WorldWideScience

Sample records for aldosterone

  1. Aldosterone blood test

    Science.gov (United States)

    ... Addison disease - serum aldosterone; Primary hyperaldosteronism - serum aldosterone; Bartter syndrome - serum aldosterone ... normal level of aldosterone may be due to Bartter syndrome (group of rare conditions that affect the kidneys) ...

  2. Pharmacological treatment of aldosterone excess

    NARCIS (Netherlands)

    Deinum, J.; Riksen, N.P.; Lenders, J.W.M.

    2015-01-01

    Primary aldosteronism, caused by autonomous secretion of aldosterone by the adrenals, is estimated to account for at least 5% of hypertension cases. Hypertension explains the considerable cardiovascular morbidity caused by aldosteronism only partly, calling for specific anti-aldosterone drugs. The

  3. 24-hour urinary aldosterone excretion test

    Science.gov (United States)

    Aldosterone - urine; Addison disease - urine aldosterone; Cirrhosis - serum aldosterone ... Laxative abuse Lower than normal levels may indicate Addison disease , a disorder in which the adrenal glands do ...

  4. Primary aldosteronism. Clinical management

    International Nuclear Information System (INIS)

    Grant, C.S.; Carpenter, P.; van Heerden, J.A.; Hamberger, B.

    1984-01-01

    We retrospectively reviewed the clinical features, methods of diagnosis and localization, and results of treatment in 105 patients with primary aldosteronism seen between 1969 and 1981. Coincident with the use of computed tomography (CT), 131 I-6-beta-iodomethyl norcholesterol scans (NP-59), and postural response studies, the study group was temporally divided into pre-1976 and post-1976 groups, and subdivided into groups with aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia. Our results indicate that aldosterone postural response studies and CT differentiate and localize APA and IHA reliably. Adrenalectomy is a safe and effective treatment for APA, whereas medical treatment alone is preferable for IHA

  5. Aldosterone and Renin Test

    Science.gov (United States)

    ... 1989. Laurence M. Demers, PhD. Distinguished Professor of Pathology and Medicine, The Pennsylvania State University College of ... 74-79, 946-951. Holt, E. (Updated 2008 March 18). Aldosterone. MedlinePlus Medical Encyclopedia On-line information]. ...

  6. 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

  7. Localization of primary aldosteronism

    International Nuclear Information System (INIS)

    Pagny, J.Y.; Chatellier, G.; Raynaud, A.; Plouin, P.F.; Corvol, P.

    1988-01-01

    After diagnosis of primary aldosteronism on the basis of biochemical evidence, the detection of the tumour is of crucial importance in the management of the disease. The efficacy of CT-Scan, Iodo-Cholesterol Scintigraphy, digitalized phlebography, adrenal vein sampling for steroid measurements (AVS), and Nuclear Magnetic Resonance (NMR) in 160 hypertensive patients with primary aldosteronism was reviewed. Diagnosis of Conn's adenoma (n=96) or Adrenal Hyperplasia (n=40) was confirmed by surgery or at least two concordant tumour localization tests. Scintigraphy gave a correct diagnosis in 53% of the 51 exams, CT-Scan in 82% of the 85 exams, and phlebography in 79% of 61 exams. Plasma Aldosterone/ Cortisol ratio was 5 times higher on the side of adenoma in 55% of the 47 cases but this ratio was also present in 23% of 22 patients with adrenal hyperplasia. Each procedure exhibited few false positive and false negative cases. NMR performed in 15 patients with Conn's adenoma identified all the cases. But tumours displayed a signal close to the liver signal and identical to the normal adrenal. These results and the risk of invasive procedure (failure of catheterization of the right adrenal vein (n=6) and adrenal haematoma (n=2) lead to propose a schema of exploration of patients with primary aldosteronism. The CT-Scan could be performed at the first step once the biological diagnosis confirmed. Phlebography and AVS will be performed only if tumour was less than 1 cm at the CT-Scan despite important biological abnormalities. This schema requires to be validated by a prospective evaluation [fr

  8. 21 CFR 862.1045 - Aldosterone test system.

    Science.gov (United States)

    2010-04-01

    ... treatment of primary aldosteronism (a disorder caused by the excessive secretion of aldosterone by the adrenal gland), hypertension caused by primary aldosteronism, selective hypoaldosteronism, edematous...

  9. Radioimmunoassay of aldosterone in ascitic fluid

    Energy Technology Data Exchange (ETDEWEB)

    Maleeva, A; Kekhajova, M [Nauchno-Izsledovatelski Inst. po Radiologiya i Radiatsionna Khigiena, Sofia (Bulgaria)

    1988-01-01

    A method was developed dor determination of aldosterone in ascitic fluid. Elevated aldosterone levels in plasma and ascitic fluid of 10 patients with advanced cirrhosis of the liver were recorded, as compared to the plasma levels in normal subjects. Elevated aldosterone levels in these patients was of definite importance for the choice of adequate diuretic drug, since the effectiveness of diuretic treatment largely depended on renin activity and aldosterone level.

  10. Radioimmunoassay of aldosterone in ascitic fluid

    International Nuclear Information System (INIS)

    Maleeva, A.; Kekhajova, M.

    1988-01-01

    A method was developed dor determination of aldosterone in ascitic fluid. Elevated aldosterone levels in plasma and ascitic fluid of 10 patients with advanced cirrhosis of the liver were recorded, as compared to the plasma levels in normal subjects. Elevated aldosterone levels in these patients was of definite importance for the choice of adequate diuretic drug, since the effectiveness of diuretic treatment largely depended on renin activity and aldosterone level

  11. Targeting the aldosterone pathway in cardiovascular disease

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Azizi, Michel; Bauersachs, Johann

    2012-01-01

    Accumulated evidence has demonstrated that aldosterone is a key player in the pathogenesis of cardiovascular (CV) disease. Multiple clinical trials have documented that intervention in the aldosterone pathway can reduce blood pressure and lower albuminuria and improve outcome in patients with heart...... failure or myocardial infarction. Recent studies have unraveled details about the role of aldosterone at the cellular level in CV disease. The relative importance of glucocorticoids and aldosterone in terms of mineralocorticoid receptor activation is currently being debated. Also, studies are addressing...... which aldosterone modulator to use, which timing of treatment to aim for, and in which population to intervene. This review provides an overview of recent developments in the understanding of the role of aldosterone in CV disease, with particular reference to mechanisms and potential targets...

  12. Aldosterone as a renal growth factor.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2011-04-05

    Aldosterone regulates blood pressure through its effects on the cardiovascular system and kidney. Aldosterone can also contribute to the development of hypertension that leads to chronic pathologies such as nephropathy and renal fibrosis. Aldosterone directly modulates renal cell proliferation and differentiation as part of normal kidney development. The stimulation of rapidly activated protein kinase cascades is one facet of how aldosterone regulates renal cell growth. These cascades may also contribute to myofibroblastic transformation and cell proliferation observed in pathological conditions of the kidney. Polycystic kidney disease is a genetic disorder that is accelerated by hypertension. EGFR-dependent proliferation of the renal epithelium is a factor in cyst development and trans-activation of EGFR is a key feature in initiating aldosterone-induced signalling cascades. Delineating the components of aldosterone-induced signalling cascades may identify novel therapeutic targets for proliferative diseases of the kidney.

  13. A Late Diagnosis of Primary Aldosteronism.

    Science.gov (United States)

    Zorzi, Francesco; Olivieri, Oliviero; Brazzarola, Paolo; Pizzolo, Francesca

    2017-09-01

    We report the case of a 41-year-old male patient with juvenile onset refractory hypertension while taking four drugs including a diuretic. Fourteen years before he underwent a complete investigation for secondary hypertension (including the aldosterone to renin ratio-ARR) that was negative. Since that, hypertension control gradually worsened, hypertensive organ damage aggravated and hypokalemia developed in spite of ACE inhibitor treatment. At the re-evaluation ARR was elevated, and the further workup for primary aldosteronism demonstrated an unilateral aldosterone producing adenoma that was surgically removed, with subsequent optimal blood pressure control with two anti-hypertensive drugs. In this case, the failure of the first screening prevented a correct diagnosis of primary aldosteronism, with consequent inadequate blood pressure control in following years and end organ damage. The case suggests the need of clinical follow-up and eventual reappraisal of patients showing a condition of refractory hypertension associated with hypokalemia despite a first negative screening test.

  14. Primary aldosteronism: diagnosis, localization, and treatment

    International Nuclear Information System (INIS)

    Weinberger, M.H.; Grim, C.E.; Hollifield, J.W.; Kem, D.C.; Ganguly, A.; Kramer, N.J.; Yune, H.Y.; Wellman, H.; Donohue, J.P.

    1979-01-01

    New diagnostic techniques have enhanced the detection of primary aldosteronism. However, the response of blood pressure after operation in unilateral and bilateral adrenal disease is different. We have compared four localizing techniques - adrenal venography, adrenal isotopic scanning, a modified adrenal venous sampling for steroid measurements, and the anomalous postural decrease in plasma aldosterone concentration - in 51 patients with primary aldosteronism, all of whom had undergone operative confirmation. Adrenalectomy resulted in normal blood pressure in 59%, improvement in 25%, and no change in 16%. Correct localization of the lesion was obtained in 47% by the adrenal isotopic scan, in 66% by adrenal venography, and in 91% by the modified adrenal venous hormone technique despite four false-positives. Of the 26 patients with an anomalous postural decrease in plasma aldosterone, 88% had a unilateral lesion

  15. Localization of aldosterone-producing tumours in primary aldosteronism by adrenal and renal vein catheterization

    DEFF Research Database (Denmark)

    Lund, J O; Nielsen, M D; Giese, Jacob

    1980-01-01

    Regional venous plasma aldosterone concentrations were determined and assessed against concurrent arterial levels in 16 patients with primary aldosteronism. The results obtained by sampling from the left adrenal vein or the left renal vein allowed correct side prediction of the presupposed adenoma...

  16. Aldosterone and aldosterone receptor antagonists in patients with chronic heart failure

    Directory of Open Access Journals (Sweden)

    Nappi J

    2011-06-01

    Full Text Available Jean M Nappi, Adam SiegClinical Pharmacy and Outcome Sciences, South Carolina College of Pharmacy, Medical University of South Carolina Campus, Charleston, SC, USAAbstract: Aldosterone is a mineralocorticoid hormone synthesized by the adrenal glands that has several regulatory functions to help the body maintain normal volume status and electrolyte balance. Studies have shown significantly higher levels of aldosterone secretion in patients with congestive heart failure compared with normal patients. Elevated levels of aldosterone have been shown to elevate blood pressure, cause left ventricular hypertrophy, and promote cardiac fibrosis. An appreciation of the true role of aldosterone in patients with chronic heart failure did not become apparent until the publication of the Randomized Aldactone Evaluation Study. Until recently, the use of aldosterone receptor antagonists has been limited to patients with severe heart failure and patients with heart failure following myocardial infarction. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF study added additional evidence to support the expanded use of aldosterone receptor antagonists in heart failure patients. The results of the EMPHASIS-HF trial showed that patients with mild-to-moderate (New York Heart Association Class II heart failure had reductions in mortality and hospitalizations from the addition of eplerenone to optimal medical therapy. Evidence remains elusive about the exact mechanism by which aldosterone receptor antagonists improve heart failure morbidity and mortality. The benefits of aldosterone receptor antagonist use in heart failure must be weighed against the potential risk of complications, ie, hyperkalemia and, in the case of spironolactone, possible endocrine abnormalities, in particular gynecomastia. With appropriate monitoring, these risks can be minimized. We now have evidence that patients with mild-to-severe symptoms

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

    Directory of Open Access Journals (Sweden)

    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

  18. Aldosterons effekt på nyrernes kaliumbalance

    DEFF Research Database (Denmark)

    Winther, Signe Abitz; Egfjord, Martin

    2011-01-01

    Recent studies have shown expression of the following regulatory WNK kinases in the kidney: the full-length WNK1 (L-WNK1), the shorter kidney specific WNK1 transcript (KS-WNK1), formed by alternative splicing, and WNK4. Aldosterone activates expression of KS-WNK1 and inhibits WNK4 via SGK1 - both...

  19. The Occurrence of Apparent Bilateral Aldosterone Suppression in Adrenal Vein Sampling for Primary Aldosteronism.

    Science.gov (United States)

    Shibayama, Yui; Wada, Norio; Naruse, Mitsuhide; Kurihara, Isao; Ito, Hiroshi; Yoneda, Takashi; Takeda, Yoshiyu; Umakoshi, Hironobu; Tsuiki, Mika; Ichijo, Takamasa; Fukuda, Hisashi; Katabami, Takuyuki; Yoshimoto, Takanobu; Ogawa, Yoshihiro; Kawashima, Junji; Ohno, Yuichi; Sone, Masakatsu; Fujita, Megumi; Takahashi, Katsutoshi; Shibata, Hirotaka; Kamemura, Kohei; Fujii, Yuichi; Yamamoto, Koichi; Suzuki, Tomoko

    2018-05-01

    In adrenal venous sampling (AVS) for patients with primary aldosteronism (PA), apparent bilateral aldosterone suppression (ABAS), defined as lower aldosterone/cortisol ratios in the bilateral adrenal veins than that in the inferior vena cava, is occasionally experienced. ABAS is uninterpretable with respect to lateralization of excess aldosterone production. We previously reported that ABAS was not a rare phenomenon and was significantly reduced after adrenocorticotropic hormone (ACTH) administration. To validate the effects of ACTH administration and adding sampling positions in the left adrenal vein on the prevalence of ABAS in the larger Japan Primary Aldosteronism Study. The data from 1689 patients with PA who underwent AVS between January 2006 and October 2016 were studied. All patients in the previous study, the West Japan Adrenal Vein Sampling study, were excluded. The prevalence of ABAS was investigated at two sampling positions in the left adrenal vein, the central vein and the common trunk, without and with ACTH administration. The prevalence of ABAS with ACTH administration was significantly lower than that without ACTH administration [without ACTH vs with ACTH: 79/440 (18.0%) vs 45/591 (7.6%); P sampling position, at the central vein and at the common trunk [33/591 (5.6%) vs 32/591 (5.4%); P = 1.00]. The effectiveness of ACTH administration for the reduction of ABAS in AVS regardless of the sampling position in the left adrenal vein was confirmed in the larger cohort.

  20. The Occurrence of Apparent Bilateral Aldosterone Suppression in Adrenal Vein Sampling for Primary Aldosteronism

    Science.gov (United States)

    Shibayama, Yui; Wada, Norio; Naruse, Mitsuhide; Kurihara, Isao; Ito, Hiroshi; Yoneda, Takashi; Takeda, Yoshiyu; Umakoshi, Hironobu; Tsuiki, Mika; Ichijo, Takamasa; Fukuda, Hisashi; Katabami, Takuyuki; Yoshimoto, Takanobu; Ogawa, Yoshihiro; Kawashima, Junji; Ohno, Yuichi; Sone, Masakatsu; Fujita, Megumi; Takahashi, Katsutoshi; Shibata, Hirotaka; Kamemura, Kohei; Fujii, Yuichi; Yamamoto, Koichi; Suzuki, Tomoko

    2018-01-01

    Abstract Context In adrenal venous sampling (AVS) for patients with primary aldosteronism (PA), apparent bilateral aldosterone suppression (ABAS), defined as lower aldosterone/cortisol ratios in the bilateral adrenal veins than that in the inferior vena cava, is occasionally experienced. ABAS is uninterpretable with respect to lateralization of excess aldosterone production. We previously reported that ABAS was not a rare phenomenon and was significantly reduced after adrenocorticotropic hormone (ACTH) administration. Objective To validate the effects of ACTH administration and adding sampling positions in the left adrenal vein on the prevalence of ABAS in the larger Japan Primary Aldosteronism Study. Patients The data from 1689 patients with PA who underwent AVS between January 2006 and October 2016 were studied. All patients in the previous study, the West Japan Adrenal Vein Sampling study, were excluded. Outcome Measurements The prevalence of ABAS was investigated at two sampling positions in the left adrenal vein, the central vein and the common trunk, without and with ACTH administration. Results The prevalence of ABAS with ACTH administration was significantly lower than that without ACTH administration [without ACTH vs with ACTH: 79/440 (18.0%) vs 45/591 (7.6%); P AVS regardless of the sampling position in the left adrenal vein was confirmed in the larger cohort. PMID:29687091

  1. Mechanisms underlying rapid aldosterone effects in the kidney.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2012-02-01

    The steroid hormone aldosterone is a key regulator of electrolyte transport in the kidney and contributes to both homeostatic whole-body electrolyte balance and the development of renal and cardiovascular pathologies. Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues. Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane and also modulate the transcriptional action of aldosterone through MR. This review describes current knowledge regarding the mechanisms and targets of rapid aldosterone action in the nephron and how aldosterone integrates these responses into the regulation of renal physiology.

  2. Mechanisms underlying rapid aldosterone effects in the kidney.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2011-03-17

    The steroid hormone aldosterone is a key regulator of electrolyte transport in the kidney and contributes to both homeostatic whole-body electrolyte balance and the development of renal and cardiovascular pathologies. Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues. Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane and also modulate the transcriptional action of aldosterone through MR. This review describes current knowledge regarding the mechanisms and targets of rapid aldosterone action in the nephron and how aldosterone integrates these responses into the regulation of renal physiology.

  3. Mass Spectrometry-Based Adrenal and Peripheral Venous Steroid Profiling for Subtyping Primary Aldosteronism

    NARCIS (Netherlands)

    Eisenhofer, G.; Dekkers, T.; Peitzsch, M.; Dietz, A.S.; Bidlingmaier, M.; Treitl, M.; Williams, T.A.; Bornstein, S.R.; Haase, M.; Rump, L.C.; Willenberg, H.S.; Beuschlein, F.; Deinum, J.; Lenders, J.W.; Reincke, M.

    2016-01-01

    BACKGROUND: Differentiating patients with primary aldosteronism caused by aldosterone-producing adenomas (APAs) from those with bilateral adrenal hyperplasia (BAH), which is essential for choice of therapeutic intervention, relies on adrenal venous sampling (AVS)-based measurements of aldosterone

  4. Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism.

    NARCIS (Netherlands)

    Kempers, M.J.E.; Lenders, J.W.M.; Outheusden, L. van; Wilt, G.J. van der; Schultze Kool, L.J.; Hermus, A.R.M.M.; Deinum, J.

    2009-01-01

    BACKGROUND: Computed tomography (CT), magnetic resonance imaging (MRI), and adrenal vein sampling (AVS) are used to distinguish unilateral from bilateral increased aldosterone secretion as a cause of primary aldosteronism. This distinction is crucial because unilateral primary aldosteronism can be

  5. Localization of aldosterone-producing tumor

    International Nuclear Information System (INIS)

    Yagi, Atsuko; Ichikawa, Shuichi; Fujita, Haruyasu; Fujie, Masao; Kumakura, Hisao; Murata, Kazuhiko

    1985-01-01

    The diagnostic validity for lateralization by abdominal computed tomography (CT), adrenal isotopic scanning, and adrenal venous sampling was studied in 11 patients with primary aldosteronism and 1 patient with idiopathic hyperaldosteronism. All of the patients with primary aldosteronism were subsequently operated and all were found to have histologically adrenal adenomas. CT scan was taken using G. E. 8800 and adrenal scintiscan was carried out after dexamethasone administration to suppress the endogenous ACTH. Adrenal venous sampling was performed under mild sodium restriction. In the cases we failed to insert catheter into the right adrenal vein, lateralization was determined by comparing plasma aldosterone concentrations in renal veins with that in the high inferior vena cava above the renal veins. The CT scan showed in as high as 98% of the patients the exact side of the adrenal lesion, whereas the adrenal scintiscan revealed as low accuracy as 60%. This value was almost the same with the procedure by the adrenal venous sampling (64%). Incorrect preoperative identification by the CT scan and adrenal scintigraphy was 0%, though it was 11% by the adrenal venous sampling. The only one case the CT scan failed to detect was a small adenoma (0.9x0.8x0.7 cm), but adrenal venous sampling showed the side correctly. These three examinations were performed in one case of idiopathic hyperaldosteronism, as all the procedures could not disclose a adrenal adenoma. (J.P.N.)

  6. Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma

    Science.gov (United States)

    Kishimoto, Rui; Oki, Kenji; Yoneda, Masayasu; Gomez-Sanchez, Celso E.; Ohno, Haruya; Kobuke, Kazuhiro; Itcho, Kiyotaka; Kohno, Nobuoki

    2016-01-01

    Abstract We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production. Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production. The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n = 13) (P APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation. PMID:27196470

  7. The regulation of cell growth and survival by aldosterone.

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2012-02-01

    The steroid hormone aldosterone is synthesized from cholesterol, mainly in the zona glomerulosa of the adrenal cortex. Aldosterone exerts its effects in the epithelial tissues of the kidney and colon and in non-epithelial tissues such as the brain and cardiovasculature. The genomic response to aldosterone involves dimerization of the mineralocorticoid receptor (MR), dissociation of heat shock proteins from MR, translocation of the aldosterone-MR complex to the nucleus and the concomitant regulation of gene expression. Rapid responses to aldosterone occur within seconds to minutes, do not involve transcription or translation and can modulate directly or indirectly the later genomic responses. Aside from the well-known effects of aldosterone on the regulation of sodium and water homeostasis, aldosterone can also produce deleterious structural changes in tissues by inducing hypertrophy and the dysregulation of proliferation and apoptosis, leading to fibrosis and tissue remodelling. Here we discuss the involvement of aldosterone-mediated rapid signalling cascades in the development of disease states such as chronic kidney disease and heart failure, and the antagonists that can inhibit these pathophysiological responses.

  8. Aldosterone and parathyroid hormone: a precarious couple for cardiovascular disease

    NARCIS (Netherlands)

    Tomaschitz, A.; Ritz, E.; Pieske, B.; Fahrleitner-Pammer, A.; Kienreich, K.; Horina, J.H.; Drechsler, C.; Marz, W.; Ofner, M.; Pieber, T.R.; Pilz, S.

    2012-01-01

    Animal and human studies support a clinically relevant interaction between aldosterone and parathyroid hormone (PTH) levels and suggest an impact of the interaction on cardiovascular (CV) health. This review focuses on mechanisms behind the bidirectional interactions between aldosterone and PTH and

  9. Regulation of Adrenal Aldosterone Production by Serine Protease Prostasin

    Directory of Open Access Journals (Sweden)

    Takehiro Ko

    2010-01-01

    Full Text Available A serine protease prostasin has been demonstrated to have a pivotal role in the activation of the epithelial sodium channel. Systemic administration of adenovirus carrying human prostasin gene in rats resulted in an increase in plasma prostasin and aldosterone levels. However, the mechanism by which the elevation of prostasin levels in the systemic circulation stimulated the plasma aldosterone levels remains unknown. Therefore, we examined if prostasin increases the aldosterone synthesis in a human adrenocortical cell line (H295R cells. Luciferase assay using CYP11B2 promoter revealed that prostasin significantly increased the transcriptional activity of CYP11B2. Prostasin significantly increased both CYP11B2 mRNA expression and aldosterone production in a dose-dependent manner. Surprisingly, treatment with camostat mesilate, a potent prostasin inhibitor, had no effect on the aldosterone synthesis by prostasin and also a protease-dead mutant of prostasin significantly stimulated the aldosterone production. A T-type/L-type calcium channel blocker and a protein kinase C (PKC inhibitor significantly reduced the aldosterone synthesis by prostasin. Our findings suggest a stimulatory effect of prostasin on the aldosterone synthesis by adrenal gland through the nonproteolytic action and indicate a new role of prostasin in the systemic circulation.

  10. Dysregulation of Aldosterone Secretion in Mast Cell-Deficient Mice.

    Science.gov (United States)

    Boyer, Hadrien-Gaël; Wils, Julien; Renouf, Sylvie; Arabo, Arnaud; Duparc, Céline; Boutelet, Isabelle; Lefebvre, Hervé; Louiset, Estelle

    2017-12-01

    Resident adrenal mast cells have been shown to activate aldosterone secretion in rat and man. Especially, mast cell proliferation has been observed in adrenal tissues from patients with aldosterone-producing adrenocortical adenoma. In the present study, we show that the activity of adrenal mast cells is stimulated by low-sodium diet and correlates with aldosterone synthesis in C57BL/6 and BALB/c mice. We have also investigated the regulation of aldosterone secretion in mast cell-deficient C57BL/6 Kit W-sh/W-sh mice in comparison with wild-type C57BL/6 mice. Kit W-sh/W-sh mice submitted to normal sodium diet had basal plasma aldosterone levels similar to those observed in wild-type animals. Conversely, low-sodium diet unexpectedly induced an exaggerated aldosterone response, which seemed to result from an increase in adrenal renin and angiotensin type 1 receptor expression. Severe hyperaldosteronism was associated with an increase in systolic blood pressure and marked hypokalemia, which favored polyuria. Adrenal renin and angiotensin type 1 receptor overexpression may represent a compensatory mechanism aimed at activating aldosterone production in the absence of mast cells. Finally, C57BL/6 Kit W-sh/W-sh mice represent an unexpected animal model of primary aldosteronism, which has the particularity to be triggered by sodium restriction. © 2017 American Heart Association, Inc.

  11. The regulation of cell growth and survival by aldosterone.

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2011-01-01

    The steroid hormone aldosterone is synthesized from cholesterol, mainly in the zona glomerulosa of the adrenal cortex. Aldosterone exerts its effects in the epithelial tissues of the kidney and colon and in non-epithelial tissues such as the brain and cardiovasculature. The genomic response to aldosterone involves dimerization of the mineralocorticoid receptor (MR), dissociation of heat shock proteins from MR, translocation of the aldosterone-MR complex to the nucleus and the concomitant regulation of gene expression. Rapid responses to aldosterone occur within seconds to minutes, do not involve transcription or translation and can modulate directly or indirectly the later genomic responses. Aside from the well-known effects of aldosterone on the regulation of sodium and water homeostasis, aldosterone can also produce deleterious structural changes in tissues by inducing hypertrophy and the dysregulation of proliferation and apoptosis, leading to fibrosis and tissue remodelling. Here we discuss the involvement of aldosterone-mediated rapid signalling cascades in the development of disease states such as chronic kidney disease and heart failure, and the antagonists that can inhibit these pathophysiological responses.

  12. Radioimmune method for determination of aldosterone in urine

    International Nuclear Information System (INIS)

    Ignatowska-Switalska, H.

    1976-01-01

    The author describes a radioimmune method for determination of 18-aldosterone glucuronide using a specific aldosterone antibody. The optimal conditions of the test were elaborated and the sensitivity, accuracy and repeatability of the test were established. The normal values of aldosterone excretion determined in 28 healthy subjects on normal sodium diet ranged from 3.3 to 15 μg/24 hours +-3.5. Aldosterone excretion on low-sodium diet increased in the group of healthy controls to 36 μg/24 hours +-21. The usefulness of the method for clinical purposes was illustrated with results of aldosterone determinations in patients with Conn's syndrome, with malignant hypertension and with Addison's disease. (author)

  13. Adrenal vein sampling in the diagnosis of aldosteronism

    Directory of Open Access Journals (Sweden)

    Deipolyi AR

    2015-06-01

    Full Text Available Amy R Deipolyi,1 Rahmi Oklu2 1Vascular and Interventional Radiology, NYU Langone Medical Center, New York, NY, USA; 2Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Abstract: Primary aldosteronism causes 15%–25% of cases of drug-resistant hypertension. Adrenal vein sampling (AVS is a procedure entailing the measurement of aldosterone from both adrenal veins, to diagnose an adrenal source of excess aldosterone secretion. Because unilateral adrenal etiologies of primary aldosteronism may be surgically resected, identifying these sources by venous sampling is critical. Technical aspects of the procedure are reviewed, with emphasis on strategies to avoid common difficulties during AVS. Keywords: primary aldosteronism, hypertension, venous sampling, adrenal adenoma

  14. Aldosterone and mortality in hemodialysis patients: role of volume overload.

    Science.gov (United States)

    Hung, Szu-Chun; Lin, Yao-Ping; Huang, Hsin-Lei; Pu, Hsiao-Fung; Tarng, Der-Cherng

    2013-01-01

    Elevated aldosterone is associated with increased mortality in the general population. In patients on dialysis, however, the association is reversed. This paradox may be explained by volume overload, which is associated with lower aldosterone and higher mortality. We evaluated the relationship between aldosterone and outcomes in a prospective cohort of 328 hemodialysis patients stratified by the presence or absence of volume overload (defined as extracellular water/total body water >48%, as measured with bioimpedance). Baseline plasma aldosterone was measured before dialysis and categorized as low (280 pg/mL). Overall, 36% (n = 119) of the hemodialysis patients had evidence of volume overload. Baseline aldosterone was significantly lower in the presence of volume overload than in its absence. During a median follow-up of 54 months, 83 deaths and 70 cardiovascular events occurred. Cox multivariate analysis showed that by using the low aldosterone as the reference, high aldosterone was inversely associated with decreased hazard ratios for mortality (0.49; 95% confidence interval, 0.25-0.76) and first cardiovascular event (0.70; 95% confidence interval, 0.33-0.78) in the presence of volume overload. In contrast, high aldosterone was associated with an increased risk for mortality (1.97; 95% confidence interval, 1.69-3.75) and first cardiovascular event (2.01; 95% confidence interval, 1.28-4.15) in the absence of volume overload. The inverse association of aldosterone with adverse outcomes in hemodialysis patients is due to the confounding effect of volume overload. These findings support treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control.

  15. 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.

  16. Intracellular mediators of potassium-induced aldosterone secretion

    International Nuclear Information System (INIS)

    Ganguly, A.; Chiou, S.; Davis, J.S.

    1990-01-01

    We have investigated the intracellular messengers of potassium in eliciting aldosterone secretion in calf adrenal glomerulosa cells since there were unresolved issues relating to the role of phosphoinositides, cAMP and protein kinases. We observed no evidence of hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) in 3 H-inositol labeled alf adrenal cells or increase of cAMP in response to potassium. Addition of calcium channel blocker, nitrendipine after stimulating adrenal glomerulosa cells with potassium, markedly inhibited aldosterone secretion. A calmodulin inhibitor (W-7) produced greater reduction of aldosterone secretion than an inhibitor of protein kinase C (H-7). These results suggest that a rise in cytosolic free calcium concentration through voltage-dependent calcium channel and calmodulin are the critical determinants of aldosterone secretion stimulated by potassium

  17. Solubilization of rat kidney plasma membrane proteins associated with 3H-aldosterone

    International Nuclear Information System (INIS)

    Ozegovic, B.; Dobrovic-Jenik, D.; Milkovic, S.

    1988-01-01

    The treatment of rat kidney plasma membranes with sodium dodecyl sulphate (SDS) did not essentially affect the ability of the membranes for 3 H-aldosterone binding as compared with the intact plasma membranes (Ozegovic et al., 1977). A gel filtration of 3 H-aldosterone - kidney plasma membranes complex on Sepharose 6B yielded 2 protein and 2 3 H-aldosterone peaks. The proteins which were eluted in the first peak were associated with the first 3 H-aldosterone peak while the second 3 H-aldosterone peak was eluted with Ve corresponding to Ve of free 3 H-aldosterone. Spironolactone, a competitive antagonist of aldosterone, prevented the binding of 3 H-aldosterone to the membrane proteins. The results demonstrated a high affinity of the kidney plasma membranes solubilized with SDS and a specificity of aldosterone binding to the plasma membrane proteins of higher molecular mass. (author)

  18. Primary aldosteronism and hypercortisolism due to bilateral functioning adrenocortical adenomas.

    Science.gov (United States)

    Oki, Kenji; Yamane, Kiminori; Sakashita, Yu; Kamei, Nozomu; Watanabe, Hiroshi; Toyota, Naoyuki; Shigeta, Masanobu; Sasano, Hironobu; Kohno, Nobuoki

    2008-10-01

    A 50-year-old male patient with a 15-year history of hypertension was referred to our hospital for evaluation of bilateral adrenal tumors. No Cushingoid features were observed. Computed tomographic scan showed 10-mm masses in each adrenal gland. Preoperative endocrinological examinations revealed autonomous cortisol and aldosterone secretion in this patient. The results of a subsequent adrenal venous catheterization study were consistent with the presence of a left cortisol-producing tumor and a right aldosterone-producing tumor. A left partial adrenalectomy was performed initially, but cortisol and aldosterone over-secretion persisted. Accordingly, the patient underwent a right adrenalectomy. Pathological examination of the resected specimens, including immunohistochemical analysis, demonstrated that both adenomas possibly produced cortisol and aldosterone. This is an extremely rare case of bilateral adrenal tumors, in which the left adrenocortical tumor produced and secreted cortisol or both cortisol and aldosterone and the right one produced and secreted both aldosterone and cortisol, as confirmed by clinical findings and pathological studies using immunohistochemical analysis.

  19. Impact of aldosterone-producing cell clusters on diagnostic discrepancies in primary aldosteronism

    Science.gov (United States)

    Kometani, Mitsuhiro; Yoneda, Takashi; Aono, Daisuke; Karashima, Shigehiro; Demura, Masashi; Nishimoto, Koshiro; Yamagishi, Masakazu; Takeda, Yoshiyu

    2018-01-01

    Adrenocorticotropic hormone (ACTH) stimulation is recommended in adrenal vein sampling (AVS) for primary aldosteronism (PA) to improve the AVS success rate. However, this method can confound the subtype diagnosis. Gene mutations or pathological characteristics may be related to lateralization by AVS. This study aimed to compare the rate of diagnostic discrepancy by AVS pre- versus post-ACTH stimulation and to investigate the relationship between this discrepancy and findings from immunohistochemical and genetic analyses of PA. We evaluated 195 cases of AVS performed in 2011–2017. All surgical specimens were analyzed genetically and immunohistochemically. Based on the criteria, AVS was successful in 158 patients both pre- and post-ACTH; of these patients, 75 showed diagnostic discrepancies between pre- and post-ACTH. Thus, 19 patients underwent unilateral adrenalectomy, of whom 16 had an aldosterone-producing adenoma (APA) that was positive for CYP11B2 immunostaining. Of them, 10 patients had discordant lateralization between pre- and post-ACTH. In the genetic analysis, the rate of somatic mutations was not significantly different between APA patients with versus without a diagnostic discrepancy. In the immunohistochemical analysis, CYP11B2 levels and the frequency of aldosterone-producing cell clusters (APCCs) in APAs were almost identical between patients with versus without a diagnostic discrepancy. However, both the number and summed area of APCCs in APAs were significantly smaller in patients with concordant results than in those whose diagnosis changed to bilateral PA post-ACTH stimulation. In conclusion, lateralization by AVS was affected by APCCs in the adjacent gland, but not by APA-related factors such as somatic gene mutations. PMID:29899838

  20. 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

  1. Molecular and cellular mechanisms of aldosterone producing adenoma development

    Directory of Open Access Journals (Sweden)

    Sheerazed eBoulkroun

    2015-06-01

    Full Text Available Primary aldosteronism (PA is the most common form of secondary hypertension with an estimated prevalence of ~10% in referred patients. PA occurs as a result of a dysregulation of the normal mechanisms controlling adrenal aldosterone production. It is characterized by hypertension with low plasma renin and elevated aldosterone and often associated with hypokalemia. The two major causes of PA are unilateral aldosterone producing adenoma (APA and bilateral adrenal hyperplasia, accounting together for ~95% of cases. In addition to the well-characterized effect of excess mineralocorticoids on blood pressure, high levels of aldosterone also have cardiovascular, renal and metabolic consequences. Hence, long-term consequences of PA include increased risk of coronary artery disease, myocardial infarction, heart failure and atrial fibrillation. Despite recent progress in the management of patients with PA, critical issues related to diagnosis, subtype differentiation and treatment of non-surgically correctable forms still persist. A better understanding of the pathogenic mechanisms of the disease should lead to the identification of more reliable diagnostic and prognostic biomarkers for a more sensitive and specific screening and new therapeutic options. In this review we will summarize our current knowledge on the molecular and cellular mechanisms of APA development. On one hand, we will discuss how various animal models have improved our understanding of the pathophysiology of excess aldosterone production. On the other hand, we will summarize the major advances made during the last few years in the genetics of APA due to transcriptomic studies and whole exome sequencing. The identification of recurrent and somatic mutations in genes coding for ion channels (KCNJ5 and CACNA1D and ATPases (ATP1A1 and ATP2B3 allowed highlighting the central role of calcium signaling in autonomous aldosterone production by the adrenal.

  2. Aldosterone and parathyroid hormone interactions as mediators of metabolic and cardiovascular disease

    NARCIS (Netherlands)

    Tomaschitz, A.; Ritz, E.; Pieske, B.; Rus-Machan, J.; Kienreich, K.; Verheyen, N.; Gaksch, M.; Grubler, M.; Fahrleitner-Pammer, A.; Mrak, P.; Toplak, H.; Kraigher-Krainer, E.; Marz, W.; Pilz, S.

    2014-01-01

    Inappropriate aldosterone and parathyroid hormone (PTH) secretion is strongly linked with development and progression of cardiovascular (CV) disease. Accumulating evidence suggests a bidirectional interplay between parathyroid hormone and aldosterone. This interaction may lead to a disproportionally

  3. Clinical Characteristics of Aldosterone- and Cortisol-Coproducing Adrenal Adenoma in Primary Aldosteronism

    Directory of Open Access Journals (Sweden)

    Lu Tang

    2018-01-01

    Full Text Available Aldosterone- and cortisol-coproducing adrenal adenoma (A/CPA cases have been observed in patients with primary aldosteronism (PA. This study investigated the incidence, clinical characteristics, and molecular biological features of patients with A/CPAs. We retrospectively identified 22 A/CPA patients from 555 PA patients who visited the Chinese People’s Liberation Army General Hospital between 2004 and 2015. Analysis of clinical parameters revealed that patients with A/CPAs had larger tumors than those with pure APAs (P<0.05. Moreover, they had higher proportions of cardiovascular complications, glucose intolerance/diabetes, and osteopenia/osteoporosis compared to the pure APA patients (P<0.001. In the molecular biological findings, quantitative real-time PCR analysis revealed similar CYP11B1 and CYP17A1 mRNA expressions in resected A/CPA specimens and in pure APA specimens. Western blot and immunochemical analyses showed CYP11B1, CYP11B2, and CYP17A1 expressions in both A/CPAs and pure APAs. Seventeen cases with KCNJ5 mutations were detected among the 22 A/CPA DNA samples, but no PRKACA or other causative mutations were observed. Each patient improved following adrenalectomy. In conclusion, A/CPAs were not rare among PA patients. These patients associated with high incidences of cardiovascular events and metabolic disorders. Screening for excess cortisol secretion is necessary for PA patients.

  4. Aldosterone breakthrough during aliskiren, valsartan, and combination (aliskiren + valsartan) therapy.

    Science.gov (United States)

    Bomback, Andrew S; Rekhtman, Yelena; Klemmer, Philip J; Canetta, Pietro A; Radhakrishnan, Jai; Appel, Gerald B

    2012-01-01

    Aldosterone levels increase in 30%-40% of patients on angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers over the long term. This "aldosterone breakthrough" may carry important clinical consequences given aldosterone's nonepithelial, pro-fibrotic actions. The renin inhibitor, aliskiren, by suppressing the renin-angiotensin-aldosterone system (RAAS) proximally, may limit breakthrough compared to conventional RAAS blockade. This open-label study (NCT01129557) randomized subjects to aliskiren 300 mg daily (A), valsartan 320 mg daily (V), or aliskiren 150 mg + valsartan 160 mg daily (A+V) for 9 months. Eligible subjects had proteinuria >300 mg/day, estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m(2), and systolic blood pressure (BP) >130 or diastolic BP >80 mm Hg. Serum and 24-hour urine aldosterone (indexed to 24-hour urine Na) were checked before initiation of therapy and at 3, 6, and 9 months. Aldosterone breakthrough was defined as a sustained increase from baseline aldosterone by study end. The study was intended to enroll 120 subjects but was terminated early by the sponsor. We present here the results of 33 subjects who completed the protocol, of which 12 were randomized to A, 11 were randomized to V, and 10 were randomized to A+V. Mean baseline eGFR was 75.5 (±23.3) mL/min/1.73 m(2); baseline proteinuria was 3104 (±2943) mg/day; and baseline BP was 134.7 (±10.5)/84.8 (±8.4) mm Hg. Three (27%) subjects on V, three (25%) subjects on A, and three (30%) subjects on A+V had aldosterone breakthrough. Mean proteinuria reduction was 31% from baseline in all subjects: 30% in subjects with breakthrough vs. 32% in subjects without breakthrough. Mean BP reduction was 11.0/8.8 mm Hg in all subjects: 8.4/6.1 mm Hg in subjects with breakthrough vs. 12.0/9.8 mm Hg in subjects without breakthrough. Aliskiren, alone or in combination with valsartan, did not reduce the incidence of aldosterone breakthrough in subjects with hypertension

  5. Prenatal diagnosis of Bartter syndrome: amniotic fluid aldosterone.

    Science.gov (United States)

    Rachid, Myriam; Dreux, Sophie; Pean de Ponfilly, Gauthier; Vargas-Poussou, Rosa; Czerkiewicz, Isabelle; Chevenne, Didier; Oury, Jean-François; Deschênes, Georges; Muller, Françoise

    2017-04-01

    Bartter syndrome is a severe inherited tubulopathy characterized at birth by salt wasting, severe polyuria, dehydration, growth retardation and secondary hyperaldosteronism. Prenatally, the disease is usually discovered following onset of severe polyhydramnios. We studied amniotic fluid aldosterone concentration in cases of Bartter syndrome and in control groups. Amniotic fluid aldosterone was assayed by radioimmunoassay. We undertook a retrospective case-control study based on 36 cases of postnatally diagnosed Bartter syndrome and 144 controls matched for gestational age. Two controls groups were defined: controls with polyhydramnios (n=72) and control without polyhydramnios (n=72). Amniotic fluid aldosterone was compared between the three groups. The median amniotic fluid aldosterone concentration in the Bartter syndrome group (90 pg/mL) did not differ significantly from that in the controls with polyhydramnios (90 pg/mL, p=0.33) or the controls without polyhydramnios (87 pg/mL, p=0.41). In conclusion, amniotic fluid aldosterone assay cannot be used for prenatal diagnosis of Bartter syndrome.

  6. The studies on aldosterone secretion rate by radioimmunoassay

    International Nuclear Information System (INIS)

    Takenouchi, Takahiko

    1974-01-01

    The aldosterone secretion rate was measured by radioimmunoassay in 12 normal subjects and 47 hypertensive patients. The values ranged from 25.0 to 60.2 ng/day with a mean of 39.6+-10.7 (S.D.) in 8 normal males and from 30.2 to 85.4 ng/day with a mean of 62.6+-26.8 (S.D.) in 4 normal females. The mean value in 21 cases with benign essential hypertension was found to be within normal range. No significant difference was found in the aldosterone secretion rate between the group of benign essential hypertension with suppressed renin activity and with nonsuppressed renin activity. Metabolic clearance rate in benign essential hypertension was observed to be within normal range. The aldosterone secretion rate in a few cases of benign essential hypertension failed to increase normally in response to sodium restriction (<50 mEq/day). The values in 11 cases of primary aldosteronism were found to be clearly higher, when compared with the values of normal subjects and subjects with benign essential hypertension. High values were found in patients suffering from malignant hypertension and in 3 with unilateral renal artery stenosis. The values in cases of bilateral renal artery stenosis, of pheochromocytoma, and of acromegaly with hypertension were within normal range. Low values in the aldosterone secretion rate were found in 3 cases each of 17α-hydroxylase deficiency and Cushing's syndrome. (JPN)

  7. Effects of Treating Primary Aldosteronism on Renal Function.

    Science.gov (United States)

    Kramers, Bart J; Kramers, Cornelis; Lenders, Jacques W M; Deinum, Jaap

    2017-03-01

    Longstanding primary aldosteronism (PA) has deleterious effects on renal function, often masked until treatment (adrenalectomy or spironolactone) is initiated. It has been suggested that PA causes relative glomerular hyperfiltration, explaining the decline in estimated glomerular filtration rate (eGFR) after treatment. In this retrospective study, the authors retrieved the clinical characteristics and eGFR of 134 PA patients before and 6 months after treatment. Using multiple regression analysis, the predictors for eGFR decline and the predictors of ultimately attained renal function in 113 patients was assessed. eGFR declined by 15.3±14.2 (range 19-63) mL/min, independent predictors were pretreatment plasma aldosterone, eGFR, plasma renin, and plasma potassium. Independent predictors of ultimately attained eGFR after treatment were pretreatment plasma aldosterone, age, eGFR, and plasma potassium. Our findings lend support to the hypothesis that higher aldosterone levels cause relative glomerular hyperfiltration. The severity of pretreatment aldosterone excess is the most important risk factor for renal function decline. ©2016 Wiley Periodicals, Inc.

  8. Changes of Aldosterone Secretion Rate Following Furosemide Administration in Normotensive Subjects with High Sodium Intake

    International Nuclear Information System (INIS)

    Sung, Ho Kyung; Ryu, Yong Wun; Koh, Joo Hwan

    1976-01-01

    Marked augmentation of urinary aldosterone excretion following furosemide administration was observed in previous experiment. In this study, author measured the changes of aldosterone secretion after furosemide administration in normotensive young volunteers with high sodium intake. After intravenous injection of 1.2- 3 H-aldosterone, urine samples were collected in course of time until 24 hours after the injection. Furosemide administration was done at 30 minutes prior to aldosterone injection. Specific activities of 3H-aldosterone during and after diuresis were measured and aldosterone secretion rates were calculated dividing the doses by specific activities. Results were as followed. 1) Furosemide resulted in a marked increase in urinary aldosterone excretion. 2) Furosemide lead to an increase in both sodium and potassium excretion. 3) Aldosterone secretion rate was also increase d during furosemide diuresis, but the rate was smaller than that of urinary excretion. 4) Continuous modest increase in aldosterone secretion rate was shown after diuresis and total excess amount of aldosterone secretion for 24 hrs was equivalent to the amount of aldosterone excretion produced by diruesis. 5) Abrupt marked loss of circulating aldosterone produced by diuresis was supplemented by long lasting increase in secretion for over twenty four hours.

  9. Recurrence of primary aldosteronism after percutaneous ethanol injection

    Directory of Open Access Journals (Sweden)

    Fan-Chi Chang

    2012-03-01

    Full Text Available Adrenalectomy is the definite treatment for aldosterone-producing adenoma (APA. Percutaneous ethanol or acetic acid injection with computed tomography (CT guidance has been described as a safe, noninvasive, and effective alternative treatment modality in patients with high surgical risk. We report on a man who was 49 years of age and presented with treatment-resistant hypertension and was later diagnosed with APA. CT-guided percutaneous ethanol injection (PEI was performed for this high surgical risk patient. He had aldosteronism recurrence 4 years after the ethanol injection, so a second PEI was performed. The tumor size was reduced and his blood pressure was normalized. Therefore, we suggest that clinicians should closely check aldosterone to renin ration and potassium level if percutaneous chemical ablation is considered in functioning adrenal adenomas.

  10. Clinicopathological features of primary aldosteronism associated with subclinical Cushing's syndrome

    International Nuclear Information System (INIS)

    Hiraishi, Kiichiro; Yoshimoto, Takanobu; Tsuchiya, Kyoichiro; Minami, Isao; Doi, Masaru; Izumiyama, Hajime; Hirata, Yukio; Sasano, Hironobu

    2011-01-01

    Primary aldosteronism (PA), an autonomous aldosterone hypersecretion from adrenal adenoma and/or hyperplasia, and subclinical Cushing syndrome (SCS), a mild but autonomous cortisol hypersecretion from adrenal adenoma without signs or symptoms of Cuhing's syndrome, are now well-recognized clinical entities of adrenal incidentaloma. However, the clinicopathological features of PA associated with SCS (PA/SCS) remain unknown. The present study was undertaken to study the prevalence of PA/SCS among PA patients diagnosed at our institute, and characterize their clinicopathlogical features. The prevalence of PA/SCS was 8 of 38 PA patients (21%) studied. These 8 PA/SCS patients were significantly older and had larger tumor, higher serum potassium levels, lower basal plasma levels of aldosterone, adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEA-S) as well as lower response of aldosterone after ACTH stimulation than those in 12 patients with aldosterone-producing adenoma without hypercortisolism. All 8 PA/SCS patients showed unilateral uptake by adrenal scintigraphy at the ipsilateral side, whereas the laterality of aldosterone hypersecretion as determined by adrenal venous sampling varied from ipsilateral (3), contralateral (2), and bilateral side (2). 6 PA/SCS patients who underwent adrenalectomy required hydrocortisone replacement postoperatively. Histopathological analysis of the resected adrenal tumors from 5 PA/SCS patients revealed a single adenoma in 3, and double adenomas in 2, with varying degrees of positive immunoreactivities for steroidgenic enzymes 3β-hydroxysteroid dehydrogenase (HSD), P450 C17 ) by immunohistochemical study as well as CYP11B2 mRNA expression as measured by real-time radiotherapy-polymerase chain reaction (RT-PCR). In conclusion, PA/SCS consists of a variety of adrenal pathologies so that therapeutic approach differs depending on the disease subtype. (author)

  11. Macrolides for KCNJ5-mutated aldosterone-producing adenoma (MAPA): design of a study for personalized diagnosis of primary aldosteronism.

    Science.gov (United States)

    Maiolino, Giuseppe; Ceolotto, Giulio; Battistel, Michele; Barbiero, Giulio; Cesari, Maurizio; Amar, Laurence; Caroccia, Brasilina; Padrini, Roberto; Azizi, Michel; Rossi, Gian Paolo

    2018-02-06

    Aldosterone-producing adenoma (APA) is the main curable cause of endocrine hypertension cause of primary aldosteronism (PA) and it is in up to 66% of all cases investigated with adrenal vein sampling (AVS). Mutations in the KCNJ5 potassium channel involve up to 70% of APA and cause the most florid PA phenotypes. The recent finding that macrolide antibiotics specifically inhibit in vitro the altered function of mutated KCNJ5 channels has opened new horizons for the diagnosis and treatment of APA with KCNJ5 mutations in that it can allow identification and target treatment of PA patients harbouring a mutated APA. Thus, we aimed at investigating if clarithromycin and roxithromycin, two macrolides that potently blunt mutated Kir3.4 channel function in vitro, affect plasma aldosterone concentration in adrenal vein blood during AVS and in peripheral blood, respectively, in PA patients with a mutated APA. We designed two proof of concept studies. In study A: consecutive patients with an unambiguous biochemical evidence of PA will be exposed to a single dose of 250 mg clarithromycin during AVS, to assess its effect on the relative aldosterone secretion index in adrenal vein blood from the gland with and without APA. In study B: consecutive hypertensive patients submitted to the work-up for hypertension will receive a single oral dose of 150 mg roxithromycin. The experimental endpoints will be the change induced by roxithromycin of plasma aldosterone concentration and other steroids, direct active renin concentration, serum K + , systolic and diastolic blood pressure. We expect to prove that: (i) clarithromycin allows identification of mutated APA before adrenalectomy and sequencing of tumour DNA; (ii) the acute changes of plasma aldosterone concentration, direct active renin concentration, and blood pressure in peripheral venous blood after roxithromycin can be a proxy for the presence of an APA with somatic mutations.

  12. 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.

  13. Development and application of a simple radioimmunoassay for urinary aldosterone

    International Nuclear Information System (INIS)

    Al-Dujaili, E.A.S.; Edwards, C.R.W.

    1981-01-01

    A simple, economical and direct assay was developed to measure aldosterone in urine, using aldosterone antibody of high specificity and gamma labelled ligand. The assay allows the direct measurement of aldosterone in 100 μl aliquots of urine after acid hydrolysis. It does not require preliminary solvent extraction and purification steps and hence a large number of samples in a single batch can be assayed simultaneously. An excellent correlation was obtained between the results of the direct assay and the levels measured after extraction and paper chromatography (Y=0.97X+0.89, r=0.99, p<0.001) or after extraction alone (Y=0.98X+1.75, r=0.99, p<0.001). The coefficients of variation for inter-assay and intra-assay determinations of samples from normal and high urine pools were 4.2-6.5% and 5.6-9.8%, respectively. Total urinary aldosterone excretion in 21 normal subjects on unrestricted sodium diet ranged from 3.8-20.2 μg/24h (10.5-55.0 nmol/24h) with a mean of 12.5 + - 4.6 (SD) μg/24h (34.7 +- 12.8 (SD) nmol/24h). (Auth.)

  14. Galectin-3 Mediates Aldosterone-Induced Vascular Fibrosis

    NARCIS (Netherlands)

    Calvier, Laurent; Miana, Maria; Reboul, Pascal; Cachofeiro, Victoria; Martinez-Martinez, Ernesto; de Boer, Rudolf A.; Poirier, Francoise; Lacolley, Patrick; Zannad, Faiez; Rossignol, Patrick; Lopez-Andres, Natalia

    Objective-Aldosterone (Aldo) is involved in arterial stiffness and heart failure, but the mechanisms have remained unclear. Galectin-3 (Gal-3), a beta-galactoside-binding lectin, plays an important role in inflammation, fibrosis, and heart failure. We investigated here whether Gal-3 is involved in

  15. Treatment of chronic heart failure with aldosterone-blocking agents

    NARCIS (Netherlands)

    van Veldhuisen, Dirk J.; Swedberg, Karl

    Three large randomized trials in advanced heart failure (RALES), in heart failure after myocardial infarction (EPHESUS), and most recently mild heart failure (EMPHASIS-HF) have firmly established the place of aldosterone-blocking agents in patients with heart failure. In this paper we will shortly

  16. Update in diagnosis and management of primary aldosteronism.

    Science.gov (United States)

    Dick, Sofia M; Queiroz, Marina; Bernardi, Bárbara L; Dall'Agnol, Angélica; Brondani, Letícia A; Silveiro, Sandra P

    2018-02-23

    Primary aldosteronism (PA) is a group of disorders in which aldosterone is excessively produced. These disorders can lead to hypertension, hypokalemia, hypervolemia and metabolic alkalosis. The prevalence of PA ranges from 5% to 12% around the globe, and the most common causes are adrenal adenoma and adrenal hyperplasia. The importance of PA recognition arises from the fact that it can have a remarkably adverse cardiovascular and renal impact, which can even result in death. The aldosterone-to-renin ratio (ARR) is the election test for screening PA, and one of the confirmatory tests, such as oral sodium loading (OSL) or saline infusion test (SIT), is in general necessary to confirm the diagnosis. The distinction between adrenal hyperplasia (AH) or aldosterone-producing adenoma (APA) is essential to select the appropriate treatment. Therefore, in order to identify the subtype of PA, imaging exams such as computed tomography or magnetic ressonance imaging, and/or invasive investigation such as adrenal catheterization must be performed. According to the subtype of PA, optimal treatment - surgical for APA or pharmacological for AH, with drugs like spironolactone and amiloride - must be offered.

