical techniques or key assumptions in these areas affect the differences in study results. In each of the PRA studies reviewed, the general descriptions of analytical approaches and descriptions of the analyses of event tree, fault tree and human interaction analyses that affected the dominant core damage sequences were reviewed. When these descriptions aroused interest because of seeming inconsistencies within the study or with other studies, they were pursued in some depth. The approaches or assumptions were contrasted to similar elements from other studies, and sensitivity analyses were performed in many cases to test the significance of results to the analytical models or assumptions. Inferences were drawn from the results regarding significance of the item to plant-specific results and, where possible, were generalized to other PRAs. This paper describes the results of the review of system dependencies and human interactions

Impact of angiotensin-converting enzyme gene polymorphism on neurohormonal responses to high- versus low-dose enalapril in advanced heart failure.

Science.gov (United States)

Tang, W H Wilson; Vagelos, Randall H; Yee, Yin-Gail; Fowler, Michael B

2004-11-01

The impact of angiotensin-converting enzyme (ACE) gene polymorphism on neurohormonal dose response to ACE inhibitor therapy is unclear. ACE Insertion (I) or Deletion (D) genotype was determined in 74 patients with chronic heart failure who were randomly assigned to receive either high-dose or low-dose enalapril over a period of 6 months. Monthly pre-enalapril and post-enalapril neurohormone levels (serum ACE activity (sACE), plasma angiotensin II (A-II), plasma renin activity (PRA), and serum aldosterone (ALDO) were compared between genotype subgroups and between patients who received high- or low-dose enalapril within each genotype subgroup. At baseline, predose/postdose sACE and postdose PRA were significantly higher in the DD genotype. At 6-month follow-up, postdose sACE was reduced in a dose-dependent fashion in all three genotypes (P sACE were consistently higher in the DD genotype when compared with ID or II subgroups. Despite a dose-dependent suppression of sACE, there were no observed statistically significant differences in ALDO and A-II suppression or escape with escalating doses of enalapril within each subgroup.

Effects of long-term inhibition of neuronal nitric oxide synthase on blood pressure and renin release

DEFF Research Database (Denmark)

Ollerstam, A.; Skøtt, O.; Ek, J.

2001-01-01

Nitric oxide (NO) produced by neuronal NO-synthase (nNOS) in macula densa cells may be involved in the control of renin release. 7-Nitro indazole (7-NI) inhibits nNOS, and we investigated the effect of short- (4 days) and long-term (4 weeks) 7-NI treatment on blood pressure (BP), plasma renin...... LS rats (107 +/- 15 vs. 56 +/- 1 mGU mL(-1)). Stimulation of PRC in LS rats was further enhanced by 7-NI after 4 days of treatment, but not affected in rats treated for 4 weeks. This suggests that inhibition of nNOS stimulates renin release but that this stimulatory effect in the long run might...

Development of fire PRA methodologies for the analysis of typical Italian NPP designs

International Nuclear Information System (INIS)

Silvestri, E.; Dore, B.; Ferro, G.; Apostolakis, G.

1987-01-01

To compute fire induced Core Melt probability, the results of hazard and propagation analyses were combined with the Core Melt frequency computed for the initiating event and the support state as determined by the fire considered. From the PRA for internal event, the average value of this frequency was found 2.5x10 -3 event/year. Using the average fire frequency the resulting fire induced Core Melt frequency is 1.4x10 -8 event/year. Although high separation of safety systems is required in Italian PWR plants, the frequency of fire induced Core Melt can reach values not negligible with respect to Italian safety standards. For this reason, fire PRA studies for the entire plant are considered necessary and should be performed with appropriate modifications of the methods used for the American plants in order to be able to estimate lower fire induced Core Melt frequencies. (orig./HP)

A local renal renin-angiotensin system activation via renal uptake of prorenin and angiotensinogen in diabetic rats.

Science.gov (United States)

Tojo, Akihiro; Kinugasa, Satoshi; Fujita, Toshiro; Wilcox, Christopher S

2016-01-01

The mechanism of activation of local renal renin-angiotensin system (RAS) has not been clarified in diabetes mellitus (DM). We hypothesized that the local renal RAS will be activated via increased glomerular filtration and tubular uptake of prorenin and angiotensinogen in diabetic kidney with microalbuminuria. Streptozotocin (STZ)-induced DM and control rats were injected with human prorenin and subsequently with human angiotensinogen. Human prorenin uptake was increased in podocytes, proximal tubules, macula densa, and cortical collecting ducts of DM rats where prorenin receptor (PRR) was expressed. Co-immunoprecipitation of kidney homogenates in DM rats revealed binding of human prorenin to the PRR and to megalin. The renal uptake of human angiotensinogen was increased in DM rats at the same nephron sites as prorenin. Angiotensin-converting enzyme was increased in podocytes, but decreased in the proximal tubules in DM rats, which may have contributed to unchanged renal levels of angiotensin despite increased angiotensinogen. The systolic blood pressure increased more after the injection of 20 μg of angiotensinogen in DM rats than in controls, accompanied by an increased uptake of human angiotensinogen in the vascular endothelium. In conclusion, endocytic uptake of prorenin and angiotensinogen in the kidney and vasculature in DM rats was contributed to increased tissue RAS and their pressor response to angiotensinogen.

A PRA case study of extended long term decay heat removal for shutdown risk assessment

International Nuclear Information System (INIS)

Roglans, J.; Ragland, W.A.; Hill, D.J.

1992-01-01

A Probabilistic Risk Assessment (PRA) of the Experimental Breeder Reactor II (EBR-II), a Department of Energy (DOE) Category A research reactor, has recently been completed at Argonne National Laboratory (ANL). The results of this PRA have shown that the decay heat removal system for EBR-II is extremely robust and reliable. In addition, the methodology used demonstrates how the actions of other systems not normally used for actions of other systems not normally used for decay heat removal can be used to expand the mission time of the decay heat removal system and further increase its reliability. The methodology may also be extended to account for the impact of non-safety systems in enhancing the reliability of other dedicated safety systems

Determinants of the renin-angiotensin-aldosterone system in cirrhosis with special emphasis on the central blood volume

DEFF Research Database (Denmark)

Møller, Søren; Bendtsen, Flemming; Henriksen, Jens H

2006-01-01

OBJECTIVE: Several studies have shown activation of the renin-angiotensin-aldosterone system (RAAS) in cirrhosis. Although the activated RAAS may have several determinants, the system is often considered a surrogate marker of effective hypovolaemia. In this study we investigated the activity...... of the RAAS and its potential determinants with special focus on the central and arterial blood volume (CBV). MATERIAL AND METHODS: Eighty-nine patients (Child class A/B/C: 19/41/29) and 32 controls were included in the study. All were given a haemodynamic examination with measurement of determinants...

Technical requirements for the ASME PRA standard for nuclear power plant applications

International Nuclear Information System (INIS)

Fleming, Karl N.; Bernsen, Sidney A.; Simard, Ronald L.

2000-01-01

In 1998 the American Society of Mechanical Engineers (ASME) formed the Committee on Nuclear Risk Management (CNRM) and a Project Team to develop a standard on PRAs for use in risk informed applications. This ASME standard is being developed to help provide an adequate level of quality in PRAs that are being used to support ASME initiatives to risk informed in-service inspection (ISI) and in-service testing (IST) of nuclear power plant components. A related need supported by the industry and the U.S. Nuclear Regulatory Commission is to reduce the level of effort that is being expended in pilot applications of risk informed initiatives to address questions about the sufficiency of quality in the supporting PRA models. The purpose of this paper is to discuss the authors' views on some of the technical issues that were encountered in the effort to develop the ASME PRA standard. Draft 12 of this standard has been issued for comment, and is currently being finalized with the aim of releasing the standard in early 2001. (author)

Normotensive sodium loading in conscious dogs: Regulation of renin secretion during beta receptor blockade

DEFF Research Database (Denmark)

Bie, Peter; Mølstrøm, Simon; Wamberg, Søren

2009-01-01

Cl (20 micromol/kg/min for 180 min, NaLoad) during regular or low-sodium diet (0.03 mmol/kg/d, LowNa) with and without metoprolol (2 mg/kg plus 0.9 mg/kg/h). Vasopressin V2 receptors were blocked by Otsuka compound OPC31260 to facilitate clearance measurements. Body fluid volume was maintained by servo-controlled...... that in this setting, renin secretion and renin-dependent sodium excretion are controlled by via the renal nerves and therefore eliminated or reduced by blocking the action of norepinephrine on the juxtaglomerular cells with the beta1-receptor antagonist metoprolol. This was tested in conscious dogs by infusion of Na...... irrespective of diet. In conclusion, PRC depended on dietary sodium and beta1-adrenergic control as expected; however, the acute sodium-driven decrease in PRC at constant MAP and GFR was unaffected by beta1-receptor blockade demonstrating that renin may be regulated without changes in MAP, GFR, or beta1...

Exercise training modulates the hepatic renin-angiotensin system in fructose-fed rats.

Science.gov (United States)

Frantz, Eliete Dalla Corte; Medeiros, Renata Frauches; Giori, Isabele Gomes; Lima, Juliana Bittencourt Silveira; Bento-Bernardes, Thais; Gaique, Thaiane Gadioli; Fernandes-Santos, Caroline; Fernandes, Tiago; Oliveira, Edilamar Menezes; Vieira, Carla Paulo; Conte-Junior, Carlos Adam; Oliveira, Karen Jesus; Nobrega, Antonio Claudio Lucas

2017-09-01

What is the central question of this study? What are the effects of exercise training on the hepatic renin-angiotensin system and their contribution to damage resulting from fructose overload in rats? What is the main finding and its importance? Exercise training attenuated the deleterious actions of the angiotensin-converting enzyme/angiotensin II/angiotensin II type 1 receptor axis and increased expression of the counter-regulatory (angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor) axis in the liver. Therefore, our study provides evidence that exercise training modulates the hepatic renin-angiotensin system, which contributes to reducing the progression of metabolic dysfunction and non-alcoholic fatty liver disease in fructose-fed rats. The renin-angiotensin system (RAS) has been implicated in the development of metabolic syndrome. We investigated whether the hepatic RAS is modulated by exercise training and whether this modulation improves the deleterious effects of fructose overload in rats. Male Wistar rats were divided into (n = 8 each) control (CT), exercise control (CT-Ex), high-fructose (HFr) and exercise high-fructose (HFr-Ex) groups. Fructose-drinking rats received d-fructose (100 g l -1 ). After 2 weeks, CT-Ex and HFr-Ex rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min day -1 , 4 days per week). We assessed body mass, glucose and lipid metabolism, hepatic histopathology, angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity, the angiotensin concentration and the expression profile of proteins affecting the hepatic RAS, gluconeogenesis and inflammation. Neither fructose overload nor exercise training influenced body mass gain and serum ACE and ACE2 activity. The HFr group showed hyperinsulinaemia, but exercise training normalized this parameter. Exercise training was effective in preventing hepatic steatosis and in preventing triacylglycerol and

Relay chatter and operator response after a large earthquake: An improved PRA methodology with case studies

International Nuclear Information System (INIS)

Budnitz, R.J.; Lambert, H.E.; Hill, E.E.

1987-08-01

The purpose of this project has been to develop and demonstrate improvements in the PRA methodology used for analyzing earthquake-induced accidents at nuclear power reactors. Specifically, the project addresses methodological weaknesses in the PRA systems analysis used for studying post-earthquake relay chatter and for quantifying human response under high stress. An improved PRA methodology for relay-chatter analysis is developed, and its use is demonstrated through analysis of the Zion-1 and LaSalle-2 reactors as case studies. This demonstration analysis is intended to show that the methodology can be applied in actual cases, and the numerical values of core-damage frequency are not realistic. The analysis relies on SSMRP-based methodologies and data bases. For both Zion-1 and LaSalle-2, assuming that loss of offsite power (LOSP) occurs after a large earthquake and that there are no operator recovery actions, the analysis finds very many combinations (Boolean minimal cut sets) involving chatter of three or four relays and/or pressure switch contacts. The analysis finds that the number of min-cut-set combinations is so large that there is a very high likelihood (of the order of unity) that at least one combination will occur after earthquake-caused LOSP. This conclusion depends in detail on the fragility curves and response assumptions used for chatter. Core-damage frequencies are calculated, but they are probably pessimistic because assuming zero credit for operator recovery is pessimistic. The project has also developed an improved PRA methodology for quantifying operator error under high-stress conditions such as after a large earthquake. Single-operator and multiple-operator error rates are developed, and a case study involving an 8-step procedure (establishing feed-and-bleed in a PWR after an earthquake-initiated accident) is used to demonstrate the methodology

Endoplasmic reticulum stress increases brain MAPK signaling, inflammation and renin-angiotensin system activity and sympathetic nerve activity in heart failure.

Science.gov (United States)

Wei, Shun-Guang; Yu, Yang; Weiss, Robert M; Felder, Robert B

2016-10-01

We previously reported that endoplasmic reticulum (ER) stress is induced in the subfornical organ (SFO) and the hypothalamic paraventricular nucleus (PVN) of heart failure (HF) rats and is reduced by inhibition of mitogen-activated protein kinase (MAPK) signaling. The present study further examined the relationship between brain MAPK signaling, ER stress, and sympathetic excitation in HF. Sham-operated (Sham) and HF rats received a 4-wk intracerebroventricular (ICV) infusion of vehicle (Veh) or the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 10 μg/day). Lower mRNA levels of the ER stress biomarkers GRP78, ATF6, ATF4, and XBP-1s in the SFO and PVN of TUDCA-treated HF rats validated the efficacy of the TUDCA dose. The elevated levels of phosphorylated p44/42 and p38 MAPK in SFO and PVN of Veh-treated HF rats, compared with Sham rats, were significantly reduced in TUDCA-treated HF rats as shown by Western blot and immunofluorescent staining. Plasma norepinephrine levels were higher in Veh-treated HF rats, compared with Veh-treated Sham rats, and were significantly lower in the TUDCA-treated HF rats. TUDCA-treated HF rats also had lower mRNA levels for angiotensin converting enzyme, angiotensin II type 1 receptor, tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and NF-κB p65, and a higher mRNA level of IκB-α, in the SFO and PVN than Veh-treated HF rats. These data suggest that ER stress contributes to the augmented sympathetic activity in HF by inducing MAPK signaling, thereby promoting inflammation and renin-angiotensin system activity in key cardiovascular regulatory regions of the brain.

Use of probabilistic risk assessment (PRA) in expert systems to advise nuclear plant operators and managers

International Nuclear Information System (INIS)

Uhrig, R.E.

1988-01-01

The use of expert systems in nuclear power plants to provide advice to managers, supervisors and/or operators is a concept that is rapidly gaining acceptance. Generally, expert systems rely on the expertise of human experts or knowledge that has been codified in publications, books, or regulations to provide advice under a wide variety of conditions. In this work, a probabilistic risk assessment (PRA) of a nuclear power plant performed previously is used to assess the safety status of nuclear power plants and to make recommendations to the plant personnel. Nuclear power plants have many redundant systems and can continue to operate when one or more of these systems is disabled or removed from service for maintenance or testing. PRAs provide a means of evaluating the risk to the public associated with the operation of nuclear power plants with components or systems out of service. While the choice of the source term and methodology in a PRA may influence the absolute probability and consequences of a core melt, the ratio of the PRA calculations for two configurations of the same plant, carried out on a consistent basis, can readily identify the increase in risk associated with going from one configuration to the other

(Pro)renin Receptor Is an Amplifier of Wnt/β-Catenin Signaling in Kidney Injury and Fibrosis.

Science.gov (United States)

Li, Zhen; Zhou, Lili; Wang, Yongping; Miao, Jinhua; Hong, Xue; Hou, Fan Fan; Liu, Youhua

2017-08-01

The (pro)renin receptor (PRR) is a transmembrane protein with multiple functions. However, its regulation and role in the pathogenesis of CKD remain poorly defined. Here, we report that PRR is a downstream target and an essential component of Wnt/ β -catenin signaling. In mouse models, induction of CKD by ischemia-reperfusion injury (IRI), adriamycin, or angiotensin II infusion upregulated PRR expression in kidney tubular epithelium. Immunohistochemical staining of kidney biopsy specimens also revealed induction of renal PRR in human CKD. Overexpression of either Wnt1 or β -catenin induced PRR mRNA and protein expression in vitro Notably, forced expression of PRR potentiated Wnt1-mediated β -catenin activation and augmented the expression of downstream targets such as fibronectin, plasminogen activator inhibitor 1, and α -smooth muscle actin ( α -SMA). Conversely, knockdown of PRR by siRNA abolished β -catenin activation. PRR potentiation of Wnt/ β -catenin signaling did not require renin, but required vacuolar H + ATPase activity. In the mouse model of IRI, transfection with PRR or Wnt1 expression vectors promoted β -catenin activation, aggravated kidney dysfunction, and worsened renal inflammation and fibrotic lesions. Coexpression of PRR and Wnt1 had a synergistic effect. In contrast, knockdown of PRR expression ameliorated kidney injury and fibrosis after IRI. These results indicate that PRR is both a downstream target and a crucial element in Wnt signal transmission. We conclude that PRR can promote kidney injury and fibrosis by amplifying Wnt/ β -catenin signaling. Copyright © 2017 by the American Society of Nephrology.