  17. Case detection and diagnosis of primary aldosteronism – The consensus of Taiwan Society of Aldosteronism

    Directory of Open Access Journals (Sweden)

    Vin-Cent Wu

    2017-12-01

    Full Text Available Background/Purpose: Even though the increasing clinical recognition of primary aldosteronism (PA as a public health issue, its heightened risk profiles and the availability of targeted surgical/medical treatment being more understood, consensus in its diagnosis and management based on medical evidence, while recognizing the constraints of our real-world clinical practice in Taiwan, has not been reached. Methods: The Taiwan Society of Aldosteronism (TSA Task Force acknowledges the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics into the management of PA. Results: When there is suspicion of PA, a plasma aldosterone to renin ratio (ARR should be obtained initially. Patients with abnormal ARR will undergo confirmatory laboratory and image tests. Subtype classification with adrenal venous sampling (AVS or NP-59 nuclear imaging, if AVS not available, to lateralize PA is recommended when patients are considered for adrenalectomy. The strengths and weaknesses of the currently available identification methods are discussed, focusing especially on result interpretation. Conclusion: With this consensus we hope to raise more awareness of PA among medical professionals and hypertensive patients in Taiwan, and to facilitate reconciliation of better detection, identification and treatment of patients with PA. Index words: Primary aldosteronism, Guideline, TAIPAI, TSA

  18. Clinical characteristics of aldosterone-producing microadenoma, macroadenoma, and idiopathic hyperaldosteronism in 93 patients with primary aldosteronism.

    Science.gov (United States)

    Omura, Masao; Sasano, Hironobu; Saito, Jun; Yamaguchi, Kunio; Kakuta, Yukio; Nishikawa, Tetsuo

    2006-11-01

    Primary aldosteronism (PA) due to aldosterone-producing adenoma (APA) is a form of surgically curable secondary hypertension, and distinguishing APA from idiopathic hyperaldosteronism (IHA) is important for treatment. We made a differential diagnosis between APA and IHA using imaging tests such as adrenal CT and MRI as well as adrenal venous sampling (AVS) in all 93 cases of PA presenting at our institutions over the last decade. We identified 27 patients with aldosterone-producing microadenoma (APmicroA), all of whom could be diagnosed by AVS but not by the imaging tests. Then, we compared the clinical and roent-genological findings of these 27 patients with those of 42 patients with aldosterone-producing macroadenoma (APmacroA) and of 24 patients with IHA. Using surgically removed adrenal tissues, histopathological examinations and immunohistochemical analyses of steroidogenic enzymes were conducted. The findings for APmicroA were similar to those for APmacroA, except with respect to the diameter of the adrenal adenomas. Endocrinological and roentgenological findings for APmicroA were similar to those for IHA, but not to those for APmacroA. The rate of cure of hypertension was much greater in patients with APmicroA than in patients with APmacroA after the unilateral adrenalectomy (odds ratio, 4.0; p=0.028). In conclusion, it is important to accurately diagnose APmicroA, in which the laterality of the hyperproduction of aldosterone is only detectable by AVS, and to treat these patients by unilateral adrenalectomy in order to avoid long-term medical treatment and prevent hypertensive vascular complications.

  19. Metoclopramide unmasks potentially misleading contralateral suppression in patients undergoing adrenal vein sampling for primary aldosteronism.

    Science.gov (United States)

    Rossitto, Giacomo; Miotto, Diego; Battistel, Michele; Barbiero, Giulio; Maiolino, Giuseppe; Bisogni, Valeria; Sanga, Viola; Rossi, Gian Paolo

    2016-11-01

    As metoclopramide stimulates aldosterone secretion, we tested its usefulness in the assessment of lateralization of primary aldosteronism by adrenal vein sampling (AVS). Prospective within-patient study in consecutive patients undergoing AVS for primary aldosteronism subtyping. We compared the diagnostic accuracy of baseline and postmetoclopramide lateralization index and relative (to cortisol) aldosterone secretion indices (RASI) for each adrenal gland with aldosterone-producing adenoma (APA) determined by the four corners criteria as the reference diagnosis. We recruited 93 consecutive patients (mean age: 52 years; women 31%). Metoclopramide increased plasma aldosterone in the inferior vena cava and in both adrenal veins. The postmetoclopramide lateralization index was accurate in identifying APA, but did not increase diagnostic accuracy over baseline lateralization index, because the RASI increased similarly in both sides. Conversely, metoclopramide raised RASI to values more than 0.90 bilaterally in non-APA patients allowing accurate identification of factitious aldosterone suppression. In contrast, RASI was 0.90 or less in 48% contralateral to the tumor in APA patients. Regression analysis showed the APA patients with persistent suppression of RASI contralaterally showed a more florid primary aldosteronism phenotype. Metoclopramide does not enhance lateralization of aldosterone excess in APA, but consistently increased the value of RASI in non-APA cases, thus unmasking potentially misleading suppression of aldosterone. Postmetoclopramide RASI may therefore allow a more precise diagnosis when AVS can be achieved only unilaterally.

  20. Analysis of postoperative biochemical values and clinical outcomes after adrenalectomy for primary aldosteronism.

    Science.gov (United States)

    Swearingen, Andrew J; Kahramangil, Bora; Monteiro, Rosebel; Krishnamurthy, Vikram; Jin, Judy; Shin, Joyce; Siperstein, Allan; Berber, Eren

    2018-04-01

    Primary aldosteronism causes hypertension and hypokalemia and is often surgically treatable. Diagnosis includes elevated plasma aldosterone, suppressed plasma renin activity, and elevated aldosterone renin ratio. Adrenalectomy improves hypertension and hypokalemia. Postoperative plasma aldosterone and plasma renin activity may be useful in documenting cure or failure. A retrospective analysis of patients who underwent adrenalectomy for primary aldosteronism from 2010 to 2016 was performed, analyzing preoperative and postoperative plasma aldosterone, plasma renin activity, hypertension, and hypokalemia. The utility of postoperative testing was assessed. Clinical cure was defined as improved hypertension control and resolution of potassium loss. Biochemical cure was defined as aldosterone renin ratio reduction to <23.6. Forty-four patients were included; 20 had plasma aldosterone and plasma renin activity checked on postoperative day 1. In the study, 40/44 (91%) were clinically cured. All clinical failures had of biochemical failure at follow-up. Postoperative day 1aldosterone renin ratio <23.6 had PPV of 95% for clinical cure. Cured patients had mean plasma aldosterone drop of 33.1 ng/dL on postoperative day 1; noncured patient experienced 3.9 ng/dL increase. A cutoff of plasma aldosterone decrease of 10 ng/dL had high positive predictive value for clinical cure. Changes in plasma aldosterone and plasma renin activity after adrenalectomy correlate with improved hypertension and hypokalemia. The biochemical impact of adrenalectomy manifests as early as postoperative day 1. We propose a plasma aldosterone decrease of 10 ng/dL as a criterion to predict clinical cure. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. A marked proportional rise in IVC aldosterone following cosyntropin administration during AVS is a signal to the presence of adrenal hyperplasia in primary aldosteronism.

    Science.gov (United States)

    Kline, G A; Pasieka, J L; Harvey, A; So, B; Dias, V C

    2014-05-01

    We hypothesized aldosteronoma responsiveness to cosyntropin may be a characterizing feature that could be determined in addition to standard adrenal vein sampling (AVS) data. We reviewed an AVS database from June 2005 to October 2011 including 65 patients with confirmed primary aldosteronism (PA) who underwent AVS and, if applicable, unilateral adrenalectomy. Patients were divided into confirmed lateralized and non-lateralized groups and subgrouped by histology. Plasma aldosterone in inferior vena cava (IVC) pre- and post-cosyntropin infusion during AVS was measured. Peak aldosterone and proportional change was compared between groups. Baseline and peak IVC aldosterone was higher in lateralized patients but incremental aldosterone rise was much greater in subjects with bilateral hyperplasia. From receiver operator characteristics (ROC) analysis, the optimized diagnostic cut point of peak IVC aldosterone of >649 pmol l(-1) would have a sensitivity of 94% for surgical disease although specificity of just 59%. A 250% increase in IVC aldosterone following cosyntropin would be specific enough to exclude 87% of surgical/lateralized disease. These diagnostic capabilities are similar to other results with non-AVS tests performed for diagnosis of lateralization. Although not specific enough to replace standard AVS interpretation, a marked IVC aldosterone increase after cosyntropin during AVS is a useful additional test to diagnose non-lateralizing forms of PA. Such a calculation requires no additional expense or tests.

  2. Decreased plasma prorenin levels in primary aldosteronism: potential diagnostic implications.

    Science.gov (United States)

    Berge, Constance; Courand, Pierre-Yves; Harbaoui, Brahim; Paget, Vinciane; Khettab, Fouad; Bricca, Giampiero; Fauvel, Jean-Pierre; Lantelme, Pierre

    2015-01-01

    Primary aldosteronism could exert a negative feedback on prorenin secretion, of possibly different magnitude, whether it is related to an aldosterone-producing adenoma (APA) or an idiopathic hyperaldosteronism (IHA). The objectives of this study were to evaluate the level of prorenin in three subgroups: APA, IHA, and essential hypertension; and the performance of the aldosterone-to-prorenin ratio (APR) for the diagnosis of an APA. Seven hundred and forty-six hypertensive patients with a standardized work-up, including a prorenin measurement, were considered. Ninety-six patients without neutral treatment and 38 patients with other forms of secondary hypertension were excluded. APA and IHA were categorized according to computed tomography scan, adrenal venous sampling, pathological analysis and improvement of hypertension after surgery. Thirty-five patients had a diagnosis of APA, 57 of IHA and 504 of essential hypertension. Prorenin was lower in APA and IHA than in essential hypertension (32.9, 40.4 and 50.3  pg/ml, respectively; P < 0.001). APR was higher in patients with APA and IHA than in those with essential hypertension (24.0, 11.8, and 4.0  pmol/l per pg/ml, respectively; P < 0.001). The APR was more discriminant than the aldosterone-to-renin ratio to identify APA compared to IHA (area under the receiver operating curve at 0.750 and 0.639, respectively; P = 0.04). The optimal cut-off values were 22  pmol/l per pg/ml for APR (sensitivity 57.0%, specificity 93.0%) and 440  pmol/l per pg/ml for aldosterone-to-renin ratio (sensitivity 54.3%, specificity 82.5%). Primary aldosteronism and particularly its most caricatural form, that is APA, seems associated with a lower level of prorenin than essential hypertension. The APR could be included in the diagnostic strategy of APA.

  3. Adrenal vein sampling in 22 patients with primary aldosteronism

    International Nuclear Information System (INIS)

    Kanamoto, Takaaki; Ueda, Hiroyuki; Hiraoka, Taizo; Ito, Hirofumi; Hayakawa, Katsumi; Chusho, Hideki; Yoshimasa, Takaaki; Tanikake, Masato

    2007-01-01

    We evaluated 22 patients who had been diagnosed with primary aldosteronism (PA) and undergone adrenal venous sampling (AVS) in our hospital. Blood sampling was technically successful in all patients and, in terms of results, endocrinologically successful in 20 and unsuccessful in 2. We achieved a success rate of over 90% by preoperatively confirming the vascular anatomy by multi detector row CT (MDCT), selecting a catheter suitable for insertion into the right adrenal vein, and using an extension tube for children at the time of sampling. Of the 14 patients diagnosed with aldosterone producing adenoma (APA) by AVS, 7 underwent adrenal adenomectomy, and achieved improvement in blood pressure and biochemical test results. Thus, AVS is useful for the diagnosis and treatment planning of PA, and the demand for it will grow in the future. (author)

  4. Raised Plasma Aldosterone and Natriuretic Peptides in Atrial Fibrillation

    DEFF Research Database (Denmark)

    Dixen, Ulrik; Ravn, Lasse Steen; Soeby-Rasmussen, Christian

    2006-01-01

    at follow-up, total duration of AF disease, ongoing medication, and the LVEF as explanatory variables showed that only ongoing treatment with diuretics was significantly associated (likelihood ratio test, p = 0.0057) with a raised log-transformed plasma aldosterone, although present AF at follow......-transformed plasma Nt-proANP. Likewise, present AF at follow-up (p = 0.0008) as well as age (p raised levels of Nt-proANP and Nt...

  5. Aldosterone and glomerular filtration--observations in the general population.

    Science.gov (United States)

    Hannemann, Anke; Rettig, Rainer; Dittmann, Kathleen; Völzke, Henry; Endlich, Karlhans; Nauck, Matthias; Wallaschofski, Henri

    2014-03-10

    Increasing evidence suggests that aldosterone promotes renal damage. Since data on the association between aldosterone and renal function in the general population are sparse, we chose to address this issue. We investigated the associations between the plasma aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) and the estimated glomerular filtration rate (eGFR) in a sample of adult men and women from Northeast Germany. A study population of 1921 adult men and women who participated in the first follow-up of the Study of Health in Pomerania was selected. None of the subjects used drugs that alter PAC or ARR. The eGFR was calculated according to the four-variable Modification of Diet in Renal Disease formula. Chronic kidney disease (CKD) was defined as an eGFR < 60 ml/min/1.73 m2. Linear regression models, adjusted for sex, age, waist circumference, diabetes mellitus, smoking status, systolic and diastolic blood pressures, serum triglyceride concentrations and time of blood sampling revealed inverse associations of PAC or ARR with eGFR (ß-coefficient for log-transformed PAC -3.12, p < 0.001; ß-coefficient for log-transformed ARR -3.36, p < 0.001). Logistic regression models revealed increased odds for CKD with increasing PAC (odds ratio for a one standard deviation increase in PAC: 1.35, 95% confidence interval: 1.06-1.71). There was no statistically significant association between ARR and CKD. Our study demonstrates that PAC and ARR are inversely associated with the glomerular filtration rate in the general population.

  6. Time-dependent aldosterone metabolism in toad urinary bladder

    International Nuclear Information System (INIS)

    Brem, A.S.; Pacholski, M.; Morris, D.J.

    1988-01-01

    Aldosterone (Aldo) metabolism was examined in the toad bladder. Bladders were incubated with [ 3 H]aldosterone (10(-7) M) for 5 h, 1 h, or 10 min. Tissues were analyzed for metabolites using high-pressure liquid chromatography (HPLC). In separate experiments, Na+ transport was assessed by the short-circuit current (SCC) technique. Following a 5-h tissue incubation, about 25% of the [ 3 H]-aldosterone was converted into metabolites including a polar monosulfate metabolite, 20 beta-dihydroaldo (20 beta-DHAldo), small quantities of 5 beta-reduced products, and a variety of 5 alpha-reduced Aldo products including 5 alpha-DHAldo, 3 alpha,5 alpha-tetrahydroaldo (3 alpha,5 alpha-THAldo), and 3 beta,5 alpha-THAldo. Tissues metabolized approximately 10% of the labeled hormone into the same compounds by 1 h. Measurable quantities of these metabolites were also synthesized by bladders exposed to Aldo for only 10 min and then incubated in buffer for an additional 50 min without Aldo. Bladders pretreated with the spironolactone, K+-canrenoate (3.5 X 10(-4) M), and stimulated with Aldo (10(-7) M) generated a peak SCC 44 +/- 6% of that observed in matched pairs stimulated with Aldo (P less than 0.001; n = 6). K+-canrenoate also markedly diminished [ 3 H]aldosterone metabolism at both 5 and 1 h. Thus, metabolic transformation of Aldo begins prior to hormone-induced increases in Na+ transport. Both the generation of certain metabolites (e.g., 5 alpha-reductase pathway products) and the increase in Na+ transport can be selectively inhibited by K+-canrenoate

  7. Bartter Syndrome with Normal Aldosterone Level: An Unusual Presentation.

    Science.gov (United States)

    Huque, S S; Rahman, M H; Khatun, S

    2016-04-01

    Bartter syndrome (BS) is a hereditary disease, with an autosomal recessive or autosomal dominant mode of transmission. It is characterized by salt wasting hypochloraemic, hypokalaemic metabolic alkalosis and hyperreninaemia with normal blood pressure. The primary defect is in the thick ascending limb of loop of Henle (TAL). Herein, we report a case that had typical features of BS like severe dehydration, severe hypokalaemia, metabolic alkalosis and failure to thrive but had normal aldosterone level which is very uncommon.

  8. 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.

  9. 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

  10. Captopril suppression: limitations for confirmation of primary aldosteronism.

    Science.gov (United States)

    Westerdahl, Christina; Bergenfelz, Anders; Isaksson, Anders; Valdemarsson, Stig

    2011-09-01

    The aldosterone/renin ratio (ARR) is the first line screening test for primary aldosteronism (PA). However, in hypertensive patients with an increased ARR, PA needs to be confirmed by other means. A 25 mg oral captopril test was performed in 16 healthy subjects to obtain reference values for aldosterone and ARR at 120 minutes after the test. Subsequently these data were applied to 46 hypertensive patients screened for PA with an increased ARR. At 120 minutes after the captopril test ARR decreased in healthy subjects within a narrow range, but remained high in patients with PA and in patients with primary hypertension, especially for those with low renin characteristics. At 120 minutes after captopril, the range of ARR in primary hypertensive patients overlapped in 88% of the cases with the range of the ARR in the PA patients. Sensitivity and specificity of basal ARR and ARR after the captopril test to diagnose PA, calculated as receiver operator characteristics, showed an area under the curve of 0.595 for basal ARR and 0.664 for ARR at 120 minutes after the test. The ARR at 120 minutes after the captopril test is only marginally better than basal ARR in diagnosing PA in hypertensive patients screened with an increased ARR. Owing to an overall limited capacity to clearly discriminate PA from primary hypertension, the test could not therefore be recommended for the confirmatory diagnosis of PA.

  11. Malignant hypertension and hypertensive encephalopathy in primary aldosteronism caused by adrenal adenoma

    Directory of Open Access Journals (Sweden)

    Bortolotto Luiz Aparecido

    2003-01-01

    Full Text Available Two cases are reported as follows: 1 1 female patient with accelerated-malignant hypertension secondary to an aldosterone-producing adrenal adenoma; and 2 1 female patient with adrenal adenoma, severe hypertension, and hypertensive encephalopathy. This association is a rare clinical finding, and malignant hypertension may modify the hormonal characteristic of primary aldosteronism, making its diagnosis more difficult. The diagnosis of primary aldosteronism should be considered in patients with malignant hypertension or hypertensive encephalopathy if persistent hypokalemia occurs. Identification of primary aldosteronism is of paramount importance for the patient's evolution, because the surgical treatment makes the prognosis more favorable.

  12. Aldosterone-induced signalling and cation transport in the distal nephron.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2008-10-01

    Aldosterone is an important regulator of Na(+) and K(+) transport in the distal nephron modulating the surface expression of transporters through the action of the mineralocorticoid receptor as a ligand-dependent transcription factor. Aldosterone stimulates the rapid activation of protein kinase-based signalling cascades that modulate the genomic effects of the hormone. Evidence is accumulating about the multi-factorial regulation of the epithelial sodium channel (ENaC) by aldosterone. Recent published data suggests that the activation of a novel PKC\\/PKD signalling pathway through the c-Src-dependent trans-activation of epidermal growth factor receptor contributes to early ENaC trafficking in response to aldosterone.

  13. 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.

  14. Body mass index predicts aldosterone production in normotensive adults on a high-salt diet.

    Science.gov (United States)

    Bentley-Lewis, Rhonda; Adler, Gail K; Perlstein, Todd; Seely, Ellen W; Hopkins, Paul N; Williams, Gordon H; Garg, Rajesh

    2007-11-01

    The mechanisms underlying obesity-mediated cardiovascular disease are not fully understood. Aldosterone and insulin resistance both are associated with obesity and cardiovascular disease. The objectives of this study were to test the hypotheses that aldosterone production is elevated and associated with insulin resistance in overweight adults on a high-sodium diet. Healthy normotensive adults were categorized as lean body mass index (BMI) less than 25 kg/m(2) (n = 63) or overweight BMI 25 kg/m(2) or greater (n = 57). After 7 d of a high-sodium diet, participants fasted overnight and remained supine throughout hemodynamic and laboratory assessments and angiotensin II (AngII) stimulation. The overweight group, compared with the lean group, had higher 24-h urinary aldosterone (9.0 +/- 0.8 vs. 6.6 +/- 0.5 microg per 24 h; P = 0.003) and higher AngII-stimulated serum aldosterone (11.4 +/- 1.0 vs. 9.0 +/- 0.6 ng/dl; P = 0.04). There were no differences in 24-h urinary cortisol or sodium or supine measurements of plasma renin activity, serum aldosterone, or serum potassium. The homeostasis model assessment of insulin resistance was predicted by urinary aldosterone excretion (r = 0.32, P = 0.03) and serum aldosterone response to AngII stimulation (r = 0.28, P = 0.02) independent of age and BMI. Urinary aldosterone excretion and AngII-stimulated aldosterone are increased in overweight, compared with lean, normotensive adults. The correlation of these measures of aldosterone production with insulin resistance suggests a potential role for aldosterone in the pathophysiology of obesity-mediated insulin resistance.

  15. New Sides of Aldosterone Action in Cardiovascular System as Potential Targets for Therapeutic Intervention.

    Science.gov (United States)

    Kolodziejczyk, Patrycjusz; Gromotowicz-Poplawska, Anna; Aleksiejczuk, Michal; Chabielska, Ewa; Tutka, Piotr; Miltyk, Wojciech

    2018-03-26

    Aldosterone, the main mineralocorticoid hormone, plays a crucial role in the regulation of electrolyte homeostasis and blood pressure. Although, this role is undoubtedly important, it is not a hormonal action that attracts the most attention. Aldosterone seems to be very important important as a local messenger in the pathology of cardiovascular diseases (CVD). In the last few years, the attention was focused on the correlation between raised aldosterone level and increased risk of cardiovascular events. It has been demonstrated that aldosterone contributes to fibrosis, inflammation, endothelial dysfunction, fibrinolytic disordes, and oxidative stress leading to CVD development and progression. It used to be thought that the effects of aldosterone are mediated via classic nuclear receptors - mineralocorticoid receptors (MR). Now we know that the mechanism of aldosterone action in cardiovascular system is much more complex, since experimental and clinical studies indicate that MR blockade may be not sufficient to abolish aldosterone-incuced harmful effects in the cardiovascular system. Therefore, the involvement of some other than MR, receptors and factors is suggested. Moreover, in addition to the generally known genomic action of aldosterone, which involves MR activation, the nongenomic pathways are postulated in the mode of hormone action. More and more attention is focused on the membrane-coupled receptors, which mediate the rapid effects of aldosterone and have been already confirmed in different cells and tissues of a cardiovascular system. The confirmation of multiple mechanisms of aldosterone action opens a new perspective for more effective therapeutic intervention in aldosterone-related CVD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Rapid Induction of Aldosterone Synthesis in Cultured Neonatal Rat Cardiomyocytes under High Glucose Conditions

    Directory of Open Access Journals (Sweden)

    Masami Fujisaki

    2013-01-01

    Full Text Available In addition to classical adrenal cortical biosynthetic pathway, there is increasing evidence that aldosterone is produced in extra-adrenal tissues. Although we previously reported aldosterone production in the heart, the concept of cardiac aldosterone synthesis remains controversial. This is partly due to lack of established experimental models representing aldosterone synthase (CYP11B2 expression in robustly reproducible fashion. We herein investigated suitable conditions in neonatal rat cardiomyocytes (NRCMs culture system producing CYP11B2 with considerable efficacy. NRCMs were cultured with various glucose doses for 2–24 hours. CYP11B2 mRNA expression and aldosterone concentrations secreted from NRCMs were determined using real-time PCR and enzyme immunoassay, respectively. We found that suitable conditions for CYP11B2 induction included four-hour incubation with high glucose conditions. Under these particular conditions, CYP11B2 expression, in accordance with aldosterone secretion, was significantly increased compared to those observed in the cells cultured under standard-glucose condition. Angiotensin II receptor blocker partially inhibited this CYP11B2 induction, suggesting that there is local renin-angiotensin-aldosterone system activation under high glucose conditions. The suitable conditions for CYP11B2 induction in NRCMs culture system are now clarified: high-glucose conditions with relatively brief period of culture promote CYP11B2 expression in cardiomyocytes. The current system will help to accelerate further progress in research on cardiac tissue aldosterone synthesis.

  17. Special problems in the radioimmunoassay of plasma aldosterone without prior extraction and purification

    International Nuclear Information System (INIS)

    Pratt, J.J.; Boonman, R.; Woldring, M.G.; Donker, A.J.M.

    1978-01-01

    A new method for the radioimmunoassay of plasma aldosterone is described. The assay is performed directly on plasma without extracting or purifying the aldosterone. The method fulfilled the usual requirements for the demonstration of accuracy. Extensive data on the properties of the antisera are given. (Auth.)

  18. 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

  19. Disparate effects of eplerenone, amlodipine and telmisartan on podocyte injury in aldosterone-infused rats

    NARCIS (Netherlands)

    Liang, Wei; Chen, Cheng; Shi, Jing; Ren, Zhilong; Hu, Fengqi; van Goor, Harry; Singhal, Pravin C.; Ding, Guohua

    Background. Several studies in patients with primary aldosteronism (PA) have suggested that aldosterone (ALD) is directly contributing to albuminuria. However, there are limited data pertaining to the direct role of ALD in (EPL), telmisartan (TEL) and amlodipine (AML) on ALD-induced renal structural

  20. Aldosterone dysregulation with aging predicts renal vascular function and cardiovascular risk.

    Science.gov (United States)

    Brown, Jenifer M; Underwood, Patricia C; Ferri, Claudio; Hopkins, Paul N; Williams, Gordon H; Adler, Gail K; Vaidya, Anand

    2014-06-01

    Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal vascular and cardiovascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1124 visits) in the General Clinical Research Center. Aldosterone regulation was characterized by the ratio of maximal suppression to stimulation (supine serum aldosterone on a liberal sodium diet divided by the same measure on a restricted sodium diet). We previously demonstrated that higher levels of this Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation. Renal plasma flow (RPF) was determined via p-aminohippurate clearance to assess basal renal hemodynamics and the renal vascular responses to dietary sodium manipulation and angiotensin II infusion. Cardiovascular risk was calculated using the Framingham Risk Score. In univariate linear regression, older age (β=-4.60; Page and SASSI, where the inverse relationship between SASSI and RPF was most apparent with older age (Page may interact to mediate renal vascular disease. Our findings suggest that the combination of aldosterone dysregulation and renal vascular dysfunction could additively increase the risk of future cardiovascular outcomes; therefore, aldosterone dysregulation may represent a modifiable mechanism of age-related vascular disease.

  1. Evaluation of radioimmunological methods for assay of plasma and urinary aldosterone

    International Nuclear Information System (INIS)

    Pakarinen, A.; Koskinen, L.; Adlercreutz, H.

    1976-01-01

    Two radioimmunological methods for assay of plasma and urinary aldosterone were carefully evaluated. In the plasma method a radioimmunoassay is preceded by chromatography on a Sephadex LH-20 column. The method for urine includes a preextraction, hydrolysis of the acid-labile conjugates of aldosterone, and a radioimmunoassay. Both methods fulfill the criteria of reliability and are suitable for both routine and demanding research assays. The plasma method, using columns of double length is also applicable to analysis of aldosterone on plasma of newborn children, and pregnant females and in cord plasma. The concentration of plasma aldosterone in healthy subjects on an ad lib salt diet was 162 π+ 93 (S.D.) pmol/l in the supine position and 312 π+ 217 (S.D.) pmol/l upright. The urinary excretion of aldosterone in healthy subjects was 28.3 π+ 16.7 (S.D.) nmol/24 h. (Auth.)

  2. Radioimmunoassay of aldosterone in adrenal venous effluent in a case of Conn's syndrome, ch. 5a

    International Nuclear Information System (INIS)

    Froelich, M.; Bruning, P.F.; Moolenaar, A.J.

    1977-01-01

    In a case of Conn's syndrome samples were obtained from the venous effluent of both adrenals and from peripheral veins during venography. The aldosterone concentration was measured by means of radioimmunoassay. The sensitivty of the aldosterone assay was 27 pg (P<0.05), the parallelism between the standard and the serum dilutions was excellent and there was no cross-reaction with cortisol, cortisone, 21-desoxycortisol, dexamethasone or spironolactone in amounts up to 1 μg per incubation. The aldosterone concentrations measured in peripheral venous blood were 220-250 ng/100 ml serum. In the effluent of the left adrenal, in which an aldosterone producing tumor was localized, an aldosterone level of 8480 ng/100 ml serum was estimated

  3. [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.

  4. Non-genomic actions of aldosterone: From receptors and signals to membrane targets.

    LENUS (Irish Health Repository)

    2012-02-01

    In tissues which express the mineralocorticoid receptor (MR), aldosterone modulates the expression of membrane targets such as the subunits of the epithelial Na(+) channel, in combination with important signalling intermediates such as serum and glucocorticoid-regulated kinase-1. In addition, the rapid \\'non-genomic\\' activation of protein kinases and secondary messenger signalling cascades has also been detected in aldosterone-sensitive tissues of the nephron, distal colon and cardiovascular system. These rapid actions are variously described as being coupled to MR or to an as yet unidentified, membrane-associated aldosterone receptor. The rapidly activated signalling cascades add a level of fine-tuning to the activity of aldosterone-responsive membrane transporters and also modulate the aldosterone-induced changes in gene expression through receptor and transcription factor phosphorylation.

  5. Non-genomic actions of aldosterone: From receptors and signals to membrane targets.

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2011-07-26

    In tissues which express the mineralocorticoid receptor (MR), aldosterone modulates the expression of membrane targets such as the subunits of the epithelial Na(+) channel, in combination with important signalling intermediates such as serum and glucocorticoid-regulated kinase-1. In addition, the rapid \\'non-genomic\\' activation of protein kinases and secondary messenger signalling cascades has also been detected in aldosterone-sensitive tissues of the nephron, distal colon and cardiovascular system. These rapid actions are variously described as being coupled to MR or to an as yet unidentified, membrane-associated aldosterone receptor. The rapidly activated signalling cascades add a level of fine-tuning to the activity of aldosterone-responsive membrane transporters and also modulate the aldosterone-induced changes in gene expression through receptor and transcription factor phosphorylation.

  6. Discordance between imaging and immunohistochemistry in unilateral primary aldosteronism.

    Science.gov (United States)

    Nanba, Aya T; Nanba, Kazutaka; Byrd, James B; Shields, James J; Giordano, Thomas J; Miller, Barbara S; Rainey, William E; Auchus, Richard J; Turcu, Adina F

    2017-12-01

    Correct subtyping of primary aldosteronism (PA) is essential for good surgical outcomes. Adrenal vein sampling (AVS) and/or computed tomography (CT) are used for PA subclassification. Clinical and/or biochemical improvement after surgery, however, is not always achieved in patients with presumed unilateral PA. We aimed to identify the pitfalls in PA subclassification leading to surgical treatment failures. We retrospectively studied 208 patients who underwent adrenal vein sampling (AVS) for PA subclassification in a tertiary referral centre, between January 2009 and August 2016. Simultaneous bilateral AVS was performed before and after cosyntropin administration. We implemented immunohistochemistry for aldosterone synthase (CYP11B2) and 17α-hydroxylase/17,20 lyase (CYP17A1) in adrenal glands resected from patients without improvement of PA after surgical treatment and from those with limitations in AVS interpretation. Of 55 patients who underwent adrenalectomy, three (5.5%) had no improvement of PA. All three patients underwent partial adrenalectomy to remove a CT-detected nodule present on the same side with AVS lateralization. Immunohistochemistry revealed a CYP11B2-negative nodule in both cases available. All patients who underwent total adrenalectomy based on AVS lateralization benefitted from surgery, including three patients with unilateral unsuccessful AVS and aldosterone suppression in the catheterized side vs inferior vena cava. Radiographically identified adrenal nodules are not always a source of PA, even when ipsilateral with AVS lateralization. These data caution against reliance on imaging findings, either alone or in conjunction with AVS, to guide surgery for PA. © 2017 John Wiley & Sons Ltd.

  7. Obesity-stimulated aldosterone release is not related to an S1P-dependent mechanism.

    Science.gov (United States)

    Werth, Stephan; Müller-Fielitz, Helge; Raasch, Walter

    2017-12-01

    Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phosphate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists. In vivo release of S1P (100-300 µg/kg bw ) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHRs), as well as in lean or obese Zucker rats. Aldosterone secretion was increased in NCI H295R cells by S1P, the selective S1PR1 agonist SEW2871 and the selective S1PR2 antagonist JTE013. Treatment with the S1PR1 antagonist W146 or fingolimod and the S1PR1/3 antagonist VPbib2319 decreased baseline and/or S1P-stimulated aldosterone release. Compared to saline-treated SD rats, plasma aldosterone increased by ~50 pg/mL after infusing S1P. Baseline levels of S1P and aldosterone were higher in obese than in lean SHRs. Adrenal S1PR expression did not differ between chow- or CD-fed rats that had the highest S1PR1 and lowest S1PR4 levels. S1P induced a short-lasting increase in plasma aldosterone in obese, but not in lean SHRs. However, 2-ANOVA did not demonstrate any difference between lean and obese rats. S1P-induced aldosterone release was also similar between obese and lean Zucker rats. We conclude that S1P is a local regulator of aldosterone production. S1PR1 agonism induces an increase in aldosterone secretion, while stimulating adrenal S1PR2 receptor suppresses aldosterone production. A significant role of S1P in influencing aldosterone secretion in states of obesity seems unlikely. © 2017 Society for Endocrinology.

  8. Hypertension in the course of primary aldosteronism during pregnancy

    Directory of Open Access Journals (Sweden)

    Magdalena Wyskida

    2015-02-01

    Full Text Available Hypertension is one of the most common cardiovascular diseases during pregnancy. Primary hyperaldosteronism (PHA is the most frequent endocrinological, secondary cause of hypertension, rarely diagnosed in pregnant women. In the available literature about 50 cases of PHA in pregnant women have been described. PHA is often a cause of resistant hypertension. PHA can cause life-threatening complications both for the pregnant woman and the fetus. Diagnosis of PHA in pregnancy is difficult due to the antagonistic effect of progesterone on aldosterone, physiological increase of aldosterone release during gestation and frequent normokalaemic clinical course. Typical pharmacological treatment of PHA is limited due to the anti‑androgenic effect of spironolactone, lack of data concerning the safety of eplerenone and limited access to amiloride in Poland. Surgical treatment is a therapeutic option only in early pregnancy. This paper presents the current state of knowledge on diagnostic methods and treatment of PHA in pregnant women and a systematic review of cases described in the literature.

  9. 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.

  10. Localization of aldosterone and corticosterone in the central nervous system, assessed by quantitative autoradiography

    International Nuclear Information System (INIS)

    Birmingham, M.K.; Sar, M.; Stumpf, W.E.

    1984-01-01

    Nuclear localization of tritiated aldosterone in the CNS was studied in rats by numerical evaluation of silver grains, deposited over neuronal cell nuclei in thaw-mounted autoradiograms, and compared with the localization obtained after prior administration of a 100-fold excess of radioinert aldosterone, corticosterone or 18-hydroxy-11-deoxycorticosterone (18-OH-DOC). Corticosterone and 18-OH-DOC completely prevented nuclear localization in most regions examined. However, in contrast to pretreatment with aldosterone, pretreatment with corticosterone and 18-OH-DOC did not completely prevent the concentration of radioactivity in the cell nuclei of the indusium griseum. Traces of radioactivity were, furthermore, retained in areas CA1 and CA2 and the dentate gyrus in rats exposed to corticosterone, but not to 18-OH-DOC, prior to [ 3 H]aldosterone. A similar profile of silver grain distribution to that noted with aldosterone was found for corticosterone except that with tritiated corticosterone the most intense concentration of radioactivity occurred in hippocampal areas CA1 and CA2 and not in the indusium griseum. The authors conclude that (1) a receptor readily shared by aldosterone, corticosterone, 18-OH-DOC and DOC, but not by dihydrotestosterone, is widely distributed throughout the CNS, (2) a receptor shared by aldosterone and 18-OH-DOC, but not by corticosterone may be present in hippocampal areas CA1 and CA2, (3) that both these as well as the receptor accepting dihydrotestosterone can be located within the same cell

  11. Plasma aldosterone and CT findings in head injury, especially in acute subdural hematoma

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Hideaki

    1988-12-01

    As we have already reported, an increase in the plasma aldosterone level was regulary found after severe head injury. And the values of plasma aldosterone in unconscious patients with increased intracranial pressure were significantly higher than those in patients without unconsciousness. Thus, plasma aldosterone in acute phase of head injury seems to be a sensitive index of increased intracranial pressure. In the present study, we measured plasma aldosterone levels in three groups ; subdural hematoma with mid-line shift (group A), cerebral contusion without mid-line shift (group B) and cerebral conceussion (group C). In group A, the peak value of aldosterone was markedly high (283.9 +- 142.5). In B, the peak value (143.7 +- 27.8) was higher than in C (116.3 +- 35.0). And, correlation between the serum aldosterone levels and CT findings, especially the mid-line shift was found. As a conclusion, the serum levels of aldosterone seems to be associated with intracranial pressure.

  12. Normotensive blood pressure in pregnancy: the role of salt and aldosterone.

    Science.gov (United States)

    Gennari-Moser, Carine; Escher, Geneviève; Kramer, Simea; Dick, Bernhard; Eisele, Nicole; Baumann, Marc; Raio, Luigi; Frey, Felix J; Surbek, Daniel; Mohaupt, Markus G

    2014-02-01

    A successful pregnancy requires an accommodating environment. Salt and water availability are critical for plasma volume expansion. Any changes in sodium intake would alter aldosterone, a hormone previously described beneficial in pregnancy. To date, it remains ambiguous whether high aldosterone or high salt intake is preferable. We hypothesized that increased aldosterone is a rescue mechanism and appropriate salt availability is equally effective in maintaining a normotensive blood pressure (BP) phenotype in pregnancy. We compared normotensive pregnant women (n=31) throughout pregnancy with young healthy female individuals (n=31-62) and performed salt sensitivity testing within the first trimester. Suppression of urinary tetrahydro-aldosterone levels by salt intake as measured by gas chromatography-mass spectrometry and urinary sodium excretion corrected for creatinine, respectively, was shifted toward a higher salt intake in pregnancy (Ppregnancy, neither high urinary tetrahydro-aldosterone nor sodium excretion was correlated with higher BP. In contrast, in nonpregnant women, systolic BP rose with aldosterone (Ppregnancy without causing aldosterone-induced hypertension. Second, salt seems to aid in BP lowering in pregnancy for reasons incompletely elucidated, yet involving renin suppression and potentially placental sensing mechanisms. Further research should identify susceptible individuals and clarify effector mechanisms.

  13. Aldosterone hypersecretion in “non-salt-losing” congenital adrenal hyperplasia

    Science.gov (United States)

    Bartter, Frederic C.; Henkin, Robert I.; Bryan, George T.

    1968-01-01

    Patients with the “non-salt-losing” form of the adrenogenital syndrome were studied before and after suppression of adrenal cortical activity with carbohydrate-active steroids. The response of aldosterone secretion to sodium deprivation was measured; in some patients response to adrenocorticotropic hormone (ACTH) was measured as well. The aldosterone secretion was normal and responded normally to sodium deprivation in all patients studied during suppression with carbohydrate-active steroids. This finding suggests that 21-hydroxylation of progesterone is normal in this syndrome. The sole abnormality in the production of aldosterone in these patients was found to be excessive secretion of aldosterone while they were not receiving suppressive doses of carbohydrate-active steroids. This finding strongly supports the view that the biogenetic pathways through which aldosterone is produced from progesterone are intact in this syndrome. No patient showed hypertension or hypokalemic alkalosis despite very high aldosterone secretion rates. This observation suggests that the hyper-aldosteronism is secondary to a tendency to sodium loss in the patient whose ACTH production is not suppressed. These studies provide additional evidence in support of the hypothesis that the salt-losing and “non-salt-losing” forms of adrenogenital syndrome are genetically and biochemically distinct. PMID:4299011

  14. Aldosterone down-regulates the slowly activated delayed rectifier potassium current in adult guinea pig cardiomyocytes.

    Science.gov (United States)

    Lv, Yankun; Bai, Song; Zhang, Hua; Zhang, Hongxue; Meng, Jing; Li, Li; Xu, Yanfang

    2015-12-01

    There is emerging evidence that the mineralocorticoid hormone aldosterone is associated with arrhythmias in cardiovascular disease. However, the effect of aldosterone on the slowly activated delayed rectifier potassium current (IK s ) remains poorly understood. The present study was designed to investigate the modulation of IK s by aldosterone. Adult guinea pigs were treated with aldosterone for 28 days via osmotic pumps. Standard glass microelectrode recordings and whole-cell patch-clamp techniques were used to record action potentials in papillary muscles and IK s in ventricular cardiomyocytes. The aldosterone-treated animals exhibited a prolongation of the QT interval and action potential duration with a higher incidence of early afterdepolarizations. Patch-clamp recordings showed a significant down-regulation of IK s density in the ventricular myocytes of these treated animals. These aldosterone-induced electrophysiological changes were fully prevented by a combined treatment with spironolactone, a mineralocorticoid receptor (MR) antagonist. In addition, in in vitro cultured ventricular cardiomyocytes, treatment with aldosterone (sustained exposure for 24 h) decreased the IK s density in a concentration-dependent manner. Furthermore, a significant corresponding reduction in the mRNA/protein expression of IKs channel pore and auxiliary subunits, KCNQ1 and KCNE1 was detected in ventricular tissue from the aldosterone-treated animals. Aldosterone down-regulates IK s by inhibiting the expression of KCNQ1 and KCNE1, thus delaying the ventricular repolarization. These results provide new insights into the mechanism underlying K(+) channel remodelling in heart disease and may explain the highly beneficial effects of MR antagonists in HF. © 2015 The British Pharmacological Society.

  15. Oxygen sensitivity of potassium- and angiotensin II-stimulated aldosterone release by bovine adrenal cells.

    Science.gov (United States)

    Brickner, R C; Raff, H

    1991-04-01

    Angiotensin II (AII) and extracellular K+, acting through different intracellular mechanisms, stimulate aldosterone release in a synergistic fashion. We have previously shown that decreases in oxygen (O2) within the physiological range inhibit AII, cyclic AMP (cAMP) and ACTH-stimulated aldosterone release. The present experiment evaluated the effect of various concentrations of O2 on K+-stimulated aldosterone release in the presence and absence of AII. Dispersed bovine adrenal glomerulosa cells were incubated with different concentrations of K+ (0.9-5.4 mmol/l) without and with AII (10 nmol/l) under different concentrations of O2 (0, 5 or 50%); 21% O2 (pO2 = 19.9 +/- 0.5 kPa,n = 9) was used as reference control for comparison. In all cases, increases in K+ stimulated aldosterone release, an effect augmented by AII. Under 0% O2 (pO2 = 8.1 +/- 0.3 kPa, n = 3) and 5% O2 (pO2 = 12.8 +/- 0.5 kPa, n = 3), aldosterone release stimulated by K+ or K+/AII was significantly inhibited compared with that under 21% O2. Conversely, under 50% O2 (pO2 = 36.3 +/- 2.5 kPa, n = 3), aldosterone release stimulated by K+ or K+/AII was significantly augmented. Cortisol secretion was not significantly affected by 5% or 50% O2 but was significantly decreased under 0% O2. The effect of O2 on K+/AII stimulation of aldosterone release, as well as previous experiments with cAMP, progesterone and ACTH, suggest a final common post-receptor oxygen-sensitive component of the aldosterone synthetic pathway. It is suggested that one or more enzymes in the aldosterone synthetic pathway is/are exquisitely sensitive to small changes in O2 within the physiological range.

  16. Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney

    Energy Technology Data Exchange (ETDEWEB)

    Sheng, Lili; Yang, Min; Ding, Wei [Department of Nephrology, Shanghai Fifth People' s Hospital, Fudan University, Shanghai 200240 (China); Zhang, Minmin [Department of Nephrology, Shanghai Huashan Hospital, Fudan University, Shanghai 200240 (China); Niu, Jianying [Department of Nephrology, Shanghai Fifth People' s Hospital, Fudan University, Shanghai 200240 (China); Qiao, Zhongdong [School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China); Gu, Yong, E-mail: yonggu@vip.163.com [Department of Nephrology, Shanghai Fifth People' s Hospital, Fudan University, Shanghai 200240 (China); Department of Nephrology, Shanghai Huashan Hospital, Fudan University, Shanghai 200240 (China)

    2016-08-01

    Aldosterone has been recognized as a risk factor for the development of chronic kidney disease (CKD). Studies have indicated that enhanced activation of epidermal growth factor receptor (EGFR) is associated with the development and progression of renal fibrosis. But if EGFR is involved in aldosterone-induced renal fibrosis is less investigated. In the present study, we examined the effect of erlotinib, an inhibitor of EGFR tyrosine kinase activity, on the progression of aldosterone-induced renal profibrotic responses in a murine model underwent uninephrectomy. Erlotinib-treated rats exhibited relieved structural lesion comparing with rats treated with aldosterone alone, as characterized by glomerular hypertrophy, mesangial cell proliferation and expansion. Also, erlotinib inhibited the expression of TGF-β, α-SMA and mesangial matrix proteins such as collagen Ⅳ and fibronectin. In cultured mesangial cells, inhibition of EGFR also abrogated aldosterone-induced expression of extracellular matrix proteins, cell proliferation and migration. We also demonstrated that aldosterone induced the phosphorylation of EGFR through generation of ROS. And the activation of EGFR resulted in the phosphorylation of ERK1/2, leading to the activation of profibrotic pathways. Taken together, we concluded that aldosterone-mediated tissue fibrosis relies on ROS induced EGFR/ERK activation, highlighting EGFR as a potential therapeutic target for modulating renal fibrosis. - Highlights: • EGFR was involved in aldosterone-induced renal profibrotic responses. • Aldosterone-induced EGFR activation was mediated by MR-dependent ROS generation. • EGFR activated the MAPK/ERK1/2 signaling to promote renal fibrosis.

  17. Localisation and characteristics of bond sites of aldosterone along the nephron of an amphibian: Xenopus laevis

    International Nuclear Information System (INIS)

    Gnionsahe, Daze Apollinaire

    1986-01-01

    The author reports an academic work which aimed at determining characteristics of the aldosterone bond along the kidney nephron of the Xenopus laevis by using auto-radiography on isolated tubular segments. The objective was to highlight tubular segments at the origin of A6 cells by comparing aldosterone bond characteristics in these cells and in different tubular segments of the kidney. Besides, the author compared the bond distribution between the two aldosterone bond sites: the high affinity type I bond site (so-called mineralocorticoids), and low affinity type II bond site (so-called glucocorticoids)

  18. A direct radio-immunoassay for plasma aldosterone: significance of endogenous cortisol

    International Nuclear Information System (INIS)

    Man, A.J.M. de; Hofman, J.A.; Hendriks, Th.; Rosmalen, F.M.A.; Ross, H.A.; Benraad, Th.J.

    1980-01-01

    A direct radio-immunoassay for plasma aldosterone was developed, using a highly specific antiserum raised in sheep. An excellent correlation was observed between its results and the levels measured after extraction and chromatography. The necessity of including a blocking agent to inhibit the binding of aldosterone to plasma proteins was investigated. It was found that in low-cortisol ( 10 μg/100 ml) the final assay result was independent of the presence of ANS. The effect of cortisol was interpreted in terms of its influence on aldosterone binding to plasma proteins in the absence of a blocking agent. (Auth.)

  19. Clinical outcomes following unilateral adrenalectomy in patients with primary aldosteronism.

    Science.gov (United States)

    Hannon, M J; Sze, W C; Carpenter, R; Parvanta, L; Matson, M; Sahdev, A; Druce, M R; Berney, D M; Waterhouse, M; Akker, S A; Drake, W M

    2017-05-01

    In approximately half of cases of primary aldosteronism (PA), the cause is a surgically-resectable unilateral aldosterone-producing adrenal adenoma. However, long-term data on surgical outcomes are sparse. We report on clinical outcomes post-adrenalectomy in a cohort of patients with PA who underwent surgery. Retrospective review of patients treated for PA in a single UK tertiary centre. Of 120 consecutive patients investigated for PA, 52 (30 male, median age 54, range 30-74) underwent unilateral complete adrenalectomy. Blood pressure, number of antihypertensive medications, and serum potassium were recorded before adrenalectomy, and after a median follow-up period of 50 months (range 7-115). Recumbent renin and aldosterone were measured, in the absence of interfering antihypertensive medication, ≥3months after surgery, to determine if PA had been biochemically cured. Overall, blood pressure improved from a median (range) 160/95 mmHg (120/80-250/150) pre-operatively to 130/80 mmHg (110/70-160/93), P < 0.0001. 24/52 patients (46.2%) had cured hypertension, with a normal blood pressure post-operatively on no medication. 26/52 (50%) had improved hypertension. 2/52 patients (3.8%) showed no improvement in blood pressure post-operatively. Median (range) serum potassium level increased from 3.2 (2.3-4.7) mmol/l pre-operatively to 4.4 mmol/l (3.3-5.3) post-operatively, P < 0.0001). Median (range) number of antihypertensive medications used fell from 3 (0-6) pre- to 1 post-operatively (range 0-4), P < 0.0001. Unilateral adrenalectomy provides excellent long-term improvements in blood pressure control, polypharmacy and hypokalaemia in patients with lateralizing PA. These data may help inform discussions with patients contemplating surgery. © The Author 2016. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  20. 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

  1. Expression of Angiotensin II and Aldosterone in Radiation-induced Lung Injury.

    Science.gov (United States)

    Cao, Shuo; Wu, Rong

    2012-12-01

    Radiation-induced lung injury (RILI) is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILI was studied. Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentrations of TGF-β1, angiotensin II, and aldosterone were determined via enzyme-linked immunosorbent assay. Statistical differences were observed in the expression levels of angiotensin II and aldosterone between the non-irradiation and irradiation groups. Moreover, the expression level of the angiotensin II-aldosterone system increased with increasing doses, and the difference was still observed as time progressed. Angiotensin II-aldosterone system has an important pathophysiological function in the progression of RILI.

  2. Expression of Angiotensin II and Aldosterone in Radiation-induced Lung Injury

    International Nuclear Information System (INIS)

    Cao, Shuo; Wu, Rong

    2012-01-01

    Radiation-induced lung injury (RILI) is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILI was studied. Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentrations of TGF-β1, angiotensin II, and aldosterone were determined via enzyme-linked immunosorbent assay. Statistical differences were observed in the expression levels of angiotensin II and aldosterone between the non-irradiation and irradiation groups. Moreover, the expression level of the angiotensin II-aldosterone system increased with increasing doses, and the difference was still observed as time progressed. Angiotensin II-aldosterone system has an important pathophysiological function in the progression of RILI

  3. 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

  4. A case of primary aldosteronism combined with acquired nephrogenic diabetes insipidus

    Directory of Open Access Journals (Sweden)

    Kitae Kim

    2014-12-01

    Full Text Available Aldosterone-producing adrenal adenoma can induce various clinical manifestations as a result of chronic exposure to aldosterone. We report a rare case of a 37-year-old man who complained of general weakness and polyuria. He was diagnosed with aldosterone-producing adrenal adenoma and nephrogenic diabetes insipidus. Aldosterone enhances the secretion of potassium in the collecting duct, which can lead to hypokalemia. By contrast, nephrogenic diabetes insipidus, which manifests as polyuria and polydipsia, can occur in several clinical conditions such as acquired tubular disease and those attributed to toxins and congenital causes. Among them, hypokalemia can also damage tubular structures in response to vasopressin. The patient’s urine output was >3 L/d and was diluted. Owing to the ineffectiveness of vasopressin, we eventually made a diagnosis of nephrogenic diabetes insipidus. Laparoscopic adrenalectomy and intraoperative kidney biopsy were subsequently performed. The pathologic finding of kidney biopsy revealed a decrease in aquaporin-2 on immunohistochemical stain.

  5. Reversed association between aldosterone and mortality in hemodialysis patients: Role of volume overload.

    Science.gov (United States)

    Hung, Szu-Chun; Tarng, Der-Cherng

    2016-07-01

    The role of aldosterone has expanded from its genomic effects that involve renal sodium transport to nongenomic effects such as cardiac and renal fibrosis. Elevated aldosterone levels are associated with increased mortality in the general population. However, the association is reversed in patients with end-stage renal disease on maintenance hemodialysis. We have shown that the inverse association between aldosterone and mortality in hemodialysis patients is due to the confounding effect of volume overload. Volume overload, which is prevalent in patients with chronic kidney disease, is associated with both lower aldosterone concentrations and higher mortality. Our findings support salt and water restriction and treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. 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

  7. ALDOSTERONE ANTAGONISTS. MODERN VIEWS ON THE MECHANISM OF ACTION AND EFFECTS OF SPIRONOLACTONE

    Directory of Open Access Journals (Sweden)

    V. I. Podzolkov

    2017-01-01

    Full Text Available The importance of renin-angiotensin-aldosterone system in pathogenesis of different clinical conditions is studied well. The key role of aldosterone receptor blockers, particularly spironolactone, in treatment of such conditions as primary hyperaldosteronism, resistant hypertension, edematous syndrome in congestive heart failure, nephrotic syndrome, and portal cirrhosis is considered in the article. Development of ideas about cardio-, vaso- and nephroprotective effects of these drugs is highlighted as well as their influence on patient prognosis.

  8. Association of Post-Saline Load Plasma Aldosterone Levels With Left Ventricular Hypertrophy in Primary Hypertension.

    Science.gov (United States)

    Catena, Cristiana; Verheyen, Nicolas D; Url-Michitsch, Marion; Kraigher-Krainer, Elisabeth; Colussi, GianLuca; Pilz, Stefan; Tomaschitz, Andreas; Pieske, Burkert; Sechi, Leonardo A

    2016-03-01

    Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity in hypertension. Current evidence suggests a contribution to LVH of plasma aldosterone levels that are inappropriately elevated for the salt status. The aim of this study was to investigate whether inappropriate modulation of aldosterone production by a saline load is associated with left ventricular (LV) mass in hypertensive patients. In 90 hypertensive patients free of clinically relevant cardiovascular complications in whom secondary forms of hypertension were ruled out, we performed a standard intravenous saline load (0.9% NaCl, 2 l in 4 hours) with measurement of plasma aldosterone and active renin at baseline and end of infusion. Bi-dimensional echocardiography was performed for the assessment of cardiac morphology and function. LVH was present in 19% of patients who had significantly worse renal function and higher body mass, blood pressure, and plasma aldosterone levels measured both at baseline and after the saline load than patients without LVH. LV mass was directly related to age, body mass, systolic blood pressure, duration of hypertension, baseline, and post-saline load plasma aldosterone levels and inversely to glomerular filtration. Multivariate regression analysis showed independent correlation of LV mass with body mass, systolic blood pressure, and plasma aldosterone levels measured after intravenous saline load, but not at baseline. In patients with hypertension, aldosterone levels measured after intravenous saline load are related to LV mass independent of age, body mass, and blood pressure, suggesting that limited ability of salt to modulate aldosterone production could contribute to LVH. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Physiological Aldosterone Concentrations Are Associated with Alterations of Lipid Metabolism: Observations from the General Population

    Directory of Open Access Journals (Sweden)

    M. Hannich

    2018-01-01

    Full Text Available Objective. Aldosterone and high-density lipoprotein cholesterol (HDL-C are involved in many pathophysiological processes that contribute to the development of cardiovascular diseases. Previously, associations between the concentrations of aldosterone and certain components of the lipid metabolism in the peripheral circulation were suggested, but data from the general population is sparse. We therefore aimed to assess the associations between aldosterone and HDL-C, low-density lipoprotein cholesterol (LDL-C, total cholesterol, triglycerides, or non-HDL-C in the general adult population. Methods. Data from 793 men and 938 women aged 25–85 years who participated in the first follow-up of the Study of Health in Pomerania were obtained. The associations of aldosterone with serum lipid concentrations were assessed in multivariable linear regression models adjusted for sex, age, body mass index (BMI, estimated glomerular filtration rate (eGFR, and HbA1c. Results. The linear regression models showed statistically significant positive associations of aldosterone with LDL-C (β-coefficient = 0.022, standard error = 0.010, p=0.03 and non-HDL-C (β-coefficient = 0.023, standard error = 0.009, p=0.01 as well as an inverse association of aldosterone with HDL-C (β-coefficient = −0.022, standard error = 0.011, p=0.04. Conclusions. The present data show that plasma aldosterone is positively associated with LDL-C and non-HDL-C and inversely associated with HDL-C in the general population. Our data thus suggests that aldosterone concentrations within the physiological range may be related to alterations of lipid metabolism.

  10. Physiological Aldosterone Concentrations Are Associated with Alterations of Lipid Metabolism: Observations from the General Population.

    Science.gov (United States)

    Hannich, M; Wallaschofski, H; Nauck, M; Reincke, M; Adolf, C; Völzke, H; Rettig, R; Hannemann, A

    2018-01-01

    Aldosterone and high-density lipoprotein cholesterol (HDL-C) are involved in many pathophysiological processes that contribute to the development of cardiovascular diseases. Previously, associations between the concentrations of aldosterone and certain components of the lipid metabolism in the peripheral circulation were suggested, but data from the general population is sparse. We therefore aimed to assess the associations between aldosterone and HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, or non-HDL-C in the general adult population. Data from 793 men and 938 women aged 25-85 years who participated in the first follow-up of the Study of Health in Pomerania were obtained. The associations of aldosterone with serum lipid concentrations were assessed in multivariable linear regression models adjusted for sex, age, body mass index (BMI), estimated glomerular filtration rate (eGFR), and HbA1c. The linear regression models showed statistically significant positive associations of aldosterone with LDL-C ( β -coefficient = 0.022, standard error = 0.010, p = 0.03) and non-HDL-C ( β -coefficient = 0.023, standard error = 0.009, p = 0.01) as well as an inverse association of aldosterone with HDL-C ( β -coefficient = -0.022, standard error = 0.011, p = 0.04). The present data show that plasma aldosterone is positively associated with LDL-C and non-HDL-C and inversely associated with HDL-C in the general population. Our data thus suggests that aldosterone concentrations within the physiological range may be related to alterations of lipid metabolism.

  11. Relationship Between Aldosterone and Parathyroid Hormone, and the Effect of Angiotensin and Aldosterone Inhibition on Bone Health

    DEFF Research Database (Denmark)

    L.S., Bislev; T., Sikjaer; L., Rolighed

    2015-01-01

    Emerging evidence suggests a stimulating effect of parathyroid hormone (PTH) on the reninnullangiotensinnullaldosterone system (RAAS). In primary hyperparathyroidism, chronic-elevated PTH levels seem to stimulate the RAAS which may explain the increased risk of cardiovascular disease (CVD......). In addition to increased PTH levels, low vitamin D levels may also directly increase risk of CVD, as vitamin D, itself, has been shown to inhibit the RAAS. Angiotensin II, aldosterone and cortisol all negatively impact bone health. Hyperaldosteronism is associated with a reversible secondary...... hyperparathyroidism due to increased renal calcium excretion. Moreover, the angiotensin II receptor is expressed by human parathyroid tissue, and angiotensin may therefore directly stimulates PTH secretion. An increased bone loss is found in patients with hyperaldosteronism. The angiotensin II receptor seems main...

  12. Polychlorinated biphenyl 126 stimulates basal and inducible aldosterone biosynthesis of human adrenocortical H295R cells

    International Nuclear Information System (INIS)

    Li, L.-A.; Wang, P.-W.; Chang, Louis W.

    2004-01-01

    To understand the effects of polychlorinated biphenyls (PCBs) on adrenal aldosterone biosynthesis, we have performed a systematical study to characterize the corresponding steroidogenic response of human adrenocortical cell line H295R to PCB126 exposure. We found that PCB126 at high concentrations stimulated basal and inducible aldosterone production. The aldosterone induction occurred concomitantly with activation of the CYP11B2 gene. Despite the fact that PCB126 acted in synergy with both potassium and angiotensin II (Ang II) in activation of aldosterone synthesis, PCB126 only modestly increased CYP11B2 mRNA expression in the presence of Ang II contrary to the synergistic transcriptional induction elicited by PCB126 and potassium. This implicated that PCB126 had differential interactions with the potassium and Ang II signaling systems in the regulation of aldosterone biosynthesis. In addition, high concentrations of PCB126 elevated transcriptional expression of the type I Ang II receptor (AT 1 ) and might thus sensitize the cellular Ang II responsiveness in both basal and inducible aldosterone biosynthesis. SF-1 was not involved in the PCB126-induced transcriptional regulation despite its importance in steroidogenic gene activation

  13. Role of calcium in effects of atrial natriuretic peptide on aldosterone production in adrenal glomerulosa cells

    International Nuclear Information System (INIS)

    Chartier, L.; Schiffrin, E.L.

    1987-01-01

    Atrial natriuretic peptide (ANP) inhibits the stimulation of aldosterone secretion by isolated adrenal glomerulosa cells produced by angiotensin II (ANG II), ACTH, and potassium. The effect of ANP on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium on isolated rat adrenal glomerulosa cells was studied. In the presence of ANP the maximal response of aldosterone output stimulated by ANG II or potassium decreased and the half-maximum (EC 50 ) of the response to ACTH was displaced to the right. Because these effects resemble those of calcium-channel blockers, the authors investigated the effect of different concentrations of nifedipine, a dihydropyridine calcium-channel blocker, on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium. Nifedipine produced effects similar to ANP. The maximal response of aldosterone stimulated by ANG II and potassium was decreased and the dose-response curve to ACTH was displaced to the right. ANP decreased the maximal response of aldosterone to the dihydropyridine derivative BAY K8644, a calcium-channel activator, without change in its EC 50 . In contrast, nifedipine displaced the dose-response curve to BAY K8644 to the right as expected of a competitive inhibitor. The effect of ANP and nifedipine on basal and stimulated 45 Ca influx into isolated rat adrenal glomerulosa cells was studied. ANP may act on the rat adrenal glomerulosa cells at least in part by interference with calcium entry

  14. Alteration of hemorrhagic aldosterone response during sodium restriction, potassium supplement and diuresis

    International Nuclear Information System (INIS)

    Sung, H.K.; Ryu, Y.W.; Joo, B.S.; Koh, J.W.; Park, K.W.; Lee, J.K.

    1977-01-01

    Effect of sodium restriction with or without potassium supplement and furosemide diuresis on plasma aldosterone response to mild hemorrhage were studied in normotensive young volunteers. After an overnight fast, blood were drawn just before and 10, 20, 30, 50, 70, 90, and 120 minutes after the 3 H-aldosterone injection. The sum of blood delivered reached over 100ml (during two hours). Plasma aldosterone and renin were measured by means of radiommunoassay. The results were as followed: 1. Hemorrhage resulted in a moderate increase in plasma aldosterone level of volunteers with normal diet. 2. The mean figures of plasma aldosterone in subjects with sodium restriction and diuresis were likewise significantly increased by hemorrhage, however, the figure of the subjects with potassium supplement who already shown higher plasma level was without effect on hemorrhage. 3. Hemorrhage produced slight decrease in serum sodium concentration in every experimental conditions, although the changes were not significant. 4. Plasma renin activities after the hemorrhage followed a similar pattern with that of aldosterone, increased during sodium restriction or diuresis and unaffected during potassium supplement. (author)

  15. Aldosterone downregulates delayed rectifier potassium currents through an angiotensin type 1 receptor-dependent mechanism.

    Science.gov (United States)

    Lv, Yankun; Wang, Yanjun; Zhu, Xiaoran; Zhang, Hua

    2018-01-01

    We have previously shown that aldosterone downregulates delayed rectifier potassium currents (I Ks ) via activation of the mineralocorticoid receptor (MR) in adult guinea pig cardiomyocytes. Here, we investigate whether angiotensin II/angiotensin type 1 receptor (AngII/AT1R) and intracellular calcium also play a role in these effects. Ventricular cardiomyocytes were isolated from adult guinea pigs and incubated with aldosterone (1 μmol·L -1 ) either alone or in combination with enalapril (1 μmol·L -1 ), losartan (1 μmol·L -1 ), nimodipine (1 μmol·L -1 ), or BAPTA-AM (2.5 μmol·L -1 ) for 24 h. We used the conventional whole cell patch-clamp technique to record the I Ks component. In addition, we evaluated expression of the I Ks subunits KCNQ1 and KCNE1 using Western blotting. Our results showed that both enalapril and losartan, but not nimodipine or BAPTA-AM, completely reversed the aldosterone-induced inhibition of I Ks and its effects on KCNQ1/KCNE1 protein levels. Furthermore, we found that AngII/AT1R mediates the inhibitory effects of aldosterone on I Ks . Finally, the downregulation of I Ks induced by aldosterone did not occur secondarily to a change in intracellular calcium concentrations. Taken together, our findings demonstrate that crosstalk between MR and AT1R underlies the effects of aldosterone, and provide new insights into the mechanism underlying potassium channels.

  16. Alteration of Hemorrhagic Aldosterone Response During Sodium Restriction, Potassium Supplement and Diuresis

    International Nuclear Information System (INIS)

    Sung, Ho Kyung; Ryu, Yong Wun; Koh, Joo Whan; Park, Kee Won; Lee, Jang Kyu

    1977-01-01

    Effect of sodium restriction with or without potassium supplement and furosemide diuresis on plasma aldosterone response to mild hemorrhage were studied in normotensive young volunteers. After an overnight fast, blood were drawn just before and 10, 20, 30, 50, 70, 90, and 120 minutes after the 3H-aldosterone injection. The sum of blood delivered reached over 100 ml (during two hours). Plasma aldosterone and renin were measured by means of radioimmunoassay. The results were as followed; 1) Hemorrhage resulted in a moderate increase in plasma aldosterone level of volunteers with normal diet. 2) The mean figures of plasma aldosterone in subjects with sodium restriction and diuresis were likewise significantly increased by hemorrhage, however, the figure of the subjects with potassium supplement who already shown higher plasma level was without effect on hemorrhage. 3) Hemorrhage produced slight decrease in serum sodium concentration in every experimental conditions, although the changes were not significant. 4) Plasma renin activities after the hemorrhage followed a similar pattern with that of aldosterone, increased during sodium restriction or diuresis and unaffected during potassium supplement.

  17. Blood-ACTH, cortisole and aldosterone levels following complex radiation treatment for cancer of the uterine cervix

    International Nuclear Information System (INIS)

    Modnikov, O.P.

    1984-01-01

    Blood-ACTH, cortisole and aldosterone levels in patients with cancer of the uterine cervix were measured radioimmunologically prior to complex radiotherapy, following a half-dose exposure of tumor focus and immediately on completion of the treatment course. Patients showed a rise in cortisole and aldosterone levels and a slight increase in ACTH. Radiation therapy inhibited production of cortisole and aldosterone matched by a rise in ACTH output

  18. Evaluation of the effects of occupational noise exposure on serum aldosterone and potassium among industrial workers

    Directory of Open Access Journals (Sweden)

    Sajad Zare

    2016-01-01

    Full Text Available The existing literature indicates that occupational exposure to noise may have adverse effects on workers′ health. The aim of this study was to evaluate the possible effects of exposure to different sound pressure levels (SPLs on serum aldosterone and potassium concentration among Iranian blue collar workers in Golgohar Mining and Industrial Company in Sirjan, Kerman Province, Iran. This case-control study was performed on 45 workers of Golgohar Mining and Industrial Company. The subjects consisted of 30 workers from manufacturing departments and 15 office employees of the mining company. The controls, mainly with administrative jobs were exposed to 72 dBA SPL. Cases, in two separate groups, were exposed to noise levels of 88 dBA and 103 dBA, respectively. Noise intensity was measured at the desired locations. Noise measurements were performed according to the International Organization for Standardization (ISO 9612. To measure the serum aldosterone and potassium concentrations, a 5 mL blood sample was taken from each worker at the specified time intervals and aldosterone concentration was determined using enzyme-linked immunosorbent assay (ELISA test in the laboratory. Repeated measurement and Spearman′s correlation coefficient analysis were used with α = 0.05. Exposure to the different levels of sound pressure resulted in different aldosterone concentrations and meanwhile an increase in the SPL did not affect the concentration of potassium. From 10:00 AM to 10:30 AM, as SPL increased, aldosterone concentrations did not increase significantly but from 13:30 PM to 14:00 PM, raised SPL led to a significant increase in aldosterone concentration. However, there was no correlation between the concentration of potassium and different factors. This study indicated that increases in SPLs affect aldosterone concentration but at the same time do not have significant effects on serum potassium level.

  19. Primary aldosteronism among newly diagnosed and untreated hypertensive patients in a Swedish primary care area.

    Science.gov (United States)

    Westerdahl, Christina; Bergenfelz, Anders; Isaksson, Anders; Nerbrand, Christina; Valdemarsson, Stig

    2011-03-01

    To evaluate the prevalence of primary aldosteronism (PA) in newly diagnosed and untreated hypertensive patients in primary care using the aldosterone/renin ratio (ARR), and to assess clinical and biochemical characteristics in patients with high and normal ARR. Patient survey study. A total of 200 consecutive patients with newly diagnosed and untreated hypertension from six primary health care centres in Sweden were included. ARR was calculated from serum aldosterone and plasma renin concentrations. The cut-off level for ARR was 65. Patients with an increased ARR were considered for confirmatory testing with the fludrocortisone suppression test (FST), followed by adrenal computed tomographic radiology (CT) and adrenal venous sampling (AVS). Of 200 patients, 36 patients had an ARR > 65. Of these 36 patients, 11 patients had an incomplete aldosterone inhibition during FST. Three patients were diagnosed with an aldosterone producing adenoma (APA) and eight with bilateral adrenal hyperplasia (BHA). Except for moderately lower level of P-K in patients with an ARR > 65 and in patients with PA, there were no biochemical or clinical differences found among hypertensive patients with PA compared with patients without PA. Eleven of 200 evaluated patients (5.5%) were considered to have PA. The diagnosis of PA should therefore be considered in newly diagnosed hypertensive subjects and screening for the diagnosis is warranted.

  20. Percutaneous computed tomography-guided ethanol injection in aldosterone-producing adrenocortical adenoma

    International Nuclear Information System (INIS)

    Rossi, R.; Savastano, S.; Tommaselli, A.P.

    1995-01-01

    The feasibility, safety and effectiveness of percutaneous computed tomography-guided ethanol injection (PEI-CT) was investigated in a patient affected by aldosterone-producing adenoma (APA). A 42-year-old male patient with typical features of hyperaldosteronism presented a solitary left adrenal adenoma measuring 2 cm, with a normal contralateral gland, evidenced by both CT scan and adrenal [ 75 Se-19]-nor-cholesterol scintigraphy. After normalization of potassium plasma levels, 4 ml of sterile 95% ethanol with 0.5 ml of 80% iothalamate sodium was injected. The procedure was completed in about 30 min. No severe pain or local complication was noted. Five hour after PEI, a fourfold and a twofold increase in aldosterone and cortisol plasma levels were observed, respectively. After 11 days on a normal sodium and potassium diet, normal potassium plasma levels and reduced aldosterone plasma levels were present, with reappearance of an aldosterone postural response. Plasma renin activity and aldosterone plasma levels normalized 1 month later, with reappearance also of a plasma renin activity postural response and maintenance of normal potassium plasma levels on a high sodium and normal potassium diet. The patient has remained hypertensive, although lower antihypertensive drug dosages have been employed. After 17 months, normal biochemical, hormonal and morphological findings were present. The authors suggested PEI-CT as a further alternative approach to surgery in the management of carefully selected patients with APA. 15 refs., 2 figs., 1 tab

  1. 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)

  2. Prevalence of KCNJ5 mutations and functional impact of a novel KCNJ5-insT149 mutation in aldosterone producing adenoma causing resistant hypertension

    OpenAIRE

    Kuppusamy, Maniselvan

    2014-01-01

    Primary aldosteronism (PA), a common form of secondary hypertension, is characterized by an excess autonomous aldosterone secretion. In a percentage ranging from a half to two thirds of the cases it is due to a surgically curable aldosterone-producing adenoma (APA) and in the rest to bilateral adrenal hyperplasia. The molecular mechanisms underlying aldosterone hypersecretion are unknown. Recent evidences suggest that amino acid residue substitutions in the selectivity filter of the Kir3....

  3. Assessment of postoperative changes in antihypertensive drug consumption in patients with primary aldosteronism using the defined daily dose

    Directory of Open Access Journals (Sweden)

    Takanobu Utsumi

    2014-10-01

    Conclusion: The defined daily dose is a useful tool for assessing total changes in the consumption of antihypertensive drugs in patients with primary aldosteronism. Using the defined daily dose, clinicians could explain in detail to patients with primary aldosteronism the predicted postoperative change in antihypertensive drug consumption.

  4. Long-term aldosterone treatment induces decreased apical but increased basolateral expression of AQP2 in CCD of rat kidney.

    NARCIS (Netherlands)

    Seigneux, S. de; Nielsen, J.; Olesen, E.T.; Dimke, H.; Kwon, T.H.; Frokiaer, J.; Nielsen, S.

    2007-01-01

    The purpose of the present studies was to determine the effects of high-dose aldosterone and dDAVP treatment on renal aquaporin-2 (AQP2) regulation and urinary concentration. Rats were treated for 6 days with either vehicle (CON; n = 8), dDAVP (0.5 ng/h, dDAVP, n = 10), aldosterone (Aldo, 150

  5. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism : an outcome-based randomised diagnostic trial

    NARCIS (Netherlands)

    Dekkers, Tanja; Prejbisz, Aleksander; Kool, Leo J. Schultze; Groenewoud, Hans J. M. M.; Velema, Marieke; Spiering, Wilko; Kolodziejczyk-Kruk, Sylwia; Arntz, Mark; Kadziela, Jacek; Langenhuijsen, Johannes F.; Kerstens, Michiel N.; van den Meiracker, Anton H.; van den Born, Bert-Jan; Sweep, Fred C. G. J.; Hermus, Ad R. M. M.; Januszewicz, Andrzej; Ligthart-Naber, Alike F.; Makai, Peter; van der Wilt, Gert-Jan; Lenders, Jacques W. M.; Deinum, Jaap

    Background The distinction between unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia as causes of primary aldosteronism is usually made by adrenal CT or by adrenal vein sampling (AVS). Whether CT or AVS represents the best test for diagnosis remains unknown. We aimed to

  6. Protein kinase D1 modulates aldosterone-induced ENaC activity in a renal cortical collecting duct cell line.

    LENUS (Irish Health Repository)

    McEneaney, Victoria

    2010-08-30

    Aldosterone treatment of M1-CCD cells stimulated an increase in epithelial Na(+) channel (ENaC) alpha-subunit expression that was mainly localized to the apical membrane. PKD1-suppressed cells constitutively expressed ENaCalpha at low abundance, with no increase after aldosterone treatment. In the PKD1-suppressed cells, ENaCalpha was mainly localized proximal to the basolateral surface of the epithelium both before and after aldosterone treatment. Apical membrane insertion of ENaCbeta in response to aldosterone treatment was also sensitive to PKD1 suppression as was the aldosterone-induced rise in the amiloride-sensitive, trans-epithelial current (I(TE)). The interaction of the mineralocorticoid receptor (MR) with specific elements in the promoters of aldosterone responsive genes is stabilized by ligand interaction and phosphorylation. PKD1 suppression inhibited aldosterone-induced SGK-1 expression. The nuclear localization of MR was also blocked by PKD1 suppression and MEK antagonism implicating both these kinases in MR nuclear stabilization. PKD1 thus modulates aldosterone-induced ENaC activity through the modulation of sub-cellular trafficking and the stabilization of MR nuclear localization.

  7. 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.

  8. Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension

    DEFF Research Database (Denmark)

    Beuschlein, Felix; Boulkroun, Sheerazed; Osswald, Andrea

    2013-01-01

    Primary aldosteronism is the most prevalent form of secondary hypertension. To explore molecular mechanisms of autonomous aldosterone secretion, we performed exome sequencing of aldosterone-producing adenomas (APAs). We identified somatic hotspot mutations in the ATP1A1 (encoding an Na+/K+ ATPase α...

  9. 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.

  10. Overexpressed cyclophilin B suppresses aldosterone-induced proximal tubular cell injury both in vitro and in vivo.

    Science.gov (United States)

    Wang, Bin; Lin, Lilu; Wang, Haidong; Guo, Honglei; Gu, Yong; Ding, Wei

    2016-10-25

    The renin-angiotensin-aldosterone system (RAAS) is overactivated in patients with chronic kidney disease. Oxidative stress and endoplasmic reticulum stress (ERS) are two major mechanisms responsible for aldosterone-induced kidney injury. Cyclophilin (CYP) B is a chaperone protein that accelerates the rate of protein folding through its peptidyl-prolyl cis-trans isomerase (PPIase) activity. We report that overexpression of wild-type CYPB attenuated aldosterone-induced oxidative stress (evidenced by reduced production of reactive oxygen species and improved mitochondrial dysfunction), ERS (indicated by reduced expression of the ERS markers glucose-regulated protein 78 [GRP78] and C/-EBP homologous protein [CHOP]), and tubular cell apoptosis in comparison with aldosterone-induced human kidney-2 (HK-2) cells. The in vivo study also yielded similar results. Hence, CYPB performs a crucial function in protecting cells against aldosterone-induced oxidative stress, ERS, and tubular cell injury via its PPIase activity.

  11. Expression and biochemical characteristics of two different aldosterone receptors in both healthy and dilated cardiomyopathy dog heart tissue.

    Science.gov (United States)

    Reynoso Palomar, Alejandro R; Rodriguez Bravo, Moncerrat; Villa Mancera, Abel E; Mucha, Carlos J

    2017-03-01

    Recently, replicates of the aldosterone receptor expression have been done in healthy heart dog tissues through immunohistochemistry, showing an apparent heterogeneous distribution in the four chambers. Recent studies have also identified immediate effects of aldosterone, suggesting aldosterone also produces non-genomic effects caused by an unidentified receptor. In order to study the molecular and quantitative expression characteristics of aldosterone binding receptors in the canine heart, we conducted studies, using Western Blot, in the heart from both healthy animals and animals with dilated cardiomyopathy. The results show the presence and distribution of two aldosterone receptors; one of 110/120 kDa molecular weight, suggested as cytosolic/nuclear and the other of undetermined location with a 250 kDa molecular weight.

  12. Changes in serum aldosterone are associated with changes in obesity-related factors in normotensive overweight and obese young adults.

    Science.gov (United States)

    Cooper, Jennifer N; Fried, Linda; Tepper, Ping; Barinas-Mitchell, Emma; Conroy, Molly B; Evans, Rhobert W; Mori Brooks, Maria; Woodard, Genevieve A; Sutton-Tyrrell, Kim

    2013-10-01

    Recent data suggest excess circulating aldosterone promotes cardiometabolic decline. Weight loss may lower aldosterone levels, but little longitudinal data is available in normotensive adults. We aimed to determine whether, independent of changes in sodium excretion, reductions in serum aldosterone are associated with favorable changes in obesity-related factors in normotensive overweight/obese young adults. We studied 285 overweight/obese young adult participants (body mass index ≥ 25 andobesity-related factors were measured at baseline, 6, 12 and 24 months. Weight loss was significant at 6 (7%), 12 (6%) and 24 months (4%; all Pobesity-related factors are associated with reductions in aldosterone in young adults with no risk factors besides excess weight, an important finding, given aldosterone's emergence as an important cardiometabolic risk factor.

  13. 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.

  14. Effects of acrolein on aldosterone release from zona glomerulosa cells in male rats.

    Science.gov (United States)

    Wang, Kai-Lee; Huang, Wen-Ching; Chou, Jou-Chun; Weng, Ting-Chun; Hu, Sindy; Lieu, Fu-Kong; Lai, Wei-Ho; Idova, Galina; Wang, Paulus S; Wang, Shyi-Wu

    2016-07-01

    A positive correlation between smoking and hypertension has been well established. Acrolein is a major toxic volatile compound found in cigarette smoke. Human exposure to low levels of acrolein is unavoidable due to its production in daily activities, such as smoke from industrial, hot oil cooking vapors, and exhaust fumes from vehicles. The toxicity and the action mechanism of acrolein to induce apoptosis have been extensively studied, but the effects of acrolein on hypertension are still unknown. The present study aimed to examine the effects of acrolein on aldosterone release both in vivo and in vitro. Male rats were divided into three groups, and intraperitoneally injected with normal saline, or acrolein (2mg/kg) for 1 (group A-1) or 3 (group A-3) days, respectively. After sacrificing, rat blood samples were obtained to measure plasma aldosterone and angiotensin II (Ang II) levels. Zona glomerulosa (ZG) cells were prepared from rat adrenal cortex, and were incubated with or without stimulants. We found that the serum aldosterone was increased by 1.2-fold (pacrolein enhanced the stimulatory effects of Ang II and 8-bromo-cyclic AMP on aldosterone secretion from ZG cells prepared in both A-1 and A-3 groups. Furthermore, the enzyme activity of P450scc, the rate-limiting step of aldosterone synthesis, was elevated after acrolein injection. Plasma level of Ang II was increased in both A-1 and A-3 groups. These results suggested that acrolein exposure increased aldosterone production, at least in part, through elevating the level of plasma Ang II and stimulating steroidogenesis pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Screening for primary aldosteronism using the newly developed IDS-iSYS® automated assay system

    Directory of Open Access Journals (Sweden)

    P.M. O’Shea

    2017-04-01

    Full Text Available Background: The recommended approach to screening for primary aldosteronism (PA in at-risk populations is to determine the ratio of aldosterone concentration (serum (SAC/plasma (PAC to renin measured in plasma as activity (PRA or concentration (DRC. However, lack of assay standardisation mandates the need for method-specific decision thresholds and clinical validation in the local population. Aim: The study objective was to establish method-specific aldosterone: renin ratio (ARR cut-offs for PA in men and women using the IDS-iSYS® assay system (IDS plc. Methods: A prospective cohort study design was used. PAC and DRC were measured immunochemically in ethylenediamine-tetraacetic acid (EDTA plasma on the IDS-iSYS® instrument. Results: A total of 437 subjects (218 men, 219 women were recruited including: healthy normotensive volunteers (n=266 and women taking the oral contraceptive pill (OCP; n=15; patients with essential hypertension (EH; n=128; confirmed PA (n=16; adrenal cortical carcinoma (ACC; n=3; Addison's disease (AD; n=4 and phaeochromocytoma/paraganglioma (PPGL; n=5. In this population, an ARR cut-off at >37.4 pmol/mIU provided 100% diagnostic sensitivity, 96% specificity and positive likelihood ratio for PA of 23:1. When the ARR decision threshold was stratified according to gender, a cut-off of >26.1 pmol/mIU in men and >113.6 pmol/mIU in women resulted in diagnostic sensitivity and specificity of 100%. Conclusion: This study demonstrates that decision thresholds for PA should not only be method-specific but also gender-specific. However, given the small number of PA patients (n=16, particularly women (n=4, further validation through a prospective study with a larger PA cohort is required before the thresholds presented here could be recommended for routine clinical use. Keywords: Primary aldosteronism, Renin, Aldosterone, Aldosterone: renin ratio (ARR, Sensitivity, Specificity

  16. Effect of KCNJ5 Mutations on Gene Expression in Aldosterone-Producing Adenomas and Adrenocortical Cells

    Science.gov (United States)

    Monticone, Silvia; Hattangady, Namita G.; Nishimoto, Koshiro; Mantero, Franco; Rubin, Beatrice; Cicala, Maria Verena; Pezzani, Raffaele; Auchus, Richard J.; Ghayee, Hans K.; Shibata, Hirotaka; Kurihara, Isao; Williams, Tracy A.; Giri, Judith G.; Bollag, Roni J.; Edwards, Michael A.; Isales, Carlos M.

    2012-01-01

    Context: Primary aldosteronism is a heterogeneous disease that includes both sporadic and familial forms. A point mutation in the KCNJ5 gene is responsible for familial hyperaldosteronism type III. Somatic mutations in KCNJ5 also occur in sporadic aldosterone producing adenomas (APA). Objective: The objective of the study was to define the effect of the KCNJ5 mutations on gene expression and aldosterone production using APA tissue and human adrenocortical cells. Methods: A microarray analysis was used to compare the transcriptome profiles of female-derived APA samples with and without KCNJ5 mutations and HAC15 adrenal cells overexpressing either mutated or wild-type KCNJ5. Real-time PCR validated a set of differentially expressed genes. Immunohistochemical staining localized the KCNJ5 expression in normal adrenals and APA. Results: We report a 38% (18 of 47) prevalence of KCNJ5 mutations in APA. KCNJ5 immunostaining was highest in the zona glomerulosa of NA and heterogeneous in APA tissue, and KCNJ5 mRNA was 4-fold higher in APA compared with normal adrenals (P APA with and without KCNJ5 mutations displayed slightly different gene expression patterns, notably the aldosterone synthase gene (CYP11B2) was more highly expressed in APA with KCNJ5 mutations. Overexpression of KCNJ5 mutations in HAC15 increased aldosterone production and altered expression of 36 genes by greater than 2.5-fold (P APA, and our data suggest that these mutations increase expression of CYP11B2 and NR4A2, thus increasing aldosterone production. PMID:22628608

  17. Aldosterone Does Not Predict Cardiovascular Events Following Acute Coronary Syndrome in Patients Initially Without Heart Failure.

    Science.gov (United States)

    Pitts, Reynaria; Gunzburger, Elise; Ballantyne, Christie M; Barter, Philip J; Kallend, David; Leiter, Lawrence A; Leitersdorf, Eran; Nicholls, Stephen J; Shah, Prediman K; Tardif, Jean-Claude; Olsson, Anders G; McMurray, John J V; Kittelson, John; Schwartz, Gregory G

    2017-01-10

    Aldosterone may have adverse effects in the myocardium and vasculature. Treatment with an aldosterone antagonist reduces cardiovascular risk in patients with acute myocardial infarction complicated by heart failure (HF) and left ventricular systolic dysfunction. However, most patients with acute coronary syndrome do not have advanced HF. Among such patients, it is unknown whether aldosterone predicts cardiovascular risk. To address this question, we examined data from the dal-OUTCOMES trial that compared the cholesteryl ester transfer protein inhibitor dalcetrapib with placebo, beginning 4 to 12 weeks after an index acute coronary syndrome. Patients with New York Heart Association class II (with LVEF coronary heart disease death, nonfatal myocardial infarction, stroke, hospitalization for unstable angina, or resuscitated cardiac arrest. Hospitalization for HF was a secondary endpoint. Over a median follow-up of 37 months, the primary outcome occurred in 366 patients (9.0%), and hospitalization for HF occurred in 72 patients (1.8%). There was no association between aldosterone and either the time to first occurrence of a primary outcome (hazard ratio for doubling of aldosterone 0.92, 95% confidence interval 0.78-1.09, P=0.34) or hospitalization for HF (hazard ratio 1.38, 95% CI 0.96-1.99, P=0.08) in Cox regression models adjusted for covariates. In patients with recent acute coronary syndrome but without advanced HF, aldosterone does not predict major cardiovascular events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00658515. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  18. Studies of radioimmunoassay for plasma aldosterone concentration by immunologic purification and extraction procedure without chromatography

    International Nuclear Information System (INIS)

    Yokoyama, Hisamitsu

    1975-01-01

    After the aldosterone fraction of plasma was specifically absorbed using highly concentrated anti-aldosterone serum(i.e. Ab-II; diluted to 1:50,000), it was applied to the radioimmunoassay: and the separation of the free from the bound fractions was performed by the saturated ammonium sulfate method. Reasonable and satisfactory standard curves were obtained, but attention should be given to environmental factors at measurement, especially to the room temperature in summer. According to our results the mean final recovery for 58 specimens was 41.8+-6.4(SD)% through the overall extraction procedure, and the minimum detectable sensitivity of the standard curve was 10pg. The mean water blank value was 7.02+-2.62 (SD) pg/tube. Possible reasons for the higher blank value than others may have been the reagent or the solvent blank, and/or the insufficient process of immunologic purification by Ad-II for the tritium-labelled aldosterone which was used for recovery and immunoassay. The precision was from 9.4 to 25.3% coefficient of variations; the accuracy and recovery rate were almost satisfactory. In our clinical application, the plasma aldosterone concentration indicated high values in the peripheral and affected adrenal venous blood of patients with primary aldosteronism. In a patient with Bartter's syndrome, hyperreninemia and secondary hyperaldosteronism were observed. Almost all of the patients with Addison's disease and with total adrenalectomy indicated the lowest or undetectable levels. A high level of plasma aldosterone concentration was measured in a patient with edema and chronic renal failure and one with juvenile hypertension associated with an orbital tumor. (JPN)

  19. Case Report: Nodule Development From Subcapsular Aldosterone-Producing Cell Clusters Causes Hyperaldosteronism.

    Science.gov (United States)

    Nishimoto, Koshiro; Seki, Tsugio; Kurihara, Isao; Yokota, Kenichi; Omura, Masao; Nishikawa, Tetsuo; Shibata, Hirotaka; Kosaka, Takeo; Oya, Mototsugu; Suematsu, Makoto; Mukai, Kuniaki

    2016-01-01

    We previously reported that the human adrenal cortex remodels to form subcapsular aldosterone-producing cell clusters (APCCs). Some APCCs were recently found to carry aldosterone-producing adenoma (APA)-associated somatic mutations in ion channel/pump genes, which implied that APCCs produce aldosterone autonomously and are an origin of APA. However, there has been no report describing an APCC-to-APA transitional lesion. A histological examination revealed unilateral multiple adrenocortical micronodules in the adrenals of two patients with primary aldosteronism (PA). Based on immunohistochemistry for aldosterone synthase, some of the micronodules were identified as possible APCC-to-APA transitional lesions (pAATLs; a tentative term used in this manuscript), which consisted of a subcapsular APCC-like portion and an inner micro-APA-like (mAPA-like) portion without an apparent histological border. Genomic DNA samples prepared from pAATL histological sections were analyzed by next-generation sequencing for the known APA-associated mutations. The mAPA-like portions from two of the three large pAATLs examined harbored mutations (KCNJ5 [p.G151R] in pAATL 3 and ATP1A1 [p.L337M] in pAATL 7), whereas their corresponding APCC-like portions did not, suggesting their role in the formation of mAPA. Another lesion carried novel mutations in ATP1A1 (p.Ile322_Ile325del and p.Ile327Ser) in both the mAPA-like and APCC-like portions, thereby supporting these portions having a clonal origin. A novel aldosterone-producing pathology, pAATL that causes unilateral PA, was detected in the adrenals of two patients. Next-generation sequencing analyses of the large pAATLs suggested that the introduction of APA-associated mutations in the ion channel/pump genes may be involved in the development of mAPA from existing APCCs.

  20. Studies of radioimmunoassay for plasma aldosterone concentration by immunologic purification and extraction procedure without chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, H [Okayama Univ. (Japan). School of Medicine

    1975-07-01

    After the aldosterone fraction of plasma was specifically absorbed using highly concentrated anti-aldosterone serum(i.e. Ab-II; diluted to 1:50,000), it was applied to the radioimmunoassay: and the separation of the free from the bound fractions was performed by the saturated ammonium sulfate method. Reasonable and satisfactory standard curves were obtained, but attention should be given to environmental factors at measurement, especially to the room temperature in summer. According to our results the mean final recovery for 58 specimens was 41.8+-6.4(SD)% through the overall extraction procedure, and the minimum detectable sensitivity of the standard curve was 10pg. The mean water blank value was 7.02+-2.62 (SD) pg/tube. Possible reasons for the higher blank value than others may have been the reagent or the solvent blank, and/or the insufficient process of immunologic purification by Ad-II for the tritium-labelled aldosterone which was used for recovery and immunoassay. The precision was from 9.4 to 25.3% coefficient of variations; the accuracy and recovery rate were almost satisfactory. In our clinical application, the plasma aldosterone concentration indicated high values in the peripheral and affected adrenal venous blood of patients with primary aldosteronism. In a patient with Bartter's syndrome, hyperreninemia and secondary hyperaldosteronism were observed. Almost all of the patients with Addison's disease and with total adrenalectomy indicated the lowest or undetectable levels. A high level of plasma aldosterone concentration was measured in a patient with edema and chronic renal failure and one with juvenile hypertension associated with an orbital tumor.

  1. Persistent Primary Aldosteronism Despite Iatrogenic Adrenal Hemorrhage After Adrenal Vein Sampling.

    Science.gov (United States)

    Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Abe, Ichiro; Kobayashi, Kunihisa; Ishii, Tatsu; Haraoka, Seiji; Urata, Hidenori

    2018-01-01

    Before surgery for primary aldosteronism (PA), localization is evaluated with adrenal vein sampling (AVS). A 56-year-old Japanese woman had a right adrenal mass, hypokalemia, and a high aldosterone/renin ratio. Stress tests confirmed the diagnosis of PA. Subsequently, preoperative AVS was performed and right adrenal hemorrhage (AH) occurred unexpectedly. Because hypertension persisted, laparoscopic right adrenalectomy was performed. Postoperatively, the blood pressure was normalized. Pathological examination revealed an adrenal cortical adenoma largely unaffected by necrosis and hemorrhage. Previous reports have also indicated that AH may not ameliorate PA. We discussed the clinical progress of AH and the measures to prevent causing AH.

  2. Persistent Primary Aldosteronism Despite Iatrogenic Adrenal Hemorrhage After Adrenal Vein Sampling

    Science.gov (United States)

    Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Abe, Ichiro; Kobayashi, Kunihisa; Ishii, Tatsu; Haraoka, Seiji; Urata, Hidenori

    2018-01-01

    Before surgery for primary aldosteronism (PA), localization is evaluated with adrenal vein sampling (AVS). A 56-year-old Japanese woman had a right adrenal mass, hypokalemia, and a high aldosterone/renin ratio. Stress tests confirmed the diagnosis of PA. Subsequently, preoperative AVS was performed and right adrenal hemorrhage (AH) occurred unexpectedly. Because hypertension persisted, laparoscopic right adrenalectomy was performed. Postoperatively, the blood pressure was normalized. Pathological examination revealed an adrenal cortical adenoma largely unaffected by necrosis and hemorrhage. Previous reports have also indicated that AH may not ameliorate PA. We discussed the clinical progress of AH and the measures to prevent causing AH. PMID:29238437

  3. Role of Nox2 and p22phox in Persistent Postoperative Hypertension in Aldosterone-Producing Adenoma Patients after Adrenalectomy

    Directory of Open Access Journals (Sweden)

    Xiaojing Geng

    2016-01-01

    Full Text Available Adrenal aldosterone-producing adenoma (APA, producing the salt-retaining hormone aldosterone, commonly causes secondary hypertension, which often persists after unilateral adrenalectomy. Although persistent hypertension was correlated with residual hormone aldosterone, the in vivo mechanism remains unclear. NADPH oxidase is the critical cause of aldosterone synthesis in vitro. Nox2 and p22phox comprise the NADPH oxidase catalytic core, serving to initiate a reactive oxygen species (ROS cascade that may participate in the pathology. mRNAs of seven NADPH oxidase isoforms in APA were evaluated by RT-PCR and Q-PCR and their proteins by immunohistochemistry and Western blotting. NADPH oxidase activity was also detected. Nox2 and p22phox were especially abundant in APA. Particularly higher Nox2 and p22phox gene and protein levels were seen in APA than controls. Significant correlations between Nox2 mRNA and aldosterone synthase (CYP11B2 mRNA (R=0.66, P<0.01 and Nox2 protein and baseline plasma aldosterone concentration (PAC (R=0.503, P<0.01 were detected in APA; however, none were found between p22phox mRNA, CYP11B2 mRNA, p22phox protein, and baseline PAC. Importantly, we found that Nox2 localized specifically in hyperplastic zona glomerulosa cells. In conclusion, our results highlight that Nox2 and p22phox may be directly involved in pathological aldosterone production and zona glomerulosa cell proliferation after APA resection.

  4. 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.

  5. Erratum Aldosterone synthase C-344T, angiotensin II type 1 receptor ...

    Indian Academy of Sciences (India)

    Aldosterone synthase C-344T, angiotensin II type 1 receptor A1166C and 11-β hydroxysteroid dehydrogenase G534A gene polymorphisms and essential hypertension in the population of Odisha, India. Manisha Patnaik, Pallabi Pati, Surendra N. Swain, Manoj K. Mohapatra, Bhagirathi Dwibedi, Shantanu K. Kar.

  6. Diagnostic value of ACTH stimulation test in determining the subtypes of primary aldosteronism.

    Science.gov (United States)

    Jiang, Yiran; Zhang, Cui; Wang, Weiqing; Su, Tingwei; Zhou, Weiwei; Jiang, Lei; Zhu, Wei; Xie, Jing; Ning, Guang

    2015-05-01

    Adrenal venous sampling is recommended as the golden standard for subtyping primary aldosteronism (PA). However, it is invasive and inconvenient, and seeking a better way to make differential diagnosis of PA is necessary. The objective of the study was to evaluate the diagnostic value of ACTH stimulation test under 1 mg dexamethasone suppression test (DST) in determining the subtypes of PA. Ninety-five patients with PA confirmed by saline infusion test were included in this study. According to adrenal venous sampling and histopathology, 39 patients were diagnosed as bilateral adrenal hyperplasia (BAH), 37 as aldosterone-producing adenoma (APA), and 19 as unilateral adrenal hyperplasia (UAH). An ACTH stimulation test under 1 mg DST was performed in all patients. Plasma aldosterone and cortisol levels were measured every 30 minutes until 120 minutes after the iv injection of 50 IU ACTH. During the ACTH stimulation test, aldosterone levels in APA and UAH were similar (P > .05) but higher than those in BAH (P APA and UAH) were significantly higher than bilateral PA (BAH) (P guide further treatment in PA patients.

  7. Secondary hypertension due to concomitant aldosterone-producing adenoma and parathyroid adenoma.

    Science.gov (United States)

    Chau, Katrina; Holmes, Daniel; Melck, Adrienne; Chan-Yan, Clifford

    2015-02-01

    There is a growing body of evidence supporting a bidirectional relationship between parathyroid hormone (PTH) and aldosterone (Aldo). We report a case of secondary hypertension due to concomitant Aldo-producing adenoma (APA) and parathyroid adenoma (PA) requiring both unilateral adrenalectomy and parathyroidectomy. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Plasma aldosterone concentrations and plasma renin activity in healthy dogs and dogs with hyperadrenocorticism

    NARCIS (Netherlands)

    Javadi, S; Mol, JA; Boer, P; Boer, WH; Runberk, A

    2003-01-01

    The mean (se) basal plasma aldosterone concentrations were significantly lower in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH) (75 [9] pmol/litre) than in 12 healthy dogs (118 [14] pmol/litre), whereas in five dogs with hyperadrenocorticism due to an adrenocortical tumour they were

  9. Genomic and nongenomic effects of aldosterone in the rat heart: why is spironolactone cardioprotective?

    NARCIS (Netherlands)

    W. Chai (Wenxia); I.M. Garrelds (Ingrid); U. Arulmani (Udayasankar); R.G. Schoemaker (Regien); J.M.J. Lamers (Jos); A.H.J. Danser (Jan)

    2005-01-01

    textabstract1. Mineralocorticoid receptor (MR) antagonism with spironolactone reduces mortality in heart failure on top of ACE inhibition. To investigate the underlying mechanism, we compared the actions of both aldosterone and spironolactone to those of angiotensin (Ang) II in the rat heart. 2.

  10. Determination of plasma aldosterone in children by thin layer chromatography and radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Parth, K; Zimprich, H; Brunel, R [The Ludwig Boltzmann Institute of Paediatric Endocrinology; The Karolinen Kinderspital, Vienna)

    1976-01-01

    An accurate and relatively simple radioimmunoassay for the determination of aldosterone concentration in peripheral plasma has been developed. 0.5-2.0 ml plasma with added ..cap alpha..1.2-/sup 3/H..omega..aldosterone is extracted with dichloromethane. Purification of the extract is achieved by thin layer chromatography in the system benzene-acetone 1:1. Recovery of ..cap alpha..1,2-/sup 3/H..omega..aldosterone is 58+-6 (sd) %. Bound and free fractions are separated by dextran-coated charcol. The intra-assay reproducibility is 8.8 % and the inter-assay reproducibility varies from 11.4-16.1%. The sensitivity of the assay for a 5 ml plasma sample can be put at 0.2 ng/100 ml. Normal values determined in 52 healthy children of different age groups are presented. Furthermore the aldosterone stimulating effect of low sodium diet (17 children), severe and prolonged vomiting (19 children) and synthetic ACTH (10 children) has been studied by our modified method.

  11. 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.

  12. 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.

  13. Diurnal Blood Pressure Variation in Pheochromocytoma, Primary Aldosteronism and Cushing's Syndrome

    Czech Academy of Sciences Publication Activity Database

    Zelinka, T.; Štrauch, B.; Pecen, Ladislav; Widimský jr., J.

    Roc. 18, c. 1 (2004), s. 107-111 ISSN 0950-9240 R&D Projects: GA MŠk LN00B107 Institutional research plan: CEZ:AV0Z1030915 Keywords : primary aldosteronism * pheochromocytoma * Cushing's syndrome * cirardian blood pressure rhythm Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 1.930, year: 2004

  14. RNA sequencing of kidney distal tubule cells reveals multiple mediators of chronic aldosterone action

    DEFF Research Database (Denmark)

    Poulsen, Søren Brandt; Limbutara, Kavee; Fenton, Robert Andrew

    2018-01-01

    The renal aldosterone-sensitive distal tubule (ASDT) is crucial for sodium reabsorption and blood pressure regulation. The ASDT consists of the late distal convoluted tubule (DCT2), connecting tubule (CNT) and collecting duct. Due to difficulties in isolating epithelial cells from the ASDT in lar...

  15. 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

  16. Aldosterone-Synthase Gene Polymorphism is Associated with Blood Pressure Levels and Left Ventricle Mass Index

    Czech Academy of Sciences Publication Activity Database

    Horký, K.; Jáchymová, M.; Heller, S.; Linhart, A.; Hlubocká, Z.; Umnerová, V.; Peleška, Jan; Pavlíková, Markéta; Jindra, A.

    2004-01-01

    Roč. 204, 1 suppl. (2004), s. 35 ISSN 0014-2565. [World Congress of Internal Medicine /27./. 26.09.2004-01.10.2004, Granada] R&D Projects: GA MŠk LN00B107 Keywords : aldosterone synthase (CYP11B) * genetic polymorphism * arterial hypertension * left ventricular hypertrophy Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  17. The Adrenal Vein Sampling International Study (AVIS) for identifying the major subtypes of primary aldosteronism.

    NARCIS (Netherlands)

    Rossi, G.P.; Barisa, M.; Allolio, B.; Auchus, R.J.; Amar, L.; Cohen, D.; Degenhart, C.; Deinum, J.; Fischer, E.; Gordon, R.; Kickuth, R.; Kline, G.; Lacroix, A.; Magill, S.; Miotto, D.; Naruse, M.; Nishikawa, T.; Omura, M.; Pimenta, E.; Plouin, P.F.; Quinkler, M.; Reincke, M.; Rossi, E.; Rump, L.C.; Satoh, F.; Schultze Kool, L.J.; Seccia, T.M.; Stowasser, M.; Tanabe, A.; Trerotola, S.; Vonend, O.; Widimsky Jr, J.; Wu, K.D.; Wu, V.C.; Pessina, A.C.

    2012-01-01

    CONTEXT: In patients who seek surgical cure of primary aldosteronism (PA), The Endocrine Society Guidelines recommend the use of adrenal vein sampling (AVS), which is invasive, technically challenging, difficult to interpret, and commonly held to be risky. OBJECTIVE: The aim of this study was to

  18. [Role of adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes].

    Science.gov (United States)

    Li, H Y; Li, P; Shen, S M; Zhang, X B; Feng, W H; Huang, H; Chen, W; Zhu, D L

    2017-11-14

    Objective: To investigate the role of adrenal vein sampling (AVS) in identifying the subtype of primary aldosteronism (PA). Methods: AVS was performed in 50 patients who were confirmed as PA between September 2010 and September 2016 in Nanjing Drum Tower Hospital. Clinical, biochemical and follow-up data were reviewed retrospectively. Bilaterally simultaneous catheterization without cosyntropin stimulation and contemporaneous cortisol measurement during AVS were used. Selectivity index (SI)≥1.5 suggested that the sample was from the adrenal vein.Lateralization index (LI) ≥2 suggested unilateral disease.Clinical data was further compared and the AVS findings were analyzed. Results: AVS was successful performed in 41 cases of 50 patients, and the success rate was 82%. According to the results of AVS and postoperative pathology, 41 cases were divided into aldosterone-producing adenoma (APA)/unilateral adrenal hyperplasia (UAH) group (24 cases) and idiopathic hyperaldosteronism (IHA) group (17 cases). Compared with IHA group, patients with APA/UAH showed longer duration of hypertension[10.0 (5.0, 13.0) y vs 4.0 (2.0, 8.0) y, P =0.046], higher proportion of hypokalemia (95.8% vs 64.7%, P =0.009). Furthermore, patients with APA/UAH demonstrated lower plasma renin activity ( P =0.089), higher plasma aldosterone concentration and aldosterone to renin ratio (ARR) (both P AVS. AVS is useful in subtype diagnosis of PA with equivocal imaging findings.

  19. Re-evaluation of the fludrocortisone test: duration, NaCl supplementation and cut-off limits for aldosterone.

    Science.gov (United States)

    Westerdahl, Christina; Bergenfelz, Anders; Larsson, Johanna; Nerbrand, Christina; Valdemarsson, Stig; Wihl, Anders; Isaksson, Anders

    2009-01-01

    Primary aldosteronism (PA) is the most common form of secondary hypertension. Thus, the aims of this study were: (1) to clarify whether the fludrocortisone suppression test (FST), which confirms autonomous aldosterone secretion, is reliable when carried out during a shorter period of time and (2) to confirm the importance of NaCl supplementation. The cut-off limits already obtained for aldosterone in healthy subjects during the FST were applied in hypertensive patients with a high aldosterone to renin ratio (ARR). The healthy subjects were allocated to three groups. Fludrocortisone was administered 4 times daily over 4 days and sodium chloride was supplemented in 3 different doses. The result was applied in 24 hypertensive patients, in 24 healthy subjects (10 women (23-38 years old) and 14 men (23-58 years old)) and in 24 patients with hypertension and high ARR (16 women (45-74 years old) and 8 men (56-73 years old)). Blood pressure, aldosterone, renin, potassium and sodium were measured. After three days of FST, there was a significant decrease in the serum level of aldosterone in the healthy subjects, regardless of high or low sodium chloride supplementation (p<0.001). The decrease in serum aldosterone was significantly less pronounced in patients with PA than in healthy subjects and hypertensive patients without PA (p<0.001). The 95th percentile of plasma aldosterone at the end of the test was 225 pmol/L. The FST can be shortened to 3 days and a daily 500 mg NaCl supplementation is sufficient. A cut-off value for aldosterone of 225 pmol/L after 4 days with FST is appropriate.

  20. 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.

  1. [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

  2. Effects of treatment with β-blocker and aldosterone antagonist on central and peripheral haemodynamics and oxygenation in cirrhosis

    DEFF Research Database (Denmark)

    Winkler, Christine; Hobolth, Lise; Krag, Aleksander

    2011-01-01

    Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with β-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics and oxyg......Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with β-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics...