Comments of the PRA Senior Review Panel on the meeting held December 1--3, 1987

International Nuclear Information System (INIS)

Sharp, D.A.

1988-01-01

This memorandum records the minutes of the PRA Senior Review Panel meeting held at Savannah River Laboratory (SRL) on December 1--3, 1987, and the report on that meeting written subsequently by the panel members. The minutes are contained as Attachment 2 of this memorandum, and the report as Attachment 1. The Panel indicated two principal concerns in their report: (1) that insufficient emphasis is being placed on the reliability data development program, and (2) that excessive detail is being built into the fault trees. These concerns have been addressed in a subsequent meeting with the Panel, held March 2--4, 1988. In addition, the members have been provided with a program document (Reference 1) indicating the extent, the timing, and the limitations of the data analysis effort for the PRA

MATILDA: A Military Laser Range Safety Tool Based on Probabilistic Risk Assessment (PRA) Techniques

Science.gov (United States)

2014-08-01

3 2.1 UK Need for a PRA-Based Approach ............................................................... 3 2.2 A Risk-Based Approach to...Figure 6: MATILDA Coordinate Transformations ....................................................... 22  Figure 7: Geocentric and MICS Coordinates...Star-Shaped Condition ................................................................................. 27  Figure 11: Points of Closest Approach

Probabilistic risk assessment course documentation. Volume 2. Probability and statistics for PRA applications

International Nuclear Information System (INIS)

Iman, R.L.; Prairie, R.R.; Cramond, W.R.

1985-08-01

This course is intended to provide the necessary probabilistic and statistical skills to perform a PRA. Fundamental background information is reviewed, but the principal purpose is to address specific techniques used in PRAs and to illustrate them with applications. Specific examples and problems are presented for most of the topics

The catalytic mechanism of mouse renin studied with QM/MM calculations.

Science.gov (United States)

Brás, Natércia F; Ramos, Maria J; Fernandes, Pedro A

2012-09-28

Hypertension is a chronic condition that affects nearly 25% of adults worldwide. As the Renin-Angiotensin-Aldosterone System is implicated in the control of blood pressure and body fluid homeostasis, its combined blockage is an attractive therapeutic strategy currently in use for the treatment of several cardiovascular conditions. We have performed QM/MM calculations to study the mouse renin catalytic mechanism in atomistic detail, using the N-terminal His6-Asn14 segment of angiotensinogen as substrate. The enzymatic reaction (hydrolysis of the peptidic bond between residues in the 10th and 11th positions) occurs through a general acid/base mechanism and, surprisingly, it is characterized by three mechanistic steps: it begins with the creation of a first very stable tetrahedral gem-diol intermediate, followed by protonation of the peptidic bond nitrogen, giving rise to a second intermediate. In a final step the peptidic bond is completely cleaved and both gem-diol hydroxyl protons are transferred to the catalytic dyad (Asp32 and Asp215). The final reaction products are two separate peptides with carboxylic acid and amine extremities. The activation energy for the formation of the gem-diol intermediate was calculated as 23.68 kcal mol(-1), whereas for the other steps the values were 15.51 kcal mol(-1) and 14.40 kcal mol(-1), respectively. The rate limiting states were the reactants and the first transition state. The associated barrier (23.68 kcal mol(-1)) is close to the experimental values for the angiotensinogen substrate (19.6 kcal mol(-1)). We have also tested the influence of the density functional on the activation and reaction energies. All eight density functionals tested (B3LYP, B3LYP-D3, X3LYP, M06, B1B95, BMK, mPWB1K and B2PLYP) gave very similar results.

Effects of dual renin-angiotensin system blockade on proteinuria in a ...

African Journals Online (AJOL)

Kidney diseases manifesting as proteinuria or elevated creatinine are increasingly prevalent complications of HIV infection. We report the effects of dual renin-angiotensin system blockade on proteinuria in a hypertensive black African HIV-infected patient.

Effects Of The Direct Renin Inhibitor Aliskiren On Oxidative Stress In Isolated Rat Heart

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Plecevic Sasa

2015-09-01

Full Text Available Increased activity of the renin-angiotensin-aldosterone system (RAAS plays a significant role in the development and progression of various cardio-metabolic diseases, such as hypertension, atherosclerosis and heart failure. Aliskiren is the newest antihypertensive drug and the first orally active direct renin inhibitor to become available for clinical use. This study investigated the acute and direct effects of Aliskiren on different parameters of oxidative stress on isolated rat heart. The hearts of male Wistar albino rats (n = 24, 8 per experimental group, age 8 weeks, body mass 180–200 g, were excised and retrogradely perfused according to the Langendorfftechnique at a gradually increasing perfusion pressure (40-120 cmH2O. Markers of oxidative stress (NO2−, TBARS, H2O2 and O2− were measured spectrophotometrically after perfusion with three different concentrations of Aliskiren (0.1 μM, 1 μM, and 10 μM. The results demonstrated possible dose-dependent cardioprotective properties of Aliskiren, particularly with higher CPP. Lipid peroxidation (TBARS levels decreased with the highest dose of Aliskiren and higher CPP, and the same trend was observed in nitrite (NO2− and hydrogen peroxide (H2O2 levels. These findings indicate that the acute effects of Aliskiren do not likely promote the production of reactive oxygen species upon higher pressure with the highest dose. Aliskiren may exert beneficial effects on oxidative stress biomarkers.

Renin-Angiotensin System in Diabetes.

Science.gov (United States)

Rein, Johannes; Bader, Michael

2017-11-17

The renin-angiotensin system (RAS) has two different axes, the classical one with the effector peptide angiotensin II and the new one with the effector peptide angiotensin (1-7). Both peptides have been shown to be involved in the pathogenesis of diabetes mellitus and its consequences, nephropathy, retinopathy and cardiomyopathy in animal models and patients. In diabetes, angiotensin II acts mostly deleterious and angiotensin (1-7) protective. In this review we summarize the knowledge about the role of the different RAS axes in diabetes mellitus and the use of drugs interfering with the RAS in the therapy of the disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pulsa o coração da cidade: errâncias, afectos e potências no dia e na noite da Praça do Ferreira

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Alice Dote

2017-12-01

Full Text Available O presente artigo aborda a potência dos usos, contra-usos e modos de habitar dos artistas de rua da Praça do Ferreira, na cidade de Fortaleza, Ceará. O trabalho apoia-se nos percursos e nas errâncias urbanas da vivência na e da Praça do Ferreira em diferentes temporalidades (diurna e noturna, especialmente no contexto de apresentações noturnas do Grupo As 10 Graças de Palhaçaria aos moradores da Praça. Através desses que têm a rua como casa, agem pelas brechas e proliferam-se pelas margens, proponho-me a perceber a potência da arte de rua, do encontro e da experiência de alteridade na Praça do Ferreira. Finalizo o texto apontando que esse local, assim ocupado, se impregna de significados outros e revela-se como um território de criação, de inventividade, de existência e resistência, portanto, de potência de vida que é, em si, potência política. Palavras-chave: Praça do Ferreira; Fortaleza; cidade; arte urbana; artista de rua

Renin secretion and total body sodium: Pathways of integrative control

DEFF Research Database (Denmark)

Bie, Peter; Damkjaer, Mads

2009-01-01

to a spring/shock absorber set-up: Non-adaptive RAAS functions determine the new steady state position while TGF controls the rate of change. Recruitment of renin-secreting cells during sustained stimulation may be essential for chronic adaptation, although details of this afferent arteriolar cell plasticity...

Recovery actions in PRA [probabilistic risk assessment] for the Risk Methods Integration and Evaluation Program (RMIEP): Volume 1, Development of the data-based method

International Nuclear Information System (INIS)

Weston, L.M.; Whitehead, D.W.; Graves, N.L.

1987-06-01

In a probabilistic risk assessment (PRA) for a nuclear power plant, the analyst identifies a set of potential core damage events consisting of equipment failures and human errors and their estimated probabilities of occurrence. If operator recovery from an event within some specified time is considered, then the probability of this recovery can be included in the PRA. This report provides PRA analysts with an improved methodology for including recovery actions in a PRA. A recovery action can be divided into two distinct phases: a Diagnosis Phase (realizing that there is a problem with a critical parameter and deciding upon the correct course of action) and an Action Phase (physically accomplishing the required action). In this methodology, simulator data are used to estimate recovery probabilities for the diagnosis phase. Different time-reliability curves showing the probability of failure of diagnosis as a function of time from the compelling cue for the event are presented. These curves are based on simulator exercises, and the actions are grouped based upon their operational similarities. This is an improvement over existing diagnosis models that rely greatly upon subjective judgment to obtain such estimates. The action phase is modeled using estimates from available sources. The methodology also includes a recommendation on where and when to apply the recovery action in the PRA process

Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction)

NARCIS (Netherlands)

Schroten, Nicolas F.; Damman, Kevin; Hemmelder, Marc H.; Voors, Adriaan A.; Navis, Gerjan; Gaillard, Carlo A. J. M.; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; Hillege, Hans L.

AIMS: We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF

RAVEN: a GUI and an Artificial Intelligence Engine in a Dynamic PRA Framework

Energy Technology Data Exchange (ETDEWEB)

C. Rabiti; D. Mandelli; A. Alfonsi; J. Cogliati; R. Kinoshita; D. Gaston; R. Martineau; C. Curtis

2013-06-01

Increases in computational power and pressure for more accurate simulations and estimations of accident scenario consequences are driving the need for Dynamic Probabilistic Risk Assessment (PRA) [1] of very complex models. While more sophisticated algorithms and computational power address the back end of this challenge, the front end is still handled by engineers that need to extract meaningful information from the large amount of data and build these complex models. Compounding this problem is the difficulty in knowledge transfer and retention, and the increasing speed of software development. The above-described issues would have negatively impacted deployment of the new high fidelity plant simulator RELAP-7 (Reactor Excursion and Leak Analysis Program) at Idaho National Laboratory. Therefore, RAVEN that was initially focused to be the plant controller for RELAP-7 will help mitigate future RELAP-7 software engineering risks. In order to accomplish this task, Reactor Analysis and Virtual Control Environment (RAVEN) has been designed to provide an easy to use Graphical User Interface (GUI) for building plant models and to leverage artificial intelligence algorithms in order to reduce computational time, improve results, and help the user to identify the behavioral pattern of the Nuclear Power Plants (NPPs). In this paper we will present the GUI implementation and its current capability status. We will also introduce the support vector machine algorithms and show our evaluation of their potentiality in increasing the accuracy and reducing the computational costs of PRA analysis. In this evaluation we will refer to preliminary studies performed under the Risk Informed Safety Margins Characterization (RISMC) project of the Light Water Reactors Sustainability (LWRS) campaign [3]. RISMC simulation needs and algorithm testing are currently used as a guidance to prioritize RAVEN developments relevant to PRA.

A Novel Single-Strand RNAi Therapeutic Agent Targeting the (Pro)renin Receptor Suppresses Ocular Inflammation.

Science.gov (United States)

Kanda, Atsuhiro; Ishizuka, Erdal Tan; Shibata, Atsushi; Matsumoto, Takahiro; Toyofuku, Hidekazu; Noda, Kousuke; Namba, Kenichi; Ishida, Susumu

2017-06-16

The receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to the (pro)renin receptor [(P)RR] dually activates the tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling. Here we revealed significant upregulation of prorenin and soluble (P)RR levels in the vitreous fluid of patients with uveitis compared to non-inflammatory controls, together with a positive correlation between these RAPS components and monocyte chemotactic protein-1 among several upregulated cytokines. Moreover, we developed a novel single-strand RNAi agent, proline-modified short hairpin RNA directed against human and mouse (P)RR [(P)RR-PshRNA], and we determined its safety and efficacy in vitro and in vivo. Application of (P)RR-PshRNA in mice caused significant amelioration of acute (uveitic) and chronic (diabetic) models of ocular inflammation with no apparent adverse effects. Our findings demonstrate the significant implication of RAPS in the pathogenesis of human uveitis and the potential usefulness of (P)RR-PshRNA as a therapeutic agent to reduce ocular inflammation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[Aldosterone response to various stimuli in hyperthyroidism: in vivo and in vitro studies].

Science.gov (United States)

Kigoshi, T; Kaneko, M; Nakano, S; Azukizawa, S; Uchida, K; Morimoto, S

1993-06-20

Responses of plasma aldosterone (PA) to alpha-ACTH-(1-24) (250 micrograms, im) injection and graded angiotensin II (AII) infusions (2, 4 and 8ng/kg/min for 30 min at each dose) on a constant sodium intake (170mEq daily) were assessed in 17 patients with Basedow's disease and 13 age-matched normal subjects. Aldosterone production in response to ACTH, AII and potassium in adrenal zona glomerulosa cells from L-thyroxine-induced hyperthyroid rats (H-rats) were also examined. Basal levels of plasma renin activity (PRA) and urinary aldosterone excretion were significantly higher (p metabolic clearance rate of aldosterone, may be involved in the abnormal aldosterone metabolism in hyperthyroidism.

Insights into PRA methodologies

International Nuclear Information System (INIS)

Gallagher, D.; Lofgren, E.; Atefi, B.; Liner, R.; Blond, R.; Amico, P.

1984-08-01

Probabilistic Risk Assessments (PRAs) for six nuclear power plants were examined to gain insight into how the choice of analytical methods can affect the results of PRAs. The PRA sreflectope considered was limited to internally initiated accidents sequences through core melt. For twenty methodological topic areas, a baseline or minimal methodology was specified. The choice of methods for each topic in the six PRAs was characterized in terms of the incremental level of effort above the baseline. A higher level of effort generally reflects a higher level of detail or a higher degree of sophistication in the analytical approach to a particular topic area. The impact on results was measured in terms of how additional effort beyond the baseline level changed the relative importance and ordering of dominant accident sequences compared to what would have been observed had methods corresponding to the baseline level of effort been employed. This measure of impact is a more useful indicator of how methods affect perceptions of plant vulnerabilities than changes in core melt frequency would be. However, the change in core melt frequency was used as a secondary measure of impact for nine topics where availability of information permitted. Results are presented primarily in the form of effort-impact matrices for each of the twenty topic areas. A suggested effort-impact profile for future PRAs is presented

Anti-stress and nootropic activity of drugs affecting the renin-angiotensin system in rats based on indirect biochemical evidence.

Science.gov (United States)

Anil Kumar, K V; Nagwar, Shrasti; Thyloor, Rama; Satyanarayana, Sreemantula

2015-12-01

Various stress hormones are responsible for bringing out stress-related changes and are implicated in learning and memory processes. The extensive clinical experience of angiotensin receptor blockers (ARBs) and direct renin inhibitor as antihypertensive agents provides anecdotal evidence of improvements in cognition. The neurochemical basis underlying the anti-stress and nootropic effects are unclear. This study was aimed to determine the effects of aliskiren, valsartan and their combination on the neuromediators of the central nervous system (CNS) and periphery as well as on cognitive function. Groups of rats were subjected to a forced swim stress for one hour after daily treatment with aliskiren, valsartan and their combination. The 24 h urinary excretion of vanillylmandellic acid (VMA), 5-hydroxyindoleacetic acid (5-HIAA), 6-β-hydroxycortisol (6-β-OH) cortisol and homovanillic acid (HVA) was determined in all groups under normal and stressed conditions. Nootropic activity was studied using cook's pole climbing apparatus and acetylcholinesterase (AChE) inhibitory activity by Ellman's method. Administration of aliskiren (10 mg/kg), valsartan (20 mg/kg) and their combination at a dose of 5 and 10 mg/kg respectively reduced the urinary metabolite levels. Further, all drugs showed significant improvement in scopolamine-impaired performance and produced inhibition of the AChE enzyme. The present study provides scientific support for the anti-stress and nootropic activities of aliskiren, valsartan and their combination. © The Author(s) 2014.

Effect of postural changes on aldosterone to plasma renin ratio in patients with suspected secondary hypertension.

Science.gov (United States)

Barigou, M; Ah-Kang, F; Orloff, E; Amar, J; Chamontin, B; Bouhanick, B

2015-06-01

To study the influence of postural changes on aldosterone to renin ratio (ARR) in patients with suspected secondary hypertension and to evaluate the sensitivity and specificity of the recommended seated ARR compared to supine and upright ARR for primary aldosteronism screening. Fifty-three hypertensive patients were prospectively hospitalized for secondary hypertension exploration (age: 51 ± 12, 66% males). After withdrawal of drugs interfering with renin angiotensin system, plasma aldosterone and direct renin concentration were measured in the morning, at bed after an overnight supine position, then out of bed after 1 hour of upright position and finally 2 hours later after 15 minutes of seating. Minimal renin value was set at 5 μUI/mL. Referring to ARR cut-off of 23 pg/μUI, the sensitivity of seated ARR was 57.1% and specificity was 92.3%. The negative and positive predictive values were 95.1% and 45.2% respectively. Compared to these results, a cut-off of 19 improved sensitivity to 85.7% with a specificity of 89.7%. Negative and positive predictive values were 98.3% and 41.1% respectively. Seated ARR mean value was lower than supine and upright ARR mean values, due to an overall increase in renin at seating compared to the supine position by factor 1.9 while aldosterone just slightly increased by factor 1.2. Seated ARR correlated to supine and upright ARR: correlation coefficients (r) 0.90 and 0.93 respectively (P<0.001). Current recommended measurement of ARR in the seating position is fairly correlated to supine and upright ARR. A suggested cut-off value of 19 instead of 23 pg/μUI increased the discriminating power of this test. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Review of KSNP LPSD PSA model based of ANS LPSD PRA standard, rev.0

International Nuclear Information System (INIS)

Jang, S. C.; Park, J. H.; Kim, T. W.; Lim, H. G.; Yang, J. E.; Ha, J. J.

2004-02-01

Recently, under the de-regulation environment, nuclear industry has attempted various approaches to improve the economics of Nuclear Power Plants (NPP). One of these efforts is the Risk Informed/Performance-based Operation (RIPBO). This approach uses the risk and performance information to manage the resources effectively and efficiently that are used in the operation of NPP. In RIPBO, PSA quality is one of the most important things. The nuclear industry and regulatory body of U.S.A have developed a measure to evaluate the quality of PSA. NEI (Nuclear Energy Institute) has developed a guidance called 'NEI PRA Peer Review Guidance,' and NRC (Nuclear Regulatory Committee) and ASME have developed the 'PRA Standard.' In Korea, several projects are on going now, such as the extension of AOT/STI of RPS/ESFAS, Risk-informed In-service Inspection (RI-ISI). However, in Korea, there have been no attempts to evaluate the quality of PSA model itself. Therefore, we cannot be sure about the quality of PSA whether or not the present PSA model can be used for the risk-informed applications such as mentioned above. We can say that the evaluation of PSA model quality is the basis for the RIPBO. In this report, we have evaluated the quality of PSA model at Low power and Shutdown operation model for Yongkwang 5 and 6 units based on the ANS LPSD PRA Standard. We, also, have derived what items are to be improved to upgrade the quality of LPSD PSA model and how it can be improved. This report can be used as the base of RIPBO work in Korea

Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis

DEFF Research Database (Denmark)

Gribouval, Olivier; Morinière, Vincent; Pawtowski, Audrey

2012-01-01

, pulmonary hypoplasia, and refractory arterial hypotension. The disease is linked to mutations in the genes encoding several components of the renin-angiotensin system (RAS): AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), and AGTR1 (angiotensin II receptor type 1). Here, we review...... the series of 54 distinct mutations identified in 48 unrelated families. Most of them are novel and ACE mutations are the most frequent, observed in two-thirds of families (64.6%). The severity of the clinical course was similar whatever the mutated gene, which underlines the importance of a functional RAS...

Brain Renin-Angiotensin System and Microglial Polarization: Implications for Aging and Neurodegeneration

Directory of Open Access Journals (Sweden)

Jose L. Labandeira-Garcia

2017-05-01

Full Text Available Microglia can transform into proinflammatory/classically activated (M1 or anti-inflammatory/alternatively activated (M2 phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory to M2 (immunoregulatory phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS on microglial polarization are less known. It is well known that there is a “classical” circulating RAS; however, a second RAS (local or tissue RAS has been observed in many tissues, including brain. The locally formed angiotensin is involved in local pathological changes of these tissues and modulates immune cells, which are equipped with all the components of the RAS. There are also recent data showing that brain RAS plays a major role in microglial polarization. Level of microglial NADPH-oxidase (Nox activation is a major regulator of the shift between M1/proinflammatory and M2/immunoregulatory microglial phenotypes so that Nox activation promotes the proinflammatory and inhibits the immunoregulatory phenotype. Angiotensin II (Ang II, via its type 1 receptor (AT1, is a major activator of the NADPH-oxidase complex, leading to pro-oxidative and pro-inflammatory effects. However, these effects are counteracted by a RAS opposite arm constituted by Angiotensin II/AT2 receptor signaling and Angiotensin 1–7/Mas receptor (MasR signaling. In addition, activation of prorenin-renin receptors may contribute to activation of the proinflammatory phenotype. Aged brains showed upregulation of AT1 and downregulation of AT2 receptor expression, which may contribute to a pro-oxidative pro-inflammatory state and the increase in neuron vulnerability. Several recent studies have shown interactions between the brain RAS and different factors involved in microglial polarization

Results and insights of a level-1 internal event PRA of a PWR during mid-loop operations

International Nuclear Information System (INIS)

Chu, T.L.; Musicki, Z.; Kohut, P.

1993-01-01

Traditionally, probabilistic risk assessments (PRA) of severe accidents in nuclear power plants have considered initiating events potentially occurring only during full power operation. Some previous screening analysis that were performed for other modes of operation suggested that risks during those modes were small relative to full power operation. However, more recent studies and operational experience have implied that accidents during low power and shutdown could be significant contributors to risk. The objective of this paper is to present the approach utilized in the level-1 PRA for the Surry plant, and discuss the results obtained. A comparison of the results with those of other shutdown studies is provided. Relevant safety issues such as plant and hardware configurations, operator training, and instrumentation and control is discussed

Capturing the dynamics of systemic Renin-Angiotensin-Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs.

Science.gov (United States)

Mochel, J P; Peyrou, M; Fink, M; Strehlau, G; Mohamed, R; Giraudel, J M; Ploeger, B; Danhof, M

2013-04-01

In dogs, activation of the Renin-Angiotensin-Aldosterone System (RAAS) is an important feature of congestive heart failure (CHF). Long-term increases in angiotensin II (AII) and aldosterone (ALD) lead to the progression of heart failure to its end stage. Angiotensin-converting enzyme inhibitors (ACEIs) are the foremost therapeutic option in the management of CHF. Recent literature has challenged the efficacy of ACEIs, based on modest reduction in urinary aldosterone (UALD) excretion despite marked inhibition of ACE activity. This study was designed to heighten the understanding of the effect of benazepril, a potent ACEI, on the RAAS, using a low-sodium diet as an experimental model of RAAS activation. Time course profiles of RAAS peptides and related areas under the curve (AUC) were used for comparison between benazepril and placebo groups. Results indicated substantial changes in the dynamics of these biomarkers. At presumed benazeprilat steady state, significant differences in AUC of plasma renin activity (+90%), angiotensin I (+43%), and AII (-53%) were found between benazepril and placebo-treated dogs. ALD decreased by 73% in plasma but only by 5% in urine. In conclusion, despite modest reduction in UALD excretion, benazepril markedly influences RAAS dynamics in dogs. © 2012 Blackwell Publishing Ltd.

Methodology and application of surrogate plant PRA analysis to the Rancho Seco Power Plant: Final report

International Nuclear Information System (INIS)

Gore, B.F.; Huenefeld, J.C.

1987-07-01

This report presents the development and the first application of generic probabilistic risk assessment (PRA) information for identifying systems and components important to public risk at nuclear power plants lacking plant-specific PRAs. A methodology is presented for using the results of PRAs for similar (surrogate) plants, along with plant-specific information about the plant of interest and the surrogate plants, to infer important failure modes for systems of the plant of interest. This methodology, and the rationale on which it is based, is presented in the context of its application to the Rancho Seco plant. The Rancho Seco plant has been analyzed using PRA information from two surrogate plants. This analysis has been used to guide development of considerable plant-specific information about Rancho Seco systems and components important to minimizing public risk, which is also presented herein

Studi Awal Pra Desain Pabrik Bioetanol dari Nira Siwalan

Directory of Open Access Journals (Sweden)

Novarian Budisetyowati

2017-01-01

Full Text Available Bioetanol kini banyak dikembangkan sebagai bahan bakar alternatif pengganti bahan bakar fosil. Bioetanol untuk campuran bensin harus memiliki kemurnian sebesar 99,5-100%. Bioetanol dapat diperoleh dengan proses fermentasi yang melibatkan mikroorganisme. Pra desain pabrik bioetanol dari nira siwalan ini menggunakan proses fermentasi. Bahan baku berupa nira siwalan diasamkan dengan menggunakan H2SO4, kemudian disterilisasi sebelum difermentasi di fermentor selama 36 jam. Adapun mikroorganisme yang digunakan adalah Saccharomyces cereviceae. Bakteri ini mampu mengurai gula tanpa kehadiran oksigen dan menghasilkan etanol dan karbondioksida. Bioetanol dapat diperoleh dengan proses fermentasi yang melibatkan mikroorganisme. Pra desain pabrik bioetanol dari nira siwalan ini menggunakan proses fermentasi. Bahan baku berupa nira siwalan diasamkan dengan menggunakan H2SO4, kemudian disterilisasi sebelum difermentasi di fermentor selama 36 jam. Adapun mikroorganisme yang digunakan adalah Saccharomyces cereviceae. Setelah dari fermentor nira yang sudah difermentasi dinetralkan pH nya menggunakan NH4OH di tangki netralisasi. Dari tangki netralisasi nira dipompakan melewati preheater sebelum masuk ke kolom distilasi. Pemurnian dilakukan dengan menggunakan kolom distilasi sebanyak 2 buah. Pada distilasi yang pertama diperoleh kadar etanol sebesar 60% dan pada distilasi yang kedua diperoleh kadar 96%. Dari kolom distilasi 2 larutan didinginkan menggunakan cooler untuk didapatkan suhu 32oC agar sesuai dengan suhu proses dehidrasi dengan menggunakan Molecular Sieve yang diinginkan. Proses dehidrasi dilakukan untuk mendapat kadar etanol 99,5%. Etanol 99,5% yang dihasilkan kemudian disimpan dalam tangki penampung. Kebutuhan bioetanol dalam negeri pada tahun 2018 diperkirakan 3.166.015,13 kL/tahun. Berdasarkan analisa ekonomi yang dilakukan, diperoleh hasil sebagai berikut internal rate of return 26,53 % per tahun, pay out time 4,73 tahun, dan BEP 34,62 % Ditinjau

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

Directory of Open Access Journals (Sweden)

Yan-Huan Feng

2016-01-01

Full Text Available 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 to study the combination therapy as an

PRA Procedures Guide: a guide to the performance of probabilistic risk assessments for nuclear power plants. Final report, Volume 1 - Chapters 1-8

International Nuclear Information System (INIS)

1983-01-01

This document, the Probabilistic Risk Assessment (PRA) Procedures Guide, is intended to provide an overview of the risk-assessment field as it exists today and to identify acceptable techniques for the systematic assessment of the risk from nuclear power plants. Topics discussed include: organization of PRA; accident-sequence definition and system modeling; human-reliability analysis; data-base development; accident-sequence quantification; physical processes of core-melt accidents; and radionuclide release and transport

Introduction of accidental procedures in the event trees of the 900MW PWR PRA

International Nuclear Information System (INIS)

Bars, G.; Champ, M.; Lanore, J.M.; Pochard, R.

1985-02-01

This paper presents the example of the small LOCA Event Trees and the studies related to the introduction of procedure actions is case of HPSI failure. The results illustrate the interest of the approach and its significant impact on the PRA. The present studies are related to the Y actions in case of small LOCAs without HPIS

Increased Aldosterone Release During Head-Up Tilt in Early Primary Hypertension.

Science.gov (United States)

Reinold, Annemarie; Schneider, Andreas; Kalizki, Tatjana; Raff, Ulrike; Schneider, Markus P; Schmieder, Roland E; Schmidt, Bernhard M W

2017-05-01

Hyperaldosteronism is well known cause of secondary hypertension. However, the importance of aldosterone for the much larger group of patients with primary hypertension is less clear. We hypothesized that in young subjects with primary hypertension, the rise of plasma aldosterone levels in response to head-up tilt testing as a stress stimulus is exaggerated. Hemodynamics (blood pressure (BP), heart rate (HR), cardiac index (CI), and total peripheral vascular resistance index (TPRI), all by TaskForce monitor) and hormones (plasma renin activity (PRA), angiotensin II (Ang II), aldosterone) were measured before and during 30 minutes of head-up tilt in 45 young hypertensive and 45 normotensive subjects. BP, HR, CI, and TPRI all increased in response to head-up tilt, with no difference between groups. There was no difference in baseline PRA, Ang II, and aldosterone between groups. During head-up tilt, PRA, and Ang II levels increased similarly. However, aldosterone levels increased to a greater extent in the hypertensive vs. normotensive subjects (P = 0.0021). Our data suggest that an increased release of aldosterone in response to orthostatic stress is a feature of early primary hypertension. The similar increase in PRA and Ang II suggests a potential role for secretagogues of aldosterone other than Ang II in this response. In addition to its established role in secondary hypertension, dysregulation of aldosterone release might contribute to the development of primary arterial hypertension. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Analysis of renin-angiotensin aldosterone system gene polymorphisms in malaysian essential hypertensive and type 2 diabetic subjects

OpenAIRE

Ramachandran, Vasudevan; Ismail, Patimah; Stanslas, Johnson; Shamsudin, Norashikin

2009-01-01

Abstract Background The renin-angiotensin aldosterone system (RAAS) plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT), MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin) of RAAS...

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

Science.gov (United States)

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;

The Improvement of Hypertension by Probiotics: Effects on Cholesterol, Diabetes, Renin, and Phytoestrogens

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Huey-Shi Lye

2009-08-01

Full Text Available Probiotics are live organisms that are primarily used to improve gastrointestinal disorders such as diarrhea, irritable bowel syndrome, constipation, lactose intolerance, and to inhibit the excessive proliferation of pathogenic intestinal bacteria. However, recent studies have suggested that probiotics could have beneficial effects beyond gastrointestinal health, as they were found to improve certain metabolic disorders such as hypertension. Hypertension is caused by various factors and the predominant causes include an increase in cholesterol levels, incidence of diabetes, inconsistent modulation of renin and imbalanced sexual hormones. This review discusses the antihypertensive roles of probiotics via the improvement and/or treatment of lipid profiles, modulation of insulin resistance and sensitivity, the modulation of renin levels and also the conversion of bioactive phytoestrogens as an alternative replacement of sexual hormones such as estrogen and progesterone.

Blockade of chloride channels by DIDS stimulates renin release and inhibits contraction of afferent arterioles

DEFF Research Database (Denmark)

Jensen, B L; Skøtt, O

1996-01-01

or without ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and DIDS were not additive. In the absence of chloride, basal renin release was suppressed and the stimulatory effect of DIDS was abolished. The DIDS-induced enhancement of renin release was not dependent on bicarbonate....... Norepinephrine (5 x 10(-7)-1 x 10(-6) M) and angiotensin II (1 x 10(-8)-10(-6) M) evoked reversible and dose-dependent contractions of microperfused rabbit afferent arterioles. DIDS (0.5 mM) did not affect the basal diameter of the arterioles but strongly inhibited the response to angiotensin II and attenuated...

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

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Norikazu Ueki

2015-01-01

Full Text Available 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.

Relative Atrial Natriuretic Peptide Deficiency and Inadequate Renin and Angiotensin II Suppression in Obese Hypertensive Men

DEFF Research Database (Denmark)

Asferg, Camilla L; Nielsen, Søren J; Andersen, Ulrik B

2013-01-01

Obesity is a strong risk factor for hypertension, but the mechanisms by which obesity leads to hypertension are incompletely understood. On this background, we assessed dietary sodium intake, serum levels of natriuretic peptides (NPs), and the activity of the renin-angiotensin system in 63 obese...... hypertensive men (obeseHT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure, ≥130/80 mm Hg), in 40 obese normotensive men (obeseNT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure,...

Variáveis meteorológicas e cobertura vegetal de espécies arbóreas em praças urbanas em Cuiabá, Brasil

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Angela Santana de Oliveira

2013-12-01

Full Text Available A influência da vegetação nas variáveis meteorológicas foi avaliada por meio do índice de área foliar (IAF e índice de sombreamento arbóreo (ISA em duas praças públicas em Cuiabá-MT, Brasil. Medidas de temperatura do ar (T e umidade relativa (UR foram obtidas sob a copa das árvores em diferentes sítios da cidade para o período seco e chuvoso no ano de 2009. A análise dos valores médios destas variáveis mostraram maiores valores de T e menores UR ocorrendo durante o período seco e sendo semelhantes nas duas praças. Com relação à UR, entretanto, não houve diferenças significativas entre a medida sob as árvores e a atmosfera. O índice de área foliar foi calculado e variou em função das espécies arbóreas das praças, e mostrou valores entre 5,64 e 2,79 m². m-2, sendo a média do IAF e do ISA na Praça Popular superiores ao da Praça 8 de Abril. Conclui-se que as espécies arbóreas melhoraram o ambiente térmico em virtude da atenuação da radiação proporcionada pelo sombreamento das diferentes espécies, principalmente no horário com menor ângulo solar.

Results and insights of a level-1 internal event PRA of a PWR during mid-loop operations

International Nuclear Information System (INIS)

Chu, T.L.; Musicki, Z.; Kohut, P.; Yang, J.; Bozoki, G.; Hsu, C.J.; Diamond, D.J.; Wong, S.M.; Holmes, B.; Su, R.F.; Dang, V.; Siu, N.; Bley, D.; Johnson, D.; Lin, J.