  3. Aldosterone Inhibits the Fetal Program and Increases Hypertrophy in the Heart of Hypertensive Mice

    Science.gov (United States)

    Azibani, Feriel; Devaux, Yvan; Coutance, Guillaume; Schlossarek, Saskia; Polidano, Evelyne; Fazal, Loubina; Merval, Regine; Carrier, Lucie; Solal, Alain Cohen; Chatziantoniou, Christos; Launay, Jean-Marie; Samuel, Jane-Lise; Delcayre, Claude

    2012-01-01

    Background Arterial hypertension (AH) induces cardiac hypertrophy and reactivation of “fetal” gene expression. In rodent heart, alpha-Myosin Heavy Chain (MyHC) and its micro-RNA miR-208a regulate the expression of beta-MyHC and of its intronic miR-208b. However, the role of aldosterone in these processes remains unclear. Methodology/Principal Findings RT-PCR and western-blot were used to investigate the genes modulated by arterial hypertension and cardiac hyperaldosteronism. We developed a model of double-transgenic mice (AS-Ren) with cardiac hyperaldosteronism (AS mice) and systemic hypertension (Ren). AS-Ren mice had increased (x2) angiotensin II in plasma and increased (x2) aldosterone in heart. Ren and AS-Ren mice had a robust and similar hypertension (+70%) versus their controls. Anatomical data and echocardiography showed a worsening of cardiac hypertrophy (+41%) in AS-Ren mice (P<0.05 vs Ren). The increase of ANP (x 2.5; P<0.01) mRNA observed in Ren mice was blunted in AS-Ren mice. This non-induction of antitrophic natriuretic peptides may be involved in the higher trophic cardiac response in AS-Ren mice, as indicated by the markedly reduced cardiac hypertrophy in ANP-infused AS-Ren mice for one month. Besides, the AH-induced increase of ßMyHC and its intronic miRNA-208b was prevented in AS-Ren. The inhibition of miR 208a (−75%, p<0.001) in AS-Ren mice compared to AS was associated with increased Sox 6 mRNA (x 1.34; p<0.05), an inhibitor of ßMyHC transcription. Eplerenone prevented all aldosterone-dependent effects. Conclusions/Significance Our results indicate that increased aldosterone in heart inhibits the induction of atrial natriuretic peptide expression, via the mineralocorticoid receptor. This worsens cardiac hypertrophy without changing blood pressure. Moreover, this work reveals an original aldosterone-dependent inhibition of miR-208a in hypertension, resulting in the inhibition of β-myosin heavy chain expression through the induction of

  4. Aldosterone inhibits the fetal program and increases hypertrophy in the heart of hypertensive mice.

    Directory of Open Access Journals (Sweden)

    Feriel Azibani

    Full Text Available BACKGROUND: Arterial hypertension (AH induces cardiac hypertrophy and reactivation of "fetal" gene expression. In rodent heart, alpha-Myosin Heavy Chain (MyHC and its micro-RNA miR-208a regulate the expression of beta-MyHC and of its intronic miR-208b. However, the role of aldosterone in these processes remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: RT-PCR and western-blot were used to investigate the genes modulated by arterial hypertension and cardiac hyperaldosteronism. We developed a model of double-transgenic mice (AS-Ren with cardiac hyperaldosteronism (AS mice and systemic hypertension (Ren. AS-Ren mice had increased (x2 angiotensin II in plasma and increased (x2 aldosterone in heart. Ren and AS-Ren mice had a robust and similar hypertension (+70% versus their controls. Anatomical data and echocardiography showed a worsening of cardiac hypertrophy (+41% in AS-Ren mice (P<0.05 vs Ren. The increase of ANP (x 2.5; P<0.01 mRNA observed in Ren mice was blunted in AS-Ren mice. This non-induction of antitrophic natriuretic peptides may be involved in the higher trophic cardiac response in AS-Ren mice, as indicated by the markedly reduced cardiac hypertrophy in ANP-infused AS-Ren mice for one month. Besides, the AH-induced increase of ßMyHC and its intronic miRNA-208b was prevented in AS-Ren. The inhibition of miR 208a (-75%, p<0.001 in AS-Ren mice compared to AS was associated with increased Sox 6 mRNA (x 1.34; p<0.05, an inhibitor of ßMyHC transcription. Eplerenone prevented all aldosterone-dependent effects. CONCLUSIONS/SIGNIFICANCE: Our results indicate that increased aldosterone in heart inhibits the induction of atrial natriuretic peptide expression, via the mineralocorticoid receptor. This worsens cardiac hypertrophy without changing blood pressure. Moreover, this work reveals an original aldosterone-dependent inhibition of miR-208a in hypertension, resulting in the inhibition of β-myosin heavy chain expression through the induction

  5. 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....

  6. Influence of Angiotensin-Aldosterone System on Ultrasound of Joints in Patients with Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    O.B. Komarova

    2014-02-01

    Full Text Available In patients with rheumatoid arthritis and high level of angiotensin II in the blood at ultrasound of joints there are often being detected effusion in the joint cavity, hypervascularization of synovium with 2–3 points and tenosynovitis characterizing inflammatory exudative processes. In patients with high level of aldosterone, hyperplasia of synovium, presence of pannus and bone and cartilage erosions, indicating proliferative-destructive processes, were predominated. Identified correlations show that with increasing levels of angiotensin II in the blood increases the intensity of the vascularization of the synovial membrane, joint effusion, and an increase in the concentration of aldosterone in the blood affects the synovial thickness indicators, the presence of pannus and bone erosions amount.

  7. Aldosterone and cortisol co-secreting bifunctional adrenal cortical carcinoma: A rare event

    Directory of Open Access Journals (Sweden)

    Puskar Shyam Chowdhury

    2014-01-01

    Full Text Available Adrenocortical carcinoma (ACC co-secreting aldosterone and cortisol is extremely rare. We report the case of a 37-yearold female who presented with paresis and facial puffiness. Evaluation revealed hypertension, hyperglycemia, severe hypokalemia and hyperaldosteronemia with elevated plasma aldosterone to renin ratio (ARR. Urinary free cortisol estimation showed elevated levels. Computed tomography scan revealed a right adrenal mass. Radical adrenalectomy specimen revealed ACC (T3N1. Post-operatively, the patient became normotensive and euglycemic with normalization of urinary cortisol and ARR. This case highlights the need for a complete evaluation in patients of hyperaldosteronism if overlapping symptoms of hypercortisolism are encountered, to avoid post-operative adrenal crisis.

  8. Early nongenomic events in aldosterone action in renal collecting duct cells: PKCalpha activation, mineralocorticoid receptor phosphorylation, and cross-talk with the genomic response.

    Science.gov (United States)

    Le Moëllic, Cathy; Ouvrard-Pascaud, Antoine; Capurro, Claudia; Cluzeaud, Francoise; Fay, Michel; Jaisser, Frederic; Farman, Nicolette; Blot-Chabaud, Marcel

    2004-05-01

    Effects of aldosterone on its target cells have long been considered to be mediated exclusively through the genomic pathway; however, evidence has been provided for rapid effects of the hormone that may involve nongenomic mechanisms. Whether an interaction exists between these two signaling pathways is not yet established. In this study, the authors show that aldosterone triggers both early nongenomic and late genomic increase in sodium transport in the RCCD(2) rat cortical collecting duct cell line. In these cells, the early (up to 2.5 h) aldosterone-induced increase in short-circuit current (Isc) is not blocked by the mineralocorticoid receptor (MR) antagonist RU26752, it does not require mRNA or protein synthesis, and it involves the PKCalpha signaling pathway. In addition, this early response is reproduced by aldosterone-BSA, which acts at the cell surface and presumably does not enter the cells (aldo-BSA is unable to trigger the late response). The authors also show that MR is rapidly phosphorylated on serine and threonine residues by aldosterone or aldosterone-BSA. In contrast, the late (4 to 24 h) aldosterone-induced increase in ion transport occurs through activation of the MR and requires mRNA and protein synthesis. Interestingly, nongenomic and genomic aldosterone actions appear to be interdependent. Blocking the PKCalpha pathway results in the inhibition of the late genomic response to aldosterone, as demonstrated by the suppression of aldosterone-induced increase in MR transactivation activity, alpha1 Na(+)/K(+)/ATPase mRNA, and Isc. These data suggest cross-talk between the nongenomic and genomic responses to aldosterone in renal cells and suggest that the aldosterone-MR mediated increase in mRNA/protein synthesis and ion transport depends, at least in part, upon PKCalpha activation. E-mail: marcel.blot-chabaud@pharmacie.univ-mrs.fr

  9. Association of Aldosterone and Cortisol with Cardiovascular Risk Factors in Prehypertension Stage

    Directory of Open Access Journals (Sweden)

    Sadiqa Badar Syed

    2012-01-01

    Full Text Available Background. The Pakistani population has higher incidence of cardiovascular (CV diseases at younger ages, due to undiagnosed, uncontrolled hypertension (HTN. A variety of associated HTN stressors is also reported. The study plans to understand the variables associated with initiation of HTN in this population. Objective. To find plasma aldosterone and cortisol relationship with some CV risk factors (obesity, dyslipidemia, hyperglycemia, sodium and potassium in different stages of HTN particularly prehypertension. Subjects and Methods. The study conducted on 276 subjects (25–60 years, classified into prehypertensive (=55, HTN stage-1 (=70 and II (=76 according to 7th JNC report and compared with normotensive controls (=75. The anthropometric profiles (height, weight, waist circumference, Body Mass index and BP recorded. Serum cortisol, aldosterone, total cholesterol, Low density lipoproteins, blood glucose, Na+ and K+, using standard laboratory techniques, were determined in fasting blood samples. Results. Subjects were mostly overweight and obese (80%, 90%, and 76% in pre-HTN, stage-I and II versus 69% in controls. The aldosterone level (ng/dl was in higher normal range (9.17–12.41 and significantly correlated to BMI (0.587 in controls, and to TC (0.726 and LDL (0.620 in pre-HTN stage-I. The cortisol level was positively correlated (25. Conclusion. Pre-HTN stage among Pakistani population with successive increase in various risk factors of HTN in relation to aldosterone and cortisol has been identified. Interaction of the risk factors with endogenous levels of these hormones may initiate stages of HTN.

  10. 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.

  11. Aldosterone induction of electrogenic sodium transport in the apical membrane vesicles of rat distal colon

    International Nuclear Information System (INIS)

    Rajendran, V.M.; Kashgarian, M.; Binder, H.J.

    1989-01-01

    Na-H exchange is present in apical membrane vesicles (AMV) isolated from distal colon of normal rats. Because in intact tissue aldosterone both induces amiloride-sensitive electrogenic sodium transport and inhibits electroneutral sodium absorption, these studies with AMV were designed to establish the effect of aldosterone on sodium transport. An outward-directed proton gradient stimulated 22Na uptake in AMV isolated from distal colon of normal and dietary sodium depleted (with elevated aldosterone levels) experimental rats. Unlike normal AMV, proton gradient-dependent 22Na uptake in experimental AMV was inhibited when uptake was measured under voltage-clamped conditions. 10 microM amiloride inhibited the initial rate of proton gradient-dependent 22Na uptake in AMV of normal and experimental rats by 30 and 75%, respectively. In contrast, 1 mM amiloride produced comparable inhibition (90 and 80%) of 22Na uptake in normal and experimental AMV. Intravesicular-negative potential stimulated 22Na uptake in experimental but not in normal AMV. This increase was inhibited by 90% by 10 microM amiloride. An analogue of amiloride, 5-(N-ethylisopropyl) amiloride (1 microM), a potent inhibitor of electroneutral Na-H exchange in AMV of normal rat distal colon, did not alter potassium diffusion potential-dependent 22Na uptake. Increasing sodium concentration saturated proton gradient-dependent 22Na uptake in normal AMV. However, in experimental AMV, 22Na uptake stimulated by both proton gradient and potassium diffusion potential did not saturate as a function of increasing sodium concentration. We conclude from these results that an electrically sensitive conductive channel, not electroneutral Na-H exchange, mediates 22Na uptake in AMV isolated from the distal colon of aldosterone rats

  12. Interacting influence of potassium and polychlorinated biphenyl on cortisol and aldosterone biosynthesis

    International Nuclear Information System (INIS)

    Li, L.-A.; Lin, Tsu-Chun Emma

    2007-01-01

    Giving human adrenocortical H295R cells 14 mM KCl for 24 h significantly induced not only aldosterone biosynthesis but also cortisol biosynthesis. Pre-treating the cells with polychlorinated biphenyl 126 (PCB126) further increased potassium-induced aldosterone and cortisol productions in a dose-dependent manner, but all examined concentrations of PCB126 had little effect on the yields of precursor steroids progesterone and 17-OH-progesterone. Subsequent examinations revealed that CYP11B1 and CYP11B2 genes, responsible for the respective final steps of the cortisol and aldosterone biosynthetic pathways, exhibited increased responsiveness to PCB126 under high potassium. While 10 -5 M PCB126 was needed to induce a significant increase in the basal mRNA abundance of either gene, PCB126 could enhance potassium-induced mRNA expression of CYP11B1 at 10 -7 M and CYP11B2 at 10 -9 M. Actually, potassium and PCB126 synergistically upregulated mRNA expression of both genes. Potassium raised the transcriptional rates of CYP11B1 and CYP11B2 probably through a conserved Ad5 cis-element, whereas PCB126 appeared to regulate these two genes at the post-transcriptional level. Positive potassium-PCB126 synergism was also detected in CYP11B2 enzyme activity estimated by aldosterone/progesterone ratio. In contrast, potassium and PCB126 increased CYP11B1 enzyme activity or cortisol/17-OH-progesterone ratio additively. Moreover, potassium improved the time effect of PCB126 on gene expression and enzyme activity of CYP11B2, but not the PCB126 time response of CYP11B1. These data demonstrated that potassium differentially enhanced the potency of PCB126 to induce CYP11B1- and CYP11B2-mediated steroidogenesis

  13. Confirmatory Tests for the Diagnosis of Primary Aldosteronism: A Prospective Diagnostic Accuracy Study.

    Science.gov (United States)

    Song, Ying; Yang, Shumin; He, Wenwen; Hu, Jinbo; Cheng, Qingfeng; Wang, Yue; Luo, Ting; Ma, Linqiang; Zhen, Qianna; Zhang, Suhua; Mei, Mei; Wang, Zhihong; Qing, Hua; Bruemmer, Dennis; Peng, Bin; Li, Qifu

    2018-01-01

    The diagnosis of primary aldosteronism typically requires at least one confirmatory test. The fludrocortisone suppression test is generally accepted as a reliable confirmatory test, but it is cumbersome. Evidence from accuracy studies of the saline infusion test (SIT) and the captopril challenge test (CCT) has provided conflicting results. This prospective study aimed to evaluate the diagnostic accuracy of the SIT and CCT using fludrocortisone suppression test as the reference standard. One hundred thirty-five patients diagnosed with primary aldosteronism and 101 patients diagnosed with essential hypertension who completed the 3 confirmatory tests were included for the diagnostic accuracy analysis. The areas under the receiver-operator characteristics curves of the CCT and SIT were 0.96 (95% confidence interval [CI], 0.92-0.98) and 0.96 (95% CI, 0.92-0.98), respectively, using post-test plasma aldosterone concentration (PAC) for diagnosis. However, the areas under the receiver-operator characteristics curves of the CCT decreased to 0.71 (95% CI, 0.65-0.77) when the PAC suppression percentage was used to diagnose primary aldosteronism. The optimal cutoff of PAC post-CCT was set at 11 ng/dL, resulting in a sensitivity of 0.90 (95% CI, 0.84-0.95) and a specificity of 0.90 (95% CI, 0.83-0.95), which were not significantly different from those of SIT (with PAC post-SIT set at 8 ng/dL, sensitivity: 0.85 [95% CI, 0.78-0.91], P =0.192; specificity: 0.92 [95% CI, 0.85-0.97], P =0.551). In conclusion, both CCT and SIT are accurate alternatives to the more complex fludrocortisone suppression test. Because CCT is safe and much easier to perform, it may serve as a more feasible alternative. When interpreting the results of CCT, PAC post-CCT is highly recommended. © 2017 American Heart Association, Inc.

  14. Akt-mediated cardioprotective effects of aldosterone in type 2 diabetic mice.

    Science.gov (United States)

    Fazal, Loubina; Azibani, Feriel; Bihry, Nicolas; Coutance, Guillaume; Polidano, Evelyne; Merval, Régine; Vodovar, Nicolas; Launay, Jean-Marie; Delcayre, Claude; Samuel, Jane-Lise

    2014-06-01

    Studies have shown that aldosterone would have angiogenic effects and therefore would be beneficial in the context of cardiovascular diseases. We thus investigated the potential involvement of aldosterone in triggering a cardiac angiogenic response in the context of type-2 diabetes and the molecular pathways involved. Male 3-wk-old aldosterone synthase (AS)-overexpressing mice and their control wild-type (WT) littermates were fed a standard or high-fat, high-sucrose (HFHS) diet. After 6 mo of diet treatment, mice were euthanized, and cardiac samples were assayed by RT-PCR, immunoblotting, and immunohistology. HFHS diet induced type-2 diabetes in WT (WT-D) and AS (AS-D) mice. VEGFa mRNAs decreased in WT-D (-43%, P<0.05 vs. WT) and increased in AS-D mice (+236%, P< 0.01 vs. WT-D). In WT-D mouse hearts, the proapoptotic p38MAPK was activated (P<0.05 vs. WT and AS-D), whereas Akt activity decreased (-64%, P<0.05 vs. WT). The AS mice, which exhibited a cardiac up-regulation of IGF1-R, showed an increase in Akt phosphorylation when diabetes was induced (P<0.05 vs. WT and AS-D). Contrary to WT-D mice, AS-D mouse hearts did not express inflammatory markers and exhibited a normal capillary density (P<0.05 vs. WT-D). To our knowledge, this is the first study providing new insights into the mechanisms whereby aldosterone prevents diabetes-induced cardiac disorders. © FASEB.

  15. A short review of primary aldosteronism in a question and answer fashion

    Directory of Open Access Journals (Sweden)

    Farrugia Frederick-Anthony

    2018-01-01

    Full Text Available Objectives. The aim of this study was to present up to date information concerning the diagnosis and treatment of primary aldosteronism (PA. PA is the most common cause of endocrine hypertension. It has been reported up to 24% of selective referred hypertensive patients. Methods. We did a search in Pub-Med and Google Scholar using the terms: PA, hyperaldosteronism, idiopathic adrenal hyperplasia, diagnosis of PA, mineralocorticoid receptor antagonists, adrenalectomy, and surgery. We also did cross-referencing search with the above terms. We had divided our study into five sections: Introduction, Diagnosis, Genetics, Treatment, and Conclusions. We present our results in a question and answer fashion in order to make reading more interesting. Results. PA should be searched in all high-risk populations. The gold standard for diagnosis PA is the plasma aldosterone/plasma renin ratio (ARR. If this test is positive, then we proceed with one of the four confirmatory tests. If positive, then we proceed with a localizing technique like adrenal vein sampling (AVS and CT scan. If the lesion is unilateral, after proper preoperative preparation, we proceed, in adrenalectomy. If the lesion is bilateral or the patient refuses or is not fit for surgery, we treat them with mineralocorticoid receptor antagonists, usually spironolactone. Conclusions. Primary aldosteronism is the most common and a treatable case of secondary hypertension. Only patients with unilateral adrenal diseases are eligible for surgery, while patients with bilateral and non-surgically correctable PA are usually treated by mineralocorticoid receptor antagonist (MRA. Thus, the distinction between unilateral and bilateral aldosterone hypersecretion is crucial.

  16. The effect of a heptapeptide angiotensin analogue on aldosterone secretion in the rabbit

    International Nuclear Information System (INIS)

    Neusy, A.J.; Steele, J.M. Jr.; Lowenstein, J.

    1980-01-01

    To investigate the effects of the heptapeptide analogue, 7 Ile A III on angiotensin II and angiotensin III, the mean blood pressure, the plasma reninactivity, and the plasma aldosteron concentration were measured under various circumstances (dexamethasan infusion, 7 Ile A III addition, bleeding). The measurements were carried out by means of RIA. The adrenal, renal, and vascular reactions to the competitive blockade are discussed with reference to the results obtained. (orig.) [de

  17. A short review of primary aldosteronism in a question and answer fashion.

    Science.gov (United States)

    Farrugia, Frederick-Anthony; Zavras, Nicolaos; Martikos, Georgios; Tzanetis, Panagiotis; Charalampopoulos, Anestis; Misiakos, Evangelos P; Sotiropoulos, Dimitrios; Koliakos, Nikolaos

    2018-01-01

    The aim of this study was to present up to date information concerning the diagnosis and treatment of primary aldosteronism (PA). PA is the most common cause of endocrine hypertension. It has been reported up to 24% of selective referred hypertensive patients. We did a search in Pub-Med and Google Scholar using the terms: PA, hyperaldosteronism, idiopathic adrenal hyperplasia, diagnosis of PA, mineralocorticoid receptor antagonists, adrenalectomy, and surgery. We also did cross-referencing search with the above terms. We had divided our study into five sections: Introduction, Diagnosis, Genetics, Treatment, and Conclusions. We present our results in a question and answer fashion in order to make reading more interesting. PA should be searched in all high-risk populations. The gold standard for diagnosis PA is the plasma aldosterone/plasma renin ratio (ARR). If this test is positive, then we proceed with one of the four confirmatory tests. If positive, then we proceed with a localizing technique like adrenal vein sampling (AVS) and CT scan. If the lesion is unilateral, after proper preoperative preparation, we proceed, in adrenalectomy. If the lesion is bilateral or the patient refuses or is not fit for surgery, we treat them with mineralocorticoid receptor antagonists, usually spironolactone. Primary aldosteronism is the most common and a treatable case of secondary hypertension. Only patients with unilateral adrenal diseases are eligible for surgery, while patients with bilateral and non-surgically correctable PA are usually treated by mineralocorticoid receptor antagonist (MRA). Thus, the distinction between unilateral and bilateral aldosterone hypersecretion is crucial.

  18. Effect of deafferentation of the rat tongue on plasma corticosterone, aldosterone, angiotensin and ACTH levels

    International Nuclear Information System (INIS)

    Polyntsev, Yu.V.; Serova, O.N.

    1987-01-01

    The effect of deafferentation of the tongue on the plasma level of hormones involved in regulation of the sodium ion level -- aldosterone, corticosterone, ACTH, and angiotensin -- was studied. Plasma hormone levels were determined by radioimmunoassay. The results indicate the important role of orosensory and taste perception in the processes of regulation of the sodium balance in the body. The experiments in this study were conducted on rats

  19. 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.

  20. 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)

  1. Antiapolipoprotein A-1 IgG chronotropic effects require nongenomic action of aldosterone on L-type calcium channels.

    Science.gov (United States)

    Rossier, Michel F; Pagano, Sabrina; Python, Magaly; Maturana, Andres D; James, Richard W; Mach, François; Roux-Lombard, Pascale; Vuilleumier, Nicolas

    2012-03-01

    Autoantibodies to apolipoprotein A-1 (antiapoA-1 IgG) have been shown to be associated with higher resting heart rate and morbidity in myocardial infarction patients and to behave as a chronotropic agent in the presence of aldosterone on isolated neonatal rat ventricular cardiomyocytes (NRVC). We aimed at identifying the pathways accounting for this aldosterone-dependent antiapoA-1 IgG-positive chronotropic effect on NRVC. The rate of regular spontaneous contractions was determined on NRVC in the presence of different steroid hormones and antagonists. AntiapoA-1 IgG chronotropic response was maximal within 20 min and observed only in aldosterone-pretreated cells but not in those exposed to other steroids. The positive antiapoA-1 IgG chronotropic effect was already significant after 5 min aldosterone preincubation, was dependent on 3-kinase and protein kinase A activities, was not inhibited by actinomycin D, and was fully abrogated by eplerenone (but not by spironolactone), demonstrating the dependence on a nongenomic action of aldosterone elicited through the mineralocorticoid receptor (MR). Under oxidative conditions (but not under normal redox state), corticosterone mimicked the permissive action of aldosterone on the antiapoA-1 IgG chronotropic response. Pharmacological and patch-clamp studies identified L-type calcium channels as crucial effectors of antiapoA-1 IgG chronotropic action, involving two converging pathways that increase the channel activity. The first one involves the rapid, nongenomic activation of the phosphatidylinositol 3-kinase enzyme by MR, and the second one requires a constitutive basal protein kinase A activity. In conclusion, our results indicate that, on NRVC, the aldosterone-dependent chronotropic effects of antiapoA-1 IgG involve the nongenomic activation of L-type calcium channels.

  2. Inappropriately low aldosterone concentrations in adults with AIDS-related diarrhoea in Zambia: a study of response to fluid challenge

    Directory of Open Access Journals (Sweden)

    Lumayi Ruth

    2008-04-01

    Full Text Available Abstract Background Chronic diarrhoea is one of the most debilitating consequences of HIV infection in sub-Saharan Africa and it carries a high mortality rate. We report unexpectedly low concentrations of circulating aldosterone in 12 patients (6 men, 6 women in the University Teaching Hospital, Lusaka, who all had diarrhoea for over one month. Changes in serum electrolytes, blood pressure, Karnofsky score and serum aldosterone concentration were being monitored during a short study of responses to saline infusion (3 litres/24 h over 72 hours. Findings At baseline, 9/12 (75% of the patients were hyponatraemic, 10/11 (91% were hypokalaemic, and 6/12 (50% had undetectable aldosterone concentrations. Blood pressure and Karnofsky score rose and creatinine concentration fell in response to the infusion. Conclusion Circulating aldosterone concentrations were inappropriately low and complicate the profound electrolyte deficiencies resulting from chronic diarrhoea. Management of these deficiencies needs to be more aggressive than is currently practised and consideration should be given to a formal clinical trial of mineralocorticoid replacement in these severely ill patients. If the inappropriately low aldosterone reflects a general adrenal failure, it may explain a considerable proportion of the high mortality seen both before and after initiation of anti-retroviral therapy.

  3. Application of a Ligand-based theoretical approach to derive conversion paths and Ligand conformations in CYP11B2-mediated aldosterone formation

    NARCIS (Netherlands)

    Roumen, L.; Hoof, van B.; Pieterse, K.; Hilbers, P.A.J.; Custers, E.M.G.; Plate, R.; Gooyer, de M.E.; Beugels, I.P.E.; Emmen, J.M.A.; Leysen, D.; Smits, J.F.M.; Ottenheijm, H.C.J.; Hermans, J.J.R.M.

    2011-01-01

    The biosynthesis of the mineralocorticoid hormone aldosterone involves a multistep hydroxylation of 11-deoxycorticosterone at the 11- and 18-positions, resulting in the formation of corticosterone and 18-hydroxycorticosterone, the final precursor of aldosterone. Two members of the cytochrome P450

  4. Protein kinase D stabilizes aldosterone-induced ERK1/2 MAP kinase activation in M1 renal cortical collecting duct cells to promote cell proliferation.

    LENUS (Irish Health Repository)

    McEneaney, Victoria

    2010-01-01

    Aldosterone elicits transcriptional responses in target tissues and also rapidly stimulates the activation of protein kinase signalling cascades independently of de novo protein synthesis. Here we investigated aldosterone-induced cell proliferation and extra-cellular regulated kinase 1 and 2 (ERK1\\/2) mitogen activated protein (MAP) kinase signalling in the M1 cortical collecting duct cell line (M1-CCD). Aldosterone promoted the proliferative growth of M1-CCD cells, an effect that was protein kinase D1 (PKD1), PKCdelta and ERK1\\/2-dependent. Aldosterone induced the rapid activation of ERK1\\/2 with peaks of activation at 2 and 10 to 30 min after hormone treatment followed by sustained activation lasting beyond 120 min. M1-CCD cells suppressed in PKD1 expression exhibited only the early, transient peaks in ERK1\\/2 activation without the sustained phase. Aldosterone stimulated the physical association of PKD1 with ERK1\\/2 within 2 min of treatment. The mineralocorticoid receptor (MR) antagonist RU28318 inhibited the early and late phases of aldosterone-induced ERK1\\/2 activation, and also aldosterone-induced proliferative cell growth. Aldosterone induced the sub-cellular redistribution of ERK1\\/2 to the nuclei at 2 min and to cytoplasmic sites, proximal to the nuclei after 30 min. This sub-cellular distribution of ERK1\\/2 was inhibited in cells suppressed in the expression of PKD1.

  5. [Farmacological effect of retabolil on aldosterone level and arterial pressure in rats under the action of vibrations].

    Science.gov (United States)

    Obut, T A; Ovsiukova, M V; Egorova, S A; Érdynieva, T A; Dement'eva, T Iu; Obut, E T

    2014-01-01

    The experiments were performed on male rats, which were subjected to single and multiply repeated vibrations (low-frequency, horizontal, high-amplitude) analogous to the action of motor transport vibrations. It is established that the administration of retabolil produces a hypotensive effect and blocks the vibration-induced increase in the level of hypertensive hormone aldosterone. Under conditions of the multiply repeated action of vibrations, both effects were realized via micro-opioid receptors. In the case of a single action, these receptors were only involved in a hypotensive effect but not mediated in aldosterone suppression. Both these effects were absent in the control group of animals (not subjected to vibrations). Therefore, retabolil can be used as a hypotensive and aldosterone-blocking drug for vibration-induced hypertension in animals and, probably, in humans.

  6. 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.

  7. Diagnosing unilateral primary aldosteronism - comparison of a clinical prediction score, computed tomography and adrenal venous sampling.

    Science.gov (United States)

    Sze, W C Candy; Soh, Lip Min; Lau, Jeshen H; Reznek, Rodney; Sahdev, Anju; Matson, Matthew; Riddoch, Fiona; Carpenter, Robert; Berney, Dan; Grossman, Ashley B; Chew, Shern L; Akker, Scott A; Druce, Maralyn R; Waterhouse, Mona; Monson, John P; Drake, William M

    2014-07-01

    In patients with primary aldosteronism (PA), adrenalectomy is potentially curative for those correctly identified as having unilateral excessive aldosterone production. It has been suggested that a recently developed and published clinical prediction score (CPS) may correctly identify some patients as having unilateral disease, without recourse to adrenal venous sampling. We have applied the CPS to a large cohort of PA patients with defined and documented outcomes. We also incorporated a minor modification to the CPS and a radiological grading score (RGS) into our analysis to assess whether its performance could be augmented. A total of 75 patients with a robust diagnosis following bilateral adrenal venous cannulation and/or strictly defined surgical outcome were analysed. Applying the CPS to this group of patients produced a sensitivity of 38·8% and a specificity of 88·5% of correctly identifying unilateral aldosterone production. Using a suggested modification to the CPS, in which different levels of hypokalaemia were given different weightings, the sensitivity rose to 40·8%, with an identical specificity. Using the RGS alone improved sensitivity to 91·7%, but specificity was reduced to 62·5%. Applying the recently developed CPS to this cohort of patients, it was not possible to reproduce the 100% specificity reported in the original publication. Using the modified score or incorporating the RGS did not improve its performance. In this cohort, we were unable to show superiority of the CPS over an imaging-based strategy. CPS may have a role in guiding clinical decision-making, especially in those whose adrenal venous sampling (AVS) has been unsuccessful. © 2013 John Wiley & Sons Ltd.

  8. Stress-induced Aldosterone Hyper-Secretion in a Substantial Subset of Patients With Essential Hypertension.

    Science.gov (United States)

    Markou, Athina; Sertedaki, Amalia; Kaltsas, Gregory; Androulakis, Ioannis I; Marakaki, Chrisanthi; Pappa, Theodora; Gouli, Aggeliki; Papanastasiou, Labrini; Fountoulakis, Stelios; Zacharoulis, Achilles; Karavidas, Apostolos; Ragkou, Despoina; Charmandari, Evangelia; Chrousos, George P; Piaditis, George P

    2015-08-01

    Aldosterone (ALD) secretion is regulated mainly by angiotensin II, K(+), and adrenocorticotropic hormone (ACTH). Mineralocorticoid receptor antagonists (MRAs) have effectively been used for the treatment of patients with hypertension who do not have primary aldosteronism (PA). We tested whether chronic stress-related ACTH-mediated ALD hypersecretion and/or zona glomerulosa hypersensitivity could be implicated in the pathogenesis of essential hypertension (ESHT). One hundred thirteen hypertensives without PA and 61 normotensive controls underwent an ultralow-dose (0.03-μg) ACTH stimulation and a treadmill test. Patients with ALD hyper-response according to the cutoffs obtained from controls received treatment with MRAs and underwent genomic DNA testing for the presence of the CYP11B1/CYP11B2 chimeric gene and KCNJ5 gene mutations. A control group of 22 patients with simple ESHT received treatment with MRAs. Based on the cutoffs of ALD and aldosterone-to-renin ratio (ARR) post-ACTH stimulation obtained from controls, 30 patients (27%) exhibited an ALD but not cortisol (F) hyper-response (HYPER group). This group had no difference in basal ACTH/renin (REN) concentrations compared with controls and the 83 patients with hypertension (73%) without an ALD hyper-response to ACTH stimulation. Patients in the HYPER group demonstrated significantly higher ALD concentrations, ARR, and ALD/ACTH ratio (AAR) in the treadmill test. Treatment with MRAs alone produced normalization of blood pressure in these patients whereas patients with hypertension with neither PA nor ALD hyper-response to ACTH stimulation who served as a control group failed to lower blood pressure. Also, two novel germline heterozygous KCNJ5 mutations were detected in the HYPER group. A number of patients with hypertension without PA show ACTH-dependent ALD hyper-secretion and benefit from treatment with MRAs. This could be related to chronic stress via ACTH hyper secretion and/or gene-mutations increasing the

  9. PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues

    Science.gov (United States)

    Felizola, Saulo J. A.; Nakamura, Yasuhiro; Ono, Yoshikiyo; Kitamura, Kanako; Kikuchi, Kumi; Onodera, Yoshiaki; Ise, Kazue; Takase, Kei; Sugawara, Akira; Hattangady, Namita; Rainey, William E.; Satoh, Fumitoshi; Sasano, Hironobu

    2014-01-01

    Purkinje cell protein 4 (PCP4) is a calmodulin (CaM) binding protein that accelerates calcium association and dissociation with CaM. It has been previously detected in aldosterone-producing adenomas (APA) but details on its expression and function in adrenocortical tissues have remained unknown. Therefore, we performed the immunohistochemical analysis of PCP4 in the following tissues: normal adrenal (NA; n=15), APA (n=15), cortisol producing adenomas (CPA; n=15) and idiopathic hyperaldosteronism cases (IHA; n=5). APA samples (n=45) were also submitted to quantitative RT-PCR (qPCR) of PCP4, CYP11B1, and CYP11B2, as well as DNA sequencing for KCNJ5 mutations. Transient transfection analysis using PCP4 siRNA was also performed in H295R adrenocortical carcinoma cells, following ELISA analysis, and CYP11B2 luciferase assays were also performed after PCP4 vector transfection in order to study the regulation of PCP4 protein expression. In our findings, PCP4 immunoreactivity was predominantly detected in APA and in the zona glomerulosa (ZG) of NA and IHA. In APA, the mRNA levels of PCP4 were significantly correlated with those of CYP11B2 (P<0.0001) and were significantly higher in cases with KCNJ5 mutation than wild-type (P=0.005). Following PCP4 vector transfection, CYP11B2 luciferase reporter activity was significantly higher than controls in the presence of angiotensin-II. Knockdown of PCP4 resulted in a significant decrease in CYP11B2 mRNA levels (P=0.012) and aldosterone production (P=0.011). Our results indicate that PCP4 is a regulator of aldosterone production in normal, hyperplastic and neoplastic human adrenocortical cells. PMID:24403568

  10. Association of plasma aldosterone with the metabolic syndrome in two German populations.

    Science.gov (United States)

    Hannemann, Anke; Meisinger, Christa; Bidlingmaier, Martin; Döring, Angela; Thorand, Barbara; Heier, Margit; Belcredi, Petra; Ladwig, Karl-Heinz; Wallaschofski, Henri; Friedrich, Nele; Schipf, Sabine; Lüdemann, Jan; Rettig, Rainer; Peters, Jörg; Völzke, Henry; Seissler, Jochen; Beuschlein, Felix; Nauck, Matthias; Reincke, Martin

    2011-05-01

    The aim of this study was to analyze the potential association of the plasma aldosterone concentration (PAC) with the metabolic syndrome (MetS) and its components in two German population-based studies. We selected 2830 and 2901 participants (31-80 years) from the follow-ups of the Study of Health in Pomerania (SHIP)-1 and the Cooperative Health Research in the Region of Augsburg (KORA) F4 respectively. MetS was defined as the presence of at least three out of the following five criteria: waist circumference ≥94 cm (men (m)) and ≥80 cm (women (w)); high-density lipoprotein (HDL) cholesterol <1.0 mmol/l (m) and <1.3 mmol/l (w); blood pressure ≥130/85 mmHg or antihypertensive treatment; non-fasting glucose (SHIP-1) ≥8 mmol/l, fasting glucose (KORA F4) ≥5.55 mmol/l or antidiabetic treatment; non-fasting triglycerides (SHIP-1) ≥2.3 mmol/l, fasting triglycerides (KORA F4) ≥1.7 mmol/l, or lipid-lowering treatment. We calculated logistic regression models by comparing the highest study- and sex-specific PAC quintiles versus all lower quintiles. MetS was common with 48.1% (m) and 34.8% (w) in SHIP-1 and 42.7% (m) and 27.5% (w) in KORA F4. Our logistic regression models revealed associations of PAC with MetS, elevated triglycerides, and decreased HDL cholesterol in SHIP-1 and KORA F4. Our findings add to the increasing evidence supporting a relation between aldosterone and MetS and suggest that aldosterone may be involved in the pathophysiology of MetS and lipid metabolism disorders.

  11. Can Screening and Confirmatory Testing in the Management of Patients with Primary Aldosteronism be Improved?

    Science.gov (United States)

    Stowasser, Michael; Ahmed, Ashraf; Guo, Zeng; Wolley, Martin; Ungerer, Jacobus; McWhinney, Brett; Poglitsch, Marko; Gordon, Richard

    2017-12-01

    Widespread application of the plasma aldosterone/renin ratio (ARR) as a screening test has led to the recognition that primary aldosteronism (PA) is the most common specifically treatable and potentially curable form of hypertension, accounting for 5-10% of patients. Maximal detection requires accurate diagnostic approaches and awareness and control of factors that confound results, including most antihypertensives, posture, time of day, dietary salt, and plasma potassium. Recent studies have revealed potential for false positives in patients on beta-adrenoceptor blockers, and, when direct renin concentration (but not plasma renin activity) is used to measure renin, in women during the luteal phase of the menstrual cycle or receiving estrogen-containing contraceptives or hormonal replacement therapy. In addition to verapamil slow release, hydralazine and prazosin, moxonidine has minimal effects on the ARR and can be used to control hypertension during work-up. Fludrocortisone suppression testing, while probably the most reliable means of definitively confirming or excluding PA, is time consuming and expensive, requiring a five day inpatient stay. A novel approach, upright (seated) saline infusion suppression testing (SST), has shown excellent reliability with much greater sensitivity than conventional recumbent SST in a recent pilot study, and requires only a day visit. Accurate measurement of aldosterone is essential for each step of PA workup: introduction of new, highly reliable high-throughput mass spectrometric methods into clinical practice has represented a major advance. In response to concerns raised about accuracy of renin assays, new mass spectrometric methods for measuring angiotensin II are currently being assessed in the clinical setting. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Reduced plasma aldosterone concentrations in randomly selected patients with insulin-dependent diabetes mellitus.

    LENUS (Irish Health Repository)

    Cronin, C C

    2012-02-03

    Abnormalities of the renin-angiotensin system have been reported in patients with diabetes mellitus and with diabetic complications. In this study, plasma concentrations of prorenin, renin, and aldosterone were measured in a stratified random sample of 110 insulin-dependent (Type 1) diabetic patients attending our outpatient clinic. Fifty-four age- and sex-matched control subjects were also examined. Plasma prorenin concentration was higher in patients without complications than in control subjects when upright (geometric mean (95% confidence intervals (CI): 75.9 (55.0-105.6) vs 45.1 (31.6-64.3) mU I-1, p < 0.05). There was no difference in plasma prorenin concentration between patients without and with microalbuminuria and between patients without and with background retinopathy. Plasma renin concentration, both when supine and upright, was similar in control subjects, in patients without complications, and in patients with varying degrees of diabetic microangiopathy. Plasma aldosterone was suppressed in patients without complications in comparison to control subjects (74 (58-95) vs 167 (140-199) ng I-1, p < 0.001) and was also suppressed in patients with microvascular disease. Plasma potassium was significantly higher in patients than in control subjects (mean +\\/- standard deviation: 4.10 +\\/- 0.36 vs 3.89 +\\/- 0.26 mmol I-1; p < 0.001) and plasma sodium was significantly lower (138 +\\/- 4 vs 140 +\\/- 2 mmol I-1; p < 0.001). We conclude that plasma prorenin is not a useful early marker for diabetic microvascular disease. Despite apparently normal plasma renin concentrations, plasma aldosterone is suppressed in insulin-dependent diabetic patients.

  13. The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity.

    Science.gov (United States)

    Mete, Ozgur; Duan, Kai

    2018-01-01

    Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype-phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations ( KCNJ5, ATP1A1, ATP2B3 , and CACNA1D ) involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5 -mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3 , and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations ( PRKACA, PRKAR1A, GNAS, PDE11A , and PDE8B ) involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH) have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

  14. The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity

    Directory of Open Access Journals (Sweden)

    Ozgur Mete

    2018-03-01

    Full Text Available Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype–phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations (KCNJ5, ATP1A1, ATP2B3, and CACNA1D involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5-mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3, and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations (PRKACA, PRKAR1A, GNAS, PDE11A, and PDE8B involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

  15. Role of adrenal vein sampling in primary aldosteronism: the Monash Health experience.

    Science.gov (United States)

    Teng, J; Hutchinson, M E; Doery, J C G; Choy, K W; Chong, W; Fuller, P J; Yang, J

    2015-11-01

    Adrenal vein sampling (AVS) is useful for distinguishing unilateral versus bilateral hypersecretion in primary aldosteronism (PA), but is technically challenging. Furthermore, the use of adrenocorticotropic hormone (ACTH)-stimulation in AVS is controversial. We implemented a Monash Health-specific AVS protocol in 2010. The audit aimed to: (i) examine the impact of a dedicated protocol on success rates of AVS at a tertiary referral centre; (ii) evaluate the impact of AVS on sub-typing of PA; and (iii) assess the utility of ACTH stimulation in AVS. AVS was performed on patients with PA confirmed by positive saline suppression testing (aldosterone level >140 pmol/L post-saline infusion), with sequential sampling of adrenal and peripheral veins, pre- and post-ACTH infusion. Patients with unilateral aldosterone-producing adenoma diagnosed on successful AVS were referred for adrenalectomy. Between 2010 and 2014 inclusive, a total of 28 AVS procedures was performed, with complete pre- and post-ACTH data for 19 procedures. Bilateral successful cannulation rates improved post-implementation of our protocol (61% vs 41%). Of the patients, 32% had discordant imaging and AVS results: four patients with unilateral adenomas did not lateralise on AVS and were managed medically; four patients with bilateral or no adenomas on imaging, lateralised on AVS and had surgery. Overall, use of ACTH did not increase successful cannulation and tended to mask lateralisation. AVS is crucial in subtype classification of PA and should be performed by a dedicated radiologist with a standardised protocol. AVS outcomes were not improved with the use of ACTH stimulation. © 2015 Royal Australasian College of Physicians.

  16. 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

  17. Study Heterogeneity and Estimation of Prevalence of Primary Aldosteronism: A Systematic Review and Meta-Regression Analysis.

    Science.gov (United States)

    Käyser, Sabine C; Dekkers, Tanja; Groenewoud, Hans J; van der Wilt, Gert Jan; Carel Bakx, J; van der Wel, Mark C; Hermus, Ad R; Lenders, Jacques W; Deinum, Jaap

    2016-07-01

    For health care planning and allocation of resources, realistic estimation of the prevalence of primary aldosteronism is necessary. Reported prevalences of primary aldosteronism are highly variable, possibly due to study heterogeneity. Our objective was to identify and explain heterogeneity in studies that aimed to establish the prevalence of primary aldosteronism in hypertensive patients. PubMed, EMBASE, Web of Science, Cochrane Library, and reference lists from January 1, 1990, to January 31, 2015, were used as data sources. Description of an adult hypertensive patient population with confirmed diagnosis of primary aldosteronism was included in this study. Dual extraction and quality assessment were the forms of data extraction. Thirty-nine studies provided data on 42 510 patients (nine studies, 5896 patients from primary care). Prevalence estimates varied from 3.2% to 12.7% in primary care and from 1% to 29.8% in referral centers. Heterogeneity was too high to establish point estimates (I(2) = 57.6% in primary care; 97.1% in referral centers). Meta-regression analysis showed higher prevalences in studies 1) published after 2000, 2) from Australia, 3) aimed at assessing prevalence of secondary hypertension, 4) that were retrospective, 5) that selected consecutive patients, and 6) not using a screening test. All studies had minor or major flaws. This study demonstrates that it is pointless to claim low or high prevalence of primary aldosteronism based on published reports. Because of the significant impact of a diagnosis of primary aldosteronism on health care resources and the necessary facilities, our findings urge for a prevalence study whose design takes into account the factors identified in the meta-regression analysis.

  18. 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)

  19. Autoradiographic demonstration of target cells for the mineralocorticoid aldosterone in the rat pineal gland

    International Nuclear Information System (INIS)

    Ruehle, H.J.; Ermisch, A.

    1987-01-01

    Male rats received [ 3 H]aldosterone 30 min before sacrifice. Autoradiograms were prepared from brain and pineal gland by a thaw-mount technique. Grain counting revealed that the pineal retained 4 times as much radioactivity as brain regions with tight capillaries. Using an appropriate method of quantitative autoradiogram evaluation, it was shown that in adrenalectomized animals, but not after shamoperiation, 28% of the pinealocytes concentrated the steroid in their nuclei. This is the first demonstration of saturable mineralocorticoid binding in the pineal gland. (author)

  20. Introductory statement: Of receptors and analogs in renin-angiotensin-aldosterone and adrenergic systems

    International Nuclear Information System (INIS)

    Eliahou, H.E.; Iaina, A.

    1980-01-01

    This article reports on the role of the octapeptides angiotensin II (A II)-effector and its receptor on hypertensive patients and in animal experiments. By applying the A-II-receptor blockers, vasodilates drugs, β-receptor blockers and by sodium depletion, the behaviour of the blood pressure, the plasmareninactivity, and of the aldosteron were investigated; a comparative investigation between the A II and A III effectors was also carried out. The iodo-hippurate uptake was reduced with an artificially produced renal arterial ischemia. In general, this investigation provided new viewpoints in the understanding of the possible pathogenetic mechanism of essential hypertonism. (APR) [de

  1. Whole body computed tomographic findings of each one case with primary aldosteronism and Cushing syndrome

    International Nuclear Information System (INIS)

    Kamata, Shuji; Kawamura, Koro; Nakamura, Motoyuki

    1980-01-01

    We here report each one case with primary aldosteronism (male, 28 years old) and Cushing syndrome (female, 37 years old). Both of the cases showed characteristic clinical signs of hypertension and typical laboratory findings of adreno-hormonal assays. In performance of whole body computed tomography, clear pictures of tumorous adenomas in both cases were taken and the sizes of adenomas in picture were completely same as the masses obtained by the lateral adrenectomies. As a result, the whole body computed tomography is very useful to diagnose the diseases of adrenal adenoma and hyperplasia. (author)

  2. Aldosterone breakthrough in dogs with naturally occurring myxomatous mitral valve disease.

    Science.gov (United States)

    Ames, M K; Atkins, C E; Eriksson, A; Hess, A M

    2017-06-01

    Aldosterone breakthrough (ABT) is the condition in which angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers fail to effectively suppress the activity of the renin angiotensin aldosterone system. The objective of this study was to determine if ABT occurs in dogs with naturally occurring myxomatous mitral valve disease receiving an ACEI, using the urine aldosterone to creatinine ratio (UAldo:C) as a measure of renin angiotensin aldosterone system activation. This study includes 39 dogs with myxomatous mitral valve disease. A UAldo:C cut-off definition (derived from a normal population of healthy, adult, and client-owned dogs) was used to determine the prevalence of ABT in this population. Spearman analysis and univariate logistic regression were used to evaluate the relationship between UAldo:C and ABT (yes/no) and eight variables (age, serum K + concentration, serum creatinine concentration, ACEI therapy duration and ACEI dosage, furosemide therapy duration and furosemide dosage, and urine sample storage time). Finally, the UAldo:C in dogs receiving spironolactone, as part congestive heart failure (CHF) therapy, was compared to dogs with CHF that were not receiving spironolactone. The prevalence of ABT was 32% in dogs with CHF and 30% in dogs without CHF. There was no relationship between either the UAldo:C or the likelihood of ABT and the eight variables. Therapy with spironolactone lead to a significant elevation of the UAldo:C. Using the UAldo:C and a relatively stringent definition of ABT, it appears that incomplete RAAS blockade is common in dogs with MMVD receiving an ACEI. The prevalence of ABT in this canine population mirrors that reported in humans. While the mechanism of ABT is likely multifactorial and still poorly understood, the proven existence of ABT in dogs offers the potential to improve the prognosis for MMVD with the addition of a mineralocorticoid receptor blocker to current therapeutic regimens

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Evaluation of the effects of various sound pressure levels on the level of serum aldosterone concentration in rats

    Directory of Open Access Journals (Sweden)

    Parvin Nassiri

    2017-01-01

    Full Text Available Introduction: Noise exposure may have anatomical, nonauditory, and auditory influences. Considering nonauditory impacts, noise exposure can cause alterations in the automatic nervous system, including increased pulse rates, heightened blood pressure, and abnormal secretion of hormones. The present study aimed at examining the effect of various sound pressure levels (SPLs on the serum aldosterone level among rats. Materials and Methods: A total of 45 adult male rats with an age range of 3 to 4 months and a weight of 200 ± 50 g were randomly divided into 15 groups of three. Three groups were considered as the control groups and the rest (i.e., 12 groups as the case groups. Rats of the case groups were exposed to SPLs of 85, 95, and 105 dBA. White noise was used as the noise to which the rats were exposed. To measure the level of rats’ serum aldosterone, 3 mL of each rat’s sample blood was directly taken from the heart of anesthetized animals by using syringes. The taken blood samples were put in labeled test tubes that contained anticoagulant Ethylenediaminetetraacetic acid. In the laboratory, the level of aldosterone was assessed through Enzyme-linked immunosorbent assay protocol. The collected data were analyzed by the use of Statistical Package for Social Sciences (SPSS version 18. Results: The results revealed that there was no significant change in the level of rats’ serum aldosterone as a result of exposure to SPLs of 65, 85, and 95 dBA. However, the level of serum aldosterone experienced a remarkable increase after exposure to the SPL of 105 dBA (P < 0.001. Thus, the SPL had a significant impact on the serum aldosterone level (P < 0.001. In contrast, the exposure time and the level of potassium in the used water did not have any measurable influence on the level of serum aldosterone (P = 0.25 and 0.39. Conclusion: The findings of this study demonstrated that serum aldosterone can be used as a biomarker in the face of sound

  5. 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...

  6. Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited.

    Science.gov (United States)

    Rossier, Bernard C; Baker, Michael E; Studer, Romain A

    2015-01-01

    Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na(+)-K(+)-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na(+)-K(+)-ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases. Copyright © 2015 the American Physiological Society.

  7. HEAT-INDUCED CHANGES IN ALDOSTERONE LEVEL AND MINERAL BALANCE IN EGYPTIAN BUFFALO CALVES

    International Nuclear Information System (INIS)

    NESSIM, M.Z.; KAMAL, T.H.

    2010-01-01

    Eight male buffalo calves (13 months old) were used in the present study. The animals were maintained in metabolic cages inside a climatic chamber for 2 weeks under mild climate at 21 0 C and 73% RH for 6 hours daily as an adjustment period followed by 7 days at the same climatic conditions as a control period then followed by a heat exposure period for 7 days at 35-42 0 C and 40-50 % RH for 6 hours daily. The animals were fed individually on concentrates and wheat straw. Plasma aldosterone was estimated on the first day after 6 hours of each mild and hot exposure periods. Sodium, potassium, calcium, phosphorus and magnesium balances were estimated on the last three days of control and heat exposure periods. Rectal temperature and respiration rate were recorded daily during both periods. The rectal temperature was raised (P 0 C by the end of 6 hours heat exposure period. The respiration rate was increased (P<0.01) at the end of 6 hours of heat exposure from 25 to 110.81 breaths/minute. Aldosterone was increased (P<0.05) from 5.79 to 37.11 pg/ml whereas sodium, potassium, calcium, phosphorus and magnesium were decreased (P<0.01) by 19.16 %, 40.70%, 46.05 %, 35.69 % and 48.99%, respectively.

  8. Is Laparoendoscopic Single-Site Adrenalectomy a Feasible Alternative in Treating Aldosterone-Producing Adenoma?

    Directory of Open Access Journals (Sweden)

    Che-Hsiung Wu

    2016-01-01

    Full Text Available Objective. To compare laparoendoscopic single-site (LESS and conventional multiport adrenalectomy in patients with aldosterone-producing adenoma (APA. Material and Methods. We retrospectively reviewed patients who had been clinically confirmed with unilateral APA and who underwent LESS or multiport adrenalectomy between 2009 and 2014. Perioperative data were obtained for all patients. Blood pressure and the levels of serum aldosterone, renin, and potassium were checked periodically. Results. We identified 45 APA patients in the LESS group and 71 in the multiport group. The baseline characteristics were matched between two groups. All adrenalectomies were completed successfully, except one with laparoscopic conversion in the single-port group and one open conversion in the multiport group. After a mean follow-up around one year, there were no significant group differences in the improvement of hypertension, number of types of medication taken, and cure of hypokalemia after operation. Conclusions. Our study confirm that LESS adrenalectomy achieved similar clinical and functional outcomes as conventional multiport adrenalectomy for management of unilateral APA.

  9. Human Adrenocortical Remodeling Leading to Aldosterone-Producing Cell Cluster Generation

    Directory of Open Access Journals (Sweden)

    Koshiro Nishimoto

    2016-01-01

    Full Text Available Background. The immunohistochemical detection of aldosterone synthase (CYP11B2 and steroid 11β-hydroxylase (CYP11B1 has enabled the identification of aldosterone-producing cell clusters (APCCs in the subcapsular portion of the human adult adrenal cortex. We hypothesized that adrenals have layered zonation in early postnatal stages and are remodeled to possess APCCs over time. Purposes. To investigate changes in human adrenocortical zonation with age. Methods. We retrospectively analyzed adrenal tissues prepared from 33 autopsied patients aged between 0 and 50 years. They were immunostained for CYP11B2 and CYP11B1. The percentage of APCC areas over the whole adrenal area (AA/WAA, % and the number of APCCs (NOA, APCCs/mm2 were calculated by four examiners. Average values were used in statistical analyses. Results. Adrenals under 11 years old had layered zona glomerulosa (ZG and zona fasciculata (ZF without apparent APCCs. Some adrenals had an unstained (CYP11B2/CYP11B1-negative layer between ZG and ZF, resembling the rat undifferentiated cell zone. Average AA/WAA and NOA correlated with age, suggesting that APCC development is associated with aging. Possible APCC-to-APA transitional lesions were incidentally identified in two adult adrenals. Conclusions. The adrenal cortex with layered zonation remodels to possess APCCs over time. APCC generation may be associated with hypertension in adults.

  10. Changes of serum aldosterone levels in patients with different stages of chronic renal insufficiency

    International Nuclear Information System (INIS)

    Zou Jun; Du Xueliang; Jiang Gengru

    2005-01-01

    Objective: To study the correlationship between the serum aldosterone levels and different stages of chronic renal insufficiency. Methods: Plasma renin activity (PRA), serum angiotensin II (Ang II) contents and serum aldosterone concentration (SACs) were determined with RIA in 42 patients with chronic renal insufficiency from various causes. The patients were divided into three groups according to their endogenous creatinine clearance rate: Group 1, (n=14) Ccr≥60ml/(min·1.73m 2 ); Group 2, (n =13) 20ml/(min·1.73m 2 ) ≤Ccr 2 ); Group 3, (n=15) Ccr 2 ). Results: The SACs values in Group 3 patients were significantly higher than those in Group 1 and Group 2 patients (P<0.01). The SACs values in Group 2 patients were also significantly higher than those in Group 1 patients (P<0.05). Ccr values were higher negatively correlated with the SACs values (r= -0.685, P<0.001). Conclusion: As the creatine clearance rate gradually deteriorated, the SACs values increased correspondingly in patients with chronic renal insufficiency from various causes. (authors)

  11. The management of aldosterone-producing adrenal adenomas--does adrenalectomy increase costs?

    Science.gov (United States)

    Reimel, Bethann; Zanocco, Kyle; Russo, Mark J; Zarnegar, Rasa; Clark, Orlo H; Allendorf, John D; Chabot, John A; Duh, Quan-Yang; Lee, James A; Sturgeon, Cord

    2010-12-01

    Most experts agree that primary hyperaldosteronism (PHA) caused by an aldosterone-producing adenoma (APA) is best treated by adrenalectomy. From a public health standpoint, the cost of treatment must be considered. We sought to compare the current guideline-based (surgical) strategy with universal pharmacologic management to determine the optimal strategy from a cost perspective. A decision analysis was performed using a Markov state transition model comparing the strategies for PHA treatment. Pharmacologic management for all patients with PHA was compared with a strategy of screening for and resecting an aldosterone-producing adenoma. Success rates were determined for treatment outcomes based on a literature review. Medicare reimbursement rates were calculated to estimate costs from a third-party payer perspective. Screening for and resecting APAs was the least costly strategy in this model. For a reference patient with 41 remaining years of life, the discounted expected cost of the surgical strategy was $27,821. The discounted expected cost of the medical strategy was $34,691. The cost of adrenalectomy would have to increase by 156% to $22,525 from $8,784 for universal pharmacologic therapy to be less costly. Screening for APA is more costly if fewer than 9.6% of PHA patients have resectable APA. Resection of APAs was the least costly treatment strategy in this decision analysis model. Copyright © 2010 Mosby, Inc. All rights reserved.

  12. Long-Term Use of Aldosterone-Receptor Antagonists in Uncontrolled Hypertension: A Retrospective Analysis

    Directory of Open Access Journals (Sweden)

    Pieter M. Jansen

    2011-01-01

    Full Text Available Background. The long-term efficacy of aldosterone-receptor antagonists (ARAs as add-on treatment in uncontrolled hypertension has not yet been reported. Methods. Data from 123 patients (21 with primary aldosteronism, 102 with essential hypertension with difficult-to-treat hypertension who received an ARA between May 2005 and September 2009 were analyzed retrospectively for their blood pressure (BP and biochemical response at first followup after start with ARA and the last follow-up available. Results. Systolic BP decreased by 22±20 and diastolic BP by 9.4±12 mmHg after a median treatment duration of 25 months. In patients that received treatment >5 years, SBP was 33±20 and DBP was 16 ± 13 mmHg lower than at baseline. Multivariate analysis revealed that baseline BP and follow-up duration were positively correlated with BP response. Conclusion. Add-on ARA treatment in difficult-to-treat hypertension results in a profound and sustained BP reduction.

  13. What are the keys to successful adrenal venous sampling (AVS) in patients with primary aldosteronism?

    Science.gov (United States)

    Young, William F; Stanson, Anthony W

    2009-01-01

    Adrenal venous sampling (AVS) is the criterion standard to distinguish between unilateral and bilateral adrenal disease in patients with primary aldosteronism. The keys to successful AVS include appropriate patient selection, careful patient preparation, focused technical expertise, defined protocol, and accurate data interpretation. The use of AVS should be based on patient preferences, patient age, clinical comorbidities, and the clinical probability of finding an aldosterone-producing adenoma. AVS is optimally performed in the fasting state in the morning. AVS is an intricate procedure because the right adrenal vein is small and may be difficult to locate - the success rate depends on the proficiency of the angiographer. The key factors that determine the successful catheterization of both adrenal veins are experience, dedication and repetition. With experience, and focusing the expertise to 1 or 2 radiologists at a referral centre, the AVS success rate can be as high as 96%. A centre-specific, written protocol is mandatory. The protocol should be developed by an interested group of endocrinologists, radiologists and laboratory personnel. Safeguards should be in place to prevent mislabelling of the blood tubes in the radiology suite and to prevent sample mix-up in the laboratory.

  14. Low plasma aldosterone despite normal plasma renin activity in uncomplicated type 1 diabetes mellitus : effects of RAAS stimulation

    NARCIS (Netherlands)

    Luik, PT; Kerstens, MN; Hoogenberg, K; Navis, GJ; Dullaart, RPF

    Background Data on levels and responsiveness of PRA and aldosterone in type 1 diabetes mellitus are conflicting. Earlier studies were not standardized with respect to the type of diabetes mellitus, the presence of diabetic complications or sodium intake. Therefore, we studied plasma renin activity

  15. Diastolic dysfunction is associated with insulin resistance, but not with aldosterone level in normotensive offspring of hypertensive families.

    Science.gov (United States)

    Zizek, Bogomir; Poredos, Pavel; Trojar, Andrej; Zeljko, Tadej

    2008-01-01

    We investigated left ventricular (LV) morphology and function in association with insulin level/insulin resistance (IR) and aldosterone level in normotensive offspring of subjects with essential hypertension (familial trait, FT). The study encompassed 76 volunteers of whom 44 were normotensive with FT (aged 28-39 years) and 32 age-matched controls without FT. LV mass and function were measured using conventional echocardiography and tissue Doppler imaging. LV diastolic function was reported as peak septal annular velocities (E(m) and E(m)/A(m) ratio) in tissue Doppler imaging. Fasting insulin and aldosterone were determined. In subjects with FT, the LV mass was higher than in controls (92.14 +/- 24.02 vs. 70.08 +/- 20.58 g; p < 0.001). The study group had a worse LV diastolic function than control subjects (lower E(m) and E(m)/A(m) ratio; p < 0.001). In subjects with FT, the E(m)/A(m) ratio was independently associated with IR (partial p = 0.029 in multivariate model, R(2) = 0.51), but not with LV mass. The aldosterone level was comparable in both groups. In normotensive individuals with FT, LV morphological and functional abnormalities were found. LV dysfunction but not an increase in LV mass is associated with IR. The aldosterone level is probably not responsible for the development of early hypertensive heart disease. (c) 2008 S. Karger AG, Basel.

  16. Tactic of diagnostic and treatment of patients with bilateral adrenal gland’s lesions associated with primary aldosteronism

    Directory of Open Access Journals (Sweden)

    А. O. Nykonenko

    2017-08-01

    Full Text Available Introduction. The problem of primary aldosteronism (PA different forms diagnosis and treatment is absolutely interesting in the 21st century as over the last 15 years it has been proved that PA syndrome had been distributed much more than previously thought. It accounts for 10-15% of all cases of hypertension. Aim: to analyze the diagnostic and treatment of patients with bilateral lesions of adrenal glands (AG with PA. Materials and Methods. During the period from 2014 to March 2017 year 14 patients with bilateral lesions of AG with PA have been examined and treated at the clinic. 8 (57.1% were women and 6 (42.9% were men. The average age of patients was 55,6±11,9 years. Adenomas of AG were diagnosed in 6 (42.9% of cases, hyperplasia of AG in 8 (57.1%. We measured the concentration of aldosterone, renin, adrenocorticotropic hormone, cortisol in plasma, levels of potassium and sodium, loading tastes, night dexamethasone suppression test, computer tomography and adrenal vein sampling (AVS. Surgical treatment was performed in 7 (50% of patients - in 3 cases (21.4% it was the laparoscopic adrenalectomy (LAE and in 1 case (7.2% – the laparoscopic resection of the adrenal gland (LRAG, for 3 (21.4% patients endovascular destruction of the AG (EVD was performed. Conservative therapy including aldosterone antagonists was prescribed for 7 (50% patients. Results and Discussion. Indication for the surgical treatment or REVD was a gradient of lateralization rated 3:1 and more. If the gradient was below a specified value, the result was regarded as idiopathic aldosteronism (IA and aldosterone antagonists (verospiron, eplerenonum with control of K+ concentration level were used. We believe that in case with bilateral adenomas of AG, if there are no conditions for the AG resection, it is necessary to perform LAE of functionally more active gland. It helps to stabilize the level of blood pressure without antihypertensive drugs prescription or with reducing of

  17. A novel haplotype of low-frequency variants in the aldosterone synthase gene among northern Han Chinese with essential hypertension.

    Science.gov (United States)

    Zhang, Hao; Li, Xueyan; Zhou, Li; Zhang, Keyong; Zhang, Qi; Li, Jingping; Wang, Ningning; Jin, Ming; Wu, Nan; Cong, Mingyu; Qiu, Changchun

    2017-09-01

    Low-frequency variants showed that there is more power to detect risk variants than to detect protective variants in complex diseases. Aldosterone plays an important role in the renin-angiotensin-aldosterone system, and aldosterone synthase catalyzes the speed-controlled steps of aldosterone biosynthesis. Polymorphisms of the aldosterone synthase gene (CYP11B2) have been reported to be associated with essential hypertension (EH). CYP11B2 polymorphisms such as -344T/C, have been extensively reported, but others are less well known. This study aimed to assess the association between human CYP11B2 and EH using a haplotype-based case-control study. A total of 1024 EH patients and 956 normotensive controls, which consist of north Han population peasants, were enrolled. Seven single nucleotide polymorphisms (SNPs) (rs28659182, rs10087214, rs73715282, rs542092383, rs4543, rs28491316, and rs7463212) covering the entire human CYP11B2 gene were genotyped as markers using the MassARRAY system. The major allele G frequency of rs542092383 was found to be risk against hypertension [odds ratio (OR) 3.478, 95% confidence interval (95% CI) 1.407-8.597, P = .004]. The AG genotype frequency of SNP rs542092383 was significantly associated with an increased risk of hypertension (OR 4.513, 95% CI 1.426-14.287, P = .010). In the haplotype-based case-control analysis, the frequency of the T-G-T haplotype was higher for EH patients than for controls (OR 5.729, 95% CI 1.889-17.371, P = .000495). All |D'| values of the seven SNPs were >0.9, and r values for rs28659182- rs10087214-rs28491316-rs7463212 SNPs were >0.8 and showed strong linkage intensity. Haplotype T-G-T may therefore be a useful genetic marker for EH.

  18. The effect of oxygen on aldosterone release from bovine adrenocortical cells in vitro: PO2 versus steroidogenesis.

    Science.gov (United States)

    Raff, H; Kohandarvish, S

    1990-08-01

    Hypoxia decreases plasma aldosterone in vivo without a decrease in PRA, angiotensin II (ANG II), ACTH, or cortisol. The present study evaluated whether this could be due to a direct, specific inhibitory effect on the zona glomerulosa related to the magnitude of the decrease in oxygen (O2). Bovine adrenocortical cells were dispersed with collagenase and studied in vitro within 48 h. Cells were stimulated for 2 h with ANG II (0.1-1000 nM) or (Bu)2cAMP (0.3-3 mM) under oxygen levels ranging from 0 to 100% O2 (PO2 from 66 +/- 4 to 561 +/- 46 torr) vs. a reference gas mixture (21% O2 PO2 approximately 140 torr). Exposure to 123 +/- 8, 110 +/- 12, 100 +/- 16, and 66 +/- 4 torr led to 27%, 30%, 40% and 70% inhibition, respectively, of 3 nM ANG II-stimulated aldosterone secretion as compared to 140 +/- 16 torr (reference). Exposure to hyperoxia (288 +/- 36 to 561 +/- 46 torr) led to a small (10%) increase in ANG II-stimulated aldosterone secretion which was not statistically significant. The P50 (half-maximal PO2) for aldosteronogenesis was approximately 95 torr. The results for other doses of ANG II and for cAMP were similar. The inhibitory effect of low O2 was reversed by returning the cells to reference conditions (140 +/- 16 torr). Cortisol secretion was not significantly affected by changes in oxygen tension. We conclude that small changes in O2 within the physiological range directly and specifically inhibit aldosteronogenesis in a dose-dependent manner with a P50 of approximately 95 torr. Inhibition of cAMP-stimulated aldosterone secretion suggests a postreceptor site of action. This direct, reversible, and specific effect on the zona glomerulosa of the adrenal cortex may account for the dissociation of renin and aldosterone during hypoxia in vivo.

  19. [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.

  20. Prognostic value of semiquantification NP-59 SPECT/CT in primary aldosteronism patients after adrenalectomy

    International Nuclear Information System (INIS)

    Lu, Ching-Chu; Cheng, Mei-Fang; Tzen, Kai-Yuan; Yen, Ruoh-Fang; Wu, Vin-Cent; Wu, Kwan-Dun; Liu, Kao-Lang; Lin, Wei-Chou

    2014-01-01

    Primary aldosteronism (PA), characterized by an excessive production of aldosterone, affects 5-13 % of patients with hypertension. Accurate strategies are needed for the timely diagnosis of PA to allow curability and prevention of excessive cardiovascular events and related damage. This study aimed to evaluate the usefulness of semiquantification of 131 I-6β-iodomethyl-norcholesterol (NP-59) single photon emission computed tomography (SPECT)/CT in differentiating aldosterone-producing adenoma (APA) from idiopathic adrenal hyperplasia (IAH) and in predicting clinical outcomes after adrenalectomy. We retrospectively reviewed 49 PA patients who had undergone adrenalectomy after NP-59 SPECT/CT within 1 year. A conventional visual scale (VS) and two semiquantitative parameters generated from SPECT/CT, adrenal to liver ratio (ALR) and lesion to contralateral ratio of bilateral adrenal glands (CON), with cutoff values calculated by receiver-operating characteristic (ROC) analysis, were compared with pathology results and postsurgical outcomes to determine the accuracy. An ALR cutoff of 1.84 and a CON cutoff of 1.15 showed an ability to distinguish adenoma from hyperplasia similar to VS (p = 0.2592 and 0.1908, respectively). An ALR cutoff of 2.28 and a CON cutoff of 1.11 yielded the highest sensitivity and specificity to predict postsurgical outcomes, and an ALR of 2.28 had an ability superior to VS (p = 0.0215), while a CON of 1.11 did not (p = 0.1015). Patients with either ALR or CON greater than the cutoff had a high probability of positive postsurgical outcomes (n = 36/38), while patients with both ALR and CON less than the cutoff had a low probability of positive postsurgical outcomes (n = 2/11). Semiquantification of NP-59 scintigraphy has an ability similar to VS in differentiating APA from IAH, but an excellent ability to predict postsurgical outcomes of adrenalectomy. An ALR or CON greater than the cutoff strongly suggests benefits from adrenalectomy, and both

  1. Prognostic value of semiquantification NP-59 SPECT/CT in primary aldosteronism patients after adrenalectomy

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Ching-Chu; Cheng, Mei-Fang; Tzen, Kai-Yuan; Yen, Ruoh-Fang [National Taiwan University Hospital and National Taiwan University College of Medicine, Department of Nuclear Medicine, Taipei (China); Wu, Vin-Cent; Wu, Kwan-Dun [National Taiwan University Hospital and National Taiwan University College of Medicine, Department of Internal Medicine, Taipei (China); Liu, Kao-Lang [National Taiwan University Hospital and National Taiwan University College of Medicine, Department of Medical Imaging, Taipei (China); Lin, Wei-Chou [National Taiwan University Hospital and National Taiwan University College of Medicine, Department of Pathology, Taipei (China); Collaboration: the TAIPAI Study Group

    2014-07-15

    Primary aldosteronism (PA), characterized by an excessive production of aldosterone, affects 5-13 % of patients with hypertension. Accurate strategies are needed for the timely diagnosis of PA to allow curability and prevention of excessive cardiovascular events and related damage. This study aimed to evaluate the usefulness of semiquantification of {sup 131}I-6β-iodomethyl-norcholesterol (NP-59) single photon emission computed tomography (SPECT)/CT in differentiating aldosterone-producing adenoma (APA) from idiopathic adrenal hyperplasia (IAH) and in predicting clinical outcomes after adrenalectomy. We retrospectively reviewed 49 PA patients who had undergone adrenalectomy after NP-59 SPECT/CT within 1 year. A conventional visual scale (VS) and two semiquantitative parameters generated from SPECT/CT, adrenal to liver ratio (ALR) and lesion to contralateral ratio of bilateral adrenal glands (CON), with cutoff values calculated by receiver-operating characteristic (ROC) analysis, were compared with pathology results and postsurgical outcomes to determine the accuracy. An ALR cutoff of 1.84 and a CON cutoff of 1.15 showed an ability to distinguish adenoma from hyperplasia similar to VS (p = 0.2592 and 0.1908, respectively). An ALR cutoff of 2.28 and a CON cutoff of 1.11 yielded the highest sensitivity and specificity to predict postsurgical outcomes, and an ALR of 2.28 had an ability superior to VS (p = 0.0215), while a CON of 1.11 did not (p = 0.1015). Patients with either ALR or CON greater than the cutoff had a high probability of positive postsurgical outcomes (n = 36/38), while patients with both ALR and CON less than the cutoff had a low probability of positive postsurgical outcomes (n = 2/11). Semiquantification of NP-59 scintigraphy has an ability similar to VS in differentiating APA from IAH, but an excellent ability to predict postsurgical outcomes of adrenalectomy. An ALR or CON greater than the cutoff strongly suggests benefits from adrenalectomy, and

  2. Primary Aldosteronism

    Science.gov (United States)

    ... in salt and water build-up and a rise in blood pressure. Uncontrolled high blood pressure can put you at risk for ... tumor in one adrenal gland (also called Conn’s syndrome), which occurs in about one-third of ... High blood pressure that requires more than three medications ...

  3. Expressions of renin, angiotensin II and aldosterone in patients with viral hepatitis or hepatic cirrhosis

    International Nuclear Information System (INIS)

    Huo Ying; Zhu Yalin; Liu Yun

    2008-01-01

    Objective: To explore the changes of renin, angiotensin and aldosterone system in patients with hepatic disorders. Methods: Plasma renin activity (PRA), AT-II and Ald levels were measured with RIA in 31 patients with viral hepatitis, 35 patients with hepatic cirrhosis and 38 controls. Results: The levels of PRA, AT-II and Ald in patients with viral hepatitis were slightly but non-significantly higher than those in controls (P>0.05). The levels of PRA, AT-II and Ald in patients with cirrhosis were significantly higher than those in controls (P<0.01). Conclusion: RAAS was activated during progression of hepatic disorders and participated in the development of hepatic fibrosis. (authors)

  4. The subtyping of primary aldosteronism by adrenal vein sampling: sequential blood sampling causes factitious lateralization.

    Science.gov (United States)

    Rossitto, Giacomo; Battistel, Michele; Barbiero, Giulio; Bisogni, Valeria; Maiolino, Giuseppe; Diego, Miotto; Seccia, Teresa M; Rossi, Gian Paolo

    2018-02-01

    The pulsatile secretion of adrenocortical hormones and a stress reaction occurring when starting adrenal vein sampling (AVS) can affect the selectivity and also the assessment of lateralization when sequential blood sampling is used. We therefore tested the hypothesis that a simulated sequential blood sampling could decrease the diagnostic accuracy of lateralization index for identification of aldosterone-producing adenoma (APA), as compared with bilaterally simultaneous AVS. In 138 consecutive patients who underwent subtyping of primary aldosteronism, we compared the results obtained simultaneously bilaterally when starting AVS (t-15) and 15 min after (t0), with those gained with a simulated sequential right-to-left AVS technique (R ⇒ L) created by combining hormonal values obtained at t-15 and at t0. The concordance between simultaneously obtained values at t-15 and t0, and between simultaneously obtained values and values gained with a sequential R ⇒ L technique, was also assessed. We found a marked interindividual variability of lateralization index values in the patients with bilaterally selective AVS at both time point. However, overall the lateralization index simultaneously determined at t0 provided a more accurate identification of APA than the simulated sequential lateralization indexR ⇒ L (P = 0.001). Moreover, regardless of which side was sampled first, the sequential AVS technique induced a sequence-dependent overestimation of lateralization index. While in APA patients the concordance between simultaneous AVS at t0 and t-15 and between simultaneous t0 and sequential technique was moderate-to-good (K = 0.55 and 0.66, respectively), in non-APA patients, it was poor (K = 0.12 and 0.13, respectively). Sequential AVS generates factitious between-sides gradients, which lower its diagnostic accuracy, likely because of the stress reaction arising upon starting AVS.

  5. Adrenal Vein Catecholamine Levels and Ratios: Reference Intervals Derived from Patients with Primary Aldosteronism.

    Science.gov (United States)

    Sze, Candy W C; O'Toole, Samuel Matthew; Tirador, Roger Kent; Akker, Scott A; Matson, Matthew; Perry, Leslie; Druce, Maralyn Rose; Dekkers, Tanja; Deinum, Jaap; Lenders, Jacques W M; Eisenhofer, Graeme; Drake, William Martyn

    2017-06-01

    Phaeochromocytoma localisation is generally reliably achieved with modern imaging techniques, particularly in sporadic cases. On occasion, however, there can be diagnostic doubt due to the presence of bilateral adrenal abnormalities, particularly in patients with mutations in genes predisposing them to the development of multiple phaeochromocytomas. In such cases, surgical intervention is ideally limited to large or functional lesions due to the long-term consequences associated with hypoadrenalism. Adrenal venous sampling (AVS) for catecholamines has been used in this situation to guide surgery, although there are few data available to support diagnostic thresholds. Retrospective analyses of AVS results from 2 centres were carried out. A total of 172 patients (88 men, 84 women) underwent AVS under cosyntropin stimulation for the diagnosis of established primary aldosteronism (PA) with measurement of adrenal and peripheral venous cortisol, aldosterone and catecholamines. Six patients (3 men, 3 women) with phaeochromocytoma underwent AVS for diagnostic purposes with subsequent histological confirmation. Reference intervals for the adrenal venous norepinephrine to epinephrine ratio were created from the PA group. Using the 97.5th centile (1.21 on the left, 1.04 on the right), the false negative rate in the phaeochromocytoma group was 0%. In conclusion, this study describes the largest dataset of adrenal venous catecholamine measurements and provides reference intervals in patients without phaeochromocytoma. This strengthens the certainty with which conclusions related to adrenal venous sampling for catecholamines can be drawn, acknowledging the procedure is not part of the routine diagnostic workup and is an adjunct for use only in difficult clinical cases. © Georg Thieme Verlag KG Stuttgart · New York.

  6. The role of potassium and other ions in the control of aldosterone synthesis

    International Nuclear Information System (INIS)

    Kenyon, C.J.; Shepherd, R.M.; Fraser, R.; Pediani, J.D.; Elder, H.Y.

    1991-01-01

    Fast and slow K+ efflux components, independently regulated by angiotensin II (AII), have been identified in bovine adrenocortical cells. The authors have further investigated the role of potassium in the control of aldosterone synthesis in two ways. Firstly, isotopic tracers, in conjunction with channel modulators, have been used to study the interrelationship of K+ and Ca2+ in the control of AII-stimulated aldosterone synthesis. Secondly, electron probe X-ray microanalysis (EPXMA) was used to quantify potassium, sodium, chlorine and phosphorous in control and AII-stimulated cells. The effects of verapamil on 43K efflux were measured at two stages during AII stimulation. During the first ten minutes of treatment, when efflux via the fast component predominates, AII and verapamil both slowed efflux and their effects were additive. If verapamil was added later, at the time when efflux by the fast component appeared exhausted and the stimulatory effect of AII on the slow efflux component was apparent, it again slowed efflux. These data suggest that verapamil prevents calcium-gated K+ channels from opening by blocking Ca2+ channels. However, verapamil had no effect on AII-stimulated calcium efflux. In addition to blocking Ca2+ channels, verapamil may directly inhibit potassium efflux. EPXMA showed a bimodal distribution of potassium concentrations in control cells. However, in cells stimulated with AII for five minutes, the mean potassium content was less than in controls and was not bimodally distributed. Sodium content was increased by AII-treatment, chlorine was lowered and phosphorus remained unchanged. The data confirm previous observations that AII inhibits Na+/K+ ATPase activity

  7. Renal type a intercalated cells contain albumin in organelles with aldosterone-regulated abundance.

    Directory of Open Access Journals (Sweden)

    Thomas Buus Jensen

    Full Text Available Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells in the interstitium by three anti-albumin antibodies. Albumin did not colocalize with markers for early endosomes (EEA1, late endosomes/lysosomes (cathepsin D or recycling endosomes (Rab11. Immuno-gold electron microscopy confirmed the presence of albumin-containing large spherical membrane associated bodies in the basal parts of intercalated cells. Message for albumin was detected in mouse renal cortex as well as in a wide variety of other tissues by RT-PCR, but was absent from isolated connecting tubules and cortical collecting ducts. Wild type I MDCK cells showed robust uptake of fluorescein-albumin from the basolateral side but not from the apical side when grown on permeable support. Only a subset of cells with low peanut agglutinin binding took up albumin. Albumin-aldosterone conjugates were also internalized from the basolateral side by MDCK cells. Aldosterone administration for 24 and 48 hours decreased albumin abundance in connecting tubules and cortical collecting ducts from mouse kidneys. We suggest that albumin is produced within the renal interstitium and taken up from the basolateral side by type-A intercalated cells by clathrin and dynamin independent pathways and speculate that the protein might act as a carrier of less water-soluble substances across the renal interstitium from the capillaries to the tubular cells.

  8. [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.

  9. Adrenal responses of large whales: Integrating fecal aldosterone as a complementary biomarker to glucocorticoids.

    Science.gov (United States)

    Burgess, Elizabeth A; Hunt, Kathleen E; Kraus, Scott D; Rolland, Rosalind M

    2017-10-01

    Until now, physiological stress assessment of large whales has predominantly focused on adrenal glucocorticoid (GC) measures. Elevated GC concentrations in feces (fGC) are known to reflect stressful disturbances, such as fishing gear entanglement and human-generated underwater noise, in North Atlantic right whales (Eubalaena glacialis). However, there can be considerable variation in GC production as a function of sex and life history stage, which may confound the interpretation of fGC levels. Additionally, GC antibodies used in immunoassays can cross-react with other fecal metabolites (i.e., non-target steroids), potentially influencing fGC data. Here, aldosterone concentrations (fALD; aldosterone and related metabolites) were measured in fecal samples from right whales (total n=315 samples), including samples from identified individuals of known life history (n=82 individual whales), to evaluate its utility as a complementary biomarker to fGC for identifying adrenal activation. Concentrations of fALD were positively correlated with fGCs in right whales (r=0.59, Pwhales, fALD concentrations showed similar patterns to those reported for fGC, with higher levels in pregnant females (35.9±7.6ng/g) followed by reproductively mature males (9.5±0.9ng/g) (Pwhales. The addition of fALD measurement as a biomarker of adrenal activation may help distinguish between intrinsic and external causes of stress hormone elevations in large whales, as well as other free-living wildlife species, providing a more comprehensive approach for associating adrenal activation with specific natural and anthropogenic stressors. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. 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

  11. Diagnosis and treatment of primary aldosteronism. An analysis of 18 cases

    International Nuclear Information System (INIS)

    Hiroi, Naoki; Yoshihara, Aya; Sue, Mariko

    2009-01-01

    Early diagnosis of primary aldosteronism (PA) is important because the worldwide prevalence of PA among unselected hypertensive patients is 5% to 15%. We examined the records of 18 patients with PA who were evaluated at Toho University Medical Center Omori Hospital. We analyzed the results of confirmatory testing and subtype differentiation among 18 patients (7 men and 11 women, mean age (mean±standard deviation (SD), 55.1±14.7 years) who had received a diagnosis of PA within the previous 2.5 years. On confirmatory testing of PA, the ratios of positive results on the furosemide-upright test, captopril-loading test, and adrenocorticotropic hormone (ACTH) stimulation test were 88.9, 69.2 and 68.8%, respectively. On subtype differentiation, among 14 patients who underwent ACTH-stimulated adrenal venous sampling (ACTH-AVS), 6 were found to have bilateral hyperaldosteronism (BHA) and 8 were found to have aldosterone-producing adrenal adenoma (APA, 1 right and 7 left adenomas). In 2 of 4 patients who did not undergo ACTH-AVS, APA with right adenoma was diagnosed by abdominal CT scan and 131 I-adosterol scintigraphy, however, determination of PA subtype was not possible in the remaining 2 patients. Patients with APA underwent adrenalectomy, and spironolactone was administered to patients with BHA. The therapeutic effectiveness of adrenalectomy and spironolactone did not differ. The furosemide-upright test should be the first choice for definitive diagnosis of PA; the captopril-loading test and ACTH stimulation test should be regarded as secondary examinations. It is necessary to use more than one confirmatory test, because these tests sometimes result in false negatives. Abdominal CT scan is not always useful for localizing adrenal tumors; therefore, we suggest a combination of CT scan, 131 I-adosterol scintigraphy, and ACTH-AVS in determining the appropriate therapy. (author)

  12. Aldosterone synthase gene polymorphism in alimentary obesity, metabolic syndrome components, some secondary forms of arterial hypertension, pathology of the adrenals glands core (literature review)

    OpenAIRE

    Koval, S.N.; Miloslavsky, D.K.; Snegurskaya, I.A.; Mysnichenko, O.V.; Penkova, M.Yu.

    2017-01-01

    Hormonal factors of adrenal origin belong to the pathophysiological mechanisms of the formation and progression of arterial hypertension (AH) and should be consi­dered while developing differentiated approaches to the treatment and prevention of hypertensive states, their primary, secondary and resistant forms. The first thing we should point up is aldosterone (AL), enzyme aldosterone synthase (AS), which takes a direct part in the formation of this hormone, as well as gene polymorphisms of A...

  13. Biosynthesis of Various Steroids in vitro by Isolated Adrenal Cells in Primary Aldosteronism, Cushing's Syndrome, and Adrenogenital Syndrome due to Adrenocortical Adenoma

    OpenAIRE

    MIZUNO, SHIGERU; FUNAHASHI, HIROOMI

    1981-01-01

    To a further understanding of the role of steroid hormones in adrenal disorders, we have prepared free cell system of adrenal cells, using adrenal tissues that had been removed by operation from (i) cases of Cushing's syndrome due to adrenocortical adenoma or adrenocortical hyperplasia, (ii) a case of primary aldosteronism, and (iii) a patient with virilizing adrenal tumor. Twelve important steroid hormones were measured, such as pregnenolone, cortisol and aldosterone, which were produced by ...

  14. Aldosterone, mortality, and acute ischaemic events in coronary artery disease patients outside the setting of acute myocardial infarction or heart failure.

    Science.gov (United States)

    Ivanes, Fabrice; Susen, Sophie; Mouquet, Frédéric; Pigny, Pascal; Cuilleret, François; Sautière, Karine; Collet, Jean-Philippe; Beygui, Farzin; Hennache, Bernadette; Ennezat, Pierre Vladimir; Juthier, Françis; Richard, Florence; Dallongeville, Jean; Hillaert, Marieke A; Doevendans, Pieter A; Jude, Brigitte; Bertrand, Michel; Montalescot, Gilles; Van Belle, Eric

    2012-01-01

    Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI. In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P acute MI, the level of

  15. Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, X.Q. [Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Department of Cardiology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei (China); Hong, H.S. [Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Lin, X.H. [Department of Emergency Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Chen, L.L. [Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Li, Y.H. [Department of Cardiology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei (China)

    2014-07-11

    The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

  16. Application of strict criteria in adrenal venous sampling increases the proportion of missed patients with unilateral disease who benefit from surgery for primary aldosteronism.

    Science.gov (United States)

    Kline, Gregory; Leung, Alexander; So, Benny; Chin, Alex; Harvey, Adrian; Pasieka, Janice L

    2018-06-01

    Adrenal vein sampling (AVS) is intended to confirm unilateral forms of primary aldosteronism, which are amenable to surgical cure. Excessively strict AVS criteria to define lateralization may result in many patients incorrectly categorized as bilateral primary aldosteronism and opportunity for surgical cure missed. Retrospective review of an AVS-primary aldosteronism database in which surgical cases are verified by standardized outcomes. Having used 'less strict' AVS criteria for lateralization, we examined the distribution of AVS lateralization indices in our confirmed unilateral primary aldosteronism cases both with and without cosyntropin stimulation. The proportion of proven unilateral cases that would have been missed with stricter AVS interpretation criteria was calculated. Particular focus was given to the proportion of missed cases according to use of international guidelines. False-positive lateralization with 'less strict' interpretation was also calculated. Of 80 surgical primary aldosteronism cases, 10-23% would have been missed with AVS lateralization indices of 3 : 1 to 5 : 1, with or without cosyntropin. If strict selectivity indices (for confirmation of catheterization) were combined with strict lateralization indices, up to 70% of unilateral primary aldosteronism cases could have been missed. Use of Endocrine Society AVS guidelines would have missed 21-43% of proven unilateral cases. 'Less strict' AVS interpretation yielded one case (1.2%) of false lateralization. Excessively strict AVS interpretation criteria will result in a high rate of missed unilateral primary aldosteronism with subsequent loss of opportunity for intervention. Use of more lenient lateralization criteria will improve the detection rate of unilateral primary aldosteronism with very low false-positive rate.

  17. Elevated pulmonary arterial and systemic plasma aldosterone levels associate with impaired cardiac reserve capacity during exercise in left ventricular systolic heart failure patients: A pilot study.

    Science.gov (United States)

    Maron, Bradley A; Stephens, Thomas E; Farrell, Laurie A; Oldham, William M; Loscalzo, Joseph; Leopold, Jane A; Lewis, Gregory D

    2016-03-01

    Elevated levels of aldosterone are a modifiable contributor to clinical worsening in heart failure with reduced ejection fraction (HFrEF). Endothelin-1 (ET-1), which is increased in HFrEF, induces pulmonary endothelial aldosterone synthesis in vitro. However, whether transpulmonary aldosterone release occurs in humans or aldosterone relates to functional capacity in HFrEF is not known. Therefore, we aimed to characterize ET-1 and transpulmonary aldosterone levels in HFrEF and determine if aldosterone levels relate to peak volume of oxygen uptake (pVO2). Data from 42 consecutive HFrEF patients and 18 controls referred for invasive cardiopulmonary exercise testing were analyzed retrospectively. Radial ET-1 levels (median [interquartile range]) were higher in HFrEF patients compared with controls (17.5 [11.5-31.4] vs 11.5 [4.4-19.0] pg/ml, p = 0.04). A significant ET-1 transpulmonary gradient (pulmonary arterial [PA] - radial arterial levels) was present in HFrEF (p reserve capacity in HFrEF. Published by Elsevier Inc.

  18. Effect of Blood Glucose Fluctuation on Some Trace Elements and Aldosterone Hormone among Type II Diabetic Patients with Metabolic Syndrome

    International Nuclear Information System (INIS)

    Ezz El-Arab, A.; El Fouly, A.H.; Mahmoud, H.H.

    2014-01-01

    There is accumulating evidence determine that the metabolism of some trace elements is altered in diabetes mellitus (DM) type II. The current study aimed to evaluate the effect of serum blood glucose fluctuation during (Random, Fasting and Postprandial 2 hours state) on some trace elements such as Cadmium (Cd), Chromium (Cr), Manganese (Mn), Magnesium (Mg), Zinc (Zn), Copper (Cu), Sodium (Na), Potassium (K), and Aldosterone hormone in type II Diabetic patients associated with metabolic syndrome in comparison with healthy volunteers. The International Diabetes Federation (IFD) consensus the diagnosis of metabolic syndrome according to central obesity, lipid profile, blood glucose level and blood pressure. A significant change was observed in trace elements level (Cd, Cr, Mg, Mn, Zn, Cu, Na, and K) and Aldosterone hormone as a result of glucose fluctuation among type II diabetic patients.

  19. [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.

  20. 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

  1. 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.

  2. Is there a role for segmental adrenal venous sampling and adrenal sparing surgery in patients with primary aldosteronism?

    Science.gov (United States)

    Satoh, Fumitoshi; Morimoto, Ryo; Seiji, Kazumasa; Satani, Nozomi; Ota, Hideki; Iwakura, Yoshitsugu; Ono, Yoshikiyo; Kudo, Masataka; Nezu, Masahiro; Omata, Kei; Tezuka, Yuta; Kawasaki, Yoshihide; Ishidoya, Shigeto; Arai, Yoichi; Takase, Kei; Nakamura, Yasuhiro; McNamara, Keely; Sasano, Hironobu; Ito, Sadayoshi

    2015-10-01

    Adrenal venous sampling (AVS) is critical to determine the subtype of primary aldosteronism (PA). Central AVS (C-AVS)--that is, the collection of effluents from bilateral adrenal central veins (CV)--sometimes does not allow differentiation between bilateral aldosterone-producing adenomas (APA) and idiopathic hyperaldosteronism. To establish the best treatment course, we have developed segmental AVS (S-AVS); that is, we collect effluents from the tributaries of CV to determine the intra-adrenal sources of aldosterone overproduction. We then evaluated the clinical utility of this novel approach in the diagnosis and treatment of PA. We performed C-AVS and/or S-AVS in 297 PA patients and assessed the accuracy of diagnosis based on the results of C-AVS (n=138, 46.5%) and S-AVS (n=159, 53.5%) by comparison with those of clinicopathological evaluation of resected specimens. S-AVS demonstrated both elevated and attenuated secretion of aldosterone from APA and non-tumorous segments, respectively, in patients with bilateral APA and recurrent APA. These findings were completely confirmed by detailed histopathological examination after surgery. S-AVS, but not C-AVS, also served to identify APA located distal from the CV. Compared to C-AVS, S-AVS served to identify APA in some patients, and its use should expand the pool of patients eligible for adrenal sparing surgery through the identification of unaffected segments, despite the fact that S-AVS requires more expertise and time. Especially, this new technique could enormously benefit patients with bilateral or recurrent APA because of the preservation of non-tumorous glandular tissue. © 2015 European Society of Endocrinology.

  3. Aldosterone Response in Severe Hypokalemia and Volume Depletion: A Case Report and Review of the Recent Research

    Directory of Open Access Journals (Sweden)

    Keiko Kai

    2016-01-01

    Full Text Available We report a case of severe hypokalemia and volume depletion complicated by chronic watery diarrhea resulting from chronic alcoholism in a 57-year-old man. Prompt replacement of normal saline with potassium chloride and cessation of alcohol intake resulted in a favorable outcome. We discuss the pathophysiology of the case, emphasizing the response of aldosterone in both hypokalemia and volume depletion, and provide a review of recent research.

  4. Direct action of aldosterone on transmembrane 22Na efflux from arterial smooth muscle. Rapid and delayed effects

    International Nuclear Information System (INIS)

    Moura, A.M.; Worcel, M.

    1984-01-01

    Acute subcutaneous (s.c.) administration of aldosterone increases ex vivo 22 Na efflux from rat tail artery smooth muscle, which appears to be due to a specific action on mineralocorticoid receptors. Indeed, this effect is blocked by the antimineralocorticoid compounds RU 28318 [17 beta-hydroxy-3-oxo,7 alpha-propyl(17 alpha)-pregn 4-ene, 21 potassium carboxylate] and spironolactone. The specific glucocorticoid receptor agonist RU 26988 does not modify 22 Na efflux. The authors show here that aldosterone has, at physiological concentrations, a mineralocorticoid specific stimulating effect on passive and sodium pump dependent transmembrane movements of sodium from the rat tail artery smooth muscle. Aldosterone exerts two types of action on sodium transport: 1) a delayed stimulation of ouabain-dependent 22 Na efflux and ouabain-independent 22 Na efflux, which are completely blocked by actinomycin D; and 2) a very rapid increase of passive 22 Na efflux, which is insensitive to actinomycin D and therefore does not seem to depend on transcription of genomic information

  5. Correlation between Serum Aldosterone Level and Hearing Condition of Elderly Patients Referred to Otolaryngology Services of Hamadan, Western Iran

    Directory of Open Access Journals (Sweden)

    Dr. Farhad Farahani

    2010-06-01

    Full Text Available Background and Aim: Recently, more attention was paid to the direct protective effect of aldosterone against hearing impairment in elderly patients. The aim of this study was determination of possible correlation between serum aldosterone level and hearing condition of elderly patients that referred to the Otolaryngology services of Hamadan in 2005-2006.Methods: In this case control study 54 (27 males,27 females persons above 60 years old were evaluated. They contained twenty eight cases with normal hearing and 26 cases with presbycusis. Persons with any abnormal biochemical finding or history of conditions that predispose them to the sensorineural hearing loss (SNHL were excluded. In both groups serum level of sodium, potassium and aldosterone were measured and hearing condition evaluated by puretone, speech and immitance audiometry.Results: Statistical relationship between serum aldostrone level and hearing condition, sex, configuration of audiogram and speech discrimination score (SDS were not significant. In addition, no significant relationship between sodium and potassium levels with hearing condition was found (p>0.05.Conclusion: This study could not confirm protective effect of aldostrone against presbycusis. This discrepancy may originate from epidemiologic differences, laboratory errors or small sample size.

  6. Pertussis toxin treatment does not block inhibition by atrial natriuretic factor of aldosterone secretion in cultured bovine zona glomerulosa cells

    International Nuclear Information System (INIS)

    De Lean, A.; Cantin, M.

    1986-01-01

    The authors have previously reported that atrial natriuretic factor (ANF) potently inhibits PGE or forskolin-stimulation aldosterone secretion in bovine zona glomerulosa (ZG) by acting through specific high affinity receptors. In order to evaluate the functional role of the regulatory protein N/sub i/ and the inhibition of adenylate cyclase activity (AC) in ZG, the authors have studied the effect of treatment with PT on inhibition by ANF of aldosterone production. Primary cultures of ZG were treated for 18 hours in serum-free F12 medium with (0-100 ng/ml PT). No effect of PT pretreatment was observed either on basal, PGE-stimulated or ANF-inhibited levels of steroidogenesis. When membranes prepared from control ZG were ADP-ribosylated with [ 32 P] NAD in the presence of PT, two toxin-specific bands with 39 Kd and 41 Kd were documented on SDS gel. Cell pretreatment with as low as 1 ng/ml drastically reduced further labelling of these two bands while higher doses completely abolished them. Since PT treatment covalently modifies completely the toxin substrate without altering ANF inhibition of adrenal steroidogenesis, the authors conclude that N/sub i/ is not involved in the mode of action of ANF on aldosterone production

  7. A NEW CLINICAL PREDICTION CRITERION ACCURATELY DETERMINES A SUBSET OF PATIENTS WITH BILATERAL PRIMARY ALDOSTERONISM BEFORE ADRENAL VENOUS SAMPLING.

    Science.gov (United States)

    Kocjan, Tomaz; Janez, Andrej; Stankovic, Milenko; Vidmar, Gaj; Jensterle, Mojca

    2016-05-01

    Adrenal venous sampling (AVS) is the only available method to distinguish bilateral from unilateral primary aldosteronism (PA). AVS has several drawbacks, so it is reasonable to avoid this procedure when the results would not affect clinical management. Our objective was to identify a clinical criterion that can reliably predict nonlateralized AVS as a surrogate for bilateral PA that is not treated surgically. A retrospective diagnostic cross-sectional study conducted at Slovenian national endocrine referral center included 69 consecutive patients (mean age 56 ± 8 years, 21 females) with PA who underwent AVS. PA was confirmed with the saline infusion test (SIT). AVS was performed sequentially during continuous adrenocorticotrophic hormone (ACTH) infusion. The main outcome measures were variables associated with nonlateralized AVS to derive a clinical prediction rule. Sixty-seven (97%) patients had a successful AVS and were included in the statistical analysis. A total of 39 (58%) patients had nonlateralized AVS. The combined criterion of serum potassium ≥3.5 mmol/L, post-SIT aldosterone AVS. The best overall classification accuracy (50/67 = 75%) was achieved using the post-SIT aldosterone level AVS. Our clinical prediction criterion appears to accurately determine a subset of patients with bilateral PA who could avoid unnecessary AVS and immediately commence with medical treatment.

  8. Diuretic effect of compounds from Hibiscus sabdariffa by modulation of the aldosterone activity.

    Science.gov (United States)

    Jiménez-Ferrer, Enrique; Alarcón-Alonso, Javier; Aguilar-Rojas, Arturo; Zamilpa, Alejandro; Jiménez-Ferrer C, Itzia; Tortoriello, Jaime; Herrera-Ruiz, Maribel

    2012-12-01

    Recent studies of Hibiscus sabdariffa Linn. have demonstrated that it presents diuretic, natriuretic, and potassium sparing effects. However, the mechanism that induces these effects has not yet been elucidated. The aim of this study was to explore the possible mechanism of action for the diuretic effect of Hibiscus sabdariffa extract and its fractions.The aqueous extract from this plant and the fractions obtained with solvents of different polarities were administered to adrenalectomized rats, and the diuretic effect was measured in the presence of deoxycorticosterone acetate (aldosterone analog).The effect on renal filtration was also evaluated in an in situ kidney model, and finally, the effect of diuretic active extracts on gene expression of the alpha subunit from the transporter (αENaC) of renal epithelial cell was quantified. The subsequent results were obtained: The aqueous extract of Hibiscus sabdariffa presented the following chemical composition, 32.4 mg/g delphinidin-3-O-sambubioside, 11.5 mg/g cyanidin-3-O-sambubioside, 11.5 mg/g quercetin, and chlorogenic acid 2.7 mg/g. The concentration of anthocyanins was diminished until disappearance due to decrease of the polarity of the solvents used in the extraction process, in contrast to the flavonoids and chlorogenic acid, which had their concentration increased. The diuretic effect caused by adrenalectomy in rats was reversed by deoxycorticosterone acetate activity. However, the effect of deoxycorticosterone acetate was antagonized by spironolactone, the aqueous extract of Hibiscus sabdariffa, and the acetonitrile : methanol 5 : 5 mixture extract, administered orally. A similar effect was observed on renal filtration obtained from the isolated kidney model.When the gene expression levels of αENaC was measured in adrenalectomized rats, it was observed that spironolactone, the aqueous extract of Hibiscus sabdariffa, the acetonitrile : methanol 5 : 5 mixture, as well as the

  9. Effect of hemorrhage on cardiac output, vasopressin, aldosterone, and diuresis during immersion in men

    Science.gov (United States)

    Greenleaf, J. E.; Simanonok, K.; Bernauer, E. M.; Wade, C. E.; Keil, L. C.

    1992-01-01

    The purpose of this research was to test the hypotesis that a reduction in blood volume would attenuate or eliminate immersion-induced increases in cardiac output (Q(sub co)) and urine excretion, and to investigate accompanying vasoactive and fluid-electrolyte hormonal responses. Eight men (19-23 yr) were supine during a 2-hr control period in air, and then sat for 5-hr test periods in air at 20 C (dry control, DC); water at 34.5 C (wet control, WC); and water (34.5 C) after hemorrhage (WH) of 14.8 plus or minus 0.3 percent of their blood volume. Blood volume was -11.6 plus or minus 0.6 percent at immersion (time 0). Mean (bar-X hrs 1-5) Q(sub co) was unchanged in WC (5.3 plus or minus 0.01 l/min) and in WH (4.5 plus or minus 0.1 l/min), but decreased (P less than 0.05) in DC to 3.6 plus or minus 0.1 l/min. Mean urine excretion rates were 1.0 plus or minus 0.2 ml/min for DC and 1.1 plus or minus 0.2 ml/min for WH; both were lower (P less than 0.05) than that for WC of 2.0 plus or minus 0.4 ml/min. Plasma (Na+) and (Osm) were unchanged in all experiments. Mean plasma vasopressin (PVP) (bar-X hrs 1-5) was 1.1 plus or minus 0.1 pg/ml in WC, and higher (P less than 0.05) in DC (2.1 plus or minus 0.2 pg/ml)and WH (2.1 plus or minus 0.1 pg/ml); it was unchanged during air and water test periods. Thus, hemorrhage attenuated the immersion-induced increase in Q(sub co), eliminated the WC diuresis, maintained plasma renin activity and PVP at DC levels and did not change immersion-induced aldosterone suppression; the osmotic diuresis during control immersion is apparently not due to either aldosterone suppression or vasopressin suppression.

  10. CACNA1H Mutations Are Associated With Different Forms of Primary Aldosteronism

    Directory of Open Access Journals (Sweden)

    Georgios Daniil

    2016-11-01

    Four different heterozygous germline CACNA1H variants were identified. A de novo Cav3.2 p.Met1549Ile variant was found in early onset PA and multiplex developmental disorder. Cav3.2 p.Ser196Leu and p.Pro2083Leu were found in two patients with FH, and p.Val1951Glu was identified in one patient with APA. Electrophysiological analysis of mutant Cav3.2 channels revealed significant changes in the Ca2+ current properties for all mutants, suggesting a gain of function phenotype. Transfections of mutant Cav3.2 in H295R-S2 cells led to increased aldosterone production and/or expression of genes coding for steroidogenic enzymes after K+ stimulation. Identification of CACNA1H mutations associated with early onset PA, FH, and APA suggests that CACNA1H might be a susceptibility gene predisposing to PA with different phenotypic presentations, opening new perspectives for genetic diagnosis and management of patients with PA.

  11. 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.

  12. Endoplasmic Reticulum Chaperon Tauroursodeoxycholic Acid Attenuates Aldosterone-Infused Renal Injury

    Directory of Open Access Journals (Sweden)

    Honglei Guo

    2016-01-01

    Full Text Available Aldosterone (Aldo is critically involved in the development of renal injury via the production of reactive oxygen species and inflammation. Endoplasmic reticulum (ER stress is also evoked in Aldo-induced renal injury. In the present study, we investigated the role of ER stress in inflammation-mediated renal injury in Aldo-infused mice. C57BL/6J mice were randomized to receive treatment for 4 weeks as follows: vehicle infusion, Aldo infusion, vehicle infusion plus tauroursodeoxycholic acid (TUDCA, and Aldo infusion plus TUDCA. The effect of TUDCA on the Aldo-infused inflammatory response and renal injury was investigated using periodic acid-Schiff staining, real-time PCR, Western blot, and ELISA. We demonstrate that Aldo leads to impaired renal function and inhibition of ER stress via TUDCA attenuates renal fibrosis. This was indicated by decreased collagen I, collagen IV, fibronectin, and TGF-β expression, as well as the downregulation of the expression of Nlrp3 inflammasome markers, Nlrp3, ASC, IL-1β, and IL-18. This paper presents an important role for ER stress on the renal inflammatory response to Aldo. Additionally, the inhibition of ER stress by TUDCA negatively regulates the levels of these inflammatory molecules in the context of Aldo.

  13. Mitochondria-Targeted Antioxidant Mito-Tempo Protects Against Aldosterone-Induced Renal Injury In Vivo

    Directory of Open Access Journals (Sweden)

    Wei Ding

    2017-11-01

    Full Text Available Background/Aims: Growing evidence suggests mitochondrial dysfunction (MtD and the Nlrp3 inflammasome play critical roles in chronic kidney disease (CKD progression. We previously reported that Aldosterone (Aldo-induced renal injury in vitro is directly caused by mitochondrial reactive oxygen species (mtROS-mediated activation of the Nlrp3 inflammasome. Here we aimed to determine whether a mitochondria-targeted antioxidant (Mito-Tempo could prevent Aldo-induced kidney damage in vivo. Methods: C57BL/6J mice were treated with Aldo and/or Mito-Tempo (or ethanol as a control for 4 weeks. Renal injury was evaluated by Periodic Acid-Schiff reagent or Masson’s trichrome staining and electron microscopy. ROS were measured by DCFDA fluorescence and ELISA. MtD was determined by real-time PCR and electron microscopy. Activation of the Nlrp3 inflammasome and endoplasmic reticulum stress (ERS was detected via western blot. Results: Compared with control mice, Aldo-infused mice showed impaired renal function, increased mtROS production and MtD, Nlrp3 inflammasome activation, and elevated ERS. We showed administration of Mito-Tempo significantly improved renal function and MtD, and reduced Nlrp3 inflammasome activation and ERS in vivo. Conclusion: Mitochondria-targeted antioxidants may attenuate Aldo-infused renal injury by inhibiting MtD, the Nlrp3 inflammasome, and ERS in vivo. Therefore, targeting mtROS might be an effective strategy for preventing CKD.

  14. Ceramide Production Mediates Aldosterone-Induced Human Umbilical Vein Endothelial Cell (HUVEC Damages.

    Directory of Open Access Journals (Sweden)

    Yumei Zhang

    Full Text Available Here, we studied the underlying mechanism of aldosterone (Aldo-induced vascular endothelial cell damages by focusing on ceramide. We confirmed that Aldo (at nmol/L inhibited human umbilical vein endothelial cells (HUVEC survival, and induced considerable cell apoptosis. We propose that ceramide (mainly C18 production might be responsible for Aldo-mediated damages in HUVECs. Sphingosine-1-phosphate (S1P, an anti-ceramide lipid, attenuated Aldo-induced ceramide production and following HUVEC damages. On the other hand, the glucosylceramide synthase (GCS inhibitor PDMP or the ceramide (C6 potentiated Aldo-induced HUVEC apoptosis. Eplerenone, a mineralocorticoid receptor (MR antagonist, almost completely blocked Aldo-induced C18 ceramide production and HUVEC damages. Molecularly, ceramide synthase 1 (CerS-1 is required for C18 ceramide production by Aldo. Knockdown of CerS-1 by targeted-shRNA inhibited Aldo-induced C18 ceramide production, and protected HUVECs from Aldo. Reversely, CerS-1 overexpression facilitated Aldo-induced C18 ceramide production, and potentiated HUVEC damages. Together, these results suggest that C18 ceramide production mediates Aldo-mediated HUVEC damages. MR and CerS-1 could be the two signaling molecule regulating C18 ceramide production by Aldo.

  15. Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas.

    Science.gov (United States)

    Murakami, Masanori; Yoshimoto, Takanobu; Nakabayashi, Kazuhiko; Nakano, Yujiro; Fukaishi, Takahiro; Tsuchiya, Kyoichiro; Minami, Isao; Bouchi, Ryotaro; Okamura, Kohji; Fujii, Yasuhisa; Hashimoto, Koshi; Hata, Ken-Ichiro; Kihara, Kazunori; Ogawa, Yoshihiro

    2017-10-01

    The pathophysiology of aldosterone-producing adenomas (APAs) has been investigated via genetic approaches and the pathogenic significance of a series of somatic mutations, including KCNJ5 , has been uncovered. However, how the mutational status of an APA is associated with its molecular characteristics, including its transcriptome and methylome, has not been fully understood. This study was undertaken to explore the molecular characteristics of APAs, specifically focusing on APAs with KCNJ5 mutations as opposed to those without KCNJ5 mutations, by comparing their transcriptome and methylome status. Cortisol-producing adenomas (CPAs) were used as reference. We conducted transcriptome and methylome analyses of 29 APAs with KCNJ5 mutations, 8 APAs without KCNJ5 mutations and 5 CPAs. Genome-wide gene expression and CpG methylation profiles were obtained from RNA and DNA samples extracted from these 42 adrenal tumors. Cluster analysis of the transcriptome and methylome revealed molecular heterogeneity in APAs depending on their mutational status. DNA hypomethylation and gene expression changes in Wnt signaling and inflammatory response pathways were characteristic of APAs with KCNJ5 mutations. Comparisons between transcriptome data from our APAs and that from normal adrenal cortex obtained from the Gene Expression Omnibus suggested similarities between APAs with KCNJ5 mutations and zona glomerulosa. The present study, which is based on transcriptome and methylome analyses, indicates the molecular heterogeneity of APAs depends on their mutational status. Here, we report the unique characteristics of APAs with KCNJ5 mutations. © 2017 Society for Endocrinology.