1994-01-01

Traditionally, probabilistic risk assessments (PRA) of severe accidents in nuclear power plants have considered initiating events potentially occurring only during full power operation. Some previous screening analysis that were performed for other modes of operation suggested that risks during those modes were small relative to full power operation. However, more recent studies and operational experience have implied that accidents during low power and shutdown could be significant contributors to risk. During 1989, the Nuclear Regulatory Commission (NRC) initiated an extensive program to carefully examine the potential risks during low power and shutdown operations. The program includes two parallel projects being performed by BNL and SNL. Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The scope of the program includes that of a level-3 PRA. The objective of this paper is to present the approach utilized in the level-1 PRA for the Surry plant, and discuss the results obtained. A comparison of the results with those of other shutdown studies is provided. Relevant safety issues such as plant and hardware configurations, operator training, and instrumentation and control is discussed

Development of margin assessment methodology of decay heat removal function against external hazards. (2) Tornado PRA methodology

International Nuclear Information System (INIS)

Nishino, Hiroyuki; Kurisaka, Kenichi; Yamano, Hidemasa

2014-01-01

Probabilistic Risk Assessment (PRA) for external events has been recognized as an important safety assessment method after the TEPCO's Fukushima Daiichi nuclear power station accident. The PRA should be performed not only for earthquake and tsunami which are especially key events in Japan, but also the PRA methodology should be developed for the other external hazards (e.g. tornado). In this study, the methodology was developed for Sodium-cooled Fast Reactors paying attention to that the ambient air is their final heat sink for removing decay heat under accident conditions. First, tornado hazard curve was estimated by using data recorded in Japan. Second, important structures and components for decay heat removal were identified and an event tree resulting in core damage was developed in terms of wind load and missiles (i.e. steel pipes, boards and cars) caused by a tornado. Main damage cause for important structures and components is the missiles and the tornado missiles that can reach those components and structures placed on high elevations were identified, and the failure probabilities of the components and structures against the tornado missiles were calculated as a product of two probabilities: i.e., a probability for the missiles to enter the intake or outtake in the decay heat removal system, and a probability of failure caused by the missile impacts. Finally, the event tree was quantified. As a result, the core damage frequency was enough lower than 10 -10 /ry. (author)

Baroreflex control of sympathetic activity in experimental hypertension

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M.C.C. Irigoyen

1998-09-01

Full Text Available The arterial baroreceptor reflex system is one of the most powerful and rapidly acting mechanisms for controlling arterial pressure. The purpose of the present review is to discuss data relating sympathetic activity to the baroreflex control of arterial pressure in two different experimental models: neurogenic hypertension by sinoaortic denervation (SAD and high-renin hypertension by total aortic ligation between the renal arteries in the rat. SAD depresses baroreflex regulation of renal sympathetic activity in both the acute and chronic phases. However, increased sympathetic activity (100% was found only in the acute phase of sinoaortic denervation. In the chronic phase of SAD average discharge normalized but the pattern of discharges was different from that found in controls. High-renin hypertensive rats showed overactivity of the renin angiotensin system and a great depression of the baroreflexes, comparable to the depression observed in chronic sinoaortic denervated rats. However, there were no differences in the average tonic sympathetic activity or changes in the pattern of discharges in high-renin rats. We suggest that the difference in the pattern of discharges may contribute to the increase in arterial pressure lability observed in chronic sinoaortic denervated rats.

The role of renin angiotensin system in retinal inflammation

OpenAIRE

Zhu, Tong

2017-01-01

Purpose: Retinopathy of prematurity (ROP) is the main cause of vision loss and blindness in children, and is replicated and intensively studied in rodent models of oxygen-induced retinopathy (OIR). One signature feature of ROP is retinal neovascularization, which is also present in patients with proliferative diabetic retinopathy (PDR). Inflammation is another feature in ROP and PDR. In both diseases, the renin angiotensin system (RAS) is dysregulated, and blockade of RAS via angiotensin II (...

Human factors assessment in PRA using task analysis linked evaluation technique (TALENT)

International Nuclear Information System (INIS)

Wells, J.E.; Banks, W.W.

1990-01-01

Human error is a primary contributor to risk in complex high-reliability systems. A 1985 U.S. Nuclear Regulatory Commission (USNRC) study of licensee event reports (LERs) suggests that upwards of 65% of commercial nuclear system failures involve human error. Since then, the USNRC has initiated research to fully and properly integrate human errors into the probabilistic risk assessment (PRA) process. The resulting implementation procedure is known as the Task Analysis Linked Evaluation Technique (TALENT). As indicated, TALENT is a broad-based method for integrating human factors expertise into the PRA process. This process achieves results which: (1) provide more realistic estimates of the impact of human performance on nuclear power safety, (2) can be fully audited, (3) provide a firm technical base for equipment-centered and personnel-centered retrofit/redesign of plants enabling them to meet internally and externally imposed safety standards, and (4) yield human and hardware data capable of supporting inquiries into human performance issues that transcend the individual plant. The TALENT procedure is being field-tested to verify its effectiveness and utility. The objectives of the field-test are to examine (1) the operability of the process, (2) its acceptability to the users, and (3) its usefulness for achieving measurable improvements in the credibility of the analysis. The field-test will provide the information needed to enhance the TALENT process

Sex differences in the aging pattern of renin-angiotensin system serum peptidases.

Science.gov (United States)

Fernández-Atucha, A; Izagirre, A; Fraile-Bermúdez, A B; Kortajarena, M; Larrinaga, G; Martinez-Lage, P; Echevarría, E; Gil, J

2017-01-01

Serum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin-angiotensin system (RAS). Dysregulation of these enzymes has been associated with hypertension and cardiovascular risk. In the present study, serum activities of RAS peptidases were analyzed to evaluate the existence of sexual differences, with a possible different pattern in pre- and post-andropausal/post-menopausal participants. One hundred and eighteen healthy men and women between 41 and 70 years of age (58 women and 60 men) were recruited to participate in the study. Serum RAS-regulating enzymes were measured by spectrofluorimetry. Enzymatic activity was recorded as units of enzyme per milliliter of serum (U/mL). Significantly lower serum APA activity was observed in men with respect to women; no sex differences were detected for ACE, ACE2, NEP, or APN. Significantly lower APA and ACE serum activity were observed in older men compared to older women. In contrast, younger (menopausia, on the critical serum enzymatic activities of the RAS, which could correlate with sexual differences in cardiovascular risk.

Changes in the renin-angiotensin-aldosterone system in response to dietary salt intake in normal and hypertensive pregnancy. A randomized trial

DEFF Research Database (Denmark)

Nielsen, Lise Hald; Ovesen, Per; Hansen, Mie R

2016-01-01

It was hypothesized that primary renal sodium retention blunted the reactivity of the renin-angiotensin-aldosterone system to changes in salt intake in preeclampsia (PE). A randomized, cross-over, double-blinded, dietary intervention design was used to measure the effects of salt tablets or place...... of plasma renin and angiotensin II in response to changes in dietary salt intake compatible with a primary increase in renal sodium reabsorption in hypertensive pregnancies.......It was hypothesized that primary renal sodium retention blunted the reactivity of the renin-angiotensin-aldosterone system to changes in salt intake in preeclampsia (PE). A randomized, cross-over, double-blinded, dietary intervention design was used to measure the effects of salt tablets or placebo...

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

Science.gov (United States)

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.

Human reliability analysis in support of a level 1 PRA for Surry during midloop operations

International Nuclear Information System (INIS)

Lin, J.C.; Bley, D.C.; Chu, T.-L.

2004-01-01

The objectives of this Level 1 probabilistic risk assessment (PRA) are to evaluate the important accident sequences initiated during midloop operations and to compare the qualitative and quantitative results with those for accidents initiated during power operations. The primary types of human actions analyzed in this study involve the dynamic operator actions and recovery actions that take place during the accident sequence following an initiating event. Two parts of the human actions were analyzed: failure to diagnose and failure to perform the action. The scope of the Level 1 PRA for Surry during midloop operations includes internal, fire, and flood initiating events. The major categories of dynamic operator actions taken during the accident sequence following an initiating event are: providing makeup to the reactor coolant system (RCS), restoring residual heat removal (RHR) cooling, establishing steam generator reflux cooling, establishing primary feed and spill, establishing gravity feed from refueling water storage tank (RWST), establishing high pressure recirculation, establishing recirculation spray, and cross-connecting RWSTs. All categories are not applicable to all initiating events and all plant operating states (POS). (author)

The secretory phospholipase A2 group IIA: a missing link between inflammation, activated renin-angiotensin system, and atherogenesis?

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Dimitar Divchev

2008-06-01

Full Text Available Dimitar Divchev, Bernhard SchiefferDepartment of Cardiology and Angiology, Medizinische Hochschule Hannover, GermanyAbstract: Inflammation, lipid peroxidation and chronic activation of the renin–angiotensin system (RAS are hallmarks of the development of atherosclerosis. Recent studies have suggested the involvement of the pro-inflammatory secretory phospholipase A2 (sPLA2-IIA in atherogenesis. This enzyme is produced by different cell types through stimulation by proinflammatory cytokines. It is detectable in the intima and in media smooth muscle cells, not only in atherosclerotic lesions but also in the very early stages of atherogenesis. sPLA2-IIA can hydrolyse the phospholipid monolayers of low density lipoproteins (LDL. Such modified LDL show increased affinity to proteoglycans. The modified particles have a greater tendency to aggregate and an enhanced ability to insert cholesterol into cells. This modification may promote macrophage LDL uptake leading to the formation of foam cells. Furthermore, sPLA2-IIA is not only a mediator for localized inflammation but may be also used as an independent predictor of adverse outcomes in patients with stable coronary artery disease or acute coronary syndromes. An interaction between activated RAS and phospholipases has been indicated by observations showing that inhibitors of sPLA2 decrease angiotensin (Ang II-induced macrophage lipid peroxidation. Meanwhile, various interactions between Ang II and oxLDL have been demonstrated suggesting a central role of sPLA2-IIA in these processes and offering a possible target for treatment. The role of sPLA2-IIA in the perpetuation of atherosclerosis appears to be the missing link between inflammation, activated RAS and lipidperoxidation.Keywords: secretory phospholipase A2, lipoproteins, renin-angiotensin system, inflammation, atherosclerosis

Nifedipine-sensitive blood pressure component in hypertensive models characterized by high activity of either sympathetic nervous system or renin-angiotensin system

Czech Academy of Sciences Publication Activity Database

Zicha, Josef; Dobešová, Zdenka; Behuliak, Michal; Pintérová, Mária; Kuneš, Jaroslav; Vaněčková, Ivana

2014-01-01

Roč. 63, č. 1 (2014), s. 13-26 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/09/0336; GA ČR(CZ) GAP304/12/0259 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : voltage-gated caclium channels * sympathetic nervous system * renin-angiotensin system * nitric oxide Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.293, year: 2014

Prostaglandin E2 EP2 and EP4 receptor activation mediates cAMP-dependent hyperpolarization and exocytosis of renin in juxtaglomerular cells

DEFF Research Database (Denmark)

Friis, Ulla Glenert; Stubbe, Jane; Uhrenholt, Torben Rene

2005-01-01

/l), AE1-259-01 (1 nmol/l), EP4-selective agonist AE1-329 (1 nmol/l), and IP agonist iloprost (1 micromol/l) significantly increased C(m) mediated by PKA. The EP4 antagonist AE3-208 (10 nmol/l) blocked the effect of EP4 agonist but did not alter the response to PGE(2). Application of both EP4 antagonist....... The membrane potential hyperpolarized significantly after PGE(2), butaprost, AE1-329 and AE1-259 and outward current was augmented in a PKA-dependent fashion. PGE(2)-stimulated outward current, but not C(m) change, was abolished by the BK(Ca) channel inhibitor iberiotoxin (300 nmol/l). EP2 and EP4 m......RNA was detected in sampled JG cells, and the preglomerular and glomerular vasculature was immunopositive for EP4. Thus IP, EP2, and EP4 receptors are associated with JG cells, and their activation leads to rapid PKA-mediated exocytotic fusion and release of renin granules....

Tissue Renin-Angiotensin Systems: A Unifying Hypothesis of Metabolic Disease

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Jeppe eSkov

2014-02-01

Full Text Available The actions of angiotensin peptides are diverse and locally acting tissue renin-angiotensin systems (RAS are present in almost all tissues of the body. An activated RAS strongly correlates to metabolic disease (e.g. diabetes and its complications and blockers of RAS have been demonstrated to prevent diabetes in humans.Hyperglycemia, obesity, hypertension, and cortisol are well-known risk factors of metabolic disease and all stimulate tissue RAS whereas glucagon-like peptide-1, vitamin D, and aerobic exercise are inhibitors of tissue RAS and to some extent can prevent metabolic disease. Furthermore, an activated tissue RAS deteriorates the same risk factors creating a system with several positive feedback pathways. The primary effector hormone of the RAS, angiotensin II, stimulates reactive oxygen species, induces tissue damage, and can be associated to most diabetic complications. Based on these observations we hypothesize that an activated tissue RAS is the principle cause of metabolic syndrome and type 2 diabetes, and additionally is mediating the majority of the metabolic complications. The involvement of positive feedback pathways may create a self-reinforcing state and explain why metabolic disease initiate and progress. The hypothesis plausibly unify the major predictors of metabolic disease and places tissue RAS regulation in the center of metabolic control.

Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression.

Science.gov (United States)

Chaudhary, Kapil; Promsote, Wanwisa; Ananth, Sudha; Veeranan-Karmegam, Rajalakshmi; Tawfik, Amany; Arjunan, Pachiappan; Martin, Pamela; Smith, Sylvia B; Thangaraju, Muthusamy; Kisselev, Oleg; Ganapathy, Vadivel; Gnana-Prakasam, Jaya P

2018-02-14

Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Increased iron accumulation is associated with several degenerative diseases. However, there are no reports on the status of retinal iron or its implications in the pathogenesis of DR. In the present study, we found that retinas of type-1 and type-2 mouse models of diabetes have increased iron accumulation compared to non-diabetic retinas. We found similar iron accumulation in postmortem retinal samples from human diabetic patients. Further, we induced diabetes in HFE knockout (KO) mice model of genetic iron overload to understand the role of iron in the pathogenesis of DR. We found increased neuronal cell death, vascular alterations and loss of retinal barrier integrity in diabetic HFE KO mice compared to diabetic wildtype mice. Diabetic HFE KO mouse retinas also exhibited increased expression of inflammation and oxidative stress markers. Severity in the pathogenesis of DR in HFE KO mice was accompanied by increase in retinal renin expression mediated by G-protein-coupled succinate receptor GPR91. In light of previous reports implicating retinal renin-angiotensin system in DR pathogenesis, our results reveal a novel relationship between diabetes, iron and renin-angiotensin system, thereby unraveling new therapeutic targets for the treatment of DR.

Análise quali-quantitativa da arborização na praça XV de novembro em Ribeirão Preto - SP, Brasil

Directory of Open Access Journals (Sweden)

Gustavo de Nobrega Romani

2012-06-01

Full Text Available A Praça XV de Novembro, implantada em meados do século XIX, tem grande valor histórico-cultural, além de se constituir em uma das principais áreas verdes do centro da cidade de Ribeirão Preto. Visando ao conhecimento detalhado da vegetação para fins de orientação do manejo e conservação dessa área, foi feito um levantamento quali-quantitativo e fitossociológico das árvores e palmeiras da praça. Foram medidas altura e Diâmetro à Altura do Peito (DAP e identificados todos os indivíduos de porte arbóreo (árvores e palmeiras presentes na Praça, em nível de espécie. A praça ocupa uma área de 15.456,00 m², onde foram amostradas 42 espécies distribuídas por 19 famílias, num total de 161 indivíduos. Apesar de o local apresentar arborização com alto índice de diversidade de espécies (Shannon-Weaver de 3,14, os exemplares necessitam de maior atenção quanto a problemas ligados à fitossanidade e podas adequadas, fazendo que resulte em espaço seguro para os frequentadores e em boa qualidade paisagística.

Effects of high doses of enalapril and benazepril on the pharmacologically activated renin-angiotensin-aldosterone system in clinically normal dogs.

Science.gov (United States)

Ames, Marisa K; Atkins, Clarke E; Lee, Seunggon; Lantis, Andrea C; zumBrunnen, James R

2015-12-01

To determine whether high doses of enalapril and benazepril would be more effective than standard doses of these drugs in suppressing the furosemide-activated renin-angiotensin-aldosterone system (RAAS). 6 healthy Beagles. 2 experiments were conducted; each lasted 10 days, separated by a 2-week washout period. In experiment 1, all dogs received furosemide (2 mg/kg, PO, q 12 h) and enalapril (1 mg/kg, PO, q 12 h) for 8 days (days 0 through 7). In experiment 2, dogs received furosemide (2 mg/kg, PO, q 12 h) and benazepril (1 mg/kg, PO, q 12 h) for 8 days. Effects on the RAAS were determined by assessing serum angiotensin-converting enzyme (ACE) activity on days -1, 3, and 7; serum aldosterone concentration on days -2, -1, 1, 3, and 7; and the urinary aldosterone-creatinine ratio (UAldo:C) in urine collected in the morning and evening of days -2, -1, 1, 3, and 7. High doses of enalapril and benazepril caused significant reductions in serum ACE activity on all days but were not more effective than standard doses used in other studies. Mean UAldo:C remained significantly higher on days 2 through 7, compared with baseline values. Serum aldosterone concentration also increased after drug administration, which mirrored changes in the UAldo:C. In this study, administration of high doses of enalapril and benazepril significantly inhibited ACE activity, yet did not prevent increases in mean urine and serum aldosterone concentrations resulting from furosemide activation of RAAS. This suggested that aldosterone breakthrough from ACE inhibition was a dose-independent effect of ACE inhibitors.