  16. Aldosterone Blockade Reduces Mortality without Changing Cardiac Remodeling in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Marcelo D.M. Cezar

    2013-11-01

    Full Text Available Background: The role of aldosterone blockers during transition from long-term compensated hypertrophy to dilated failure is not completely understood. In this study we evaluated the effects of early administration of spironolactone on cardiac remodeling, myocardial function, and mortality in spontaneously hypertensive rats (SHR. Methods: Sixteen-month-old SHR received no treatment (SHR-C, n=72 or spironolactone (SHR-SPR, 20 mg/kg/day, n=34 for six months. Echocardiogram was performed before and after treatment. Myocardial function was analyzed in left ventricular (LV papillary muscle preparations. Myocardial collagen and hydroxyproline concentration were evaluated by morphometry and spectrophotometry, respectively. LV gene expression was assessed by real time RT-PCR. Statistics: Student's t test; Log rank test (Kaplan Meyer. Results: SHR-C and SHR-SPR presented mortality rates of 71 and 38%, respectively (p=0.004. Systolic arterial pressure did not differ between groups (SHR-C 199±43; SHR-SPR 200±35 mmHg. Initial and final echocardiograms did not show significant differences in cardiac structures or LV function between groups. Myocardial function was similar between groups at basal and after inotropic stimulation. Collagen fractional area, hydroxyproline concentration, gene expression for α- and β-myosin heavy chain, atrial natriuretic peptide, and Serca2a were not different between groups. Conclusion: Early spironolactone administration reduces mortality without changing cardiac remodeling in spontaneous hypertensive rats.

  17. Plasma renin activity, aldosterone and catecholamine levels when swimming and running.

    Science.gov (United States)

    Guezennec, C Y; Defer, G; Cazorla, G; Sabathier, C; Lhoste, F

    1986-01-01

    The purpose of this study was to determine the response of plasma renin activity (PRA), plasma aldosterone concentration (PAC) and catecholamines to two graded exercises differing by posture. Seven male subjects (19-25 years) performed successively a running rest on a treadmill and a swimming test in a 50-m swimming pool. Each exercise was increased in severity in 5-min steps with intervals of 1 min. Oxygen consumption, heart rate and blood lactate, measured every 5 min, showed a similar progression in energy expenditure until exhaustion, but there was a shorter time to exhaustion in the last step of the running test. PRA, PAC and catecholamines were increased after both types of exercise. The PRA increase was higher after the running test (20.9 ng AngI X ml-1 X h-1) than after swimming (8.66 ng AngI X ml-1 X h-1). The PAC increase was slightly greater after running (123 pg X ml-1) than swimming (102 pg X ml-1), buth the difference was not significant. Plasma catecholamine was higher after the swimming test. These results suggest that the volume shift induced by the supine position and water pressure during swimming decreased the PRA response. The association after swimming compared to running of a decreased PRA and an enhanced catecholamine response rule out a strict dependence of renin release under the effect of plasma catecholamines and is evidence of the major role of neural pathways for renin secretion during physical exercise.

  18. Early effects of aldosterone on Na-K pump in rat cortical collecting tubules

    International Nuclear Information System (INIS)

    Fujii, Y.; Takemoto, F.; Katz, A.I.

    1990-01-01

    Sustained exposure to aldosterone (Aldo) increases the abundance and activity of the Na-K pump in cortical collecting tubules (CCT). However, the onset and mechanism of the early interaction of Aldo with the CCT pump, especially in adrenal-intact animals, are unclear. We evaluated the short-term effects of the hormone on Na-K-adenosinetriphosphatase (ATPase) activity and on ouabain-sensitive 86Rb uptake, a measure of the transporting rate of the pump, in microdissected CCT from adrenal-intact rats. Incubation with Aldo (10(-8) M, 2 h) had no effect on Na-K-ATPase activity (Vmax), whereas it produced at least a twofold increase in 86Rb uptake. This effect was generated by physiological concentrations of the hormone (threshold 10(-10) M; apparent K1/2 approximately 10(-9) M), after a short lag of less than or equal to 30 min. Incubation with Aldo in the presence of amiloride or nystatin or in a Na-free medium (choline chloride) did not prevent the enhanced 86Rb uptake seen after Aldo alone; possible interpretations of these observations are discussed. We conclude that Aldo produces a rapid stimulation of pump function in CCT that precedes its induction of new pump synthesis; the physiological significance of this effect is suggested by its occurrence in tubules from adrenal-intact animals within the time frame and concentration range of the hormone's effects on electrolyte transport

  19. 8C.03: A KEY ROLE FOR ENDOTHELIN-1 IN THE PATHOGENESIS OF PREECLAMPSIA AND THE ASSOCIATED SUPPRESSION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM.

    Science.gov (United States)

    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

  20. Mineralocorticoid hypertension: clinical and laboratory studies with special reference to selective percutaneous venography combined with aldosterone assay in the adrenal venous blood

    International Nuclear Information System (INIS)

    Wajchenberg, B.L.; Liberman, B.; Novaes, M.

    1977-01-01

    With the purpose of demonstrating the presence of hypertension, hypokalemia and alkalosis were studied. The presence of daily aldosteronism was verified in five patients; the sixth one presented no daily aldosteronism but an increase of 18-OH-DOCA production, an ACTH dependente mineralocorticoid. The presence of tumor (less than 0.9cm) could not be shown in two patients by bilateral selective adrenal venography. The aldosterone assay during catherization of adrenal vein of those patients permitted to determine the tumoral side. Attention must be given to the fact that the blood collection of adrenal vein must always be made during adrenal venography to demonstrate the presence of short unilateral tumor or bilateral disease [pt

  1. Analysis of renin-angiotensin aldosterone system gene polymorphisms in malaysian essential hypertensive and type 2 diabetic subjects

    Directory of Open Access Journals (Sweden)

    Stanslas Johnson

    2009-02-01

    Full Text Available 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 genes in Malaysian essential hypertensive and type 2 diabetic subjects. Methods RAAS gene polymorphisms were determined using mutagenically separated PCR and PCR-RFLP method in a total of 270 subjects consisting of 70 hypertensive subjects without type 2 diabetes mellitus (T2DM, 60 T2DM, 65 hypertensive subjects with T2DM and 75 control subjects. Results There was significant difference found in age, body mass index, systolic/diastolic blood pressure, fasting plasma glucose and high density lipoprotein cholesterol levels between the hypertensive subjects with or without T2DM and control subjects. No statistically significant differences between groups were found in the allele frequency and genotype distribution for A20C variant of AGT gene, MboI of renin, Gly460Trp of aldosterone and Lys173Arg of adducin (p > 0.05. However, the results for A6G of AGT gene revealed significant differences in allele and genotype frequencies in essential hypertension with or without T2DM (p Conclusion Among the five polymorphisms of RAAS genes only A6G variant of AGT gene was significantly associated in Malaysian essential hypertensive and type 2 diabetic subjects. Therefore, A6G polymorphism of the AGT gene could be a potential genetic marker for increased susceptibility to essential hypertension with or without T2DMin Malaysian subjects.

  2. Effect of felodipine on myocardial and renal injury induced by aldosterone-high salt hypertension in uninephrectomized rats

    Directory of Open Access Journals (Sweden)

    B.B. Matsubara

    2010-05-01

    Full Text Available It has been recently shown that calcium channel blockers might have a protective effect on cardiac fibrogenesis induced by aldosterone. The objective of this study was to evaluate the protective effect of felodipine, a dihydropyridine calcium channel blocker, against heart and kidney damage caused by aldosterone-high sodium intake in uninephrectomized rats. Wistar rats were divided into three groups: CNEP (uninephrectomized + 1% NaCl in the drinking water, N = 9; ALDO (same as CNEP group plus continuous infusion of 0.75 µg/h aldosterone, N = 12; ALDOF (same as ALDO group plus 30 mg·kg-1·day-1 felodipine in the drinking water, N = 10. All results were compared with those of age-matched, untreated rats (CTL group, N = 10. After 6 weeks, tail cuff blood pressure was recorded and the rats were killed for histological analysis. Blood pressure (mmHg was significantly elevated (P < 0.05 in ALDO (180 ± 20 and ALDOF (168 ± 13 compared to CTL (123 ± 12 and CNEP (134 ± 13. Heart damage (lesion scores - median and interquartile range was 7.0 (5.5-8.0 in ALDO and was fully prevented in ALDOF (1.5; 1.0-2.0. Also, left ventricular collagen volume fraction (% in ALDOF (2.9 ± 0.5 was similar to CTL (2.9 ± 0.5 and CNEP (3.4 ± 0.4 and decreased compared to ALDO (5.1 ± 1.6. Felodipine partially prevented kidney injury since the damage score for ALDOF (2.0; 2.0-3.0 was significantly decreased compared to ALDO (7.5; 4.0-10.5, although higher than CTL (null score. Felodipine has a protective effect on the myocardium and kidney as evidenced by decreased perivascular inflammation, myocardial necrosis and fibrosis.

  3. Modulation of the cardiac sodium/bicarbonate cotransporter by the renin angiotensin aldosterone system: pathophysiological consequences.

    Science.gov (United States)

    De Giusti, Verónica C; Ciancio, María C; Orlowski, Alejandro; Aiello, Ernesto A

    2013-01-01

    The sodium/bicarbonate cotransporter (NBC) is one of the major alkalinizing mechanisms in the cardiomyocytes. It has been demonstrated the existence of at least two functional isoforms, one that promotes the co-influx of 1 molecule of Na(+) per 1 molecule of HCO(-) 3 (electroneutral isoform; NBCn1) and the other one that generates the co-influx of 1 molecule of Na(+) per 2 molecules of HCO(-) 3 (electrogenic isoform; NBCe1). Both isoforms are important to maintain intracellular pH (pH i ) and sodium concentration ([Na(+)] i ). In addition, NBCe1 generates an anionic repolarizing current that modulates the action potential duration (APD). The renin-angiotensin-aldosterone system (RAAS) is implicated in the modulation of almost all physiological cardiac functions and is also involved in the development and progression of cardiac diseases. It was reported that angiotensin II (Ang II) exhibits an opposite effect on NBC isoforms: it activates NBCn1 and inhibits NBCe1. The activation of NBCn1 leads to an increase in pH i and [Na(+)] i , which indirectly, due to the stimulation of reverse mode of the Na(+)/Ca(2+) exchanger (NCX), conduces to an increase in the intracellular Ca(2+) concentration. On the other hand, the inhibition of NBCe1 generates an APD prolongation, potentially representing a risk of arrhythmias. In the last years, the potentially altered NBC function in pathological scenarios, as cardiac hypertrophy and ischemia-reperfusion, has raised increasing interest among investigators. This review attempts to draw the attention on the relevant regulation of NBC activity by RAAS, since it modulates pH i and [Na(+)] i , which are involved in the development of cardiac hypertrophy, the damage produced by ischemia-reperfusion and the generation of arrhythmic events, suggesting a potential role of NBC in cardiac diseases.

  4. 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

  5. MODULATION OF THE CARDIAC SODIUM/BICARBONATE COTRANSPORTER BY THE RENIN ANGIOTENSIN ALDOSTERONE SYSTEM: PATHOPHYSIOLOGICAL CONSEQUENCES.

    Directory of Open Access Journals (Sweden)

    Verónica Celeste De Giusti

    2014-01-01

    Full Text Available The sodium/bicarbonate cotransporter (NBC is one of the major alkalinizing mechanisms in the cardiomyocytes. It has been demonstrated the existence of at least two functional isoforms, one that promotes the co-influx of 1 molecule of Na+ per 1 molecule of HCO3- (electroneutral isoform; NBCn1 and the other one that generates the co-influx of 1 molecule of Na+ per 2 molecules of HCO3- (electrogenic isoform; NBCe1. Both isoforms are important to maintain intracellular pH (pHi and sodium concentration ([Na+]i. In addition, NBCe1 generates an anionic repolarizing current that modulates the action potential duration (APD. The renin-angiotensin-aldosterone system (RAAS is implicated in the modulation of almost all physiological cardiac functions and is also involved in the development and progression of cardiac diseases. It was reported that angiotensin II (Ang II exhibits an opposite effect on NBC isoforms: it activates NBCn1 and inhibits NBCe1. The activation of NBCn1 leads to an increase in pHi and [Na+]i, which indirectly, due to the stimulation of reverse mode of the Na+/Ca2+ exchanger (NCX, conduces to an increase in the intracellular Ca2+ concentration. On the other hand, the inhibition of NBCe1 generates an APD prolongation, potentially representing a risk of arrhythmias. In the last years, the potentially altered NBC function in pathological scenarios, as cardiac hypertrophy and ischemia-reperfusion, has raised increasing interest among investigators. This review attempts to draw the attention on the relevant regulation of NBC activity by RAAS, since it modulates pHi and [Na+]i, which are involved in the development of cardiac hypertrophy, the damage produced by ischemia-reperfusion and the generation of arrhythmic events, suggesting a potential role of NBC in cardiac diseases.

  6. 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

  7. Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in patients with acute decompensated heart failure on treatment containing intravenous atrial natriuretic peptide

    International Nuclear Information System (INIS)

    Kasama, Shu; Toyama, Takuji; Kurabayashi, Masahiko; Iwasaki, Toshiya; Sumino, Hiroyuki; Kumakura, Hisao; Minami, Kazutomo; Ichikawa, Shuichi; Matsumoto, Naoya; Nakata, Tomoaki

    2014-01-01

    Aldosterone prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, inhibits aldosterone synthase gene expression in cultured cardiocytes. We evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity (CSNA) and aldosterone suppression in patients with acute decompensated heart failure (ADHF). We studied 182 patients with moderate nonischemic ADHF requiring hospitalization and treated with standard therapy containing intravenous ANP and 10 age-matched normal control subjects. ANP was continuously infused for >96 h. In all subjects, delayed total defect score (TDS), heart to mediastinum ratio, and washout rate were determined by 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography. All patients with acute heart failure (AHF) were examined once within 3 days and then 4 weeks after admission, while the control subjects were examined only once (when their hemodynamics were normal). Moreover, for 62 AHF patients, plasma aldosterone concentrations were measured at admission and 1 h before stopping ANP infusion. 123 I-MIBG scintigraphic and echocardiographic parameters in normal subjects were more favorable than those in patients with AHF (all p < 0.001). After treatment, all these parameters improved significantly in AHF patients (all p < 0.001). We also found significant correlation between percent changes of TDS and aldosterone concentrations (r = 0.539, p < 0.001) in 62 AHF patients. The CSNA and LV performance were all improved in AHF patients. Furthermore, norepinephrine uptake of myocardium may be ameliorated by suppressing aldosterone production after standard treatment containing intravenous ANP. (orig.)

  8. 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.

  9. Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in patients with acute decompensated heart failure on treatment containing intravenous atrial natriuretic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Iwasaki, Toshiya; Sumino, Hiroyuki; Kumakura, Hisao; Minami, Kazutomo; Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Matsumoto, Naoya [Nihon University School of Medicine, Department of Cardiology, Tokyo (Japan); Nakata, Tomoaki [Sapporo Medical University School of Medicine, Second (Cardiology) Department of Internal Medicine, Sapporo, Hokkaido (Japan)

    2014-09-15

    Aldosterone prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, inhibits aldosterone synthase gene expression in cultured cardiocytes. We evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity (CSNA) and aldosterone suppression in patients with acute decompensated heart failure (ADHF). We studied 182 patients with moderate nonischemic ADHF requiring hospitalization and treated with standard therapy containing intravenous ANP and 10 age-matched normal control subjects. ANP was continuously infused for >96 h. In all subjects, delayed total defect score (TDS), heart to mediastinum ratio, and washout rate were determined by {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography. All patients with acute heart failure (AHF) were examined once within 3 days and then 4 weeks after admission, while the control subjects were examined only once (when their hemodynamics were normal). Moreover, for 62 AHF patients, plasma aldosterone concentrations were measured at admission and 1 h before stopping ANP infusion. {sup 123}I-MIBG scintigraphic and echocardiographic parameters in normal subjects were more favorable than those in patients with AHF (all p < 0.001). After treatment, all these parameters improved significantly in AHF patients (all p < 0.001). We also found significant correlation between percent changes of TDS and aldosterone concentrations (r = 0.539, p < 0.001) in 62 AHF patients. The CSNA and LV performance were all improved in AHF patients. Furthermore, norepinephrine uptake of myocardium may be ameliorated by suppressing aldosterone production after standard treatment containing intravenous ANP. (orig.)

  10. 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

  11. 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...

  12. Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin

    DEFF Research Database (Denmark)

    Stolzenburg Oxlund, Christina; Kurt, Birgül; Schwarzensteiner, Ilona

    2017-01-01

    The proteinase prostasin is a candidate mediator for aldosterone-driven proteolytic activation of the epithelial sodium channel (ENaC). It was hypothesized that the aldosterone-mineralocorticoid receptor (MR) pathway stimulates prostasin abundance in kidney and urine. Prostasin was measured...... spironolactone compared to control. Urinary prostasin and albumin related directly and were reduced by spironolactone. In patients with nephrotic syndrome, urinary prostasin protein was elevated compared to controls. In rat nephrosis, proteinuria coincided with increased urinary prostasin, unchanged kidney...... the result of an improved glomerular filtration barrier function and generally reduced proteinuria....

  13. Central role for sodium in the pathogenesis of blood pressure changes independent of angiotensin, aldosterone and catecholamines in type 1 (insulin-dependent) diabetes mellitus

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B; Mathiesen, E R; Deckert, T

    1987-01-01

    .41, p less than 0.01). Extracellular volume was increased in patients (p less than 0.05), whereas plasma volume was normal. Supine serum angiotensin II was suppressed in the patients (p less than 0.001). A negative correlation was found between mean blood pressure and supine serum aldosterone (n = 68, r...... = -0.24, p less than 0.05), and exchangeable sodium and aldosterone (n = 66, r = -0.36, p less than 0.002) in all patients. The catecholamine levels were also suppressed or normal in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)...

  14. Aberrant gonadotropin-releasing hormone receptor (GnRHR) expression and its regulation of CYP11B2 expression and aldosterone production in adrenal aldosterone-producing adenoma (APA).

    Science.gov (United States)

    Nakamura, Yasuhiro; Hattangady, Namita G; Ye, Ping; Satoh, Fumitoshi; Morimoto, Ryo; Ito-Saito, Takako; Sugawara, Akira; Ohba, Koji; Takahashi, Kazuhiro; Rainey, William E; Sasano, Hironobu

    2014-03-25

    Aberrant expression of gonadotropin-releasing hormone receptor (GnRHR) has been reported in human adrenal tissues including aldosterone-producing adenoma (APA). However, the details of its expression and functional role in adrenals are still not clear. In this study, quantitative RT-PCR analysis revealed the mean level of GnRHR mRNA was significantly higher in APAs than in human normal adrenal (NA) (P=0.004). GnRHR protein expression was detected in human NA and neoplastic adrenal tissues. In H295R cells transfected with GnRHR, treatment with GnRH resulted in a concentration-dependent increase in CYP11B2 reporter activity. Chronic activation of GnRHR with GnRH (100nM), in a cell line with doxycycline-inducible GnRHR (H295R-TR/GnRHR), increased CYP11B2 expression and aldosterone production. These agonistic effects were inhibited by blockers for the calcium signaling pathway, KN93 and calmidazolium. These results suggest GnRH, through heterotopic expression of its receptor, may be a potential regulator of CYP11B2 expression levels in some cases of APA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Study on plasma levels of brain natriuretic peptide, angiotensin and aldosterone in patients with congestive heart failure

    International Nuclear Information System (INIS)

    Cheng Yu; Hong Liquan; Chen Zhaojun

    2009-01-01

    Objective: To investigate the relationship between brain natriuretic peptide (BNP), angiotensin (AT-II), and aldosterone (ALD) levels in patients with congestive heart failure (CHF). Methods: Plasma levels of BNP (with CLIA) and Angiotensin II (AT-II), aldosterone (ALD) (with RIA) were measured in 98 patients with CHF, 76 cardiac patients without heart faclure, and 86 controls. Results: The plasma levels of BNP, AT-II and ALD in patients (with RIA) CHF were significantly higher than those in the controls. The levels of BNP, AT-II and ALD, CHF patients after therapy were markedly dropped and were significantly lower than those patients before therapy (P<0.01). BNP levels were positively correlated with AT-II and ALD in levels CHF (P<0.05). Conclusion: The over activity of RAA systems may be one of the mechanisms of heart failure. Dynamic observation of changes of BNP, AT-II and ALD may be very useful in assessment of severity and prognosis of patients with CHF. (authors)

  16. Adrenal vein sampling in primary aldosteronism: concordance of simultaneous vs sequential sampling.

    Science.gov (United States)

    Almarzooqi, Mohamed-Karji; Chagnon, Miguel; Soulez, Gilles; Giroux, Marie-France; Gilbert, Patrick; Oliva, Vincent L; Perreault, Pierre; Bouchard, Louis; Bourdeau, Isabelle; Lacroix, André; Therasse, Eric

    2017-02-01

    Many investigators believe that basal adrenal venous sampling (AVS) should be done simultaneously, whereas others opt for sequential AVS for simplicity and reduced cost. This study aimed to evaluate the concordance of sequential and simultaneous AVS methods. Between 1989 and 2015, bilateral simultaneous sets of basal AVS were obtained twice within 5 min, in 188 consecutive patients (59 women and 129 men; mean age: 53.4 years). Selectivity was defined by adrenal-to-peripheral cortisol ratio ≥2, and lateralization was defined as an adrenal aldosterone-to-cortisol ratio ≥2, the contralateral side. Sequential AVS was simulated using right sampling at -5 min (t = -5) and left sampling at 0 min (t = 0). There was no significant difference in mean selectivity ratio (P = 0.12 and P = 0.42 for the right and left sides respectively) and in mean lateralization ratio (P = 0.93) between t = -5 and t = 0. Kappa for selectivity between 2 simultaneous AVS was 0.71 (95% CI: 0.60-0.82), whereas it was 0.84 (95% CI: 0.76-0.92) and 0.85 (95% CI: 0.77-0.93) between sequential and simultaneous AVS at respectively -5 min and at 0 min. Kappa for lateralization between 2 simultaneous AVS was 0.84 (95% CI: 0.75-0.93), whereas it was 0.86 (95% CI: 0.78-0.94) and 0.80 (95% CI: 0.71-0.90) between sequential AVS and simultaneous AVS at respectively -5 min at 0 min. Concordance between simultaneous and sequential AVS was not different than that between 2 repeated simultaneous AVS in the same patient. Therefore, a better diagnostic performance is not a good argument to select the AVS method. © 2017 European Society of Endocrinology.

  17. Effects of low-sodium diet vs. high-sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride (Cochrane Review)

    DEFF Research Database (Denmark)

    Graudal, Niels A; Hubeck-Graudal, Thorbjørn; Jürgens, Gesche

    2012-01-01

    The question of whether reduced sodium intake is effective as a health prophylaxis initiative is unsolved. The purpose was to estimate the effects of low-sodium vs. high-sodium intake on blood pressure (BP), renin, aldosterone, catecholamines, and lipids....

  18. 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.

  19. Muzzle secretion electrolytes as a possible indicator of sodium status in buffalo (Bubalus bubalis) calves: effects of sodium depletion and aldosterone administration.

    Science.gov (United States)

    Kumar, S; Singh, S P

    1981-01-01

    In two separate experiments, the effects of sodium depletion and aldosterone administration on sodium and potassium concentrations in muzzle secretion, saliva and urine were studied in buffalo calves. Sodium deficiency in the animals was experimentally produced by unilateral parotid saliva deprivation for 18 days. During sodium depletion, the sodium levels in saliva and muzzle secretion gradually fell while the potassium level gradually rose. The concentrations of both of these cations in urine gradually fell during the course of sodium depletion. Aldosterone administration in normal (sodium-replete) animals simulated the effects of sodium depletion as far as cationic changes in saliva were concerned. However, aldosterone did not affect sodium and potassium concentration in the urine and in muzzle secretion in a manner similar to that caused by sodium depletion. Though the hormone decreased urinary sodium without affecting urinary potassium, it did not affect the muzzle sodium or potassium. Results suggest that aldosterone affects the composition of saliva and urine in buffaloes as it does in sheep and other ruminants. Similar changes in composition of muzzle secretion and saliva during sodium depletion indicate that the concentration of sodium in muzzle secretion could possibly be used to evaluate the sodium status of animals.

  20. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort

    NARCIS (Netherlands)

    Williams, T.A.; Lenders, J.W.M.; Mulatero, P.; Burrello, J.; Rottenkolber, M.; Adolf, C.; Satoh, F.; Amar, L.; Quinkler, M.; Deinum, J.; Beuschlein, F.; Kitamoto, K.K.; Pham, U.; Morimoto, R.; Umakoshi, H.; Prejbisz, A.; Kocjan, T.; Naruse, M.; Stowasser, M.; Nishikawa, T.; Young, W.F., Jr.; Gomez-Sanchez, C.E.; Funder, J.W.; Reincke, M.

    2017-01-01

    BACKGROUND: Although unilateral primary aldosteronism is the most common surgically correctable cause of hypertension, no standard criteria exist to classify surgical outcomes. We aimed to create consensus criteria for clinical and biochemical outcomes and follow-up of adrenalectomy for unilateral

  1. Effects of cilnidipine on sympathetic nerve activity and cardiorenal function in hypertensive patients with type 2 diabetes mellitus: association with BNP and aldosterone levels.

    Science.gov (United States)

    Tanaka, Masami; Sekioka, Risa; Nishimura, Takeshi; Ichihara, Atsuhiro; Itoh, Hiroshi

    2014-12-01

    Hypertension stimulates the sympathetic nervous system and this phenomenon is exacerbated by diabetes mellitus. We investigated the effects of cilnidipine, an N/L-type calcium channel blocker, on aspects of this system in patients with type 2 diabetes mellitus. In 33 hypertensive patients with type 2 diabetes mellitus treated with a calcium channel blocker other than cilnidipine, we evaluated the influence of switching to cilnidipine on blood pressure, heart rate, catecholamine, plasma renin and aldosterone concentration, brain natriuretic peptide, urine liver-type fatty acid binding protein, and urinary albumin excretion ratio in the same patients by a cross-over design. Other biochemical parameters were also evaluated. Switching to cilnidipine did not change blood pressure but caused reduction in catecholamine concentrations in blood and urine and plasma aldosterone concentration, accompanied by significant reduction in brain natriuretic peptide, urine liver-type fatty acid binding protein, and albumin excretion ratio. These parameters other than brain natriuretic peptide were significantly increased after cilnidipine was changed to the original calcium channel blocker. In 33 hypertensive patients with type 2 diabetes mellitus, compared to other calcium channel blockers, cilnidipine suppressed sympathetic nerve activity and aldosterone, and significantly improved markers of cardiorenal disorders. Therefore, cilnidipine may be an important calcium channel blocker for use in combination with renin-angiotensin-aldosterone system inhibitors when dealing with hypertension complicated with diabetes mellitus. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. A single-centre experience of the implementation of adrenal vein sampling procedure: the impact on the diagnostic work-up in primary aldosteronism

    NARCIS (Netherlands)

    Kadziela, J.; Prejbisz, A.; Michalowska, I.; Kolodziejczyk-Kruk, S.; Schultze Kool, L.J.; Kabat, M.; Janaszek-Sitkowska, H.; Toutounchi, S.; Galazka, Z.; Ambroziak, U.; Bednarczuk, T.; Ptasinska-Wnuk, D.; Hoffmann, M.; Januszewicz, M.; Januszewicz, A.; Witkowski, A.

    2017-01-01

    BACKGROUND: Primary aldosteronism is one of the most common causes of secondary hypertension. Adrenal vein sampling (AVS) remains a "gold standard" procedure in differentiation between unilateral (adenoma) and bilateral (hyperplasia) disease. AIM: The aim of this study was to present our

  3. 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.

  4. Varying patterns of the antihypertensive and antialbuminuric response to higher doses of renin-angiotensin-aldosterone system blockade in albuminuric hypertensive type 2 diabetes mellitus patients

    DEFF Research Database (Denmark)

    Weir, Matthew R; Hollenberg, Norman K; Remuzzi, Giuseppe

    2011-01-01

    In patients with type 2 diabetes mellitus (T2DM), blocking of the renin-angiotensin-aldosterone system (RAAS) has demonstrated efficacy in lowering blood pressure (BP) and urinary albumin excretion rate (UAER). Nonetheless, not all patients successfully respond to RAAS blockade with a reduction...

  5. Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial

    NARCIS (Netherlands)

    de Vries, Laura V.; Dobrowolski, Linn C.; van den Bosch, Jacqueline J. O. N.; Riphagen, Ineke J.; Krediet, C. T. Paul; Bemelman, Frederike J.; Bakker, Stephan J. L.; Navis, Gerjan

    2016-01-01

    In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore

  6. Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade : A Randomized Clinical Trial

    NARCIS (Netherlands)

    de Vries, Laura V; Dobrowolski, Linn C; van den Bosch, Jacqueline J O N; Riphagen, Ineke J; Krediet, C T Paul; Bemelman, Frederike J; Bakker, Stephan J L; Navis, Gerjan

    BACKGROUND: In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown.

  7. Multilocus analyses of renin-angiotensin-aldosterone system gene variants on blood pressure at rest and during behavioral stress in young normotensive subjects

    NARCIS (Netherlands)

    Ge, Dongliang; Zhu, Haidong; Huang, Ying; Treiber, Frank A.; Harshfield, Gregory A.; Snieder, Harold; Dong, Yanbin

    The renin-angiotensin-aldosterone system (RAAS) is a proteolytic cascade that regulates and maintains blood pressure (BP). This study aimed to explore the interactive and integrative effects of multiple RAAS polymorphisms on BP at rest and during behavioral stress in a normotensive population. A

  8. CHANGES IN THE LEVELS OF ANGIOTENSIN II, ALDOSTERONE, AND FIBROBLAST GROWTH FACTOR IN PATIENTS WITH RHEUMATOID ARTHRITIS IN RELATION TO CLINICAL FEATURES

    Directory of Open Access Journals (Sweden)

    E. B. Komarova

    2016-01-01

    Full Text Available Angiotensin II, aldosterone, and fibroblast growth factor (FGF stimulate neoangiogenesis, fibroblast proliferation, and elaboration of proinflammatory cytokines, which in turn contributes to increased pannus mass and the development of joint tissue destruction in rheumatoid arthritis (RA.Objective: to establish the specific features of changes in the blood levels of angiotensin II, aldosterone, and FGF in patients with RA in relation to the duration and severity of the disease.Subjects and methods. Examinations were made in 194 patients diagnosed with RA without comorbidity; the patients’ mean age was 47.7±10.2 years; the disease duration was 3.82±3.43 years. DAS28 scores for RA were calculated based on C-reactive protein levels. An enzyme immunoassay was used to determine the serum levels of anti-cyclic citrullinated peptide antibodies (ACCPA, angiotensin II, aldosterone, and FGF.Results and discussion. All the examinees were ascertained to have increases in the concentration of angiotensin II and aldosterone in blood by twice and in that of FGF by 2.5 times compared to the controls (p < 0.05. In patients with a RA duration of < 2 years, the blood level of angiotensin II was 25% higher than in those with a RA duration of > 5 years and the concentrations of aldosterone and FGF in patients with long-term RA were twice as high as in those with early RA. In patients with high RA activity, the blood level of angiotensin II was 1.5-fold higher than in those with low and moderate disease activity (p < 0.05. In patients with a high blood ACCPA level, the concentrations of angiotensin II, aldosterone, and FGF were 20, 30, and 25%, respectively, higher than in those with low ACCPA levels. The correlation of DAS28 with blood angiotensin II levels increased with enhanced RA activity. The high aldosterone and FGF values in RA patients are associated with the progression of joint radiographic changes.

  9. Circulating aldosterone induces the apical accumulation of the proton pumping V-ATPase and increases proton secretion in clear cells in the caput epididymis.

    Science.gov (United States)

    Roy, Jeremy W; Hill, Eric; Ruan, Ye Chun; Vedovelli, Luca; Păunescu, Teodor G; Brown, Dennis; Breton, Sylvie

    2013-08-15

    Clear cells express the vacuolar proton-pumping H(+)-ATPase (V-ATPase) and acidify the lumen of the epididymis, a process that is essential for male fertility. The renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance in the epididymis, and a previous study showed binding of aldosterone exclusively to epididymal clear cells (Hinton BT, Keefer DA. Steroid Biochem 23: 231-233, 1985). We examined here the role of aldosterone in the regulation of V-ATPase in the epididymis. RT-PCR showed expression of the mineralocorticoid receptor [MR; nuclear receptor subfamily 3, group C member 2 (NR3C2)] and 11-β-dehydrogenase isozyme 2 (HSD11β2) mRNAs specifically in clear cells, isolated by fluorescence-activated cell sorting from B1-enhanced green fluorescent protein (EGFP) mice. Tail vein injection of adult rats with aldosterone, 1,2-dioctanoyl-sn-glycerol (DOG), or 8-(4-chlorophenylthio)-cAMP (cpt-cAMP) induced V-ATPase apical membrane accumulation and extension of V-ATPase-labeled microvilli in clear cells in the caput epididymis but not in the cauda. V-ATPase activity was measured in EGFP-expressing clear cells using the intracellular pH (pHi)-sensing dye seminaphthorhodafluor-5F-5-(and 6)-carboxylic acid, acetoxymethyl ester acetate (SNARF-5F). Aldosterone induced a rapid increase in the rate of Na(+)- and bicarbonate-independent pHi recovery following an NH4Cl-induced acid load in clear cells isolated from the caput but not the cauda. This effect was abolished by concanamycin A, spironolactone, and chelerythrine but not myristoylated-protein kinase inhibitor (mPKI) or mifepristone. Thus aldosterone increases V-ATPase-dependent proton secretion in clear cells in the caput epididymis via MR/NR3C2 and PKC activation. This study, therefore, identifies aldosterone as an active member of the RAAS for the regulation of luminal acidification in the proximal epididymis.

  10. Leptin-Aldosterone-Neprilysin Axis: Identification of Its Distinctive Role in the Pathogenesis of the Three Phenotypes of Heart Failure in People With Obesity.

    Science.gov (United States)

    Packer, Milton

    2018-04-10

    Obesity (especially visceral adiposity) can be associated with 3 different phenotypes of heart failure: heart failure with a reduced ejection fraction, heart failure with a preserved ejection fraction, and high-output heart failure. All 3 phenotypes are characterized by an excessive secretion of aldosterone and sodium retention. In addition, obesity is accompanied by increased signaling through the leptin receptor, which can promote activation of both the sympathetic nervous system and the renin-angiotensin system and can directly stimulate the secretion of aldosterone. The deleterious interaction of leptin and aldosterone is potentiated by the simultaneous action of adiposity and the renal sympathetic nerves to cause overactivity of neprilysin; the loss of the counterbalancing effects of natriuretic peptides is exacerbated by an additional effect of both obesity and heart failure to interfere with adiponectin signaling. This intricate neurohormonal interplay leads to plasma volume expansion as well as to adverse ventricular remodeling and cardiac fibrosis. Furthermore, the activity of aldosterone and neprilysin is not only enhanced by obesity, but these mechanisms can also promote adipogenesis and adipocyte dysfunction, thereby enhancing the positive feedback loop. Last, in elderly obese women, changes in quantity and biology of epicardial adipose tissue further enhances the release of leptin and other proinflammatory adipokines, thereby leading to cardiac and systemic inflammation, end-organ fibrosis, and multiple comorbidities. Regardless of the phenotypic expression, activation of the leptin-aldosterone-neprilysin axis appears to contribute importantly to the evolution and progression of heart failure in people with obesity. Efforts to interfere with the detrimental interactions of this distinctive neurohormonal ecosystem with existing or novel therapeutic agents are likely to yield unique clinical benefits. © 2018 American Heart Association, Inc.

  11. Biosensor cell assay for measuring real-time aldosterone-induced release of histamine from mesenteric arteries

    DEFF Research Database (Denmark)

    Dalgaard, Emil G; Andersen, Kenneth; Svenningsen, Per

    2017-01-01

    as a sensitive biosensor assay for histamine release from isolated mouse mesenteric arteries. Activation of the H1 receptor by histamine was measured as an increased number of intracellular Ca(2+) transient peaks using fluorescence imaging RESULTS: The developed biosensor was sensitive to histamine...... in physiological relevant concentrations and responded to substances released by the artery preparation. Aldosterone treatment of mesenteric arteries from wild type mice for 50 minutes resulted in an increased number of intracellular Ca(2+) transient peaks in the biosensor cells, which was significantly inhibited...... by the histamine H1 blocker pyrilamine. Mesenteric arteries from mast cell deficient SASH mice induced similar pyrilamine-sensitive Ca(2+) transient response in the biosensor cells. Mesenteric arteries from wild type and SASH mice expressed histamine decarboxylase mRNA, indicating that mast cells are not the only...

  12. A high sodium intake reduces antiproteinuric response to renin-angiotensin-aldosterone system blockade in kidney transplant recipients.

    Science.gov (United States)

    Monfá, Elena; Rodrigo, Emilio; Belmar, Lara; Sango, Cristina; Moussa, Fozi; Ruiz San Millán, Juan Carlos; Piñera, Celestino; Fernández-Fresnedo, Gema; Arias, Manuel

    Post-transplant proteinuria is associated with lower graft and patient survival. Renin-angiotensin-aldosterone system blockers are used to reduce proteinuria and improve renal outcome. Although it is known that a high salt intake blunts the antiproteinuric effect of ACEI and ARB drugs in non-transplant patients, this effect has not been studied in kidney transplant recipients. To analyse the relationship between sodium intake and the antiproteinuric effect of ACEI/ARB drugs in kidney transplant recipients. We selected 103 kidney transplant recipients receiving ACEI/ARB drugs for more than 6 months due to proteinuria>1 g/day. Proteinuria was analysed at baseline and at 6 months after starting ACEI/ARB treatment. Salt intake was estimated by urinary sodium to creatinine ratio (uNa/Cr). Proteinuria fell to less than 1g/day in 46 patients (44.7%). High uNa/Cr was associated with a smaller proteinuria decrease (r=-0.251, P=.011). The percentage proteinuria reduction was significantly lower in patients in the highest uNa/Cr tertile [63.9% (IQR 47.1%), 60.1% (IQR 55.4%), 38.9% (IQR 85.5%), P=.047]. High uNa/Cr independently relates (OR 2.406 per 100 mEq/g, 95% CI: 1.008-5.745, P=.048) to an antiproteinuric response <50% after renin-angiotensin-aldosterone system blockade. A high salt intake results in a smaller proteinuria decrease in kidney transplant recipients with proteinuria treated with ACEI/ARB drugs. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  13. The role of tissue renin angiotensin aldosterone system in the development of endothelial dysfunction and arterial stiffness

    Directory of Open Access Journals (Sweden)

    Annayya R Aroor

    2013-10-01

    Full Text Available Epidemiological studies support the notion that arterial stiffness is an independent predictor of adverse cardiovascular events contributing significantly to systolic hypertension, impaired ventricular-arterial coupling and diastolic dysfunction, impairment in myocardial oxygen supply and demand, and progression of kidney disease. Although arterial stiffness is associated with aging, it is accelerated in the presence of obesity and diabetes. The prevalence of arterial stiffness parallels the increase of obesity that is occurring in epidemic proportions and is partly driven by a sedentary life style and consumption of a high fructose, high salt and high fat western diet. Although the underlying mechanisms and mediators of arterial stiffness are not well understood, accumulating evidence supports the role of insulin resistance and endothelial dysfunction. The local tissue renin angiotensin aldosterone system (RAAS in the vascular tissue and immune cells and perivascular adipose tissue is recognized as an important element involved in endothelial dysfunction which contributes significantly to arterial stiffness. Activation of vascular RAAS is seen in humans and animal models of obesity and diabetes, and associated with enhanced oxidative stress and inflammation in the vascular tissue. The cross talk between angiotensin and aldosterone underscores the importance of mineralocorticoid receptors in modulation of insulin resistance, decreased bioavailability of nitric oxide, endothelial dysfunction and arterial stiffness. In addition, both innate and adaptive immunity are involved in this local tissue activation of RAAS. In this review we will attempt to present a unifying mechanism of how environmental and immunological factors are involved in this local tissue RAAS activation, and the role of this process in the development of endothelial dysfunction and arterial stiffness and targeting tissue RAAS activation.

  14. The influence of a tilt training programme on the renin-angiotensin-aldosterone system activity in patients with vasovagal syncope.

    Science.gov (United States)

    Gajek, Jacek; Zyśko, Dorota; Krzemińska, Sylwia; Mazurek, Walentyna

    2009-08-01

    We assessed the influence of short-term and long-term tilt training on the activity of the renin-angiotensin-aldosterone system (RAAS) in vasovagal patients. Thirty-nine patients (28 F, 11 M) aged 39.7 +/- 11.2 years with a history of vasovagal syncope and a positive head-up tilt test (HUT) were studied. Blood samples for plasma renin activity (PRA) and aldosterone (ALDO) concentration were drawn at the baseline, immediately after HUT and 10 min after HUT, during the diagnostic, the negative short-term (2-5 days) follow-up HUT and long-term (1-3 months) follow-up HUT. Tilt training was started after diagnostic HUT. In diagnostic HUT, PRA increased significantly immediately after HUT comparing to the baseline, during recovery the values did not change. ALDO concentration increased after HUT comparing to baseline and further increased during recovery. After short-term tilt training, PRA and ALDO concentrations did not significantly change compared to their corresponding values in diagnostic HUT. After long-term tilt training, PRA did not significantly change compared to the values in the diagnostic and short-term follow-up HUT. ALDO concentration also did not change significantly at the baseline and immediately after HUT, and 10 min after HUT ALDO concentration was significantly lower than after diagnostic HUT. Tilt training changes the response of RAAS to the prolonged orthostasis in vasovagal patients. The coupling between PRA and ALDO after diagnostic HUT has been found to be altered and the physiological relationship was restored after long-term tilt training. The beneficial effect of tilt training depends partially on changed RAAS activation.

  15. 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....

  16. 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...

  17. Aldosterone synthase gene is not a major susceptibility gene for progression of chronic kidney disease in patients with autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Gnanasambandan Ramanathan

    2017-01-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is the most common heritable kidney disease and is characterized by bilateral renal cysts. Hypertension is a frequent cause of chronic kidney disease (CKD and mortality in patients with ADPKD. The aldosterone synthase gene polymorphisms of the renin-angiotensin-aldosterone system have been extensively studied as hypertension candidate genes. The present study is aimed to investigate the potential modifier effect of CYP11B2 gene on the progression of CKD in ADPKD. One hundred and two ADPKD patients and 106 healthy controls were recruited based on Ravine inclusion and exclusion criteria. The three tag-SNPs within CYP11B2 gene (rs3802230, rs4543, and rs4544 were genotyped using FRET-based KASPar method. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Mantel- Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms. Of the three tag-SNPs genotyped, rs4544 polymorphism was monomorphic and rs3802230 deviated Hardy-Weinberg equilibrium. The CYP11B2 tag-SNPs did not show significant association with ADPKD or CKD. Further, these polymorphisms did not exhibit confounding effect on the relationship between CKD progression and hypertension. Our results suggest that aldosterone synthase gene is not a major susceptibility gene for progression of CKD in South Indian ADPKD patients.

  18. 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.

  19. 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.

  20. Case Report: A case report of acromegaly associated with primary aldosteronism [v1; ref status: indexed, http://f1000r.es/2ny

    Directory of Open Access Journals (Sweden)

    Joanna Matrozova

    2014-02-01

    Full Text Available We describe a patient with a rare combination of acromegaly and primary aldosteronism. A 37 year-old female patient was diagnosed with acromegaly on the basis of typical clinical, hormonal and image characteristics. She presented also with one of the most common co-morbidities – arterial hypertension. The patient has been regularly followed-up and after three surgical interventions, irradiation and adjuvant treatment with a dopamine agonist, acromegaly was finally controlled in 2008 (20 years after diagnosis. Arterial hypertension however, remained a therapeutic problem even after prescription of four antihypertensive drugs. She had normal biochemical parameters, except for low potassium levels 3.2 (3.5-5.6 mmol/l. This raised the suspicion of primary hyperaldosteronism, confirmed by a high aldosterone to plasma rennin activity ratio, high aldosterone level after a Captopril challenge test and visualization of a 35 mm left adrenal nodule on a CT scan. After an operation, the patient recovered from hypokalemia and antihypertensive therapy was reduced to a small dose of a Ca blocker. Co-morbid arterial hypertension is common in acromegaly, though it is rare for this to be caused by Conn’s adenoma. The association of Conn’s adenoma with acromegaly has been interpreted in two lines: as a component of multiple endocrine neoplasia type (MEN1 syndrome or as a direct mitogenic effect of hyperactivated GH-IGF1 axis.

  1. Renin–angiotensin–aldosterone system related gene polymorphisms and urinary total arsenic is related to chronic kidney disease

    International Nuclear Information System (INIS)

    Chen, Wei-Jen; Huang, Ya-Li; Shiue, Horng-Sheng; Chen, Tzen-Wen; Lin, Yuh-Feng; Huang, Chao-Yuan; Lin, Ying-Chin; Han, Bor-Cheng; Hsueh, Yu-Mei

    2014-01-01

    A recent study demonstrated that an increased risk of chronic kidney disease (CKD) was associated with high urinary total arsenic levels. However, whether genomic instability is related to CKD remains unclear. An association between CKD and genetic polymorphisms of regulation enzymes of the renin–angiotensin–aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type I receptor (AT1R), and aldosterone synthase (CYP11B2) has not been shown. The aim of the present study was to investigate the relationship between arsenic, genetic polymorphisms of RAAS enzymes and CKD. A total of 233 patients and 449 age- and gender-matched controls were recruited from the Taipei Medical University Hospital, Taipei Municipal Wan Fang Hospital and the Shin Kong Wu Ho-Su Memorial Hospital. Concentrations of urinary arsenic were determined by a high-performance liquid chromatography-linked hydride generator, and atomic absorption spectrometry. Polymorphisms of ACE(I/D), AGT(A[− 20]C), (T174M), (M235T), AT1R(A1166C) and CYP11B2(C[− 344]T) were examined by polymerase chain reaction and restriction fragment length polymorphism. Subjects carrying the CYP11B2 TT genotype had a higher odds ratio (OR), 1.39 (0.96–2.01), of CKD; while those with the AGT(A[− 20]C) CC genotype had an inverse OR of CKD (0.20 (0.05–0.81)), and a high-risk genotype was defined as A/A + A/C for AGT(A[− 20C]) and T/T for CYP11B2(C[− 344]T). The trend test showed a higher OR for CKD in patients who had either high urinary total arsenic levels or carried the high-risk genotype, or both, compared to patients with low urinary total arsenic levels, who carried the low-risk genotype, and could also be affected by the hypertension or diabetes status. - Highlights: • AGT(− 20 C) and CYP11B2(− 344 T) genotypes were significantly associated with CKD. • Combined effect of high-risk genotypes and high urinary total arsenic on OR of CKD. • Combined

  2. Renin–angiotensin–aldosterone system related gene polymorphisms and urinary total arsenic is related to chronic kidney disease

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wei-Jen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Huang, Ya-Li [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan (China); Chen, Tzen-Wen [Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Lin, Yuh-Feng [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, New Taipei, Taiwan (China); Huang, Chao-Yuan [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Lin, Ying-Chin [Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, New Taipei, Taiwan (China); Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan (China); Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Han, Bor-Cheng [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2014-09-01

    A recent study demonstrated that an increased risk of chronic kidney disease (CKD) was associated with high urinary total arsenic levels. However, whether genomic instability is related to CKD remains unclear. An association between CKD and genetic polymorphisms of regulation enzymes of the renin–angiotensin–aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type I receptor (AT1R), and aldosterone synthase (CYP11B2) has not been shown. The aim of the present study was to investigate the relationship between arsenic, genetic polymorphisms of RAAS enzymes and CKD. A total of 233 patients and 449 age- and gender-matched controls were recruited from the Taipei Medical University Hospital, Taipei Municipal Wan Fang Hospital and the Shin Kong Wu Ho-Su Memorial Hospital. Concentrations of urinary arsenic were determined by a high-performance liquid chromatography-linked hydride generator, and atomic absorption spectrometry. Polymorphisms of ACE(I/D), AGT(A[− 20]C), (T174M), (M235T), AT1R(A1166C) and CYP11B2(C[− 344]T) were examined by polymerase chain reaction and restriction fragment length polymorphism. Subjects carrying the CYP11B2 TT genotype had a higher odds ratio (OR), 1.39 (0.96–2.01), of CKD; while those with the AGT(A[− 20]C) CC genotype had an inverse OR of CKD (0.20 (0.05–0.81)), and a high-risk genotype was defined as A/A + A/C for AGT(A[− 20C]) and T/T for CYP11B2(C[− 344]T). The trend test showed a higher OR for CKD in patients who had either high urinary total arsenic levels or carried the high-risk genotype, or both, compared to patients with low urinary total arsenic levels, who carried the low-risk genotype, and could also be affected by the hypertension or diabetes status. - Highlights: • AGT(− 20 C) and CYP11B2(− 344 T) genotypes were significantly associated with CKD. • Combined effect of high-risk genotypes and high urinary total arsenic on OR of CKD. • Combined

  3. Evaluation of aldosterone-and cortisol levels in blood plasma in normal conditions of ingestion of sodium and potassium, after saline-increase and depletion, in regard to position, and after stimulation with ACTH and angiotensin II

    International Nuclear Information System (INIS)

    Okada, H.

    1979-01-01

    Methods for the determination of plasma aldosterone and cortisol, by radioimmunoassay, were performed utilizing highly specific antisera. With this methodology it was possible to evaluate cortisol and aldosterone secretion, in six normal subjects, submitted to a basal rice diet on standing and recumbent positions, the effects of exogenous cortrosyn (β1-24 ACTH) and angiotensin II and the same manoevres with progressively increased Na + content of the diet. Aldosterone basal levels decreased with the increase of Na + content in the diet. However, there were no significant differences between the relative increments observed on the recumbent position, at the three levels of sodium intake. The relative increase of plasma aldosterone after ACTH was similar for each basal level of aldosterone induced by different sodium intakes. The responsiveness of aldosterone secretion to cortrosyn and standing position was similar, with no relation to the sodium intake. The infusion of angiotensin II induced an increase in plasma aldosterone, and the relative increment in the levels of the hormone were higher with high sodium than on the rice diet. The average basal cortisol value at the different levels of sodium intake was significantly different being greater on the basal, rice diet, and there was a decrease in cortisol level after recumbency, with the theree diets. The injection of ACTH induced similar cortisol secretion with no relation to the sodium intake. The infusion of non-hypertensive doses of angiotensin II resulted in an anomalous fall in cortisol level, probably because of 'shunt' of substrates to biosynthesis with the added effect of cortisol diurnal rhythmycity. (Author) [pt

  4. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort.

    Science.gov (United States)

    Williams, Tracy A; Lenders, Jacques W M; Mulatero, Paolo; Burrello, Jacopo; Rottenkolber, Marietta; Adolf, Christian; Satoh, Fumitoshi; Amar, Laurence; Quinkler, Marcus; Deinum, Jaap; Beuschlein, Felix; Kitamoto, Kanako K; Pham, Uyen; Morimoto, Ryo; Umakoshi, Hironobu; Prejbisz, Aleksander; Kocjan, Tomaz; Naruse, Mitsuhide; Stowasser, Michael; Nishikawa, Tetsuo; Young, William F; Gomez-Sanchez, Celso E; Funder, John W; Reincke, Martin

    2017-09-01

    Although unilateral primary aldosteronism is the most common surgically correctable cause of hypertension, no standard criteria exist to classify surgical outcomes. We aimed to create consensus criteria for clinical and biochemical outcomes and follow-up of adrenalectomy for unilateral primary aldosteronism and apply these criteria to an international cohort to analyse the frequency of remission and identify preoperative determinants of successful outcome. The Primary Aldosteronism Surgical Outcome (PASO) study was an international project to develop consensus criteria for outcomes and follow-up of adrenalectomy for unilateral primary aldosteronism. An international panel of 31 experts from 28 centres, including six endocrine surgeons, used the Delphi method to reach consensus. We then retrospectively analysed follow-up data from prospective cohorts for outcome assessment of patients diagnosed with unilateral primary aldosteronism by adrenal venous sampling who had undergone a total adrenalectomy, consecutively included from 12 referral centres in nine countries. On the basis of standardised criteria, we determined the proportions of patients achieving complete, partial, or absent clinical and biochemical success in accordance with the consensus. We then used logistic regression analyses to identify preoperative factors associated with clinical and biochemical outcomes. Consensus was reached for criteria for six outcomes (complete, partial, and absent success of clinical and biochemical outcomes) based on blood pressure, use of antihypertensive drugs, plasma potassium and aldosterone concentrations, and plasma renin concentrations or activities. Consensus was also reached for two recommendations for the timing of follow-up assessment. For the international cohort analysis, we analysed clinical data from 705 patients recruited between 1994 and 2015, of whom 699 also had biochemical data. Complete clinical success was achieved in 259 (37%) of 705 patients, with a

  5. Role of MicroRNAs in Renin-Angiotensin-Aldosterone System-Mediated Cardiovascular Inflammation and Remodeling

    Directory of Open Access Journals (Sweden)

    Maricica Pacurari

    2015-01-01

    Full Text Available MicroRNAs are endogenous regulators of gene expression either by inhibiting translation or protein degradation. Recent studies indicate that microRNAs play a role in cardiovascular disease and renin-angiotensin-aldosterone system- (RAAS- mediated cardiovascular inflammation, either as mediators or being targeted by RAAS pharmacological inhibitors. The exact role(s of microRNAs in RAAS-mediated cardiovascular inflammation and remodeling is/are still in early stage of investigation. However, few microRNAs have been shown to play a role in RAAS signaling, particularly miR-155, miR-146a/b, miR-132/122, and miR-483-3p. Identification of specific microRNAs and their targets and elucidating microRNA-regulated mechanisms associated RAS-mediated cardiovascular inflammation and remodeling might lead to the development of novel pharmacological strategies to target RAAS-mediated vascular pathologies. This paper reviews microRNAs role in inflammatory factors mediating cardiovascular inflammation and RAAS genes and the effect of RAAS pharmacological inhibition on microRNAs and the resolution of RAAS-mediated cardiovascular inflammation and remodeling. Also, this paper discusses the advances on microRNAs-based therapeutic approaches that may be important in targeting RAAS signaling.