Functional interactions between 7TM receptors in the renin-angiotensin system--dimerization or crosstalk?

DEFF Research Database (Denmark)

Lyngsø, Christina; Erikstrup, Niels; Hansen, Jakob L

2008-01-01

. The importance of the RAS is clearly emphasised by the widespread use of drugs targeting this system in clinical practice. These include, renin inhibitors, angiotensin II receptor type I blockers, and inhibitors of the angiotensin converting enzyme. Some of the important effectors within the system are 7...... be important for receptor function, and in the development of cardiovascular diseases. This is very significant, since "dimers" may provide pharmacologists with novel targets for improved drug therapy. However, we know that 7TM receptors can mediate signals as monomeric units, and so far it has been very......The Renin-Angiotensin System (RAS) is important for the regulation of cardiovascular physiology, where it controls blood pressure, and salt- and water homeostasis. Dysregulation of RAS can lead to severe diseases including hypertension, diabetic nephropathy, and cardiac arrhythmia, and -failure...

Direct renin inhibitors – new approaches in the treatment of patients with arterial hypertension associated with obesity, diabetes mellitus, menopause and kidneys’ disorders

OpenAIRE

Syvolap, V. V.; Gerasko, M. P.

2013-01-01

In this review composed on the data of multicentred randomized investigations the advantages of direct renin inhibitors for patients with arterial hypertension are discussed. The prospects of using direct renin inhibitors in the cases of arterial hypertension associated with obesity, diabetes mellitus, menopause and kidneys’ disorders are studied.

Brain renin angiotensin system in cardiac hypertrophy and failure

Directory of Open Access Journals (Sweden)

Luciana eCampos

2012-01-01

Full Text Available Brain renin-angiotensin system (RAS is significantly involved in the roles of the endocrine RAS in cardiovascular regulation. Our studies indicate that the brain RAS participates in the development of cardiac hypertrophy and fibrosis through sympathetic activation. Inhibition of sympathetic hyperactivity after myocardial infarction through suppression of the brain RAS appears beneficial. The brain RAS is involved in the modulation of circadian rhythms of arterial pressure, contributing to nondipping hypertension. We conclude that the brain RAS in pathophysiological states interacts synergistically with the chronically overactive RAS through a positive biofeedback in order to maintain a state of alert diseased conditions, such as cardiac hypertrophy and failure. Therefore, targeting brain RAS with drugs such as angiotensin converting inhibitors or receptor blockers having increased brain penetrability could be of advantage. These RAS-targeting drugs are first-line therapy for all heart failure patients. Since the RAS has both endocrine and local tissue components, RAS drugs are being developed to attain increased tissue penetrability and volume of distribution and consequently an efficient inhibition of both RAS components.

Analysis of climate and anthropogenic impacts on runoff in the Lower Pra River Basin of Ghana.

Science.gov (United States)

Awotwi, Alfred; Anornu, Geophrey Kwame; Quaye-Ballard, Jonathan; Annor, Thompson; Forkuo, Eric Kwabena

2017-12-01

The Lower Pra River Basin (LPRB), located in the forest zone of southern Ghana has experienced changes due to variability in precipitation and diverse anthropogenic activities. Therefore, to maintain the functions of the ecosystem for water resources management, planning and sustainable development, it is important to differentiate the impacts of precipitation variability and anthropogenic activities on stream flow changes. We investigated the variability in runoff and quantified the contributions of precipitation and anthropogenic activities on runoff at the LPRB. Analysis of the precipitation-runoff for the period 1970-2010 revealed breakpoints in 1986, 2000, 2004 and 2010 in the LPRB. The periods influenced by anthropogenic activities were categorized into three periods 1987-2000, 2001-2004 and 2005-2010, revealing a decrease in runoff during 1987-2000 and an increase in runoff during 2001-2004 and 2005-2010. Assessment of monthly, seasonal and annual runoff depicted a significant increasing trend in the runoff time series during the dry season. Generally, runoff increased at a rate of 9.98 × 10 7 m 3 yr -1 , with precipitation variability and human activities contributing 17.4% and 82.3% respectively. The dominant small scale alluvial gold mining activity significantly contributes to the net runoff variability in LPRB.

Avaliação qualitativa e quantitativa da arborização das praças de Vinhedo, SP.

Directory of Open Access Journals (Sweden)

Roberval de Cássia Salvador Ribeiro

2006-06-01

Full Text Available O inventário das espécies arbóreas e dos respectivos números de indivíduos das praças da cidade de Vinhedo foi realizado no perímetro urbano, excetuando-se os condomínios, as áreas de parques e as de preservação de mananciais. Para a localização das áreas, consultou-se a planta do município de 1997. Realizou-se o inventário da vegetação arbórea, considerando-se apenas os indivíduos com CAP (circunferência à altura do peito acima de 10 cm listando-se as seguintes informações: nomes comum e científico das espécies; CAP; altura; aspecto geral; diâmetro de copa; presença de pragas, doenças ou parasitas; ocorrência de podas (drástica e/ou de condução; fitossanidade da raiz, tronco e copa. Foram registradas 22 praças por nome, localização e número total de árvores, totalizando 764 indivíduos pertencentes a 23 famílias botânicas e 53 espécies, além de 32 indivíduos não identificados. A espécie de maior abundância relativa foi Syagrus romanzoffiana (jerivá, com 31,94% do número total de indivíduos. Em 63,64% das praças 33,13% das espécies eram exóticas. A maior parte dos indivíduos tinha aspecto geral normal, demonstrando prática de tratos culturais adequados. Na maioria dos casos, as podas foram feitas corretamente, ou não houve a necessidade de nenhuma intervenção. Do total de 22 praças, apenas cinco tinham bom estado geral de conservação dos elementos naturais (arbustos, canteiros e gramados. Em 68,18% das praças as árvores tinham altura superior a 6 metros, indicando que essas áreas necessitavam apenas de procedimentos de manutenção de rotina. E 22,72% necessitavam de práticas de manutenção mais direcionadas ao desenvolvimento das árvores, tais como adubações periódicas, capinas, podas de condução e, finalmente, em 13,64% deveriam ocorrer intervenções tanto de manutenção, como de recuperação por meio de novos plantios, ou mesmo, de planejamento para remodelação da área.

Primer uticaja filtriranja slike u sistemima za praćenje ciljeva primenom termovizije / An example of image filtering in target tracking systems with thermal imagery

Directory of Open Access Journals (Sweden)

Zvonko M. Radosavljević

2003-07-01

Full Text Available U radu je dat primer primene jedne vrste niskofrekventnog filtriranja sa usrednjavanjem, koje se primenjuje u sistemima za detekciju i praćenje ciljeva u vazdušnom prostoru primenom termovizije. Date su dve metode filtriranja slike. Prva metoda koristi niskofrekventno konvoluciono filtriranje a druga usrednjavajući filtar na osnovu srednje vrednosti nivoa sivog. Ovi filtri su primenjeni u sistemima za praćenje uz pomoć infracrvenih senzora. Određivanje nivoa praga filtriranja vrši se uz pomoć statističkih osobina slike. Veoma važan korak u procesu praćenja je određivanje prozora praćenja, koji maze biti, po dimenzijama, fiksan ili adaptibilan. Pogrešna procena o postojanju cilja u prozoru može se doneti u slučaju prisustva šuma pozadine, predpojačavača, detektora, itd. Filtriranje je neophodan korak u ovim sistemima, kao značajan činilac U povećanju brzine i tačnosti praćenja. / A case of image filtering in air target detecting and tracking systems is described in this paper. Two image filtering methods are given. The first method is performed using a low pass convolving filter and the second one uses the mean value of gray level filter. The main goal of the cited filtering is implementation in IR (infra red systems. Some statistical features of the images were used for selecting the threshold level. The next step in the algorithm is the determination of a 'tracking window' that can be fixed or adaptive in size. A false estimation of a target existing in the window may be influenced by the background noise, low noise amplifier detector, etc.

Implications of an HRA framework for quantifying human acts of commission and dependency: Development of a methodology for conducting an integrated HRA/PRA

International Nuclear Information System (INIS)

Barriere, M.T.; Luckas, W.J.; Brown, W.S.; Cooper, S.E.; Wreathall, J.; Bley, D.C.

1994-01-01

To support the development of a refined human reliability analysis (HRA) framework, to address identified HRA user needs and improve HRA modeling, unique aspects of human performance have been identified from an analysis of actual plant-specific events. Through the use of the refined framework, relationships between the following HRA, human factors and probabilistic risk assessment (PRA) elements were described: the PRA model, plant states, plant conditions, PRA basic events, unsafe human actions, error mechanisms, and performance shaping factors (PSFs). The event analyses performed in the context of the refined HRA framework, identified the need for new HRA methods that are capable of: evaluating a range of different error mechanisms (e.g., slips as well as mistakes); addressing errors of commission (EOCs) and dependencies between human actions; and incorporating the influence of plant conditions and multiple PSFs on human actions. This report discusses the results of the assessment of user needs, the refinement of the existing HRA framework, as well as, the current status on EOCs, and human dependencies

Implications of an HRA framework for quantifying human acts of commission and dependency: Development of a methodology for conducting an integrated HRA/PRA

International Nuclear Information System (INIS)

Barriere, M.T.; Luckas, W.J.; Brown, W.S.; Cooper, S.E.; Wreathall, J.; Bley, D.C.

1993-01-01

To support the development of a refined human reliability analysis (HRA) framework, to address identified HRA user needs and improve HRA modeling, unique aspects of human performance have been identified from an analysis of actual plant-specific events. Through the use of the refined framework, relationships between the following HRA, human factors and probabilistic risk assessment (PRA) elements were described: the PRA model, plant states, plant conditions, PRA basic events, unsafe human actions, error mechanisms, and performance shaping factors (PSFs). The event analyses performed in the context of the refined HRA framework, identified the need for new HRA methods that are capable of: evaluating a range of different error mechanisms (e.g., slips as well as mistakes); addressing errors of commission (EOCs) and dependencies between human actions; and incorporating the influence of plant conditions and multiple PSFs on human actions. This report discusses the results of the assessment of user needs, the refinement of the existing HRA framework, as well as, the current status on EOCs, and human dependencies

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

Science.gov (United States)

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.

Two decades of PRA: What next?

International Nuclear Information System (INIS)

Rasmussen, N.C.

1992-01-01

Two decades ago, in the spring of 1972, the Reactor Safety Study was undertaken for the US Atomic Energy Commission (AEC). The goal of this study was to assess the risk to the public posed by the nuclear power plants operating in the US. Some three and one-half years later in October 1975, the study group issued its final report titled The Reactor Safety Study, also commonly known by its document number WASH 1400. Because it was issued at a time of heated public debate about nuclear safety, WASH 1400 received considerable critical review. By the late 1970s, as a result of the Lewis Report and the accident at Three Mile Island, the value of the WASH 1400 methodology was gradually recognized. A number of utilities undertook such studies of their own plants. The field of probabilistic risk assessment (PRA) developed from these efforts. Challenges remain. Among these are how to effectively communicate the results of the analysis. Just what does a probability of one in a million mean? Is there a de minimis probability - one so small that it can be ignored? How should society make decisions under substantial uncertainty? A number of these questions pose real challenges for the future

Involvement of skeletal renin-angiotensin system and kallikrein-kinin system in bone deteriorations of type 1 diabetic mice with estrogen deficiency.

Science.gov (United States)

Zhang, Yan; Wang, Liang; Liu, Jin-Xin; Wang, Xin-Luan; Shi, Qi; Wang, Yong-Jun

This study was aimed to investigate the involvement of skeletal renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) in bone deteriorations of mice in response to the combination treatment of estrogen deficiency and hyperglycemia. The female C57BL/6J mice were sham-operated or ovariectomized with vehicle or streptozotocin (STZ) treatment. Two weeks later, the biochemistries in serum and urine were determined by standard colorimetric methods or ELISA. The H&E and TRAP staining were performed at the tibial proximal metaphysis. The polymerase chain reaction and immunoblotting were applied for molecular analysis on mRNA and protein expression. The mice after treating with ovariectomy and STZ showed the decreased level of serum Ca and the increased level of serum PTH and urine Ca. The H&E staining showed trabecular bone abnormalities as demonstrated by the loss, disconnection and separation of trabecular bone network as well as the loss of chondrocytes and appearance of chondrocyte cluster at growth plate of tibia. The significant increase of matured osteoclast number was shown in group with double treatments. The combination treatment significantly up-regulated mRNA expression of AGT, ACE, renin receptor, MMP-9 and CAII, and protein expression of renin, and decreased the ratio of OPG/RANKL and the expression of bradykinin receptors in bone tissue. Ovariectomy combined with STZ induction produced more detrimental actions on bone through the activation of local bone RAS and the down-regulation of bradykinin receptors, as compared to the respective single treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Expression of genes of the cardiac and renal renin-angiotensin systems in preterm piglets: is this system a suitable target for therapeutic intervention?

Science.gov (United States)

Kim, Eleanor; Eiby, Yvonne; Lumbers, Eugenie; Boyce, Amanda; Gibson, Karen; Lingwood, Barbara

2015-10-01

The newborn circulating, cardiac and renal renin-angiotensin systems (RASs) are essential for blood pressure control, and for cardiac and renal development. If cardiac and renal RASs are immature this may contribute to cardiovascular compromise in preterm infants. This study measured mRNA expression of cardiac and renal RAS components in preterm, glucocorticoid (GC) exposed preterm, and term piglets. Renal and cardiac RAS mRNA levels were measured using real-time polymerase chain reaction (PCR). Genes studied were: (pro)renin receptor, renin, angiotensinogen, angiotensin converting enzyme (ACE), ACE2, angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R). All the genes studied were expressed in the kidney; neither renin nor AT2R mRNA were detected in the heart. There were no gestational changes in (pro)renin receptor, renin, ACE or AT1R mRNA levels. Right ventricular angiotensinogen mRNA levels in females were lower in preterm animals than at term, and GC exposure increased levels in male piglets. Renal angiotensinogen mRNA levels in female term piglets were lower than females from both preterm groups, and lower than male term piglets. Left ventricular ACE2 mRNA expression was lower in GC treated preterm piglets. Renal AT2R mRNA abundance was highest in GC treated preterm piglets, and the AT1R/AT2R ratio was increased at term. Preterm cardiac and renal RAS mRNA levels were similar to term piglets, suggesting that immaturity of these RASs does not contribute to preterm cardiovascular compromise. Since preterm expression of both renal and cardiac angiotensin II-AT1R is similar to term animals, cardiovascular dysfunction in the sick preterm human neonate might be effectively treated by agents acting on their RASs. © The Author(s), 2015.

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

Science.gov (United States)

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

Renin inhibition improves cardiac function and remodeling after myocardial infarction independent of blood pressure

NARCIS (Netherlands)

D. Westermann (Dirk); A. Riad (Alexander); O. Lettau (Olga); A.J.M. Roks (Anton); K. Sawatis (Konstantinos); P.M. Becher (Peter Moritz); F. Escher (Felicitas); A.H.J. Danser (Jan); H.P. Schultheiss (Heinz-Peter); C. Tschöpe (Carsten)

2008-01-01

textabstractPharmacological renin inhibition with aliskiren is an effective antihypertensive drug treatment, but it is currently unknown whether aliskiren is able to attenuate cardiac failure independent of its blood pressure-lowering effects. We investigated the effect of aliskiren on cardiac

Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin-angiotensin system inhibitors in the community increases the risk of acute kidney injury.

Science.gov (United States)

Dreischulte, Tobias; Morales, Daniel R; Bell, Samira; Guthrie, Bruce

2015-08-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI) when used in triple combination with renin-angiotensin system inhibitors and diuretics, but previous research reported that NSAIDs in dual combinations with either renin-angiotensin system inhibitors or diuretics alone were not. However, earlier studies relied on hospital coding to define AKI, which may underestimate true risk. This nested case-control study characterized the risk of community-acquired AKI associated with NSAID use among 78,379 users of renin-angiotensin system inhibitors and/or diuretics, where AKI was defined as a 50% or greater increase in creatinine from baseline. The AKI incidence was 68/10,000 person-years. The relative increase in AKI risk was similar for NSAID use in both triple (adjusted rate ratio 1.64 (95% CI 1.25-2.14)) and dual combinations with either renin-angiotensin system inhibitors (1.60 (1.18-2.17)) or diuretics (1.64 (1.17-2.29)). However, the absolute increase in AKI risk was higher for NSAIDs used in triple versus dual combinations with renin-angiotensin system inhibitors or diuretics alone (numbers needed to harm for 1 year treatment with NSAID of 158 vs. over 300). AKI risk was highest among users of loop diuretic/aldosterone antagonist combinations, in those over 75 years of age, and in those with renal impairment. Thus, the nephrotoxic potential of both dual and triple combinations of NSAIDs with renin-angiotensin system inhibitors and/or diuretics yields a higher incidence of AKI than previously thought.