  6. Effects of stress, circadian rhythms, and dietary sodium on brain cell-nuclear uptake of aldosterone and corticosterone

    International Nuclear Information System (INIS)

    Yongue, B.G.

    1985-01-01

    The binding of the adrenal steroid hormones aldosterone (ALD) and corticosterone (CORT) in brain cell-nuclei has been implicated as a necessary step in the behavioral and physiological actions of these hormones. In vivo uptake of radioactively labeled ALD and CORT in adrenalectomized (ADX) rats indicates a strong cell-nuclear localization of both of these hormones in limbic brain regions (such as hippocampus, septum and amygdala). Research using sub-cellular fractionation and radioimmunoassay (RIA), has confirmed both the presence of endogenously secreted CORT in cell-nuclei and its limbic localization in the brains of adrenal-intact rats. In this study, environmental and dietary factors were manipulated to induce variation in serum ALD and CORT. A series of experiments employing sub-cellular fractionation and RIA were performed, which reveal that: (1) endogenously secreted ALD and CORT, are concentrated by cell-nuclei of the brain in adrenal-intact rats, (2) the majority of the corticosteroids measured in ethanol extracts of brain cell-nuclei are associated with receptor molecules, and (3) the regional distribution of endogenously secreted ALD differs markedly from the predominantly limbic pattern predicted from in vivo uptake of labeled ALD in ADX rats. Instead, brain cell-nuclear ALD is heavily concentrated in the hypothalamus, which supports the hypothesized relationship between the interaction of ALD and angiotensin in the brain and the behavioral regulation of fluid/electrolyte balance

  7. Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride.

    Science.gov (United States)

    Graudal, Niels Albert; Hubeck-Graudal, Thorbjorn; Jurgens, Gesche

    2017-04-09

    In spite of more than 100 years of investigations the question of whether a reduced sodium intake improves health is still unsolved. To estimate the effects of low sodium intake versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum levels of renin, aldosterone, catecholamines, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides. The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to March 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the reference lists of relevant articles. Studies randomising persons to low-sodium and high-sodium diets were included if they evaluated at least one of the above outcome parameters. Two review authors independently collected data, which were analysed with Review Manager 5.3. A total of 185 studies were included. The average sodium intake was reduced from 201 mmol/day (corresponding to high usual level) to 66 mmol/day (corresponding to the recommended level).The effect of sodium reduction on blood pressure (BP) was as follows: white people with normotension: SBP: mean difference (MD) -1.09 mmHg (95% confidence interval (CI): -1.63 to -0.56; P = 0.0001); 89 studies, 8569 participants; DBP: + 0.03 mmHg (MD 95% CI: -0.37 to 0.43; P = 0.89); 90 studies, 8833 participants. High-quality evidence. Black people with normotension: SBP: MD -4.02 mmHg (95% CI:-7.37 to -0.68; P = 0.002); seven studies, 506 participants; DBP: MD -2.01 mmHg (95% CI:-4.37 to 0.35; P = 0.09); seven studies, 506 participants. Moderate-quality evidence. Asian people with normotension: SBP: MD -0.72 mmHg (95% CI: -3.86 to 2.41; P = 0.65); DBP: MD -1.63 mmHg (95% CI:-3.35 to 0

  8. Effect of all-trans retinoic acid treatment on prohibitin and renin-angiotensin-aldosterone system expression in hypoxia-induced renal tubular epithelial cell injury.

    Science.gov (United States)

    Zhou, Tian-Biao; Ou, Chao; Rong, Liang; Drummen, Gregor P C

    2014-09-01

    All-trans retinoic acid (ATRA) exerts various effects on physiological processes such as cell growth, differentiation, apoptosis and inflammation. Prohibitins (PHB), including prohibitin 1 (PHB1) and prohibitin 2 (PHB2), are evolutionary conserved and pleiotropic proteins implicated in various cellular functions, including proliferation, tumor suppression, apoptosis, transcription, and mitochondrial protein folding. The renin-angiotensin-aldosterone system plays a pivotal role in the regulation of blood pressure and volume homeostasis. All these factors and systems have been implicated in renal interstitial fibrosis. Therefore, the objective of this study was to investigate the effect of ATRA treatment on the renin-angiotensin-aldosterone system and expression of prohibitins to further understand its role in the processes leading to renal interstitial fibrosis. The hypoxic and oxidative stress conditions in obstructive renal disease were simulated in a hypoxia/reoxygenation model with renal tubular epithelial cells (RTEC) as a model system. Subsequently, the effect of ATRA on mRNA and protein expression levels was determined and correlations were established between factors involved in the renin-angiotensin-aldosterone system, the prohibitins, cellular redox status, renal interstitial fibrosis and ATRA treatment. Correlation analysis showed that both PHB1 and PHB2 protein levels were negatively correlated with angiotensin I, ACE1, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA (PHB1: r = -0.792, -0.834, -0.805, -0.795, -0.778, -0.798, -0.751, -0.682; PHB2: r = -0.872, -0.799, -0.838, -0.773, -0.769, -0.841, -0.794, -0.826; each p system under hypoxia/reoxygenation conditions. © The Author(s) 2014.

  9. Maternal corticosterone exposure in the mouse programs sex-specific renal adaptations in the renin-angiotensin-aldosterone system in 6-month offspring.

    Science.gov (United States)

    Cuffe, James S M; Burgess, Danielle J; O'Sullivan, Lee; Singh, Reetu R; Moritz, Karen M

    2016-04-01

    Short-term maternal corticosterone (Cort) administration at mid-gestation in the mouse reduces nephron number in both sexes while programming renal and cardiovascular dysfunction in 12-month male but not female offspring. The renal renin-angiotensin-aldosterone system (RAAS), functions in a sexually dimorphic manner to regulate both renal and cardiovascular physiology. This study aimed to identify if there are sex-specific differences in basal levels of the intrarenal RAAS and to determine the impact of maternal Cort exposure on the RAAS in male and female offspring at 6 months of age. While intrarenal renin concentrations were higher in untreated females compared to untreated males, renal angiotensin II concentrations were higher in males than females. Furthermore, basal plasma aldosterone concentrations were greater in females than males. Cort exposed male but not female offspring had reduced water intake and urine excretion. Cort exposure increased renal renin concentrations and elevated mRNA expression of Ren1, Ace2, and Mas1 in male but not female offspring. In addition, male Cort exposed offspring had increased expression of the aldosterone receptor, Nr3c2 and renal sodium transporters. In contrast, Cort exposure increased Agtr1a mRNA levels in female offspring only. This study demonstrates that maternal Cort exposure alters key regulators of renal function in a sex-specific manner at 6 months of life. These finding likely contribute to the disease outcomes in male but not female offspring in later life and highlights the importance of renal factors other than nephron number in the programming of renal and cardiovascular disease. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  10. Comparison of stress-induced changes in adults and pups: is aldosterone the main adrenocortical stress hormone during the perinatal period in rats?

    Directory of Open Access Journals (Sweden)

    János Varga

    Full Text Available Positive developmental impact of low stress-induced glucocorticoid levels in early development has been recognized for a long time, while possible involvement of mineralocorticoids in the stress response during the perinatal period has been neglected. The present study aimed at verifying the hypothesis that balance between stress-induced glucocorticoid and mineralocorticoid levels is changing during postnatal development. Hormone responses to two different stressors (insulin-induced hypoglycaemia and immune challenge induced by bacterial lipopolysaccharid measured in 10-day-old rats were compared to those in adults. In pups corticosterone responses to both stressors were significantly lower than in adults, which corresponded well with the stress hyporesponsive period. Importantly, stress-induced elevations in aldosterone concentration were significantly higher in pups compared both to corticosterone elevations and to those in adulthood with comparable adrenocorticotropin concentrations in the two age groups. Greater importance of mineralocorticoids compared to glucocorticoids in postnatal period is further supported by changes in gene expression and protein levels of gluco- (GR and mineralocorticoid receptors (MR and selected enzymes measured by quantitative PCR and immunohystochemistry in the hypothalamus, hippocampus, prefrontal cortex, liver and kidney. Gene expression of 11beta-hydroxysteroid dehydrogenase 2 (11β-HSD2, an enzyme enabling preferential effects of aldosterone on mineralocorticoid receptors, was higher in 10-day-old pups compared to adult animals. On the contrary, the expression and protein levels of GR, MR and 11β-HSD1 were decreased. Presented results clearly show higher stress-induced release of aldosterone in pups compared to adults and strongly suggest greater importance of mineralocorticoids compared to glucocorticoids in stress during the postnatal period.

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

    Science.gov (United States)

    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.

  12. Favorable surgical outcomes of aldosterone-producing adenoma based on lateralization by CT imaging and hypokalemia: a non-AVS-based strategy.

    Science.gov (United States)

    Li, Hai; Liu, Jianbin; Feng, Xiujuan; Liu, Liehua; Wei, Guohong; Cao, Xiaopei; Li, Yanbing

    2017-12-01

    To test the efficacy of a strategy based on CT imaging and clinical characteristics on lateralizing origin of excess aldosterone secretion in primary aldosteronism. Consecutive patients with diagnosed primary hyperaldosteronism from June 2006 to July 2012 in our center underwent adrenal surgeries without pre-operational adrenal venous sampling (AVS) if all the three criteria were met: (1) round- or oval-shaped occupational lesion of low density after contrast enhancement with diameter >1 cm on CT scan was located in one adrenal gland; (2) unequivocally normal contralateral adrenal gland; (3) serum potassium level lower than 3.5 mmol/L. Subjects who had received operation were taken into analysis and follow-ups. One hundred and twenty-five patients fulfilled the criteria and were recruited into our research. One hundred and twenty-two operated patients (97.6%) experienced complete resolution of hypokalemia as well as resolution or improvement in hypertension with reduction in antihypertensive medication, while 3 patients (2.4%) failed to obtain normal kalemia and continued on spironolactone therapy. At a median of 65-month (range 21-93) follow-up of these 122 subjects, 27 patients dropped out (22.1%). The 95 responding patients reported no episodes of paralysis or confirmed hypokalemia or any supplementation of potassium. Multivariate linear correlation analysis showed that plasma potassium level was correlated inversely with tumor diameter (r = -0.258, 95% CI -0.076, -0.514, p = 0.037) and basal plasma aldosterone level (r = -0.251, 95% CI -0.040, -0.464, p = 0.042). Most patients with typical unilateral adrenal macroadenomas, normal contralateral glands and hypokalemia could attain favorable surgical therapeutic outcomes without pre-operational AVS lateralization.

  13. Renin-angiotensin II-aldosterone system blockers and time to renal replacement therapy in children with CKD.

    Science.gov (United States)

    Abraham, Alison G; Betoko, Aisha; Fadrowski, Jeffrey J; Pierce, Christopher; Furth, Susan L; Warady, Bradley A; Muñoz, Alvaro

    2017-04-01

    Clinical care decisions to treat chronic kidney disease (CKD) in a growing child must often be made without the benefit of evidence from clinical trials. We used observational data from the Chronic Kidney Disease in Children cohort to estimate the effectiveness of renin-angiotensin II-aldosterone system blockade (RAAS) to delay renal replacement therapy (RRT) in children with CKD. A total of 851 participants (median age: 11 years, median glomerular filtration rate [GFR]: 52 ml/min/1.73 m 2 , median urine protein to creatinine ratio: 0.35 mg/mg) were included. RAAS use was reported at annual study visits. Both Cox proportional hazards models with time-varying RAAS exposure and Cox marginal structural models (MSM) were used to evaluate the effect of RAAS use on time to RRT. Analyses were adjusted or weighted to control for age, male sex, glomerular diagnosis, GFR, nephrotic range proteinuria, anemia, elevated blood pressure, acidosis, elevated phosphate and elevated potassium. There were 217 RRT events over a 4.1-year median follow-up. At baseline, 472 children (55 %) were prevalent RAAS users, who were more likely to be older, have a glomerular etiology, have higher urine protein, be anemic, have elevated serum phosphate and potassium, take more medications, but less likely to have elevated blood pressure, compared with non-users. RAAS use was found to reduce the risk of RRT by 21 % (hazard ratio: 0.79) to 37 % (hazard ratio: 0.63) from standard regression adjustment and MSM models, respectively. These results support inferences from adult studies of a substantial benefit of RAAS use in pediatric CKD patients.

  14. Renin-angiotensin-aldosterone system inhibitors improve membrane stability and change gene-expression profiles in dystrophic skeletal muscles.

    Science.gov (United States)

    Chadwick, Jessica A; Bhattacharya, Sayak; Lowe, Jeovanna; Weisleder, Noah; Rafael-Fortney, Jill A

    2017-02-01

    Angiotensin-converting enzyme inhibitors (ACEi) and mineralocorticoid receptor (MR) antagonists are FDA-approved drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) and are used to treat heart failure. Combined treatment with the ACEi lisinopril and the nonspecific MR antagonist spironolactone surprisingly improves skeletal muscle, in addition to heart function and pathology in a Duchenne muscular dystrophy (DMD) mouse model. We recently demonstrated that MR is present in all limb and respiratory muscles and functions as a steroid hormone receptor in differentiated normal human skeletal muscle fibers. The goals of the current study were to begin to define cellular and molecular mechanisms mediating the skeletal muscle efficacy of RAAS inhibitor treatment. We also compared molecular changes resulting from RAAS inhibition with those resulting from the current DMD standard-of-care glucocorticoid treatment. Direct assessment of muscle membrane integrity demonstrated improvement in dystrophic mice treated with lisinopril and spironolactone compared with untreated mice. Short-term treatments of dystrophic mice with specific and nonspecific MR antagonists combined with lisinopril led to overlapping gene-expression profiles with beneficial regulation of metabolic processes and decreased inflammatory gene expression. Glucocorticoids increased apoptotic, proteolytic, and chemokine gene expression that was not changed by RAAS inhibitors in dystrophic mice. Microarray data identified potential genes that may underlie RAAS inhibitor treatment efficacy and the side effects of glucocorticoids. Direct effects of RAAS inhibitors on membrane integrity also contribute to improved pathology of dystrophic muscles. Together, these data will inform clinical development of MR antagonists for treating skeletal muscles in DMD. Copyright © 2017 the American Physiological Society.

  15. Increased prevalence of diabetes mellitus and the metabolic syndrome in patients with primary aldosteronism of the German Conn's Registry.

    Science.gov (United States)

    Hanslik, Gregor; Wallaschofski, Henri; Dietz, Anna; Riester, Anna; Reincke, Martin; Allolio, Bruno; Lang, Katharina; Quack, Ivo; Rump, Lars C; Willenberg, Holger S; Beuschlein, Felix; Quinkler, Marcus; Hannemann, Anke

    2015-11-01

    Abnormalities in glucose homeostasis have been described in patients with primary aldosteronism (PA) but most studies show inconsistent results. Therefore, we aimed to compare the prevalence of type 2 diabetes mellitus and metabolic syndrome (MetS) in newly diagnosed PA patients to a matched control cohort of the background population. In total, 305 PA patients of the prospective German Conn's Registry were compared to the population-based Study of Health In Pomerania (SHIP1; n=2454). A 1:1 match regarding sex, age, and BMI resulted in 269 matched pairs regarding type 2 diabetes and 183 matched pairs regarding MetS. Of the total, 153 PA patients underwent oral glucose tolerance testing (OGTT) at diagnosis and 38 PA patients were reevaluated at follow-up. Type 2 diabetes and MetS were significantly more frequent in PA patients than in the control population (17.2% vs 10.4%, P=0.03; 56.8% vs 44.8%, P=0.02 respectively). Also, HbA1c levels were higher in PA patients than in controls (P<0.01). Of the total, 35.3% of non-diabetic PA patients showed an abnormal OGTT (¼ newly diagnosed type 2 diabetes and ¾ impaired glucose tolerance). PA patients with an abnormal OGTT at baseline presented with significantly improved 2 h OGTT glucose (P=0.01) at follow-up. We detected a negative correlation between 2 h OGTT glucose levels and serum potassium (P<0.01). Type 2 diabetes and MetS are more prevalent in patients with PA than in controls matched for sex, age, BMI, and blood pressure. This may explain in part the increased cardiovascular disease morbidity and mortality in PA patients. © 2015 European Society of Endocrinology.

  16. Reversing the established order: Should adrenal venous sampling precede cross-sectional imaging in the evaluation of primary aldosteronism?

    Science.gov (United States)

    Asmar, Melissa; Wachtel, Heather; Yan, Yan; Fraker, Douglas L; Cohen, Debbie; Trerotola, Scott O

    2015-08-01

    Adrenal venous sampling (AVS) is the definitive evaluation for primary aldosteronism (PA). Pre-AVS cross-sectional imaging does not reduce the need for AVS. The goal of this study was to examine whether performing AVS prior to imaging could decrease the use of imaging in the evaluation of PA at a high volume, experienced center. We performed a retrospective analysis of all AVS procedures (n = 337) done for PA from 2001-2013. Patients whose cross-sectional imaging reports were unavailable (n = 90) or AVS was non-diagnostic (n = 12) were excluded. AVS was performed using modified Mayo technique. Univariate analysis utilized the χ² test and fisher's exact test. Of the 235 patients analyzed, 63% (n = 148) were male. The mean age was 55 ± 11 years. AVS was non-lateralizing in 43% (n = 101); these patients might have avoided imaging with an AVS-first approach. Imaging and AVS were concordant in 52% (n = 123). In patients ≤40yo (n = 23), 35% (n = 8) had no lateralization on AVS, and might have avoided imaging in an AVS-first approach. Imaging and AVS were concordant in 52% (n = 12) of patients ≤ 40yo, versus 52% (n = 111) of patients > 40 yo (P = 0.987). An AVS-first, imaging-second approach could have avoided CT/MRI in 43% of patients. At a high volume, experienced center, performing AVS first on patients with PA may reduce unnecessary cross-sectional imaging studies. © 2015 Wiley Periodicals, Inc.

  17. Renin-angiotensin-aldosterone system inhibitors lower hemoglobin and hematocrit only in renal transplant recipients with initially higher levels.

    Science.gov (United States)

    Mikolasevic, I; Zaputovic, L; Zibar, L; Begic, I; Zutelija, M; Klanac, A; Majurec, I; Simundic, T; Minazek, M; Orlic, L

    2016-04-01

    We have analyzed the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on evolution of hemoglobin (Hb) and hematocrit (Htc) levels as well as on the evaluation of kidney graft function in stable renal transplant recipients (RTRs) in respect with initially higher or lower Hb and Htc values. The study group comprised of 270 RTRs with stable graft function. Besides other prescribed antihypertensive therapy, 169 of them have been taking RAAS inhibitors. We wanted to analyze the effect of the use of RAAS inhibitors on Hb and Htc in patients with initially higher or lower Hb/Htc values. For this analysis, only RTRs that were taking RAAS inhibitors were stratified into two groups: one with higher Hb and Htc (initial Hb≥150g/L and Htc≥45%) and another one with lower Hb and Htc (initial Hb<150g/L and Htc<45%) values. Thirty-four RTRs with initially higher Hb and 41 RTRs with initially higher Htc had a statistically significant decrease in Hb (p=0.006) and Htc (p<0.0001) levels after 12-months of follow-up. In the group of patients with initially lower Hb (135 RTRs) and Htc (128 RTRs) there was a significant increase in Hb (p=0.0001) and Htc (p=0.004) levels through the observed period. The use of RAAS inhibitors has been associated with a trend of slowing renal insufficiency in RTRs (p=0.03). RAAS inhibitors lower Hb and Htc only in RTRs with initially higher levels. In patients with initially lower Hb and Htc levels, the use of these drugs is followed by beneficial impact on erythropoiesis and kidney graft function. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  18. 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.

  19. Vascular complications in patients with aldosterone producing adenoma in Japan: comparative study with essential hypertension. The Research Committee of Disorders of Adrenal Hormones in Japan.

    Science.gov (United States)

    Takeda, R; Matsubara, T; Miyamori, I; Hatakeyama, H; Morise, T

    1995-05-01

    The incidence of vascular complications in 224 patients with aldosterone-producing adenoma (APA) which was proven on adrenal surgery, was compared to that in 224 sex- and age-matched patients with essential hypertension (EHT). The incidence of cerebral hemorrhage was significantly higher (p < 0.05) in the patients with APA when compared to the EHT group. On the other hand, the incidence of myocardial infarction and/or congestive heart failure in the APA group was lower, although this difference did not reach statistical significance. Diastolic blood pressure in the APA group was significantly higher (p < 0.001) in the EHT group. However, a significant difference in diastolic blood pressure was not detected between the APA groups with and without vascular complications, whereas in the EHT group diastolic blood pressure was significantly higher (p < 0.001) in cases with vascular complications as compared to those without complications. As a possible factor contributing to the higher incidence of cerebral hemorrhage in the APA group, proteinuria was suggested. It was recommended that patients with primary aldosteronism should undergo operation when localization of the APA is established.

  20. 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.

  1. Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling.

    Science.gov (United States)

    Resch, Jon M; Fenselau, Henning; Madara, Joseph C; Wu, Chen; Campbell, John N; Lyubetskaya, Anna; Dawes, Brian A; Tsai, Linus T; Li, Monica M; Livneh, Yoav; Ke, Qingen; Kang, Peter M; Fejes-Tóth, Géza; Náray-Fejes-Tóth, Anikó; Geerling, Joel C; Lowell, Bradford B

    2017-09-27

    Sodium deficiency increases angiotensin II (ATII) and aldosterone, which synergistically stimulate sodium retention and consumption. Recently, ATII-responsive neurons in the subfornical organ (SFO) and aldosterone-sensitive neurons in the nucleus of the solitary tract (NTS HSD2 neurons) were shown to drive sodium appetite. Here we investigate the basis for NTS HSD2 neuron activation, identify the circuit by which NTS HSD2 neurons drive appetite, and uncover an interaction between the NTS HSD2 circuit and ATII signaling. NTS HSD2 neurons respond to sodium deficiency with spontaneous pacemaker-like activity-the consequence of "cardiac" HCN and Na v 1.5 channels. Remarkably, NTS HSD2 neurons are necessary for sodium appetite, and with concurrent ATII signaling their activity is sufficient to produce rapid consumption. Importantly, NTS HSD2 neurons stimulate appetite via projections to the vlBNST, which is also the effector site for ATII-responsive SFO neurons. The interaction between angiotensin signaling and NTS HSD2 neurons provides a neuronal context for the long-standing "synergy hypothesis" of sodium appetite regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. 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.

  3. 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.

  4. 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

  5. A Model to Determine the Level of Serum Aldosterone in the Workers Attributed to the Combined Effects of Sound Pressure Level, Exposure Time and Serum Potassium Level: A Field-Based Study

    Directory of Open Access Journals (Sweden)

    Parvin Nassiri

    2016-09-01

    Full Text Available Background Occupational exposure to excessive noise is one of the biggest work-related challenges in the world. This phenomenon causes the release of stress-related hormones, which in turn, negatively affects cardiovascular risk factors. Objectives The current study study aimed to determine the level of workers’ serum aldosterone in light of the combined effect of sound pressure level, exposure time and serum potassium level. Methods This cross-sectional, descriptive, analytical study was conducted on 45 workers of Gol-Gohar Mining and Industrial Company in the fall of 2014. The subjects were divided into three groups (one control and two case groups, each including 15 workers. Participants in the control group were selected from workers with administrative jobs (exposure to the background noise. On the other hand, participants in the case groups were selected from the concentrator and pelletizing factories exposed to excessive noise. Serum aldosterone and potassium levels of participants were assessed at three different time intervals: at the beginning of the shift and before exposure to noise (7:30 - 8:00 AM, during exposure to noise (10:00 - 10:30 AM, and during continuous exposure (1:30 - 2:00 PM. The obtained data were transferred into SPSS ver. 18. Repeated measures analysis of variance (ANOVA was used to develop the statistical model of workers’ aldosterone level in light of the combined effect of sound pressure level, exposure time, and serum potassium level. Results The results of the final statistical model to determine the level of serum aldosterone based on the combined effect of sound pressure level, exposure time and serum potassium level indicated that the sound pressure level had a significant influence on the human’s serum aldosterone level (P = 0.04. In addition, the effects of exposure time and serum potassium on aldosterone level were statistically significant with P-values of 0.008 and 0.001, respectively. Conclusions

  6. The renin–angiotensin–aldosterone system blockade in patients with advanced diabetic kidney disease

    Directory of Open Access Journals (Sweden)

    Sheila Bermejo

    2018-03-01

    Full Text Available Background and objectives: Diabetic kidney disease is the leading cause of end-stage chronic kidney disease (CKD. The renin–angiotensin–aldosterone system (RAAS blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up. Materials and methods: Retrospective study. 197 diabetic kidney disease patients were included and divided into three groups according to the treatment: patients who had never received RAAS blockade (non-RAAS blockade, patients who at some point had received RAAS blockade (inconstant-RAAS blockade and patients who received RAAS blockade (constant-RAAS blockade. Clinical characteristics and analytical variables such as renal function, electrolytes, glycosylated hemoglobin and glomerular filtration rate according to CKD-EPI and MDRD formulas were assessed. We also studied their clinical course (baseline, 1 and 3 years follow-up in terms of treatment group, survival, risk factors and renal prognosis. Results: Non-RAAS blockade patients had worse renal function and older age (p < 0.05 at baseline compared to RAAS blockade patients. Patients who received RAAS blockade were not found to have greater toxicity or chronic kidney disease progression and no differences in renal prognosis were identified. Mortality was higher in non-RAAS blockade patients, older patients and patients with worse renal function (p < 0.05. In the multivariate analysis, older age and worse renal function were risk factors for mortality. Conclusions: Treatment with RAAS blockade is more common in diabetic kidney disease patients with eGFR ≥ 30 ml/min/1.73 m2. In our study, there were no differences in the evolution of renal function

  7. 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.

  8. A Multi-institutional Comparison of Adrenal Venous Sampling in Patients with Primary Aldosteronism: Caution Advised if Successful Bilateral Adrenal Vein Sampling is Not Achieved.

    Science.gov (United States)

    Wang, Tracy S; Kline, Greg; Yen, Tina W; Yin, Ziyan; Liu, Ying; Rilling, William; So, Benny; Findling, James W; Evans, Douglas B; Pasieka, Janice L

    2018-02-01

    In patients with primary aldosteronism (PA), adrenal venous sampling (AVS) is recommended to differentiate between unilateral (UNI) or bilateral (BIL) adrenal disease. A recent study suggested that lateralization could be predicted, based on the ratio of aldosterone/cortisol levels (A/C) between the left adrenal vein (LAV) and inferior vena cava (IVC), with a 100% positive predictive value (PPV). This study aimed to validate those findings utilizing a larger, multi-institutional cohort. A retrospective review was performed of patients with PA who underwent AVS from 2 tertiary-care institutions. Laterality was predicted by an A/C ratio of >3:1 between the dominant and non-dominant adrenal. AVS results were compared to LAV/IVC ratios utilizing the published criteria (Lt ≥ 5.5; Rt ≤ 0.5). Of 222 patients, 124 (57%) had UNI and 98 (43%) had BIL disease based on AVS. AVS and LAV/IVC findings were concordant for laterality in 141 (64%) patients (69 UNI, 72 BIL). Using only the LAV/IVC ratio, 54 (24%) patients with UNI disease on AVS who underwent successful surgery would have been assumed to have BAH unless AVS was repeated, and 24 (11%) patients with BIL disease on AVS may have been incorrectly offered surgery (PPV 70%). Based on median LAV/IVC ratios (left 5.26; right 0.31; BIL 2.84), no LAV/IVC ratio accurately predicted laterality. This multi-institutional study of patients with both UNI and BIL PA failed to validate the previously reported PPV of LAV/IVC ratio for lateralization. Caution should be used in interpreting incomplete AVS data to differentiate between UNI versus BIL disease and strong consideration given to repeat AVS prior to adrenalectomy.

  9. Aldosterone synthase gene polymorphism in alimentary obesity, metabolic syndrome components, some secondary forms of arterial hypertension, pathology of the adrenals glands core (literature review

    Directory of Open Access Journals (Sweden)

    S.N. Koval

    2017-08-01

    Full Text Available Hormonal factors of adrenal origin belong to the pathophysiological mechanisms of the formation and progression of arterial hypertension (AH and should be consi­dered while developing differentiated approaches to the treatment and prevention of hypertensive states, their primary, secondary and resistant forms. The first thing we should point up is aldosterone (AL, enzyme aldosterone synthase (AS, which takes a direct part in the formation of this hormone, as well as gene polymorphisms of AS, which have not only molecular genetic, but also differential diagnostic and therapeutic significance for secondary forms of arterial hypertension, abdominal obesity (AO, metabolic syndrome (MS, adrenal pathology and other endocrine disorders. AL is a steroid (mineralocorticoid hormone of the adrenal cortex, which is synthesized from cholesterol (CH, mainly in the glomerular zone of the adrenal glands, is released under the action of angiotensin II (A II and potassium ions (K+. AL acti­vity is mediated through the corresponding mineralocorticoid receptors (MKR. The particular importance in AH and MS development belongs to AL activation and MKR density in adipocytes, this phenomenon is accompanied by increased expression of pro-inflammatory cytokines, leptin, an adipogenic effect, and the inhibition of MCR activity is accompanied by increased production of adiponectin, which is more pronounced in patients with AH. Aldosterone synthase, a mitochondrial human enzyme encoded by the CYP11B2 gene (cytochrome P450, family 11, subfamily B, polypeptide 2 is located on the 8th chromosome. AS belongs to the superfamily of cytochrome P450 and regulates the synthesis of AL hormone. The CYP11B2 gene encodes the key enzyme for the synthesis of AL 18-hydroxylase. In scientific papers, single nucleotide polymorphism (SNP of AS gene is often studied, such as 5312T, Intron 2, Lys-173/Arg; T-344C, 3097 C/A. 227 SNP of the AS gene were identified in different

  10. Aliskiren suppresses the renin–angiotensin–aldosterone system and reduces blood pressure and albuminuria in elderly chronic kidney disease patients with hypertension

    Directory of Open Access Journals (Sweden)

    Morishita Y

    2012-09-01

    Full Text Available Yoshiyuki Morishita,1 Toshihiro Yasui,2 Akihiko Numata,1 Akira Onishi,1 Kenichi Ishibashi,3 Eiji Kusano11Department of Internal Medicine, Jichi Medical University, Shimotsuke, Japan; 2National Health Insurance Yukawa Clinic, Niimi, Japan; 3Department of Medical Physiology, Meiji Pharmaceutical University, Tokyo, JapanBackground: We investigated the effects of aliskiren in terms of its inhibition of the renin–angiotensin–aldosterone system (RAAS as well as that on blood pressure (BP, and renal and cardiac protection in elderly chronic kidney disease (CKD patients with hypertension.Methods: Nineteen elderly CKD patients (nine males, ten females, aged 74.6 ± 5.8 years were assigned to receive 150 mg/day of aliskiren added to existing antihypertensives for 6 months. Changes in plasma renin activity (PRA, angiotensin I (Ang I, angiotensin II (Ang II, aldosterone (Ald, BP, estimated glomerular filtration rate (eGFR, urine albumin/creatinine ratio (UACR, left ventricular ejection fraction (LVEF, interventricular septum thickness (IVST, left ventricular posterior wall thickness (LVPWT, and plasma brain natriuretic peptide (BNP levels were evaluated.Results: Aliskiren suppressed the RAAS as follows: PRA 1.3 ± 1.0 to 0.3 ± 0.3 ng/mL/hour, P < 0.05; Ang I 59.5 ± 32.1 to 26.0 ± 17.3 pg/mL, P < 0.05; Ang II 58.4 ± 62.1 to 14.3 ± 9.0 pg/mL, P < 0.05; and Ald 86.1 ± 38.3 to 80.1 ± 52.6 pg/mL, not significant (NS. Aliskiren reduced BP (153.6/77.2 ± 14.9/10.4 to 130.9/72.2 ± 15.6/9.9 mmHg, P < 0.05. It also reduced UACR (747.1 ± 1121.4 to 409.6 ± 636.8 mg/g, P < 0.05, whereas it did not change eGFR (52.1 ± 29.2 to 51.2 ± 29.3 mL/min/1.73 m2, NS, LVEF (66.8 ± 7.9 to 66.5% ± 6.8%, NS, IVST (10.1 ± 1.8 to 9.9 ± 1.8 mm, NS, LVPWT (10.0 ± 1.6 mm to 10.0 ± 1.4 mm, NS, or BNP (48.2 ± 46.0 to 54.9 ± 41.1 pg/mL, NS.Conclusion: Aliskiren was effective for BP control and reduced UACR while maintaining eGFR and heart function in elderly CKD

  11. 8D.04: CLINICAL BENEFITS OF ADMINISTERING SUPER-SELECTIVE SEGMENTAL ADRENAL VENOUS SAMPLING AND PERFORMING ADRENAL SPARING SURGERY IN THE PATIENTS WITH PRIMARY ALDOSTERONISM.

    Science.gov (United States)

    Satoh, F; Morimoto, R; Ono, Y; Iwakura, Y; Omata, K; Kudo, M; Satani, N; Ota, H; Seiji, K; Takase, K; Nakamura, Y; Sasano, H; Ito, S

    2015-06-01

    Adrenal venous sampling (AVS) has been well known to play pivotal roles in clinical differential diagnosis of unilateral aldosterone producing adenoma (APA) from bilateral idiopathic hyperaldosteronism (IHA). However, it is also true that a central vein AVS or c-AVS which collects the blood from right and left central adrenal veins can by no means discriminate bilateral APA from BHA. There have been no published studies reporting the reliable clinical differential diagnosis between bilateral APA and IHA, especially IHA cases with bilateral non-functioning adenomas (NFA), which has been considered practically impossible in clinical differential diagnosis. As an attempt to this clinical dilemma, segmental AVS (S-AVS), which could evaluate segmental effluents from adrenal tributary veins, has been recently developed. We have performed S-AVS in these patients above following C-AVS, via the insertion of a microcatheter in up to three intra-adrenal first-degree tributary veins on bilateral adrenals. S-AVS did enable us to evaluate the intra-adrenal localization of corticosteroidogenesis. These data did indicate that S-AVS should be performed in the PA patients who had increased aldosterone levels in bilateral central vein and demonstrated space occupying lesions in the bilateral adrenals in order to avoid bilateral adrenalectomy or long lasting medical treatment toward persistent PA. In addition to the situations above, we have administere S-AVS to the following patients; those who had clinically suspected APA but not sufficiently high lateralization indexes according to the results of C-AVS, very young ones with higher clinical probability of recurrence and those who could benefit from partial adrenalectomy by demonstrating the sites of specific steroidogenesis. However, it is also entirely true that S-AVS is more expensive, time-consuming and labor-intensive compared to C-AVS.(Figure is included in full-text article.)The angiography during S-AVS (A, B), the coronal CT

  12. Prognostic Impact of Loop Diuretics in Patients With Chronic Heart Failure - Effects of Addition of Renin-Angiotensin-Aldosterone System Inhibitors and β-Blockers.

    Science.gov (United States)

    Miura, Masanobu; Sugimura, Koichiro; Sakata, Yasuhiko; Miyata, Satoshi; Tadaki, Soichiro; Yamauchi, Takeshi; Onose, Takeo; Tsuji, Kanako; Abe, Ruri; Oikawa, Takuya; Kasahara, Shintaro; Nochioka, Kotaro; Takahashi, Jun; Shimokawa, Hiroaki

    2016-05-25

    It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients. From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission. On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, loop diuretics use was associated with worse prognosis with hazard ratio (HR) 1.28 (Pdiuretics were associated with worse prognosis with HR 1.32 and 1.56, respectively (both Pdiuretics. Chronic use of loop diuretics is significantly associated with worse prognosis in CHF patients in a dose-dependent manner, whereas the triple combination of RAAS inhibitor(s), MRA, and β-blocker(s) is associated with better prognosis when combined with low-dose loop diuretics. (Circ J 2016; 80: 1396-1403).

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

    Directory of Open Access Journals (Sweden)

    Elena Montes-Cobos

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

  14. C-Arm Computed Tomography-Assisted Adrenal Venous Sampling Improved Right Adrenal Vein Cannulation and Sampling Quality in Primary Aldosteronism.

    Science.gov (United States)

    Park, Chung Hyun; Hong, Namki; Han, Kichang; Kang, Sang Wook; Lee, Cho Rok; Park, Sungha; Rhee, Yumie

    2018-05-04

    Adrenal venous sampling (AVS) is a gold standard for subtype classification of primary aldosteronism (PA). However, this procedure has a high failure rate because of the anatomical difficulties in accessing the right adrenal vein. We investigated whether C-arm computed tomography-assisted AVS (C-AVS) could improve the success rate of adrenal sampling. A total of 156 patients, diagnosed with PA who underwent AVS from May 2004 through April 2017, were included. Based on the medical records, we retrospectively compared the overall, left, and right catheterization success rates of adrenal veins during the periods without C-AVS (2004 to 2010, n=32) and with C-AVS (2011 to 2016, n=134). The primary outcome was adequate bilateral sampling defined as a selectivity index (SI) >5. With C-AVS, the rates of adequate bilateral AVS increased from 40.6% to 88.7% (PAVS was an independent predictor of adequate bilateral sampling in the multivariate model (odds ratio, 9.01; PAVS improved the overall success rate of AVS, possibly as a result of better catheterization of right adrenal vein. Copyright © 2018 Korean Endocrine Society.

  15. 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.

  16. Nephroprotective action of renin-angiotensin-aldosterone system blockade in chronic kidney disease patients: the landscape after ALTITUDE and VA NEPHRON-D trails.

    Science.gov (United States)

    Rutkowski, Boleslaw; Tylicki, Leszek

    2015-03-01

    The intervention in the renin-angiotensin-aldosterone system (RAAS) is currently the most effective strategy that combines blood pressure lowering and renoprotection. Several large, randomized, controlled trials evidenced the renoprotective potential of the angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in nephropathies of almost any etiology. Mineralocorticoid receptor antagonists and direct renin inhibitor, aliskiren, as add-on treatments to standard therapy including the optimal dose of ACEIs or ARBs reduce albuminuria or proteinuria and slow development of renal dysfunction more than placebo. No clinical evidence is available however about whether these strategies may influence on long-term kidney outcome. Three recent trials suggested that aggressive RAAS blockade, that is, combination of 2 RAAS-blocking agents, does not decrease cardiovascular and renal morbidity and may carry an increased risk of serious complications. This article reviews an evidence-based approach on the use of RAAS-inhibiting agents in chronic kidney disease and considers the implementation of dual RAAS blockade with reference to the results of ALTITUDE and VA NEPHRON-D trails aiming to aid clinicians in their treatment decisions for patients with chronic kidney disease. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  17. Estímulos para la liberación de aldosterona durante una actividad física intensa y de larga duración Stimuli for aldosterone secretion during an intense, long duration physucak activity

    Directory of Open Access Journals (Sweden)

    Hilda Norha Jaramillo Londoño

    2001-01-01

    Full Text Available Objetivo: establecer los posibles factores causales de la secreción de aldosterona durante una actividad física intensa y de larga duración, bajo condiciones ambientales neutras, en nueve corredores de fondo. Materiales y métodos: después de 10 minutos de calentamiento, en banda rodante con una pendiente del 1% y al 55% de la capacidad física de trabajo máxima (PWCmax, siguieron 90 minutos de carrera, al 80%; finalmente, 90 minutos de recuperación pasiva. No se hizo reposición hídrica durante DH (deshidratado; durante RH (rehidratado se repuso el 51% del peso corporal perdido en DH. Resultados: en DH hubo pérdida de peso corporal y reducción porcentual del volumen plasmático (%VP. Se observaron hiperosmolaridad, hipernatremia, hipercaliemia, hiperaldosteronemia, pero no hiperreninemia. Al hacer corrección por hemoconcentración y calcular el porcentaje de cambio de las variables en estudio, sólo se observaron hipercaliemia e hiperaldosteronemia. En RH la pérdida de peso corporal fue menor, pero la reducción %VP fue similar; se evitaron la hiperosmolaridad y la hipernatremia, pero no la hipercaliemia durante el ejercicio ni la hiperaldosteronemia durante todo el procedimiento, un comportamiento similar al observado al hacer corrección por hemoconcentración. Conclusiones: Durante la realización de una actividad física intensa la concentración plasmática de aldosterona presentó un incremento proporcional a la duración del ejercicio e independiente de la reducción porcentual del volumen plasmático. La hipersecreción de aldosterona es, al parecer, multicausal y el potasio es uno de los factores determinantes. Objective: To establish the possible causal factors of aldosterone secretion during an intense, long duration physical activity, under neutral environmental conditions in nine long-distance runners. Methods: After a 10-minute warm-up period on a treadmill, 1% grade and at 55% of PWCmax, followed by 90 minutes test in

  18. The role of renin-angiotensin-aldosterone system genes in the progression of chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study.

    Science.gov (United States)

    Kelly, Tanika N; Raj, Dominic; Rahman, Mahboob; Kretzler, Matthias; Kallem, Radhakrishna R; Ricardo, Ana C; Rosas, Sylvia E; Tao, Kaixiang; Xie, Dawei; Hamm, Lotuce Lee; He, Jiang

    2015-10-01

    We conducted single-marker, gene- and pathway-based analyses to examine the association between renin-angiotensin-aldosterone system (RAAS) variants and chronic kidney disease (CKD) progression among Chronic Renal Insufficiency Cohort study participants. A total of 1523 white and 1490 black subjects were genotyped for 490 single nucleotide polymorphisms (SNPs) in 12 RAAS genes as part of the ITMAT-Broad-CARe array. CKD progression phenotypes included decline in estimated glomerular filtration rate (eGFR) over time and the occurrence of a renal disease event, defined as incident end-stage renal disease or halving of eGFR from baseline. Mixed-effects models were used to examine SNP associations with eGFR decline, while Cox proportional hazards models tested SNP associations with renal events. Gene- and pathway-based analyses were conducted using the truncated product method. All analyses were stratified by race, and a Bonferroni correction was applied to adjust for multiple testing. Among white and black participants, eGFR declined an average of 1.2 and 2.3 mL/min/1.73 m(2)/year, respectively, while renal events occurred in a respective 11.5 and 24.9% of participants. We identified strong gene- and pathway-based associations with CKD progression. The AGT and RENBP genes were consistently associated with risk of renal events in separate analyses of white and black participants (both P renal events in both groups (both P < 1.00 × 10(-6)). No single-marker associations with CKD progression were observed. The current study provides strong evidence for a role of the RAAS in CKD progression. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  19. Biochemical monitoring after initiation of aldosterone antagonist therapy in users of renin-angiotensin system blockers: a UK primary care cohort study.

    Science.gov (United States)

    Sinnott, Sarah-Jo; Mansfield, Kathryn E; Schmidt, Morten; Bhaskaran, Krishnan; Smeeth, Liam; Nitsch, Dorothea; Tomlinson, Laurie A

    2017-11-16

    To determine the frequency of biochemical monitoring after initiation of aldosterone antagonists(AA) in patients also using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB). UK primary care. ACEI/ARB users who initiated AA between 2004 and 2014. We calculated the proportions with: (1) biochemical monitoring ≤2 weeks post initiation of AA, (2) adverse biochemical values ≤2 months (potassium ≥6 mmol/L, creatinine ≥220 µmol/L and ≥30% increase in creatinine from baseline) and (3) discontinuers of AA in those with an adverse biochemical value. We used logistic regression to study patient characteristics associated with monitoring and adverse biochemical values. In 10 546 initiators of AA, 3291 (31.2%) had a record of biochemical monitoring ≤2 weeks post initiation. A total of 2.0% and 2.7% of those with follow-up monitoring within 2 months of initiation experienced potassium ≥6 mmol/L and creatinine ≥220 µmol/L, respectively, whereas 13.5% had a ≥30% increase in creatinine. Baseline potassium (OR 3.59, 95% CI 2.43 to 5.32 for 5.0-5.5 mmol/L compared with monitoring within 2 weeks of initiating AAs. Higher levels of monitoring may reduce adverse biochemical events. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Method development and validation of liquid chromatography-tandem/mass spectrometry for aldosterone in human plasma: Application to drug interaction study of atorvastatin and olmesartan combination

    Directory of Open Access Journals (Sweden)

    Rakesh Das

    2014-01-01

    Full Text Available In the present investigation, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS method was developed for the quantification of aldosterone (ALD a hormone responsible for blood pressure in human plasma. The developed method was validated and extended for application on human subjects to study drug interaction of atorvastatin (ATSV and olmesartan (OLM on levels of ALD. The ALD in plasma was extracted by liquid-liquid extraction with 5 mL dichloromethane/ethyl ether (60/40% v/v. The chromatographic separation of ALD was carried on Xterra, RP-Column C18 (150 mm× 4.6 mm × 3.5 μm at 30°C followed by four-step gradient program composed of methanol and water. Step 1 started with 35% methanol for first 1 min and changed linearly to 90% in next 1.5 min in Step 2. Step 3 lasted for next 2 min with 90% methanol. The method finally concluded with Step 4 to achieve initial concentration of methanol that is, 35% thus contributing the total method run time of 17.5 min. The flow rate was 0.25 mL/min throughout the process. The developed method was validated for specificity, accuracy, precision, stability, linearity, sensitivity, and recovery. The method was linear and found to be acceptable over the range of 50-800 ng/mL. The method was successfully applied for the drug interaction study of ATSV + OLM in combination against OLM treatment on blood pressure by quantifying changes in levels of ALD in hypertensive patients. The study revealed levels of ALD were significantly higher in ATSV + OLM treatment condition when compared to OLM as single treated condition. This reflects the reason of low effectiveness of ATSV + OLM in combination instead of synergistic activity.

  1. Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the distal nephron from type 1 diabetic rats.

    Directory of Open Access Journals (Sweden)

    Eduardo Molina-Jijón

    Full Text Available Hyperglycemia in diabetes alters tight junction (TJ proteins in the kidney. We evaluated the participation of aldosterone (ALD, and the effect of spironolactone (SPL, a mineralocorticoid receptor antagonist, on the expressions of claudin-2, -4, -5 and -8, and occludin in glomeruli, proximal and distal tubules isolated from diabetic rats. Type 1 diabetes was induced in female Wistar rats by a single tail vein injection of streptozotocin (STZ, and SPL was administrated daily by gavage, from days 3-21. Twenty-one days after STZ injection the rats were sacrificed. In diabetic rats, the serum ALD levels were increased, and SPL-treatment did not have effect on these levels or in hyperglycemia, however, proteinuria decreased in SPL-treated diabetic rats. Glomerular damage, evaluated by nephrin and Wilm's tumor 1 (WT1 protein expressions, and proximal tubular damage, evaluated by kidney injury molecule 1 (Kim-1 and heat shock protein 72 kDa (Hsp72 expressions, were ameliorated by SPL. Also, SPL prevented decrement in claudin-5 in glomeruli, and claudin-2 and occludin in proximal tubules by decreasing oxidative stress, evaluated by superoxide anion (O2●- production, and oxidative stress markers. In distal tubules, SPL ameliorated increase in mRNA, protein expression, and phosphorylation in threonine residues of claudin-4 and -8, through a serum and glucocorticoid-induced kinase 1 (SGK1, and with-no-lysine kinase 4 (WNK4 signaling pathway. In conclusion, this is the first study that demonstrates that ALD modulates the expression of renal TJ proteins in diabetes, and that the blockade of its actions with SPL, may be a promising therapeutic strategy to prevent alterations of TJ proteins in diabetic nephropathy.

  2. Aldosterone glucuronidation inhibition as a potential mechanism for arterial dysfunction associated with chronic celecoxib and diclofenac use in patients with rheumatoid arthritis.

    Science.gov (United States)

    Crilly, Michael A; Mangoni, Arduino A; Knights, Kathleen M

    2013-01-01

    Adverse cardiovascular (CV) effects of non-steroidal anti-inflammatory drugs (NSAIDs) are largely independent of their cyclooxygenase (COX) enzyme selectivity, but could be a consequence of aldosterone 18ß-glucuronidation inhibition (AGI), which varies between NSAIDS. This study assesses the chronic effects of celecoxib (selective COX-2 inhibitor) versus diclofenac (non-selective NSAID) therapy on arterial dysfunction in patients with rheumatoid arthritis (RA). AGI was assessed in vitro using human kidney cortical microsomes. Arterial function was measured clinically as the extent (augmentation index, AIX%) and timing (reflected wave transit time, RWTT, msec) of arterial wave reflection using radial applanation pulse wave analysis (SphygmoCor PWA device) in 39 RA patients without overt CV disease aged 40-65. A higher AIX% (and lower RWTT) indicates arterial dysfunction. Clinical assessment on a single occasion included a fasting blood sample, patient questionnaire and medical record review. Multivariable analysis was used to adjust for sex, mean blood pressure, arthritis duration, cumulative ESR-years and current DMARD therapy. The inhibition constant (Ki) for celecoxib was lower than that of diclofenac (Ki, 3.5 vs. 8.4 μM). Chronic celecoxib use was associated with a higher AIX% (34.8 vs. 32.3) and lower RWTT (130.1 vs. 132.7 msec) compared with diclofenac. Adjusted mean differences were AIX% 4.7 (95%CI 0.6 to 8.9; p=0.03) and RWTT -3.6 (95%CI -10.0 to 2.7; p=0.26). Celecoxib has a greater potency for AGI than diclofenac and its use is associated with a significantly higher AIX%. Our findings support AGI as a plausible mechanism for the CV toxicity of NSAIDs.

  3. Similar to spironolactone, oxymatrine is protective in aldosterone-induced cardiomyocyte injury via inhibition of calpain and apoptosis-inducing factor signaling.

    Directory of Open Access Journals (Sweden)

    Ting-Ting Xiao

    Full Text Available Accumulating evidence indicates that oxymatrine (OMT possesses variously pharmacological properties, especially on the cardiovascular system. We previously demonstrated that activated calpain/apoptosis-inducing factor (AIF-mediated pathway was the key molecular mechanism in aldosterone (ALD induces cardiomyocytes apoptosis. In the present study, we extended the experimentation by investigating the effect of OMT on cardiomyocytes exposed to ALD, as compared to spironolactone (Spiro, a classical ALD receptor antagonist. Cardiomyocytes were pre-incubated with OMT, Spiro or vehicle for 1 h, and then, cardiomyocytes were exposed to ALD 24 h. The cell injury was evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and lactate dehydrogenase (LDH leakage ratio. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL assay, annexin V/PI staining, and relative caspase-3 activity assay. Furthermore, expression of pro-apoptotic proteins including truncated Bid (tBid, calpain and AIF were evaluated by western blot analysis. ALD stimulation increased cardiomyocytes apoptosis, caspase-3 activity and protein expression of calpain, tBid and AIF in the cytosol (p<0.05. Pre-incubated with cardiomyocytes injury and increased caspase-3 activity were significantly attenuated (p<0.05. Furthermore, OMT suppressed ALD-induced high expression of calpain and AIF. And these effects of OMT could be comparable to Spiro. These findings indicated that OMT might be a potential cardioprotective-agent against excessive ALD-induced cardiotoxicity, at least in part, mediated through inhibition of calpain/AIF signaling.

  4. Menopause not aldosterone-to-renin ratio predicts blood pressure response to a mineralocorticoid receptor antagonist in primary care hypertensive patients.

    Science.gov (United States)

    Olivieri, Oliviero; Pizzolo, Francesca; Ciacciarelli, Alberto; Corrocher, Roberto; Signorelli, Denise; Falcone, Salvatore; Blengio, Gian S

    2008-09-01

    It has been suggested that hypertensive patients with raised aldosterone-to-renin ratio (ARR) are specifically sensitive to mineralocorticoid receptor antagonists (MRAs). We have previously shown that patients with an elevated ARR are relatively frequent in the setting of primary care. We therefore designed an interventional study to ascertain whether primary care hypertensive patients with an elevated ARR presented a superior response to MRA treatment than subjects with normal ratio. According to the previously observed distribution in general population, 1/3 and 2/3 of hypertensive patients with high or normal ARR, respectively, were treated with kanrenoate 50-100 mg/day for 2 months. To avoid uncontrolled blood pressure (BP), 49% of patients continued also "ARR-neutral" drugs such as verapamil and/or alpha-adrenergic blockers. Patients groups were matched for most features but an elevated ARR was more frequent in female than in male gender; moreover, 90% of women with raised ARR were in menopause. A clear reduction of BP values was recorded after both the first and the second month of treatment with kanrenoate, with the maximal effect obtained when the dosage titration at 100 mg/day was accomplished. However, patients previously identified by a raised ARR did not have a larger response to MRA treatment than patients with normal ratio. In contrast, MRA was twofold more effective in reducing SBP in women than in men (after 2 months of treatment -16.4 mm Hg vs.-8.2 mm Hg). These results suggest that postmenopausal hypertension is largely dependent on mineralocorticoid receptor activation and selectively sensitive to MRAs.

  5. Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial.