Cardiac remodeling during and after renin-angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats

DEFF Research Database (Denmark)

Heijnen, Bart Fj; Pelkmans, Leonie Pj; Danser, Ah Jan

2013-01-01

This study investigated renin-angiotensin system (RAS)-induced cardiac remodeling and its reversibility in the presence and absence of high blood pressure (BP) in Cyp1a1-Ren2 transgenic inducible hypertensive rats (IHR). In IHR (pro)renin levels and BP can be dose-dependently titrated by oral...... administration of indole-3-carbinol (I3C). Young (four-weeks old) and adult (30-weeks old) IHR were fed I3C for four weeks (leading to systolic BP >200 mmHg). RAS-stimulation was stopped and animals were followed-up for a consecutive period. Cardiac function and geometry was determined echocardiographically...

Use of probabilistic risk assessment in maintenance activities at Palo Verde

International Nuclear Information System (INIS)

Lindquist, R.C.; Pobst, D.S.

1993-01-01

Probabilistic risk assessment (PRA) is an important tool in addressing various maintenance activities. At the Palo Verde nuclear generating station (PVNGS), the PRA has been used in a variety of ways to support a wide and diverse selection of maintenance-related activities. For on-line or at-power maintenance, the PRA was used to evaluate combinations of maintenance activities possible with the 12-week or floating maintenance schedule. The maintenance schedule was evaluated to identify any higher risk, undesirable combinations of equipment outages, such as the sole steam-driven auxiliary feedwater pump and the same train emergency diesel generator. Table I is a sampling of the results from the maintenance schedule evaluation in terms of increase in conditional core damage frequency (CDF) above the base- line value due to maintenance on some important key safety systems and combinations thereof. The baseline CDF is 7.4 x 10 -7 per 72 h

Applications of PRA in nuclear criticality safety

International Nuclear Information System (INIS)

McLaughlin, T.P.

1992-01-01

Traditionally, criticality accident prevention at Los Alamos has been based on a thorough review and understanding of proposed operations of changes to operations, involving both process supervision and criticality safety staff. The outcome of this communication was usually an agreement, based on professional judgement, that certain accident sequences were credible and had to be reduced in likelihood either by administrative controls or by equipment design and others were not credible, and thus did not warrant expenditures to further reduce their likelihood. The extent of analysis and documentation was generally in proportion to the complexity of the operation but did not include quantified risk assessments. During the last three years nuclear criticality safety related Probabilistic Risk Assessments (PRAs) have been preformed on operations in two Los Alamos facilities. Both of these were conducted in order to better understand the cost/benefit aspects of PRA's as they apply to largely ''hands-on'' operations with fissile material for which human errors or equipment failures significant to criticality safety are both rare and unique. Based on these two applications and an appreciation of the historical criticality accident record (frequency and consequences) it is apparent that quantified risk assessments should be performed very selectively

Acute change in glomerular filtration rate with inhibition of the renin-angiotensin system does not predict subsequent renal and cardiovascular outcomes.

Science.gov (United States)

Clase, Catherine M; Barzilay, Joshua; Gao, Peggy; Smyth, Andrew; Schmieder, Roland E; Tobe, Sheldon; Teo, Koon K; Yusuf, Salim; Mann, Johannes F E

2017-03-01

Initiation of blockade of the renin-angiotensin system may cause an acute decrease in glomerular filtration rate (GFR): the prognostic significance of this is unknown. We did a post hoc analysis of patients with, or at risk for, vascular disease, in two randomized controlled trials: Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized AssessmeNt Study in ACE iNtolerant participants with cardiovascular Disease (TRANSCEND), whose median follow-up was 56 months. In 9340 patients new to renin-angiotensin system blockade, who were then randomized to renin-angiotensin system blockade, a fall in GFR of 15% or more at 2 weeks after starting renin-angiotensin system blockade was seen in 1480 participants (16%), with persistence at 8 weeks in 700 (7%). Both acute increases and decreases in GFR after initiation of renin-angiotensin system blockade were associated with tendencies, mostly not statistically significant, to increased risk of cardiovascular outcomes, which occurred in 1280 participants, and of microalbuminuria, which occurred in 864. Analyses of creatinine-based outcomes were suggestive of regression to the mean. In more than 3000 patients randomized in TRANSCEND to telmisartan or placebo, there was no interaction between acute change in GFR and renal or cardiovascular benefit from telmisartan. Thus, both increases and decreases in GFR on initiation of renin-angiotensin system blockade are common, and may be weakly associated with increased risk of cardiovascular and renal outcomes. Changes do not predict increased benefit from therapy. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Treatment of complementary events in event trees in constructing linked fault trees for level 1 and level 2 PRA

International Nuclear Information System (INIS)

Jo, Y. G.

2008-01-01

Complementary events in the event trees for a PRA model should be treated properly in order to evaluate plant risk correctly. In this study, the characteristics of the following three different cut-set generation methods were investigated first in order to find the best practical way for treating complementary events: 1) exact method which treats complementary events logically, 2) no-delete term method which does not treat complementary events at all, and 3) delete term method which treats complementary events by deleting nonsense cut-sets which are generated as a result of ignoring complementary events. Then, practical methods for treating complementary events in constructing linked fault trees for level 1 and level 2 PRA in EPRI R and R workstation software environment, where CAFTA is the fault tree editor and FORTE is the cut-set engine, were suggested and demonstrated. The suggested methods deal with the following selected four typical cases: Case 1: an event tree event (E) is represented by a fault tree gate whose inputs consist of only fault tree gates, Case 2: E is represented by a single basic event, Case 3: E is represented by an OR fault tree gate which has a single basic event and a fault tree gate as inputs, and Case 4: E is represented by an AND fault tree gate which has a single basic event and a fault tree gate as inputs. In the suggested methods, first the high level logic structures of event tree events are examined and restructured, if needed. Then, the delete term method, the exact method, and the combination of the two methods are applied to Case 1, Case 2, and Cases 3 and 4, respectively. Also, it is recommended to treat complementary events, using the suggested methods, before level 1 and level 2 PRA fault trees are coupled. It should be noted that the selected four typical cases may not cover all different cases encountered in level 1 and level 2 PRA modeling. However, a process similar to the one suggested in this study may be used to find

Pro Atrial Natriuretic Peptide (1-30) and 6-keto PGF1α Activity Affects Na(+) Homeostasis in Non-modulating Hypertension.

Science.gov (United States)

Sanchez, Ramiro A; Gilbert, Bernardo H; Masnatta, Lucas; Giannone, Carlos; Pesiney, Carlina; Ramirez, Agustin J

2015-01-01

Non-modulating hypertension (NMHT) is a high renin subtype of salt sensitive hypertension, which fails to achieve renal vasodilatation and a correct Na(+) handling during sodium load. We investigate, in MHT and NMHT, the role of ANP, the renin-angiotensin system and PgI2, in the renal sodium handling mechanisms. After 10 days of low (20mmol.L) or after 72hs of high (250mmol.L) sodium intake, 13 NMHT (34±5y; 9 male) and 13 MHT (32±4y; 10male) were studied. Pro-ANP (1-30) PgI2, PRA and total exchangeable Na(+)24 (ENa(+)) were measured. Under low sodium intake, PRA (4.2±0.5ng.ml.h; p<0.05) and Pro-ANP (78.6±2pg/ml, p<0.05) were higher than in NMHT under (3.1±0.4ng.ml.h and 69.8±3 pg/ml). After 72h of high Na(+) intake, Pro-ANP (1-30) increased significantly only in MHT (82.1±3pg/ml, p<0.05). PgI2, under low sodium intake (1.83±0.2pg/24h), increased in MHT after 72h under high sodium (2.58±0.5pg/ 24h, p<0.02). Under low sodium diet, PgI2 (2.16±0.11pg/24h) was as higher in NMHT, as in MHT. After 72h under high Na+ intake, it failed to show any change (2.61±0.36 pg/24h; p=ns). A significant correlation between variations in ENa(+) and mean blood pressure (r=0.50, p<0.01), variations in Pro-ANP (1-30) values and ENa(+) in MHT (r=0.95; p<0.001) while a negative correlation between ENa(+) variations and ENa(+) (r=0.81, p<0.05) was observed in NMHT. ENa(+) variations were only significantly related to variations in FF in MHT. Thus, in NMHT, there is an unbalanced relationship between vasonstrictor and vasodilator mediators. From these, as an extrarenal homeostatic mediator, ANP seems to play an important role to compensate the altered renal sodium handling.

Contribution of the basolateral isoform of the Na-K-2Cl- cotransporter (NKCC1/BSC2) to renin secretion

DEFF Research Database (Denmark)

Castrop, Hayo; Lorenz, John N; Hansen, Pernille B

2005-01-01

Acute administration of loop diuretics like furosemide leads to a stimulation of renin secretion, an effect thought to result from inhibition of Na-K-2Cl cotransporter (NKCC2)-mediated salt transport at the luminal surface of the macula densa (MD). However, loop diuretics also inhibit NKCC1......, the second isoform of the Na-K-2Cl cotransporter, with similar potency. In the present study, we examined the influence of furosemide on renin secretion in NKCC1-deficient mice to distinguish between effects of the loop diuretic involving NKCC2 and, by implication, the MD pathway, and effects that might...

Impaired endogenous nighttime melatonin secretion relates to intrarenal renin-angiotensin system activation and renal damage in patients with chronic kidney disease.

Science.gov (United States)

Ishigaki, Sayaka; Ohashi, Naro; Isobe, Shinsuke; Tsuji, Naoko; Iwakura, Takamasa; Ono, Masafumi; Sakao, Yukitoshi; Tsuji, Takayuki; Kato, Akihiko; Miyajima, Hiroaki; Yasuda, Hideo

2016-12-01

Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. The circadian rhythm of intrarenal RAS activation leads to renal damage and hypertension, which are associated with diurnal blood pressure (BP) variation. The activation of intrarenal RAS following reactive oxygen species (ROS) activation, sympathetic hyperactivity and nitric oxide (NO) inhibition leads to the development of renal damage. Melatonin is a hormone regulating the circadian rhythm, and has multiple functions such as anti-oxidant and anti-adrenergic effects and enhancement of NO bioavailability. Nocturnal melatonin concentrations are lower in CKD patients. However, it is not known if impaired endogenous melatonin secretion is related to BP, intrarenal RAS, or renal damage in CKD patients. We recruited 53 CKD patients and conducted 24-h ambulatory BP monitoring. urine was collected during the daytime and nighttime. We investigated the relationship among the melatonin metabolite urinary 6-sulphatoxymelatonin (U-aMT6s), BP, renal function, urinary angiotensinogen (U-AGT), and urinary albumin (U-Alb). Patients' U-aMT6s levels were significantly and negatively correlated with clinical parameters such as renal function, systolic BP, U-AGT, and U-Alb, during both day and night. Multiple regression analyses for U-aMT6s levels were performed using age, gender, renal function, and each parameter (BPs, U-AGT or U-Alb), at daytime and nighttime. U-aMT6s levels were significantly associated with U-AGT (β = -0.31, p = 0.044) and U-Alb (β = -0.25, p = 0.025) only at night. Impaired nighttime melatonin secretion may be associated with nighttime intrarenal RAS activation and renal damage in CKD patients.

Giving Student Groups a Stronger Voice: Using Participatory Research and Action (PRA) to Initiate Change to a Curriculum

Science.gov (United States)

O'Neill, Geraldine; McMahon, Sinead

2012-01-01

Traditional student feedback mechanisms have been criticised for being teacher-centred in design and, in particular, for their absence of transparent follow-up actions. In contrast, this study describes the process and the evaluation of a participatory research and action (PRA) approach used in an undergraduate physiotherapy degree. This approach…

Shifts in renin-angiotensin system components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa region of streptozotocin-induced diabetic mice.

Science.gov (United States)

Qian, Xiaobing; Lin, Leilei; Zong, Yao; Yuan, Yongguang; Dong, Yanmin; Fu, Yue; Shao, Wanwen; Li, Yujie; Gao, Qianying

2018-03-01

This study aimed to analyse shifts in renin-angiotensin system (RAS) components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa (LC) region in streptozotocin (STZ)-induced diabetic mice. Six months after diabetes induction, the retinal vessels of male C57BL/6 J mice were observed by colour photography, fundus fluorescein angiography (FFA), and immunofluorescent staining following incubation with CD31. Immunofluorescence for glial fibrillary acidic protein (GFAP), alpha-smooth muscle actin (α-SMA),and NG2 was also performed. Angiotensin-converting enzyme 1 (ACE1), angiotensin II type I receptor (AT1R), renin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and haeme oxygenase 1 (HO-1) expression levels were confirmed by immunohistochemical and western blotting analyses. Compared with control mice, diabetic mice had significantly higher blood glucose concentrations (p diabetic mice; however, immunostaining of whole-mount retinas revealed an increased number of retinal vessels. Furthermore, histopathological staining showed significant reduction in the whole retinal thickness. GFAP expression was slightly higher, whereas fewer NG2 + pericytes were observed in diabetic mice than in control mice. ACE1, AT1R, renin, HIF-1α, VEGF, VEGFR2, and HO-1 expression were up-regulated in the LC of the STZ-induced diabetic mice. Collectively, ACE 1, AT1R, HIF-1α, VEGF, VEGFR2, and HO-1 activation in the LC region in diabetic mice may be involved in diabetes via the RAS and induction of angiogenesis and oxidative stress.

Renoprotection by blockade of the renin-angiotensin-aldosterone system in diabetic and non-diabetic chronic kidney disease. Specific involvement of intra-renal angiotensin-converting enzyme activity in therapy resistance?

NARCIS (Netherlands)

Vogt, L.; Kocks, M. J. A.; Laverman, G. D.; Navis, G.

2004-01-01

Data of numerous clinical trials show that lowering of blood pressure is prerequisite for reducing the rate of renal function loss in chronic renal disease. There is evidence supporting that blood pressure lowering obtained by intervention in the renin-angiotensin-aldosterone system (RAAS) has an

Neuronal nitric oxide synthase supports Renin release during sodium restriction through inhibition of phosphodiesterase 3

DEFF Research Database (Denmark)

Sällström, Johan; Jensen, Boye L; Skøtt, Ole

2010-01-01

NOS supports renin release by cyclic guanosine monophosphate (cGMP)-mediated inhibition of cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase 3 (PDE3) in juxtaglomerular (JG) cells. METHODS: The experiments were performed in conscious nNOS⁻(/)⁻ and wild types after 10 days on a low-sodium diet...... by measurements of inulin- and para-amino hippuric acid (PAH) clearances, respectively. RESULTS: The basal PRC was reduced in nNOS⁻(/)⁻ compared to the wild types. Administration of milrinone caused a more pronounced PRC increase in nNOS⁻(/)⁻, resulting in normalized renin levels, whereas PDE5 inhibition did...... not affect PRC in any genotype. The blood pressure was similar in both genotypes, and milrinone did not affect blood pressure compared to vehicle. GFR and RPF were similar at baseline and were reduced by milrinone. CONCLUSIONS: The present study provides in vivo evidence supporting the view that NO...

Top event prevention analysis: A deterministic use of PRA

International Nuclear Information System (INIS)

Worrell, R.B.; Blanchard, D.P.

1996-01-01

This paper describes the application of Top Event Prevention Analysis. The analysis finds prevention sets which are combinations of basic events that can prevent the occurrence of a fault tree top event such as core damage. The problem analyzed in this application is that of choosing a subset of Motor-Operated Valves (MOVs) for testing under the Generic Letter 89-10 program such that the desired level of safety is achieved while providing economic relief from the burden of testing all safety-related valves. A brief summary of the method is given, and the process used to produce a core damage expression from Level 1 PRA models for a PWR is described. The analysis provides an alternative to the use of importance measures for finding the important combination of events in a core damage expression. This application of Top Event Prevention Analysis to the MOV problem was achieve with currently available software

Espaços livres em praças inglesas do século XVII: o caso de Convent Garden

Directory of Open Access Journals (Sweden)

Maria Fernanda Derntl

2006-12-01

Full Text Available Covent Garden é considerada uma experiência modelar entre as primeiras transformações no espaço urbano ainda de aparência medieval de Londres no século XVII. A partir da iconografia da época e das indicações da bibliografia pertinente, procura-se apresentar uma análise abrangente da configuração formal dessa praça. Destaca-se a existência de diferentes tipos de espaços livres contribuindo para determinar seu desenho: além do espaço central, também fizeram parte da praça o pátio da igreja de St. Paul, a oeste e os jardins da mansão Bedford, ao sul. Conclui-se que o desenho apresentado por Covent Garden não era completamente regular ou simétrico e teria sido bem diferente das squares londrinas dos séculos XVII e XVIII.

Development of a methodology for conducting an integrated HRA/PRA --. Task 1, An assessment of human reliability influences during LP&S conditions PWRs

Energy Technology Data Exchange (ETDEWEB)

Luckas, W.J.; Barriere, M.T.; Brown, W.S. [Brookhaven National Lab., Upton, NY (United States); Wreathall, J. [Wreathall (John) and Co., Dublin, OH (United States); Cooper, S.E. [Science Applications International Corp., McLean, VA (United States)

1993-06-01

During Low Power and Shutdown (LP&S) conditions in a nuclear power plant (i.e., when the reactor is subcritical or at less than 10--15% power), human interactions with the plant`s systems will be more frequent and more direct. Control is typically not mediated by automation, and there are fewer protective systems available. Therefore, an assessment of LP&S related risk should include a greater emphasis on human reliability than such an assessment made for power operation conditions. In order to properly account for the increase in human interaction and thus be able to perform a probabilistic risk assessment (PRA) applicable to operations during LP&S, it is important that a comprehensive human reliability assessment (HRA) methodology be developed and integrated into the LP&S PRA. The tasks comprising the comprehensive HRA methodology development are as follows: (1) identification of the human reliability related influences and associated human actions during LP&S, (2) identification of potentially important LP&S related human actions and appropriate HRA framework and quantification methods, and (3) incorporation and coordination of methodology development with other integrated PRA/HRA efforts. This paper describes the first task, i.e., the assessment of human reliability influences and any associated human actions during LP&S conditions for a pressurized water reactor (PWR).

Role of the intrarenal renin-angiotensin system in the progression of renal disease.

Science.gov (United States)

Urushihara, Maki; Kagami, Shoji

2017-09-01

The intrarenal renin-angiotensin system (RAS) has many well-documented pathophysiologic functions in both blood pressure regulation and renal disease development. Angiotensin II (Ang II) is the major bioactive product of the RAS. It induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation. In addition, Ang II regulates the gene expression of bioactive substances and activates multiple intracellular signaling pathways that are involved in renal damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, intracellular formation of reactive oxygen species, cell proliferation, and extracellular matrix synthesis, which in turn facilities renal injury. Involvement of angiotensinogen (AGT) in intrarenal RAS activation and development of renal disease has previously been reported. Moreover, studies have demonstrated that the urinary excretion rates of AGT provide a specific index of the intrarenal RAS status. Enhanced intrarenal AGT levels have been observed in experimental models of renal disease, supporting the concept that AGT plays an important role in the development and progression of renal disease. In this review, we focus on the role of intrarenal RAS activation in the pathophysiology of renal disease. Additionally, we explored the potential of urinary AGT as a novel biomarker of intrarenal RAS status in renal disease.

Elastin and Mechanics of Pig Pericardial Resistance Arteries (pPRA)

DEFF Research Database (Denmark)

Bloksgaard, Maria; Leurgans, Thomas; Rosenstand, Kristoffer

Resistance arteries are remodeled in hypertension and diabetes. Elastin was reported to play a role herein. The parietal pericardium is opened during cardio-thoracic surgeries and might be a valuable biopsy for research in cardio-vascular diseases. We tested the hypothesis that resistance arteries...... can be isolated from the pericardium to study the micro-architecture of elastin and vascular wall mechanics. The pericardium of pigs served to test the hypothesis. pPRAs were microdissected. Their structure was examined using multiphoton excitation fluorescence microscopy. Diameter......-tension and pressure-diameter-length relationships were recorded in myographs. Findings are compared to rodent mesenteric resistance arteries and –basilar arteries (rMRA, rBA) with comparable lumen diameter (±300µm at 100mmHg). pPRA have no clear external elastic lamina (present in rMRA, but not rBA), scant elastin...

High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion.

Science.gov (United States)

Li, Caixia; Culver, Silas A; Quadri, Syed; Ledford, Kelly L; Al-Share, Qusai Y; Ghadieh, Hilda E; Najjar, Sonia M; Siragy, Helmy M

2015-11-01

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene (Cc1(-/-)) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type (Cc1(+/+)) and Cc1(-/-) mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1(-/-) mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85α (Tyr(508)) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1(+/+) mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1(-/-) mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85α (Tyr(508)) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1(-/-) mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis. Copyright © 2015 the American Physiological Society.

Review of UCN 5,6 Fire PSA Model based on ANS Fire PRA Standard

International Nuclear Information System (INIS)

Yang, Joon Eon; Lee, Yoon Hwan

2006-12-01

Recently, under the de-regulation environment, nuclear industry has attempted various approaches to improve the economics of Nuclear Power Plants (NPP). This approach uses the fire risk and performance information to manage the resources effectively and efficiently that are used in the operation of NPP. In fire risk informed/performance-based decision/operation, fire PSA quality is one of the most important things. The nuclear industry and regulatory body of U.S.A have developed a measure to evaluate the quality of fire PSA. ANS (American Nuclear Society) has developed a guidance called 'ANS Fire PRA Methodology Standard'. However, in Korea, there have been no attempts to evaluate the quality of fire PSA model itself. Therefore, we cannot be sure about the quality of fire PSA whether or not the present fire PSA model can be used for the risk-informed applications such as mentioned above. We can say that the evaluation of fire PSA model quality is the basis for the fire risk informed/performance-based decision/operation. In this report, we have evaluated the quality of fire PSA model for Ulchin 5 and 6 units based on the ANS Fire PRA Standard. We, also, have derived what items are to be improved to upgrade the quality of fire PSA model and how it can be improved. This report can be used as the base of the fire risk informed/performance-based decision/operation work in Korea

Radioisotope-pharmacodynamic studies without exposure to radiation

International Nuclear Information System (INIS)

Graul, H.

1983-01-01

On the basis of a clinico-pharmacological study using a new diuretic combination it is shown that not only the RIA determination, but also the measurement of the total amount of potassium in the body with the aid of the 40 K potassium-nuclide confirmed therapeutic efficacy. Furosemide (30 mg) and the combination furosemide-retard (30 mg) and triamterene (50 mg) influence the plasmarenin-aldosterone system (PRA-system) differently. After both furosemide alone and the combination, the plasma-renin activity increased significantly (p 40 /K potassium nuclide - decreased after 8 days of treatment with the combination of furosemide-retard and triamterene. Both methods have proved of value in the clinico-pharmacological examination of diuretics. They are of great importance, easy to apply, involve no exposure to radiation, and are inexpensive. (orig.) [de

Structural adaptation to ischemia in skeletal muscle: effects of blockers of the renin-angiotensin system

NARCIS (Netherlands)

Scheidegger, K. J.; Nelissen-Vrancken, M. H.; Leenders, P. J.; Daemen, M. J.; Smits, J. F.; Wood, J. M.

1997-01-01

To investigate the effects of long-term treatment with blockers of the renin-angiotensin system on capillarization and growth of fibers in ischemic hind-limb muscles and in muscles under normal growth conditions. Ischemia was induced by partial ligation of the left common iliac artery. Ischemia

Role of proteinuria in the regulation of renal renin-angiotensin system components in unilateral proteinuric rats

NARCIS (Netherlands)

Deelman, LE; Navis, G; Wietses, M; de Zeeuw, D; Henning, RH

Renin-angiotensin system (RAS) overactivity has been implied in progressive renal function loss. We investigated whether changes in the renal expression of RAS components are specifically associated with the proteinuric kidney. Unilateral adriamycin-induced proteinuria was obtained by clamping the

The Kallikrein-Kinin System in Bartter's Syndrome and Its Response to Prostaglandin Synthetase Inhibition

Science.gov (United States)

Vinci, Joseph M.; Gill, John R.; Bowden, Robert E.; Pisano, John J.; Izzo, Joseph L.; Radfar, Nazam; Taylor, Addison A.; Zusman, Randall M.; Bartter, Frederic C.; Keiser, Harry R.

1978-01-01

The kallikrein-kinin system was characterized in seven patients with Bartter's syndrome on constant metabolic regimens before, during, and after treatment with prostaglandin synthetase inhibitors. Patients with Bartter's syndrome had high values for plasma bradykinin, plasma renin activity (PRA), urinary kallikrein, urinary immunoreactive prostaglandin E excretion, and urinary aldosterone; urinary kinins were subnormal and plasma prekallikrein was normal. Treatment with indomethacin or ibuprofen which decreased urinary immunoreactive prostaglandin E excretion by 67%, decreased mean PRA (patients recumbent) from 17.3±5.3 (S.E.M.) ng/ml per h to 3.3±1.1 ng/ml per h, mean plasma bradykinin (patients recumbent) from 15.4±4.4 ng/ml to 3.9±0.9 ng/ml, mean urinary kallikrein excretion from 24.8±3.2 tosyl-arginine-methyl ester units (TU)/day to 12.4±2.0 TU/day, but increased mean urinary kinin excretion from 3.8±1.3 μg/day to 8.5±2.5 μg/day. Plasma prekallikrein remained unchanged at 1.4 TU/ml. Thus, with prostaglandin synthetase inhibition, values for urinary kallikrein and kinin and plasma bradykinin returned to normal pari passu with changes in PRA, in aldosterone, and in prostaglandin E. The results suggest that, in Bartter's syndrome, prostaglandins mediate the low urinary kinins and the high plasma bradykinin, and that urinary kallikrein, which is aldosterone dependent, does not control kinin excretion. The high plasma bradykinin may be a cause of the pressor hyporesponsiveness to angiotensin II which characterizes the syndrome. PMID:96139

Renin-Angiotensin System Blockade Improves Cardiac Indices in Acromegaly Patients.

Science.gov (United States)

Thomas, Julia D J; Dattani, Abhishek; Zemrak, Filip; Burchell, Thomas; Akker, Scott A; Kaplan, Felicity J L; Khoo, Bernard; Aylwin, Simon; Grossman, Ashley B; Davies, L Ceri; Korbonits, Márta

2017-06-01

Blockade of the angiotensin-renin system, with angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), has been shown to improve cardiac outcomes following myocardial infarction and delay progression of heart failure. Acromegaly is associated with a disease-specific cardiomyopathy, the pathogenesis of which is poorly understood.The cardiac indices of patients with active acromegaly with no hypertension (Group A, n=4), established hypertension not taking ACEi/ARBs (Group B, n=4) and established hypertension taking ACEi/ARBs (Group C, n=4) were compared using cardiac magnetic imaging.Patients taking ACEi/ARBs had lower end diastolic volume index (EDVi) and end systolic volume index (ESVi) than the other 2 groups ([C] 73.24 vs. [A] 97.92 vs. [B] 101.03 ml/m 2 , ANOVA p=0.034, B vs. C pAcromegaly patients on ACEi/ARBs for hypertension demonstrate improved cardiac indices compared to acromegaly patients with hypertension not taking these medications. Further studies are needed to determine if these drugs have a beneficial cardiac effect in acromegaly in the absence of demonstrable hypertension. © Georg Thieme Verlag KG Stuttgart · New York.

Perbandingan Tinggi Tulang Maksila dan Mandibula di Regio Interisisivi Sentral antara Pra dan Pasca Perawatan Ortodontik dengan Pencabutan ke Empat Gigi Premolar Pertama (Kajian pada Foto Panoramik

Directory of Open Access Journals (Sweden)

Wayan Ardhana

2012-12-01

Full Text Available Latar belakang. Perawatan ortodontik pada kasus-kasus gigi berjejal dan protusif sering membutuhkan pencabutan gigi premolar untuk penyediaan ruang agar gigi berjejal dapat dirapikan dan gigi depan yang protusif dapat diundurkan. Gigi insisivus sentral merupakan salah satu gigi yang paling banyak mengalami pergerakan selama proses retrusi. Pergerakan gigi insisivus mengakibatkan terjadinya perubahan pada puncak tulang alveolar selama perawatan yang mungkin akan mempengaruhi tinggi tulang maksila dan mandibula pasca perawatan. Tujuan penelitian. Membandingkan tinggi tulang maksila dan mandibula di daerah interdental gigi insisivi sentral pada foto panoramic antara pra dan pasca perawatan maloklusi dengan pencabutan ke empat gigi premolar pertama. Metode penelitian. Digunakan 30 pasang foto panoramic pra dan pasca perawatan yang dipilih sesuai dengan kriteria penelitian dari pasien-pasien peneliti yang telah selesai mendapat perawatan aktif dengan teknik edgewise. Analisis Kolmogorov-Smirnov dan Shaviro-Wilk digunakan untuk uji normalitas dan Student t-test data berpasangan digunakan untuk menguji perbedaan tinggi tulang maksila dan mandibula antara pra dan pasca perawatan. Hasil Penelitian. Tidak didapatkan perbedaan (p>0,05 tinggi tulang maksila dan amndibula antara pra dan pasca perawatan ortodontik dengan pencabutan keempat gigi premolar pertama.   Background. In orthodontic treatment, premolar extractions are often needed in crowding and prostrusive cases to provide space for the teeth can be aligned and retracted to their desire position. Central incisor teeth are the teeth that mostly undergone more movement during retrusion. The change of the alveolar bone crest in this incisors might affect the maxillary and mandibular bone height post-treatment. Research objectives. The present study aimed to compare the bone height in the interdental maxillary and mandibular central incisors regions before and after orthodontic treatment with four

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

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Indu Dhar

Full Text Available 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.

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

Science.gov (United States)

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.

Relationship between aldosterone and the metabolic syndrome in patients with obstructive sleep apnea hypopnea syndrome: effect of continuous positive airway pressure treatment.

Directory of Open Access Journals (Sweden)

Antonia Barceló

Full Text Available BACKGROUND: Metabolic syndrome (MS occurs frequently in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS. We hypothesized that aldosterone levels are elevated in OSAHS and associated with the presence of MS. METHODS: We studied 66 patients with OSAHS (33 with MS and 33 without MS and 35 controls. The occurrence of the MS was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III clinical criteria. Measurements of plasma renin activity (PRA, aldosterone, aldosterone:PRA ratio, creatinine, glucose, triglycerides, cholesterol and HDL cholesterol were obtained at baseline and after CPAP treatment. RESULTS: Aldosterone levels were associated with the severity of OSAHS and higher than controls (p = 0.046. Significant differences in aldosterone levels were detected between OSAHS patients with and without MS (p = 0.041. A significant reduction was observed in the aldosterone levels in patients under CPAP treatment (p = 0.012. CONCLUSION: This study shows that aldosterone levels are elevated in OSAHS in comparison to controls, and that CPAP therapy reduces aldosterone levels. It also shows that aldosterone levels are associated with the presence of metabolic syndrome, suggesting that aldosterone excess might predispose or aggravate the metabolic and cardiovascular complications of OSAHS. TRIAL REGISTRATION: The study is not a randomized controlled trial and was not registered.

Renin-angiotensin system antagonists, glomerular filtration rate and blood pressure

Directory of Open Access Journals (Sweden)

D.D. Ivanov

2018-02-01

Full Text Available The article deals with the mModern data on the influence of renin-angiotensin system blockers on the glomerular filtration rate, the level of arterial pressure and the outcome of chronic kidney disease. The strategy of  rennin-angiotensine blockade is offered to be changed depending on the criteria va­lues of glomerular filtration rate: a combination of inhibitors of angiotensin-converting enzyme + angiotensin receptors blo­ckers, monotherapy and drug withdrawal in glomerular filtration rate under 15–30 ml/min/m2. The formula BRIMONEL for treatment of chronic kidney disease is given.

Use of PRA techniques to optimize the design of the IRIS nuclear power plant

International Nuclear Information System (INIS)

Muhlheim, M.D.; Cletcher, J.W. II

2003-01-01

True design optimization of a plants inherent safety and performance characteristics results when a probabilistic risk assessment (PRA) is integrated with the plant-level design process. This is the approach being used throughout the design of the International Reactor Innovative and Secure (IRIS) nuclear power plant to maximize safety. A risk-based design optimization tool employing a 'one-button' architecture is being developed by the Oak Ridge National Laboratory to evaluate design changes; new modeling approaches, methods, or theories modeling uncertainties and completeness; physical assumptions; and data changes on component, cabinet, train, and system bases. Unlike current PRAs, the one-button architecture allows components, modules, and data to be interchanged at will with the probabilistic effect immediately apparent. Because all of the current and previous design, and data sets are available via the one-button architecture, the safety ramifications of design options are evaluated, feedback on design alternatives is immediate, and true optimization and understanding can be achieved. Thus, for the first time, PRA analysts and designers can easily determine the probabilistic implications of different design configurations and operating conditions in various combinations for the entire range of initiating events. The power of the one-button architecture becomes evident by the number of design alternatives that can be evaluated C11 component choices yielded 160 design alternatives. Surprisingly, the lessons learned can be counter-intuitive and significant. For example, one of the alternative designs for IRIS evaluated via this architecture revealed that because of common-cause failure probabilities, using the most reliable components actually decreased systems' reliability. (author)

Renin angiotensin system and gender differences in dopaminergic degeneration

Directory of Open Access Journals (Sweden)

Rodriguez-Perez Ana I

2011-08-01

Full Text Available Abstract Background There are sex differences in dopaminergic degeneration. Men are approximately two times as likely as premenopausal women of the same age to develop Parkinson's disease (PD. It has been shown that the local renin angiotensin system (RAS plays a prominent role in sex differences in the development of chronic renal and cardiovascular diseases, and there is a local RAS in the substantia nigra and dopaminergic cell loss is enhanced by angiotensin via type 1 (AT1 receptors. Results In the present study, we observed that intrastriatal injection of 6-hydroxydopamine induced a marked loss of dopaminergic neurons in the substantia nigra of male rats, which was significantly higher than the loss induced in ovariectomized female rats given estrogen implants (i.e. rats with estrogen. However, the loss of dopaminergic neurons was significantly lower in male rats treated with the AT1 antagonist candesartan, and similar to that observed in female rats with estrogen. The involvement of the RAS in gender differences in dopaminergic degeneration was confirmed with AT1a-null mice lesioned with the dopaminergic neurotoxin MPTP. Significantly higher expression of AT1 receptors, angiotensin converting enzyme activity, and NADPH-oxidase complex activity, and much lower levels of AT2 receptors were observed in male rats than in female rats with estrogen. Conclusions The results suggest that brain RAS plays a major role in the increased risk of developing PD in men, and that manipulation of brain RAS may be an efficient approach for neuroprotective treatment of PD in men, without the feminizing effects of estrogen.

Effect of maternal renin-angiotensin-aldosterone system activation on social coping strategies and gene expression of oxytocin and vasopressin in the brain of rat offspring in adulthood.

Science.gov (United States)

Senko, Tomáš; Svitok, Pavel; Kršková, Lucia

2017-10-01

The intrauterine condition in which the mammalian foetus develops has an important role in prenatal programming. The aim of this study was to determine the extent to which activation of the maternal renin-angiotensin-aldosterone system (RAAS) could influence social behaviour strategies in offspring via changes in social neurotransmitters in the brain. Pregnant female Wistar rats were implanted with osmotic minipumps which continually released angiotensin II for 14 days at concentration of 2 μg/kg/h. The adult offspring (angiotensin and control groups) underwent a social interaction test. The mRNA expression of vasopressin, oxytocin and the oxytocin receptor in selected brain areas was measured by in situ hybridisation. Prenatal exposure to higher levels of angiotensin II resulted in a strong trend toward decreased total social interaction time and significantly decreased time spent in close proximity and frequency of mutual sniffing. The angiotensin group showed no changes in oxytocin mRNA expression in the hypothalamic paraventricular or supraoptic nuclei, but this group had reduced vasopressin mRNA expression in the same areas. We concluded that maternal activation of RAAS (via higher levels of angiotensin II) caused inhibition of some socio-cohesive indicators and decreased vasopressinergic activity of offspring. Taken together, these results suggest a reactive rather than proactive social coping strategy.

Blockade of AT1 receptors by losartan did not affect renin gene expression in kidney medulla

Czech Academy of Sciences Publication Activity Database

Tybitanclová, K.; Szabová, L.; Grima, M.; Ingert, C.; Železná, Blanka; Zórad, Š.

2006-01-01

Roč. 25, č. 1 (2006), s. 43-51 ISSN 0231-5882 Grant - others:VEGA(SK) 2/5090/25 Institutional research plan: CEZ:AV0Z50520514 Keywords : AT1 receptor * renin-angiotensin system * kidneys Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.771, year: 2006

Salt sensitivity of renin secretion, glomerular filtration rate and blood pressure in conscious Sprague-Dawley rats

DEFF Research Database (Denmark)

Isaksson, G L; Stubbe, J; Hansen, Per Lyngs

2014-01-01

We hypothesized that in normal rats in metabolic steady state, (i) the plasma renin concentration (PRC) is log-linearly related to Na(+) intake (NaI), (ii) the concurrent changes in mean arterial pressure (MABP) and glomerular filtration rate (GFR) are negligible and (iii) the function PRC...

An overview of insights gained and lessons learned from U.S. plant-specific PRA studies

International Nuclear Information System (INIS)

Joksimovich, V.

1985-01-01

Probabilistic Risk Assessment (PRA) has been under development for over twenty years, but it has reached the level of widespread use only in the aftermath of the TMI accident. Over thirty PRAs have now been completed in the U.S. PRAs have been in the mainstream of many licensing decisions because the NRC recognizes that they provide independent and comprehensive plant safety audit. Some difficulties have been experienced leading to interpretive and intercomparison studies. Numerous global and plant-specific insights have been derived. A new application termed risk management is clearly emerging. (orig./HP)

Between-patient differences in the renal response to renin-angiotensin system intervention : clue to optimising renoprotective therapy?

NARCIS (Netherlands)

Laverman, GD; de Zeeuw, D; Navis, G

2002-01-01

Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II (Ang II), AT(1)-receptor blockers (ARB) is the cornerstone of renoprotective therapy. Still, the number of patients with end-stage renal disease is increasing worldwide,

Sulfhydryl group content of chicken progesterone receptor: effect of oxidation on DNA binding activity

International Nuclear Information System (INIS)

Peleg, S.; Schrader, W.T.; O'Malley, B.W.

1988-01-01

DNA binding activity of chicken progesterone receptor B form (PRB) and A form (PRA) has been examined. This activity is strongly dependent upon the presence of thiols in the buffer. Stability studies showed that PRB was more sensitive to oxidation that was PRA. Receptor preparations were fractionated by DNA-cellulose chromatography to DNA-positive and DNA-negative subpopulations, and sulfhydryl groups were quantified on immunopurified receptor by labeling with [ 3 H]-N-ethylmaleimide. Labeling of DNA-negative receptors with [ 3 H]-N-ethylmaleimide showed 21-23 sulfhydryl groups on either PRA or PRB form when the proteins were reduced and denatured. A similar number was seen without reduction if denatured DNA-positive receptor species were tested. In contrast, the DNA-negative PRB had only 10-12 sulfhydryl groups detectable without reduction. A similar number (12-13 sulfhydryl groups) was found for PRA species that lost DNA binding activity after exposure to a nonreducing environment in vitro. The authors conclude that the naturally occurring receptor forms unable to bind to DNA, as well as receptor forms that have lost DNA binding activity due to exposure to nonreducing environment in vitro, contain 10-12 oxidized cysteine residues, likely present as disulfide bonds. Since they were unable to reduce the disulfide bonds when the native DNA-negative receptor proteins were treated with dithiothreitol (DTT), they speculate that irreversible loss of DNA binding activity of receptor in vitro is due to oxidation of cysteine residues that are not accessible to DTT in the native state

Development of risk assessment methodology against natural external hazards for sodium-cooled fast reactors: project overview and strong Wind PRA methodology - 15031

International Nuclear Information System (INIS)

Yamano, H.; Nishino, H.; Kurisaka, K.; Okano, Y.; Sakai, T.; Yamamoto, T.; Ishizuka, Y.; Geshi, N.; Furukawa, R.; Nanayama, F.; Takata, T.; Azuma, E.

2015-01-01

This paper describes mainly strong wind probabilistic risk assessment (PRA) methodology development in addition to the project overview. In this project, to date, the PRA methodologies against snow, tornado and strong wind were developed as well as the hazard evaluation methodologies. For the volcanic eruption hazard, ash fallout simulation was carried out to contribute to the development of the hazard evaluation methodology. For the forest fire hazard, the concept of the hazard evaluation methodology was developed based on fire simulation. Event sequence assessment methodology was also developed based on plant dynamics analysis coupled with continuous Markov chain Monte Carlo method in order to apply to the event sequence against snow. In developing the strong wind PRA methodology, hazard curves were estimated by using Weibull and Gumbel distributions based on weather data recorded in Japan. The obtained hazard curves were divided into five discrete categories for event tree quantification. Next, failure probabilities for decay heat removal related components were calculated as a product of two probabilities: i.e., a probability for the missiles to enter the intake or out-take in the decay heat removal system, and fragility caused by the missile impacts. Finally, based on the event tree, the core damage frequency was estimated about 6*10 -9 /year by multiplying the discrete hazard probabilities in the Gumbel distribution by the conditional decay heat removal failure probabilities. A dominant sequence was led by the assumption that the operators could not extinguish fuel tank fire caused by the missile impacts and the fire induced loss of the decay heat removal system. (authors)

Neuronal nitric oxide synthase-deficient mice have impaired Renin release but normal blood pressure

DEFF Research Database (Denmark)

Sällström, Johan; Carlström, Mattias; Jensen, Boye L

2008-01-01

BackgroundNitric oxide deficiency is involved in the development of hypertension, but the mechanisms are currently unclear. This study was conducted to further elucidate the role of neuronal nitric oxide synthase (nNOS) in blood pressure regulation and renin release in relation to different sodiu......-116; doi:10.1038/ajh.2007.16American Journal of Hypertension (2008) 21 111-116; doi:10.1038/ajh.2007.16....

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism

OpenAIRE

KOBORI, HIROYUKI; ICHIHARA, ATSUHIRO; SUZUKI, HIROMICHI; TAKENAKA, TSUNEO; MIYASHITA, YUTAKA; HAYASHI, MATSUHIKO; SARUTA, TAKAO

1997-01-01

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was onl...

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

Science.gov (United States)

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

2015-06-11

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.

"VEM PRA RUA": THE POLITICAL AND THE POLITICS ON THE WEB

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Benedito Fernando Pereira

2014-12-01

Full Text Available Considering the political and the social division of senses, this paper seeks to check how is the process of signification in a society increasingly challenged by electronic discourse and the ways in which political and policy find themselves affected by it. In order do that, we make the analysis of discursive statements “vem pra rua” and “somos a rede social” that were present in banners and posters in street protests in Brazil in 2013, which were organized and delivered, in large part, by virtual means. We observed that such utterances go through a process of appropriation and re-signification, with shifting meanings that run of market logic, go to the social politics and go back to the market logic. We had also observed how the urban environment is affected by the electronic discourse that now constitutes the ways it makes sense.

Application of RIA of PRA, AT II and NPY in typing and therapy of EH patients

International Nuclear Information System (INIS)

Yang Yongqing; Wang Xiaozhou; Jiang Qinian

2001-01-01

Objective: To study the typing and AT II receptor inhibitor therapy for essential hypertension (EH) patients. Methods: Plasma RA, AT II and NPY levels were measured by radioimmunoassay (RIA) in 208 Patients with EH and 100 controls; plasma NPY levels were measured in 40 EH patients before and after AT II receptor inhibitor therapy. The mean coefficient of variation for intra and inter batch-assay were less than 10% and 15% respectively. Results: In 208 EH patients plasma PRA levels were increased, normal and decreased in 17.8%, 71.6% and 10.6% respectively, while in 128 EH patients Plasma AT II levels were increased, normal and decreased in 20.3%, 64.1% and 15.6% respectively. In 69 EH Plasma NPY levels were significantly higher than those in 40 control subjects. (17 grade I EH, 137.3 +- 32.6 pg/mL; 28 grade II EH, 148.5 +- 41.1 pg/mL; 24 grade III EH, 162.4 +- 42.7 pg/mL; 40 controls, 118.5 +- 30.5 pg/mL). In 40 EH patients plasma NPY levels were decreased after AT II receptor inhibitor therapy as the blood pressure decreased. Conclusion: Typing of EH patients according to levels of plasma PRA and AT II is useful in guiding treatment. AT II receptor inhibitors are indicated in those patients with increased plasma levels and NPY levels can be used for appraisal of the treatment efficacy

Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma Express Components of the Renin-Angiotensin System

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Therese Featherston

2016-09-01

Full Text Available Aim We have recently identified and characterized cancer stem cell (CSC subpopulations within moderately differentiated buccal mucosal squamous cell carcinoma (MDBMSCC. We hypothesized that these CSCs express components of the renin-angiotensin system (RAS.Methods 3,3-Diaminobenzidine (DAB immunohistochemical (IHC staining was performed on formalin-fixed paraffin-embedded MDBMSCC samples to investigate the expression of the components of the RAS: pro(renin receptor (PRR, angiotensin converting enzyme (ACE, angiotensin II receptor 1 (ATIIR1 and angiotensin II receptor 2 (ATIIR2. NanoString mRNA gene expression analysis and Western Blotting (WB were performed on snap-frozen MDBMSCC samples to confirm gene expression and translation of these transcripts, respectively. Double immunofluorescent (IF IHC staining of these components of the RAS with the embryonic stem cell markers OCT4 or SALL4 was performed to demonstrate their localization in relation to the CSC subpopulations within MDBMSCC.Results DAB IHC staining demonstrated expression of PRR, ACE, ATIIR1 and ATIIR2 in MDBMSCC. IF IHC staining showed that PRR was expressed by the CSC subpopulations within the tumor nests, the peri-tumoral stroma and the endothelium of the microvessels within the peri-tumoral stroma. ATIIR1 and ATIIR2 were localized to the CSC subpopulations within the tumor nests and the peri-tumoral stroma, while ACE was localized to the endothelium of the microvessels within the peri-tumoral stroma. WB and NanoString analyses confirmed protein expression and transcription activation of PRR, ACE and ATIIR1 but not of ATIIR2, respectively.

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

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Man Lung eFung

2014-09-01

Full Text Available 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.

A Feasibility Study of Bevacizumab Plus Dose-Dense Doxorubicin–Cyclophosphamide (AC) Followed by Nanoparticle Albumin–Bound Paclitaxel in Early-Stage Breast Cancer

Science.gov (United States)

McArthur, Heather L.; Rugo, Hope; Nulsen, Benjamin; Hawks, Laura; Grothusen, Jill; Melisko, Michelle; Moasser, Mark; Paulson, Matthew; Traina, Tiffany; Patil, Sujata; Zhou, Qin; Steingart, Richard; Dang, Chau; Morrow, Monica; Cordeiro, Peter; Fornier, Monica; Park, John; Seidman, Andrew; Lake, Diana; Gilewski, Theresa; Theodoulou, Maria; Modi, Shanu; D’Andrea, Gabriella; Sklarin, Nancy; Robson, Mark; Moynahan, Mary Ellen; Sugarman, Steven; Sealey, Jane E.; Laragh, John H.; Merali, Carmen; Norton, Larry; Hudis, Clifford A.; Dickler, Maura N.

2016-01-01

Purpose Bevacizumab confers benefits in metastatic breast cancer but may be more effective as adjuvant therapy. We evaluated the cardiac safety of bevacizumab plus dose-dense doxorubicin–cyclophosphamide (ddAC)→nanoparticle albumin−bound (nab)-paclitaxel in human epidermal growth factor receptor 2 normal early-stage breast cancer. Experimental Design Eighty patients with normal left ventricular ejection fraction (LVEF) were enrolled. Bevacizumab was administered for 1 year, concurrently with ddAC→nab-paclitaxel then as a single agent. LVEF was evaluated at months 0, 2, 6, 9, and 18. This regimen was considered safe if fewer than three cardiac events or fewer than two deaths from left ventricular dysfunction occurred. Correlative studies of cardiac troponin (cTn) and plasma renin activity (PRA) were conducted. Results The median age was 48 years (range, 27−75 years), and baseline LVEF was 68% (53%−82%). After 39 months’ median follow-up (5−45 months): median LVEF was 68% (53%−80%) at 2 months (n=78), 64% (51%−77%) at 6 months (n=66), 63% (48%−77%) at 9 months (n=61), and 66% (42%−76%) at 18 months (n=54). One patient developed symptomatic LV dysfunction at month 15. Common toxicities necessitating treatment discontinuation were hypertension (HTN, 4%), wound-healing complications (4%), and asymptomatic LVEF declines (4%). Neither cTn nor PRA predicted CHF or HTN, respectively. Conclusions Bevacizumab with ddAC→nab-paclitaxel had a low rate of cardiac events; cTn and PRA levels are not predictive of CHF or HTN, respectively. The efficacy of bevacizumab as adjuvant treatment will be established in several ongoing phase III trials. PMID:21350003

Local Bone Marrow Renin-Angiotensin System and Atherosclerosis

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Yavuz Beyazit

2011-01-01

Full Text Available Local hematopoietic bone marrow (BM renin-angiotensin system (RAS affects the growth, production, proliferation differentiation, and function of hematopoietic cells. Angiotensin II (Ang II, the dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in pathobiological states. RAS, especially Ang II and Ang II type 1 receptor (AT1R, has considerable proinflammatory and proatherogenic effects on the vessel wall, causing progression of atherosclerosis. Recent investigations, by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1R, disclosed that AT1R in BM cells participates in the pathogenesis of atherosclerosis. Therefore, AT1R blocking not only in vascular cells but also in the BM could be an important therapeutic approach to prevent atherosclerosis. The aim of this paper is to review the function of local BM RAS in the pathogenesis of atherosclerosis.

Renal Kallikrein Activation and Renoprotection after Dual Blockade of Renin-Angiotensin System in Diet-Induced Diabetic Nephropathy

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Xia Zou

2015-01-01

Full Text Available Purpose. The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN. Methods. Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histopathology, function and immunohistochemical stain of kallikrein, macrophage marker CD68, and profibrotic markers transforming growth factor- (TGF- β and α-smooth muscle action (SMA. Results. DN rats showed enlarged kidneys with glomerulosclerosis, interstitial chronic inflammation and fibrosis, and proteinuria. All the pathological damage and functional impairments were improved after the RAS blockades (all P<0.05. Compared with monotherapy, combined treatment further alleviated the kidney impairments in parallel to increased tubular immunoreactivity for kallikrein and decreased immunopositive cells for CD68, TGF-β, and α-SMA. Conclusion. The renoprotective effects of the dual RAS blockade in diabetic nephropathy may be attributed to improved tubular kallikrein expression and interstitial inflammatory response.

Study of the components of renin-angiotensinaldosterone system and KalliKrein -Kinin system in normal pregnancy