    Science.gov (United States)

    de Vries, Laura V; Dobrowolski, Linn C; van den Bosch, Jacqueline J O N; Riphagen, Ineke J; Krediet, C T Paul; Bemelman, Frederike J; Bakker, Stephan J L; Navis, Gerjan

    2016-06-01

    In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore studied the effects of dietary sodium restriction on BP and urinary albumin excretion (UAE) in kidney transplant recipients receiving RAAS blockade. Two-center randomized crossover trial. Stable outpatient kidney transplant recipients with creatinine clearance > 30mL/min, BP ≥120/80mmHg, receiving stable RAAS blockade therapy. 6-week regular-sodium diet (target, 150mmol/24 h) and a 6-week low-sodium diet (target, 50mmol/24 h). Main outcome parameters were systolic and diastolic BP, UAE, and estimated glomerular filtration rate (eGFR) at the end of each diet period. Dietary adherence was assessed by 24-hour urinary sodium excretion. We randomly assigned 23 kidney transplant recipients, of whom 22 (mean age, 58±8 [SD] years; 50% men; mean eGFR, 51±21mL/min/1.73m(2)) completed the study. One patient withdrew from the study because of concerns regarding orthostatic hypotension on the low-sodium diet. Sodium excretion decreased from 164±50mmol/24 h during the regular-sodium diet to 87±55mmol/24 h during the low-sodium diet (mean difference, -77 [95% CI, -110 to -44] mmol/24 h; Padherence to sodium diet was achieved in 86% of patients. In stable kidney transplant recipients receiving RAAS blockade, dietary sodium restriction effectively reduces BP without affecting eGFR. Dietary sodium restriction is relevant to BP management in kidney transplant recipients receiving RAAS blockade. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  6. High risk of adrenal toxicity of N1-desoxy quinoxaline 1,4-dioxide derivatives and the protection of oligomeric proanthocyanidins (OPC) in the inhibition of the expression of aldosterone synthetase in H295R cells

    International Nuclear Information System (INIS)

    Wang, Xu; Yang, Chunhui; Ihsan, Awais; Luo, Xun; Guo, Pu; Cheng, Guyue; Dai, Menghong; Chen, Dongmei; Liu, Zhenli; Yuan, Zonghui

    2016-01-01

    Highlights: • N1-QCT, N1-MEQ and N1-CYA showed more adrenal toxicity than other metabolites. • N1-desoxy QdNOs reduced expression of CYP11B1, CYP11B2 and transcription factors. • OPC increased expression of transcription factors, including CYP11B1 and CYP11B2. • OPC reduced adrenal toxicity induced by N1-desoxy QdNOs. • The results provided a mechanism of adrenal damage caused by QdNO metabolites. - Abstract: Quinoxaline 1,4-dioxide derivatives (QdNOs) with a wide range of biological activities are used in animal husbandry worldwide. It was found that QdNOs significantly inhibited the gene expression of CYP11B1 and CYP11B2, the key aldosterone synthases, and thus reduced aldosterone levels. However, whether the metabolites of QdNOs have potential adrenal toxicity and the role of oxidative stress in the adrenal toxicity of QdNOs remains unclear. The relatively new QdNOs, cyadox (CYA), mequindox (MEQ), quinocetone (QCT) and their metabolites, were selected for elucidation of their toxic mechanisms in H295R cells. Interestingly, the results showed that the main toxic metabolites of QCT, MEQ, and CYA were their N1-desoxy metabolites, which were more harmful than other metabolites and evoked dose and time-dependent cell damage on adrenal cells and inhibited aldosterone production. Gene and protein expression of CYP11B1 and CYP11B2 and mRNA expression of transcription factors, such as NURR1, NGFIB, CREB, SF-1, and ATF-1, were down regulated by N1-desoxy QdNOs. The natural inhibitors of oxidant stress, oligomeric proanthocyanidins (OPC), could upregulate the expression of diverse transcription factors, including CYP11B1 and CYP11B2, and elevated aldosterone levels to reduce adrenal toxicity. This study demonstrated for the first time that N1-desoxy QdNOs have the potential to be the major toxic metabolites in adrenal toxicity, which may shed new light on the adrenal toxicity of these fascinating compounds and help to provide a basic foundation for the

  7. Congenital primary adrenal insufficiency and selective aldosterone defects presenting as salt-wasting in infancy: a single center 10-year experience.

    Science.gov (United States)

    Bizzarri, Carla; Olivini, Nicole; Pedicelli, Stefania; Marini, Romana; Giannone, Germana; Cambiaso, Paola; Cappa, Marco

    2016-08-02

    Salt-wasting represents a relatively common cause of emergency admission in infants and may result in life-threatening complications. Neonatal kidneys show low glomerular filtration rate and immaturity of the distal nephron leading to reduced ability to concentrate urine. A retrospective chart review was conducted for infants hospitalized in a single Institution from 1(st) January 2006 to 31(st) December 2015. The selection criterion was represented by the referral to the Endocrinology Unit for hyponatremia (serum sodium <130 mEq/L) of suspected endocrine origin at admission. Fifty-one infants were identified. In nine infants (17.6 %) hyponatremia was related to unrecognized chronic gastrointestinal or renal salt losses or reduced sodium intake. In 10 infants (19.6 %) hyponatremia was related to central nervous system diseases. In 19 patients (37.3 %) the final diagnosis was congenital adrenal hyperplasia (CAH). CAH was related to 21-hydroxylase deficiency in 18 patients, and to 3β-Hydroxysteroid dehydrogenase (3βHSD) deficiency in one patient. Thirteen patients (25.5 %) were affected by different non-CAH salt-wasting forms of adrenal origin. Four familial cases of X-linked adrenal hypoplasia congenita due to NROB1 gene mutation were identified. Two unrelated girls showed aldosterone synthase deficiency due to mutation of the CYP11B2 gene. Two unrelated infants were affected by familial glucocorticoid deficiency due to MC2R gene mutations. One girl showed pseudohypoaldosteronism related to mutations of the SCNN1G gene encoding for the epithelial sodium channel. Transient pseudohypoaldosteronism was identified in two patients with renal malformations. In two infants the genetic aetiology was not identified. Emergency management of infants presenting with salt wasting requires correction of water losses and treatment of electrolyte imbalances. Nevertheless, the differential diagnosis may be difficult in emergency settings, and sometimes hospitalized infants

  8. Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    Directory of Open Access Journals (Sweden)

    Hai-Ha Le

    Full Text Available Sudden cardiac death (SCD is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF or post myocardial infarction (MI. Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects.We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia.Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67-0.98; p = 0.03; all-cause mortality by 19% (RR 0.81; 95% CI, 0.74-0.88, p<0.00001 and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70-0.89, p<0.00001. In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66-0.98; p = 0.03, 15% (RR 0.85; 95% CI, 0.76-0.95, p = 0.003 and 17% (RR 0.83; 95% CI, 0.74-0.94, p = 0.003, respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71-0.92; p = 0.002 for SCD, 18% (RR 0.82; 95% CI, 0.77-0.88, p < 0.0001 for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74-0.87, p < 0.0001 for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly

  9. Effect of Losartan on Right Ventricular Dysfunction: Results From the Double-Blind, Randomized REDEFINE Trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) in Adults With Repaired Tetralogy of Fallot.

    Science.gov (United States)

    Bokma, Jouke P; Winter, Michiel M; van Dijk, Arie P; Vliegen, Hubert W; van Melle, Joost P; Meijboom, Folkert J; Post, Martijn C; Berbee, Jacqueline K; Boekholdt, S Matthijs; Groenink, Maarten; Zwinderman, Aeilko H; Mulder, Barbara J M; Bouma, Berto J

    2018-04-03

    The effect of angiotensin II receptor blockers on right ventricular (RV) function is still unknown. Angiotensin II receptor blockers are beneficial in patients with acquired left ventricular dysfunction, and recent findings have suggested a favorable effect in symptomatic patients with systemic RV dysfunction. The current study aimed to determine the effect of losartan, an angiotensin II receptor blocker, on subpulmonary RV dysfunction in adults after repaired tetralogy of Fallot. The REDEFINE trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) is an investigator-initiated, multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled study. Adults with repaired tetralogy of Fallot and RV dysfunction (RV ejection fraction [EF] 0.30 for all). In predefined subgroup analyses, losartan did not have a statistically significant impact on RV EF in subgroups with symptoms, restrictive RV, RV EFtetralogy of Fallot. Future larger studies may determine whether there might be a role for losartan in specific vulnerable subgroups. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02010905. © 2017 American Heart Association, Inc.

  10. Polymorphisms of three genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system are not associated with blood pressure salt sensitivity: A systematic meta-analysis.

    Science.gov (United States)

    Sun, Jiahong; Zhao, Min; Miao, Song; Xi, Bo

    2016-01-01

    Many studies have suggested that polymorphisms of three key genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system (RAAS) play important roles in the development of blood pressure (BP) salt sensitivity, but they have revealed inconsistent results. Thus, we performed a meta-analysis to clarify the association. PubMed and Embase databases were searched for eligible published articles. Fixed- or random-effect models were used to pool odds ratios and 95% confidence intervals based on whether there was significant heterogeneity between studies. In total, seven studies [237 salt-sensitive (SS) cases and 251 salt-resistant (SR) controls] for ACE gene I/D polymorphism, three studies (130 SS cases and 221 SR controls) for AGT gene M235T polymorphism and three studies (113 SS cases and 218 SR controls) for CYP11B2 gene C344T polymorphism were included in this meta-analysis. The results showed that there was no significant association between polymorphisms of these three polymorphisms in the RAAS and BP salt sensitivity under three genetic models (all p > 0.05). The meta-analysis suggested that three polymorphisms (ACE gene I/D, AGT gene M235T, CYP11B2 gene C344T) in the RAAS have no significant effect on BP salt sensitivity.

  11. Effects of single and repeated doses of the calcium antagonist felodipine on blood pressure, renal function, electrolytes and water balance, and renin-angiotensin-aldosterone system in hypertensive patients.

    Science.gov (United States)

    Leonetti, G; Gradnik, R; Terzoli, L; Fruscio, M; Rupoli, L; Cuspidi, C; Sampieri, L; Zanchetti, A

    1986-01-01

    Doses of 10 mg b.i.d. of the new dihydropyridine calcium antagonist, felodipine, were tested for seven consecutive days in 11 hospitalized hypertensive patients. A significant reduction of both systolic and diastolic blood pressures, with patients in both the supine and upright positions, occurred immediately after the first dose and was maintained (daily average 15%) throughout the following days. An increase in heart rate was observed after the first dose (15 and 23 beats/min, in supine and upright postures), and subsequently declined to average values of 8 and 14 beats/min on the seventh day. There was a marked natriuretic response during the first and second day, during which an average negative sodium balance of 95 mmol developed; on the following days sodium output was not significantly different from control, but a negative balance averaging 135 mmol was still present on the seventh day of felodipine administration. A moderate negative potassium balance also progressively developed and reached -48 mmol on the seventh day. Glomerular filtration rate was unchanged, but renal plasma flow increased significantly during administration of felodipine. Plasma renin activity and plasma aldosterone were also increased very moderately by felodipine. Compared with previous observations by our group with higher doses of felodipine (12.5, 25, and 50 mg t.i.d.), 10 mg b.i.d. of this new calcium antagonist appear to exert a marked and prolonged blood pressure reduction, accompanied by a definite natriuretic instead of an antinatriuretic effect.

  12. Detection, Diagnosis, and Treatment of Primary Aldosteronism

    Science.gov (United States)

    ... process? Treatment of high blood pressure is more effective when combined with a healthy lifestyle even if the cause is PA. In fact, diet and exercise are critical to long- term cardiovascular health. In patients with PA, it is especially important ...

  13. Genetics Home Reference: aldosterone-producing adenoma

    Science.gov (United States)

    ... Nat Genet. 2013 Sep;45(9):1055-60. doi: 10.1038/ng.2716. Epub 2013 Aug 4. ... 2013 Apr;45(4):440-4, 444e1-2. doi: 10.1038/ng.2550. Epub 2013 Feb 17. ... Science. 2011 Feb 11;331(6018):768-72. doi: 10.1126/science.1198785. Citation on PubMed or ...

  14. Aldosterone synthase C-344T, angiotensin II type 1 receptor ...

    Indian Academy of Sciences (India)

    2014-12-26

    Dec 26, 2014 ... other causes of secondary hypertension), diabetes or under any kind of .... used for the analysis of CYP11B2 C-344T and ATR1 A1166C ...... Staessen J. A., Li Y. and Thijs L. 2007 Meta-analysis of blood pres- sure and the ...

  15. 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

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

    African Journals Online (AJOL)

    Purpose: To investigate the dual effect of angiotensin blockade by irbesartan and enalapril on proteinuria in diabetic patients with azotemia. Methods: Patients with diabetes of > 5 years duration, proteinuria at a nephrotic level and serum creatinine > 1.5 mg/dL were enrolled in the study. Forty-five enrolled patients were ...

  17. 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.

  18. 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

  19. Expression of Angiotensin II and Aldosterone in Radiation-induced Lung Injury

    OpenAIRE

    Cao, Shuo; Wu, Rong

    2012-01-01

    Objective Radiation-induced lung injury (RILI) is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILI was studied. Methods Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentration...

  20. Adrenal Vein Catecholamine Levels and Ratios: Reference Intervals Derived from Patients with Primary Aldosteronism

    NARCIS (Netherlands)

    Sze, C.W.C.; O'Toole, S.M.; Tirador, R.K.; Akker, S.A; Matson, M.; Perry, L.; Druce, M.R.; Dekkers, T.; Deinum, J.; Lenders, J.W.M.; Eisenhofer, G.; Drake, W.M.

    2017-01-01

    Phaeochromocytoma localisation is generally reliably achieved with modern imaging techniques, particularly in sporadic cases. On occasion, however, there can be diagnostic doubt due to the presence of bilateral adrenal abnormalities, particularly in patients with mutations in genes predisposing them

  1. Novel description of aldosterone synthase CYP11B2 - 344 T>C ...

    African Journals Online (AJOL)

    user

    344 T>C gene polymorphism related to hypertension in. Mexican Amerindians: ... ischemic stroke, atrial fibrillation, heart failure, hypertension, blood pressure and coronary artery disease ..... disease secondary to IgA nephropaty. Chin Med J.

  2. Aldosterone-mineralocorticoid receptor promotes urine prostasin through glomerular barrier injury and not tissue abundance

    DEFF Research Database (Denmark)

    Stolzenburg Oxlund, Christina; Kurt, B.; Schwarzensteiner, I.

    2015-01-01

    with placebo or the mineralocorticoid antagonist spironolactone. Western immunoblotting of creatinine-normalized urine samples was performed from placebo and spironolactone treated patients with and without albuminuria. Tissue prostasin was measured in membranes from human nephrectomy recieving either ACE......-i/ANGII or no antihypertensive treatment prior to operation. Urine and tissue prostasin was measured in puromycin-induced nephrotic syndrome rats. Results: Plasma prostasin concentration increased significantly with spironolactone but was not changed with placebo. Urine prostasin concentration was below detection limit....... Puromycin-induced nephrotic syndrome in rats was associated with significant increase in u-prostasin while kidney tissue prostasin protein abundance was not changed. Prostasin protein abundance was similar in membranes from human nephrectomy homogenate from patients treated preoperatively with ACE...

  3. Aldosterone deficiency after unilateral adrenalectomy for Conn’s syndrome: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Ekua Yorke

    2015-01-01

    Conclusion: It is important to be aware of the risk of postoperative hypoaldosteronism in this patient population. Close postoperative follow-up is necessary and strongly recommended, especially in patients with certain risk factors. Patients may need mineralocorticoid supplementation during this period.

  4. Inhibition of the Renin-Angiotensin-Aldosterone System for Cerebrorenal Protection

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo; Toyoda, K

    2013-01-01

    Blood pressure is a strong risk factor for ischemic and atherosclerotic events such as stroke. Blood pressure is often elevated in patients with chronic kidney disease. Consequently, chronic kidney disease patients are at high risk of developing cardiovascular and cerebrovascular damage. Blood

  5. The renin-angiotensin-aldosterone system in cerebral small vessel disease

    NARCIS (Netherlands)

    Brenner, D.; Labreuche, J.; Pico, F.; Scheltens, P.; Poirier, O.; Cambien, F.; Amarenco, P.

    2008-01-01

    Introduction: Cerebral small vessel disease (SVD) appears on magnetic resonance imaging (MRI) as leukoaraiosis (LA), état criblé (EC), and multiple lacunar infarctions (MLI). Although the pathophysiology of SVD is poorly understood, there is evidence of a genetic contribution. We sought to analyze

  6. Role of adrenal vein sampling in primary aldosteronism: Impact of imaging, localization, and age.

    Science.gov (United States)

    Wachtel, Heather; Zaheer, Salman; Shah, Parth K; Trerotola, Scott O; Karakousis, Giorgos C; Roses, Robert E; Cohen, Debbie L; Fraker, Douglas L

    2016-04-01

    The role of adrenal vein sampling (AVS) has been debated, with some authorities advocating selective use in younger patients (≤40 years), and those localized by preoperative imaging. We examined our experience to determine the impact of AVS in patients who routinely underwent AVS with a high success rate. A retrospective cohort study was performed using a prospectively maintained database of patients referred for evaluation of PA (1997-2013). Patients were classified as localized (L) if a unilateral mass was identified on imaging, and non-localized (NL) otherwise. Of 367 patients, 94% (n = 345) underwent successful AVS. Seventy-two percent (n = 265) were L; AVS was lateralizing 58% (n = 214). AVS changed management in 43% of patients (n = 158). In patients ≤40 years, AVS changed management in 30% (n = 15). In patients ≤40 years with a ≥1 cm adrenal mass, 12% (n = 3) would have undergone unnecessary surgery based on imaging results alone; in patients >40 years with a ≥1 cm adrenal mass, 3% (n = 5) would have undergone wrong-side surgery, and 30% (n = 50) would have undergone unnecessary surgery based on imaging. AVS changed management in a significant minority of patients regardless of age and imaging findings. AVS should be routinely recommended in all patients with PA, to direct operative therapy. J. Surg. Oncol. 2016;113:532-537. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Progression of Renal Insufficiency in Patients with Essential Hypertension Treated with Renin Angiotensin Aldosterone System Blockers: An Electrocardiographic Correlation.

    Science.gov (United States)

    Rodriguez-Padial, Luis; Akerström, Finn; Barderas, María G; Vivanco, Fernando; Arias, Miguel A; Segura, Julian; Ruilope, Luis M

    2017-12-08

    There is a frequent association between renal insufficiency and cardiovascular disease in patients with essential hypertension (HTN). The aim of this study was to analyze the relationship between ECG parameters and the progress of renal damage in patients with treated HTN. 109 patients with HTN had their microalbuminuria monitored over a 3-year time frame. During the last 3 months of follow-up, an ECG was recorded. Patients were divided into 3 groups according to the deterioration of their renal function: normoalbuminuria during the study period (normo-normo; n = 51); normoalbuminuria developing microalbuminuria (normo-micro; n = 29); and microalbuminuria at baseline (micro-micro; n = 29). There were no differences in presence of left ventricular hypertrophy between the 3 groups. RV6/RV5 >1 was observed more frequently as renal function declined ( p = 0.025). The 12-lead QRS-complex voltage-duration product was significantly increased in patients without microalbuminuria at baseline who went on to develop microalbuminuria ( p = 0.006). Patients who developed microalbuminuria during follow-up, with positive Cornell voltage criteria, showed a lesser degree of progression of microalbuminuria when compared with the rest of the subgroups ( p = 0.044). Furthermore, patients with microalbuminuria at baseline treated with angiotensin receptor blockers and diuretics, and positive Cornell voltage criteria, showed a higher degree of microalbuminuria compared to those with negative Cornell voltage criteria ( p = 0.016). In patients with HTN, we identified some ECG parameters, which predict renal disease progression in patients with HTN, which may permit the identification of patients who are at risk of renal disease progression, despite optimal antihypertensive pharmacotherapy.

  8. Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride

    DEFF Research Database (Denmark)

    Jürgens, G; Graudal, N A

    2004-01-01

    One of the controversies in preventive medicine is, whether a general reduction in sodium intake can decrease the blood pressure of a population and thereby reduce cardiovascular mortality and morbidity. In recent years the debate has been extended by studies indicating that reducing sodium intake...... has effects on the hormone and lipid profile....

  9. Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride

    DEFF Research Database (Denmark)

    Graudal, Niels Albert; Hubeck-Graudal, Thorbjorn; Jurgens, Gesche

    2011-01-01

    In spite of more than 100 years of investigations the question of reduced sodium intake as a health prophylaxis initiative is still unsolved.......In spite of more than 100 years of investigations the question of reduced sodium intake as a health prophylaxis initiative is still unsolved....

  10. Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride

    DEFF Research Database (Denmark)

    Graudal, Niels Albert; Hubeck-Graudal, Thorbjorn; Jurgens, Gesche

    2017-01-01

    Background: In spite of more than 100 years of investigations the question of whether a reduced sodium intake improves health is still unsolved. Objectives: To estimate the effects of low sodium intake versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum...... results: A total of 185 studies were included. The average sodium intake was reduced from 201 mmol/day (corresponding to high usual level) to 66 mmol/day (corresponding to the recommended level). The effect of sodium reduction on blood pressure (BP) was as follows: white people with normotension: SBP.......0005) and triglyceride (P sodium intake as compared with high sodium intake. All effects were stable in 125 study populations with a sodium intake below 250 mmol/day and a sodium reduction intervention of at least one week. Authors' conclusions: Sodium reduction from an average high usual sodium...

  11. 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.)

  12. From preeclampsia to renal disease : a role of angiogenic factors and the renin-angiotensin aldosterone system?

    NARCIS (Netherlands)

    van der Graaf, Anne Marijn; Toering, Tsjitske J.; Faas, Marijke M.; Lely, A. Titia

    2012-01-01

    Complicating up to 8% of pregnancies, preeclampsia is the most common glomerular disease worldwide and remains a leading cause of infant and maternal morbidity and mortality. Although the exact pathogenesis of this syndrome of hypertension and proteinuria is still incomplete, a consistent line of

  13. Influence of renal impairment on aldosterone status, calcium metabolism, and vasopressin activity in outpatients with systolic heart failure

    DEFF Research Database (Denmark)

    Bosselmann, Helle; Tonder, Niels; Sölétormos, György

    2017-01-01

    AIMS: Renal dysfunction (RD) is associated with increased morbidity and mortality in heart failure (HF). At present, no specific treatment for patients with RD, to prevent progression of HF, has been developed. How different hormone axes-and thereby potential treatment options-are affected by RD...... in HF warrants further investigations. METHODS AND RESULTS: Patients with left ventricular ejection fraction (LVEF) Chronic Kidney Disease Epidemiology Collaboration equation (e...

  14. Pooled Analysis of Multiple Crossover Trials To Optimize Individual Therapy Response to Renin-Angiotensin-Aldosterone System Intervention

    DEFF Research Database (Denmark)

    Petrykiv, Sergei I; Laverman, Gozewijn Dirk; Persson, Frederik

    2017-01-01

    to angiotensin receptor blockers; n=5) or NSAIDs (n=1), changing from RAASi to NSAIDs (n=2), and changing from high to low sodium intake (n=5). A two-stage meta-analysis was conducted: Deming regression was conducted in each study to assess correlations in response, and individual study results were then meta...

  15. Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways

    Directory of Open Access Journals (Sweden)

    Aiqing Zhang

    2015-06-01

    Full Text Available Aims: This study aimed to explore the precise mechanism and signaling pathways of mesangial cell (MC proliferation from a new point of view considering Connexin 43 (Cx43. Methods: MC proliferation was measured by the incorporation of 3H-thymidine (3H-TdR. Cx43 was over-expressed in MC cells using lipofectamine 2000, and the expression level was tested with reverse transcription-polymerase chain reaction (RT-PCR and Western blot analyses. The gap junction channel function was explored by Lucifer Yellow scrape loading and dye transfer (SLDT, and the intracellular calcium concentrations ([Ca2+]i were characterized by confocal microscopy on cells loaded with Fura-3/AM. Results: There was an inverse correlation between Cx43 expression and MC proliferation (P0.05. Our data also showed that the mineralcorticoid receptor (MR antagonist spironolactone, ERK1/2 inhibitor PD98059 and PKC inhibitor GF109203X could attenuate the down-regulation of Cx43 expression in Aldo-induced MC proliferation; however, the PI3K inhibitor LY294002 could block MC proliferation without affecting Cx43 expression at either the mRNA or protein level. In addition, Aldo promoted MC proliferation in parallel with increasing [Ca2+]i (PConclusions: Our study provides preliminary evidence that Cx43 is an important regulator of Aldo-promoted MC proliferation. Furthermore, reduced Cx43 expression promoted MC proliferation independent of the gap junction channel function, and this process might be mediated through the ERK1/2- and PKC-dependent pathways.

  16. QGQS Granule in SHR Serum Metabonomics Study Based on Tools of UPLC-Q-TOF and Renin-Angiotensin-Aldosterone System Form Protein Profilin-1

    Directory of Open Access Journals (Sweden)

    Ke Li

    2017-01-01

    Full Text Available QGQS granule is effective for the therapeutic of hypertension in clinic. The aim of this research is to observe the antihypertension effect of QGQS granule on SHR and explain the mechanism of its lowering blood pressure. 30 SHR were selected as model group, captopril group, and QGQS group, 10 WKYr were used as control group, and RBP were measured on tail artery consciously. And all the serum sample analysis was carried out on UPLC-TOF-MS system to determine endogenous metabolites and to find the metabonomics pathways. Meanwhile, ELISA kits for the determination pharmacological indexes of PRA, AngI, AngII, and ALD were used for pathway confirmatory; WB for determination of profilin-1 protein expression was conducted for Ang II pathway analysis as well. It is demonstrated that QGQS granule has an excellent therapeutic effect on antihypertension, which exerts effect mainly on metabonomics pathway by regulating glycerophospholipid, sphingolipid, and arachidonic acid metabolism, and it could inhibit the overexpression of the profilin-1 protein. We can come to a conclusion that RAAS should be responsible mainly for the metabonomics pathway of QGQS granule on antihypertension, and it plays a very important role in protein of profilin-1 inhibition.

  17. The efficacy and safety of dual blockage of the renin-angiotensin-aldosterone system in patients with type 2 diabetes, hypertension and obesity without renal dysfunction

    Directory of Open Access Journals (Sweden)

    2012-09-01

    Full Text Available The purpose of the study was to evaluate the clinical efficacy and safety of dual RAAS blockage during treatment with angiotensin-converting enzyme (ACE inhibitors in combination with a direct renin inhibitor (PIR aliskiren versus combination therapy with ACE inhibitors and angiotensin receptor blocker II (ARB valsartan in patients with type 2 diabetes mellitus (T2DM, arterial hypertension (AH and obesity, without renal dysfunction. Materials and methods. The study included 26 patients with T2DM (10 men and 16 women, mean age 59,0±6,2 years with inadequate control of blood pressure (over 130 and/or 80 mm Hg on prior antihypertensive therapy and without renal dysfunctions (glomerular filtration rate (GFR> 60 ml/min/1, 73 m2 and the of albumin/creatinine (A/C ratio in the morning urine sample <10 mg/mol. After screening with the continuation of the initial therapy, including ACE inhibitors, 14 patients were added aliskiren 150–300 mg/day, 12 patients – valsartan 80–160 mg/day. Evaluation of the treatment effectiveness in terms of blood pressure (mean of three consecutive measurements in the sitting position and the parameters of renal function (serum creatinine and potassium, GFR, A/C ratio in the urine was performed at 4, 12 and 24 weeks of therapy. Results. In the group of patients treated with aliskiren, after 4 weeks of treatment a significant decrease in systolic and diastolic blood pressure (SBP and DBP, respectively was noted as compared to baseline: 146,1 and 138,9 mm Hg, p<0,05, 87,1 and 81,1 mm Hg, p <0,05, respectively; with systolic BP after 24 weeks of treatment decreased to 127,8 (-18,2 mm Hg, p<0,05, diastolic BP to 75,0 (-12, 1 mm Hg, p<0,05, the target blood pressure (≤130/80 mm Hg was achieved in 83% of patients. The group of patients treated with valsartan, after 4 weeks of therapy showed a significant reduction in systolic BP 148 and 141,6 mm Hg, p <0,05, diastolic BP - to 85,8 and 81,7 mm Hg, p=0,059; after 24 weeks systolic BP decreased to 128,7 (-19,3 mm Hg, p=0,05, diastolic BP – to 77,5 (-8,3 mm Hg, p=0,07, the target blood pressure was achieved in 78% of patients. When monitoring the safety of therapy in terms of potassium, serum creatinine, GFR, and A/C urine ratio statistically significant differences between the groups at 4, 12, 24 weeks of treatment were observed. Conclusion. Results of the study demonstrate the efficacy and safety of dual RAAS blockage in patients with T2DM and obesity with no prior renal impairment.

  18. Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY)

    DEFF Research Database (Denmark)

    Lindhardt, Morten; Persson, Frederik; Currie, Gemma

    2016-01-01

    INTRODUCTION: Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment...... AND DISSEMINATION: The study will be conducted under International Conference on Harmonisation - Good clinical practice (ICH-GCP) requirements, ethical principles of Declaration of Helsinki and national laws. This first new biomarker-directed intervention trial aiming at primary prevention of diabetic nephropathy...

  19. Effect of renin-angiotensin -aldosterone system blockers on myocardial remodeling processes and risk for atrial fibrillation in patients with arterial hypertension

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2014-07-01

    Full Text Available The given review considers the mechanisms underlying the development and maintenance of atrial fibrillations (AF. It is noted that the processes of atrial fibrosis, ion channel remodeling, inflammation, apoptosis, impaired intercellular interactions, and myocardiocyte hypertrophy may give rise to atrial structural and functional changes in AF. The efficacy of angiotensinonverting enzyme inhibitors and angiotensin receptor antagonists is justified in patients with left ventricular systolic dysfunction.

  20. Eplerenone attenuates pulse wave reflection in chronic kidney disease stage 3-4--a randomized controlled study

    DEFF Research Database (Denmark)

    Boesby, Lene; Elung-Jensen, Thomas; Strandgaard, Svend

    2013-01-01

    Patients with chronic kidney disease (CKD) have high cardiovascular mortality and morbidity associated with increased arterial stiffness. Plasma aldosterone levels are increased in CKD, and aldosterone has been found to increase vascular inflammation and fibrosis. It was hypothesized...

  1. Diagnosis of adrenal adenoma and hyperplasia by CT and adrenal scintigraphy

    International Nuclear Information System (INIS)

    Miura, Kentaro; Itami, Jun; Nawano, Shigeru; Okada, Junichi; Ogino, Takashi; Uno, Koichi; Arimizu, Noboru

    1985-01-01

    The evaluation of X-CT and adrenal scintigraphy in diagnosis of Cushing syndrome and primary aldosteronism was studied in 18 patients. In Cushing syndrome, CT appearance of adenoma is commonly larger than that of primary aldosteronism and cleary deliniated by surrounding fat. So, in Cushing syndrome, diagnosis of adenoma on CT is much easier than that of primary aldosteronism, and absence of adenoma on CT suggests adrenal hyperplasia. In primary aldosteronism both of CT and scintigraphy must be performed. (author)

  2. Hormonal regulation of Na+-K+-ATPase in cultured epithelial cells

    International Nuclear Information System (INIS)

    Johnson, J.P.; Jones, D.; Wiesmann, W.P.

    1986-01-01

    Aldosterone and insulin stimulate Na + transport through mechanisms involving protein synthesis. Na + -K + -ATPase has been implicated in the action of both hormones. The authors examined the effect of aldosterone and insulin on Na + -K + -ATPase in epithelial cells in culture derived from toad urinary bladder (TB6C) and toad kidney (A6). Aldosterone, but not insulin, increases short-circuit current (I/sub sc/) in TB6C cells. Aldosterone increases Na + -K + -[ 32 P]ATPase activity after 18 h of incubation, but no effect can be seen at 3 and 6 h. Amiloride, which inhibits aldosterone-induced increases in I/sub sc/, has no effect on either basal or aldosterone stimulated enzyme activity. Both aldosterone and insulin increase I/sub sc/ in A6 cells and when added together are synergistic. Aldosterone stimulates enzyme activity in A6 cells, but insulin alone has no effect. However, aldosterone and insulin together stimulate enzyme activity more than aldosterone alone. It appears that stimulation of Na + -K + -ATPase activity is involved in aldosterone action in both cell lines but does not appear to be due to increased Na + entry, since enhanced enzyme activity is not inhibited by amiloride. In contrast, insulin alone has no direct effect on Na + -K + -ATPase, although the increased enzyme activity following both agents in combination may explain their synergism on I/sub sc/

  3. Hormonal regulation of Na -K -ATPase in cultured epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, J.P.; Jones, D.; Wiesmann, W.P.

    1986-08-01

    Aldosterone and insulin stimulate Na transport through mechanisms involving protein synthesis. Na -K -ATPase has been implicated in the action of both hormones. The authors examined the effect of aldosterone and insulin on Na -K -ATPase in epithelial cells in culture derived from toad urinary bladder (TB6C) and toad kidney (A6). Aldosterone, but not insulin, increases short-circuit current (I/sub sc/) in TB6C cells. Aldosterone increases Na -K -(TSP)ATPase activity after 18 h of incubation, but no effect can be seen at 3 and 6 h. Amiloride, which inhibits aldosterone-induced increases in I/sub sc/, has no effect on either basal or aldosterone stimulated enzyme activity. Both aldosterone and insulin increase I/sub sc/ in A6 cells and when added together are synergistic. Aldosterone stimulates enzyme activity in A6 cells, but insulin alone has no effect. However, aldosterone and insulin together stimulate enzyme activity more than aldosterone alone. It appears that stimulation of Na -K -ATPase activity is involved in aldosterone action in both cell lines but does not appear to be due to increased Na entry, since enhanced enzyme activity is not inhibited by amiloride. In contrast, insulin alone has no direct effect on Na -K -ATPase, although the increased enzyme activity following both agents in combination may explain their synergism on I/sub sc/.

  4. Endokrin hypertension

    DEFF Research Database (Denmark)

    Poulsen, Per Løgstrup; Ibsen, Hans

    2009-01-01

    Endocrine hypertension is rare, but frequently refractory. Adenomas are common incidental findings. Biochemical tests confirm the diagnosis. Primary aldosteronism is the most common form. Hypokalaemia is an important sign, but 50% of patients may be normokalaemic. The plasma-aldosterone-to-renin ......Endocrine hypertension is rare, but frequently refractory. Adenomas are common incidental findings. Biochemical tests confirm the diagnosis. Primary aldosteronism is the most common form. Hypokalaemia is an important sign, but 50% of patients may be normokalaemic. The plasma...

  5. Therapeutic Drug Monitoring

    Science.gov (United States)

    ... 27 weeks) Pregnancy: Third Trimester (28 weeks to delivery) Primary Aldosteronism (Conn Syndrome) Prostate Cancer Protein in Urine (Proteinuria) Reactive Arthritis Rheumatoid Arthritis Sarcoidosis ...

  6. Antihypertensive effects of double the maximum dose of valsartan in African-American patients with type 2 diabetes mellitus and albuminuria

    DEFF Research Database (Denmark)

    Weir, Matthew R; Hollenberg, Norman K; Zappe, Dion H

    2010-01-01

    The blood pressure (BP)-lowering response to renin-angiotensin-aldosterone system blockade in hypertensive African-Americans is typically less than in whites. To determine whether higher than conventional doses of renin-angiotensin-aldosterone system blockade can improve BP reduction in African-A...

  7. Circadian changes in urinary Na + /K + ratio in humans: is there a ...

    African Journals Online (AJOL)

    Background: There are indications that the renal excretion of Na+ and K+ is affected by the body's circadian rhythm. Aldosterone is known to be the major determinant of urinary Na+/K+ ratio. However, recent reports suggest that the circadian rhythm of K+ excretion does not depend on endogenous aldosterone.

  8. CHAPTER 1

    African Journals Online (AJOL)

    Dr Olaleye

    nocturnal changes in urinary Na+/K+ ratio, and to test if aldosterone plays a key role. Methods: We investigated the Na+/K+ ratios ... This nocturnal dipping in blood pressure may be as a result of the circadian rhythm, which .... animals have shown that in the absence of endogenous aldosterone, the circadian excretion of K+ ...

  9. Cardiovascular Risk in Primary Hyperaldosteronism

    NARCIS (Netherlands)

    Prejbisz, A.; Warchol-Celinska, E.; Lenders, J.W.M.; Januszewicz, A.

    2015-01-01

    After the first cases of primary aldosteronism were described and characterized by Conn, a substantial body of experimental and clinical evidence about the long-term effects of excess aldosterone on the cardiovascular system was gathered over the last 5 decades. The prevalence of primary

  10. Cardiovascular Risk in Primary Hyperaldosteronism.

    Science.gov (United States)

    Prejbisz, A; Warchoł-Celińska, E; Lenders, J W M; Januszewicz, A

    2015-12-01

    After the first cases of primary aldosteronism were described and characterized by Conn, a substantial body of experimental and clinical evidence about the long-term effects of excess aldosterone on the cardiovascular system was gathered over the last 5 decades. The prevalence of primary aldosteronism varies considerably between different studies among hypertensive patients, depending on patient selection, the used diagnostic methods, and the severity of hypertension. Prevalence rates vary from 4.6 to 16.6% in those studies in which confirmatory tests to diagnose primary aldosteronism were used. There is also growing evidence indicating that prolonged exposure to elevated aldosterone concentrations is associated with target organ damage in the heart, kidney, and arterial wall, and high cardiovascular risk in patients with primary aldosteronism. Therefore, the aim of treatment should not be confined to BP normalization and hypokalemia correction, but rather should focus on restoring the deleterious effects of excess aldosterone on the cardiovascular system. Current evidence convincingly demonstrates that both surgical and medical treatment strategies beneficially affect cardiovascular outcomes and mortality in the long term. Further studies can be expected to provide better insight into the relationship between cardiovascular risk and complications and the genetic background of primary aldosteronism. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Feline primary hyperaldosteronism: an emerging endocrine disease

    Directory of Open Access Journals (Sweden)

    Daniel Diola Bento

    2016-04-01

    Full Text Available ABSTRACT: The primary hyperaldosteronism, an endocrine disease increasingly identified in cats, is characterized by adrenal gland dysfunction that interferes with the renin-angiotensin-aldosterone system, triggering the hypersecretion of aldosterone. Pathophysiological consequences of excessive aldosterone secretion are related to increased sodium and water retention, and increased excretion of potassium, which induce hypertension and severe hypokalemia, respectively. The most common clinical findings in cats include: polydipsia, nocturia, polyuria, generalized weakness, neck ventroflexion, syncope, anorexia, weight loss, pendulous abdomen and blindness. Diagnosis is based on the evidence of hormonal hypersecretion with suppression of renin release, imaging and histopathological evaluation of adrenal glands. Treatment may be curative with adrenalectomy, in cases of unilateral disease, or conservative, through administration of aldosterone antagonists, potassium supplementation and antihypertensives. Prognosis varies from fair to good with the appropriate therapy. This article reviews the main aspects of primary aldosteronism in cats, providing the clinician with important information for the diagnosis of this disease.

  12. Mineralocorticoid and apparent mineralocorticoid syndromes of secondary hypertension.

    Science.gov (United States)

    Ardhanari, Sivakumar; Kannuswamy, Rohini; Chaudhary, Kunal; Lockette, Warren; Whaley-Connell, Adam

    2015-05-01

    The mineralocorticoid aldosterone is a key hormone in the regulation of plasma volume and blood pressure in man. Excessive levels of this mineralocorticoid have been shown to mediate metabolic disorders and end-organ damage more than what can be attributed to its effects on blood pressure alone. Inappropriate excess levels of aldosterone contribute significantly to the cardiorenal metabolic syndrome and target organ injury that include atherosclerosis, myocardial hypertrophy, fibrosis, heart failure, and kidney disease. The importance of understanding the role of excess mineralocorticoid hormones such as aldosterone in resistant hypertension and in those with secondary hypertension should be visited. Primary aldosteronism is one of the commonly identified causes of hypertension and is treatable and/or potentially curable. We intend to review the management of mineralocorticoid-induced hypertension in the adult population along with other disease entities that mimic primary aldosteronism. Copyright © 2015 National Kidney Foundation, Inc. All rights reserved.

  13. Dietary Sodium Restriction Decreases Insulin Secretion Without Affecting Insulin Sensitivity in Humans

    Science.gov (United States)

    Byrne, Loretta M.; Yu, Chang; Wang, Thomas J.; Brown, Nancy J.

    2014-01-01

    Context: Interruption of the renin-angiotensin-aldosterone system prevents incident diabetes in high-risk individuals, although the mechanism remains unclear. Objective: To test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system or exogenous aldosterone impairs insulin secretion in humans. Design: We conducted a randomized, blinded crossover study of aldosterone vs vehicle and compared the effects of a low-sodium versus a high-sodium diet. Setting: Academic clinical research center. Participants: Healthy, nondiabetic, normotensive volunteers. Interventions: Infusion of exogenous aldosterone (0.7 μg/kg/h for 12.5 h) or vehicle during low or high sodium intake. Low sodium (20 mmol/d; n = 12) vs high sodium (160 mmol/d; n = 17) intake for 5–7 days. Main Outcome Measures: Change in acute insulin secretory response assessed during hyperglycemic clamps while in sodium balance during a low-sodium vs high-sodium diet during aldosterone vs vehicle. Results: A low-sodium diet increased endogenous aldosterone and plasma renin activity, and acute glucose-stimulated insulin (−16.0 ± 5.6%; P = .007) and C-peptide responses (−21.8 ± 8.4%; P = .014) were decreased, whereas the insulin sensitivity index was unchanged (−1.0 ± 10.7%; P = .98). Aldosterone infusion did not affect the acute insulin response (+1.8 ± 4.8%; P = .72) or insulin sensitivity index (+2.0 ± 8.8%; P = .78). Systolic blood pressure and serum potassium were similar during low and high sodium intake and during aldosterone infusion. Conclusions: Low dietary sodium intake reduces insulin secretion in humans, independent of insulin sensitivity. PMID:25029426

  14. Applications of radioimmunoassay techniques in endocrine studies. Part of a coordinated programme on in vitro assay techniques

    International Nuclear Information System (INIS)

    Marusic, E.T.

    1977-04-01

    The final report consists of a description of the research done, a reference to where the abstract of the results obtained was published, and a list of the corresponding publications and of those in preparation. Work has been done on radioimmunoassay techniques for measuring plasma corticoid values, plasma renin activity (with own reagents), and clinical and research studies measuring aldosterone, corticosterone, and cortisol in control and hypophysectomized patients. Diagnosis of primary aldosteronism has been initiated by radioimmunoassay techniques. Another study concerned the mechanism of K ions on aldosterone production

  15. Angiotensin II and Renal Tubular Ion Transport

    Directory of Open Access Journals (Sweden)

    Patricia Valles

    2005-01-01

    Evidence for the regulation of H+-ATPase activity in vivo and in vitro by trafficking/exocytosis has been provided. An additional level of H+-ATPase regulation via protein synthesis may be important as well. Recently, we have shown that both aldosterone and angiotensin II provide such a mechanism of regulation in vivo at the level of the medullary collecting tubule. Interestingly, in this part of the nephron, the effects of aldosterone and angiotensin II are not sodium dependent, whereas in the cortical collecting duct, both aldosterone and angiotensin II, by contrast, affect H+ secretion by sodium-dependent mechanisms.

  16. Remodelação miocárdica após infarto agudo do miocárdio experimental em ratos: efeito do bloqueio do sistema renina angiotensina aldosterona Myocardial remodeling after experimental acute myocardial infarction in rats: effect of renin-angiotensin-aldosterone system blockade

    Directory of Open Access Journals (Sweden)

    Hindalis Ballesteros Epifanio

    2005-01-01

    Full Text Available OBJETIVO: Verificar a ação do lisinopril e do losartan sobre a remodelação miocárdica no infarto experimental em ratos. MÉTODOS: Ratos machos Wistar foram submetidos a infarto e tratados com lisinopril 20 mg/kg/dia (LIS, n=13 ou losartan 20 mg/kg/dia (LOS, n=11, ou mantidos sem tratamento (NT, n=11, por três meses e os resultados comparados com grupo controle (CONT, n=11 de ratos sem infarto. Após a eutanásia, o ventrículo esquerdo foi separado e pesado. Foram medidas a área seccional dos miócitos (AC, fração de colágeno intersticial (CVF e a hidroxiprolina (HOP miocárdica. As variáveis foram comparadas pela ANOVA de uma via, para nível de significância de pOBJECTIVE: To assess the effect of lisinopril and losartan on myocardial remodeling in experimental infarction in rats. METHODS: Male Wistar rats underwent myocardial infarction and were either treated with lisinopril [20 mg/kg/day (LIS, n=13] or losartan [20 mg/kg/day (LOS, n=11], or kept without any treatment (NT, n=11 for 3 months. Their results were compared with those of a control group (CONT, n=11 comprising noninfarcted rats. After euthanasia, the left ventricle was isolated and weighed. The following measurements were taken: the sectional area of myocytes (AC, interstitial collagen fraction (CVF, and myocardial hydroxyproline (HOP. The variables were compared by using 1-way ANOVA, with a significance level of P<0.05. RESULTS: Acute myocardial infarction caused left ventricular hypertrophy. The treatments with lisinopril or losartan could prevent hypertrophy, which was quantified by use of left ventricular weight (LOS=1.06±0.12g, LIS=0.97±0.18g, NT=1.26±0.17g, CONT=1.02±0.09g; P<0.05, of left ventricular weight-to-body weight ratio LV/BW (LOS=2.37± 0.21mg/g, LIS=2.41±0.38mg/g, NT=2.82±0.37mg/g, CONT=2.27± 0.15mg/g, and of left ventricular AC measure-ment (LOS=210±39µ², LIS=217±35µ², NT=256±35µ², CONT=158±06 µ²; P<0.05. The CVF was significantly greater in the left ventricle of the infarcted group, and its increase was prevented with treatment (LOS=1.16±0.4%, LIS=1.27±0.5%, NT=1.8± 0.4%, CONT=0.7±0.5%. Myocardial hydroxyproline was greater in the infarcted group (NT=6.91±2.98mg/g vs. CONT=2.81± 1.21mg/g and did not change with treatment. CONCLUSION: Myocardial remodeling after infarction is characterized by an increase in the remaining ventricular mass and in interstitial collagen. The angiotensin-converting-enzyme blockers and the selective angiotensin II AT1 antagonist prevent hypertrophy of the myocyte and interstitial fibrosis.

  17. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease

    DEFF Research Database (Denmark)

    de Zeeuw, Dick; Akizawa, Tadao; Audhya, Paul

    2013-01-01

    Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown....

  18. Effects of ethanol and/or chloroquine with low protein dietary intake

    African Journals Online (AJOL)

    filtration rate, aldosterone synthesis and alteration of kidney structure [8]. ... faeces and urine to pass into a lower compartment filled with sawdust preventing any .... Figure 3: Serum levels of urea in ethanol and/or chloroquine-treated rats, fed.

  19. Use of angiotensin receptor – neprilysin inhibitors in heart failure: a ...

    African Journals Online (AJOL)

    aldosterone both increase sodium and water retention which ... steeply with advancing age, making it a growing public health problem. ... reduced ejection fraction This article will highlight the impact of this new therapy and its potential use in ...

  20. Corticosteroids in sports-related injuries: Friend or Foe

    African Journals Online (AJOL)

    2002-03-16

    Mar 16, 2002 ... the field of play. But to what extent ... Mineralocorticoids on the other hand (e.g. aldosterone) influence .... a player's return to play and reduce the game and practice ... Elbow: golfer's elbow (medial epicondylitis), tennis elbow.

  1. Value of serum tenascin-C in patients with acute myocardial infarction

    African Journals Online (AJOL)

    Rania Gaber

    2015-10-09

    Oct 9, 2015 ... Aliquots of serum were delivered into Eppendorf tubes. Serum samples have been .... Tenascin-C induced by aldosterone-mediated inflammation. J · Cardiovasc .... nosis estimation and targeted therapy. Cell Adh Migr 2015 ...

  2. Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: A systematic review and meta-analysis

    NARCIS (Netherlands)

    Currie, G. (Gemma); Taylor, A.H.M. (Alison H. M.); Fujita, T. (Toshiro); Ohtsu, H. (Hiroshi); Lindhardt, M. (Morten); K. Rossing; Boesby, L. (Lene); Edwards, N.C. (Nicola C.); Ferro, C.J. (Charles J.); J. Townend (Jonathan); A.H. van den Meiracker (Anton); Saklayen, M.G. (Mohammad G.); Oveisi, S. (Sonia); Jardine, A.G. (Alan G.); C. Delles (Christian); Preiss, D.J. (David J.); Mark, P.B. (Patrick B.)

    2016-01-01

    textabstractBackground: Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease.

  3. Case–control association study of polymorphisms in the ...

    Indian Academy of Sciences (India)

    2Department of Genetics, Medical School of Ribeirão Preto, University of São Paulo, Av. ... rennin–angiotensin–aldosterone system; single-nucleotide polymorphism; ethnicity. .... Brazilian CAD cases were more frequently of male gender,. 64.

  4. Sodium restriction potentiates the renoprotective effects of combined vitamin D receptor activation and angiotensin-converting enzyme inhibition in established proteinuric nephropathy.

    NARCIS (Netherlands)

    Mirkovic, K.; Frenay, A.S.; Born, J. van den; Goor, H van; Navis, G.; Borst, M.H. de; Bindels, R.J.M.; Hoenderop, J.G.J.; Hillebrands, J.L.

    2017-01-01

    BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) blockade provides renoprotective effects in chronic kidney disease (CKD); yet progressive renal function loss remains common. Dietary sodium restriction potentiates the renoprotective effects of RAAS blockade. Vitamin D receptor activator

  5. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Intraethnic variation in steroid-5-alpha-reductase polymorphisms in prostate cancer patients: a potential factor implicated in 5-alpha-reductase inhibitor treatment ... Aldosterone synthase C-344T, angiotensin II type 1 receptor A1166C and ...

  6. A SELECTIVE ANTAGONIST OF MINERALOCORTICOID RECEPTOR EPLERENONE IN CARDIOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    B. B. Gegenava

    2015-01-01

    Full Text Available The role of aldosterone in pathophysiological processes is considered. The effects of the selective antagonist of mineralocorticoid receptor eplerenone are analyzed. The advantages of eplerenone compared with spironolactone are discussed.

  7. Primary hyperaldosteronism in cats: expanding the diagnostic net

    NARCIS (Netherlands)

    Djajadiningrat-Laanen, S.C.

    2014-01-01

    Primary hyperaldosteronism or low-renin hyperaldosteronism in cats is characterized by inappropriately high aldosterone secretion from one or both adrenal glands, with systemic arterial hypertension and hypokalemia as leading clinical manifestations. In this thesis, non-tumorous primary

  8. Left ventricular structure and diastolic function in subjects with two hypertensive parents

    DEFF Research Database (Denmark)

    Andersen, U B; Steensgaard-Hansen, F; Rokkedal, J

    2001-01-01

    -parental hypertension and 26 matched controls with normotensive parents. Families with non-insulin-dependent diabetes or morbid obesity were excluded. (i) Echocardiography; (ii) plasma concentrations of renin, angiotensin-II, aldosterone, epinephrine and norepinephrine; (iii) euglycaemic, hyperinsulinemic clamp study...

  9. Lupus nephritis: An approach to diagnosis and treatment in South ...

    African Journals Online (AJOL)

    In all patients, treatment should include adjunctive therapies such as renin angiotensin aldosterone system .... Switching to an alternative agent is recommended for ... gastritis, cataracts, avascular necrosis of femur, cushingoid appearance.

  10. EVIDENCE-BASED USE OF EPLERENONE

    Directory of Open Access Journals (Sweden)

    S. R. Gilyarevski

    2012-01-01

    Full Text Available Data of the negative effect of high concentrations of aldosterone in the blood for cardiovascular disease, which served as the theoretical basis for wider use in clinical practice of the drugs belonging to the class of aldosterone receptor blockers is presented. Evidence-based data on efficacy and safety of aldosterone receptor blockers, which were obtained in the course of several randomized clinical trials is performed. Particular attention is paid to aspects of the clinical use of selective aldosterone receptor blocker eplerenone, including current data, which makes reasonable extension of indications for its use in treating patients with chronic heart failure. Data on indications of eplerenone use in patients with hypertension, especially in the case of associated target organ damage is presented.

  11. EVIDENCE-BASED USE OF EPLERENONE

    Directory of Open Access Journals (Sweden)

    S. R. Gilyarevski

    2014-07-01

    Full Text Available Data of the negative effect of high concentrations of aldosterone in the blood for cardiovascular disease, which served as the theoretical basis for wider use in clinical practice of the drugs belonging to the class of aldosterone receptor blockers is presented. Evidence-based data on efficacy and safety of aldosterone receptor blockers, which were obtained in the course of several randomized clinical trials is performed. Particular attention is paid to aspects of the clinical use of selective aldosterone receptor blocker eplerenone, including current data, which makes reasonable extension of indications for its use in treating patients with chronic heart failure. Data on indications of eplerenone use in patients with hypertension, especially in the case of associated target organ damage is presented.

  12. Renal tubular acidosis complicated with hyponatremia due to cortisol insufficiency

    OpenAIRE

    Izumi, Yuichiro; Nakayama, Yushi; Onoue, Tomoaki; Inoue, Hideki; Mukoyama, Masashi

    2015-01-01

    Adrenocortical insufficiency such as occurs in Addison's disease causes hyponatremia and renal tubular acidosis (RTA). Hyponatremia results from both aldosterone and cortisol insufficiency. RTA is due to aldosterone insufficiency. The involvement of cortisol in RTA is unclear. Here, we report a woman in her 70s who was admitted to our hospital with severe hyponatremia (106 mEq/l) and RTA. The patient exhibited low plasma cortisol levels with little response to rapid adrenocorticotropic hormon...

  13. Electrolyte transport in distal colon of sodium-depleted rats: Effect of sodium repletion

    International Nuclear Information System (INIS)

    Turnamian, S.G.; Binder, H.J.

    1988-01-01

    Dietary sodium depletion increases plasma aldosterone level and, as a result, induces amiloride-sensitive electrogenic sodium absorption and electrogenic potassium secretion and stimulates Na + -K + -ATPase activity in rat distal colon, while inhibiting electroneutral sodium chloride absorption. To assess the events that occur as the aldosterone-stimulated colon reverts to normal, unidirectional 22 Na and 36 Cl fluxes were measured under voltage-clamp conditions across isolated distal colonic mucosa of rats that were initially dietary sodium depleted for 7 days and then sodium repleted for varying periods of time before the study. Within 8 h of dietary sodium repletion, plasma aldosterone level and Na + -K + -ATPase activity declined to normal, amiloride-sensitive electrogenic sodium absorption decreased by >90%, and active electrogenic potassium secretion also decreased markedly. In contrast, electroneutral sodium chloride absorption did not completely return to levels seen in normal animals until ∼64-68 h. These results demonstrate that maintenance of electrogenic sodium absorption and potassium secretion are directly dependent on elevated plasma aldosterone levels. The inhibition of electroneutral sodium absorption, although initiated by excess aldosterone, persists after normalization of the plasma aldosterone level, thereby implying that the inhibition is dependent on additional factor(s)

  14. Mineralocorticoid hypertension

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Hypertension affects about 10 - 25% of the population and is an important risk factor for cardiovascular and renal disease. The renin-angiotensin system is frequently implicated in the pathophysiology of hypertension, be it primary or secondary. The prevalence of primary aldosteronism increases with the severity of hypertension, from 2% in patients with grade 1 hypertension to 20% among resistant hypertensives. Mineralcorticoid hypertension includes a spectrum of disorders ranging from renin-producing pathologies (renin-secreting tumors, malignant hypertension, coarctation of aorta, aldosterone-producing pathologies (primary aldosteronism - Conns syndrome, familial hyperaldosteronism 1, 2, and 3, non-aldosterone mineralocorticoid producing pathologies (apparent mineralocorticoid excess syndrome, Liddle syndrome, deoxycorticosterone-secreting tumors, ectopic adrenocorticotropic hormones (ACTH syndrome, congenitalvadrenal hyperplasia, and drugs with mineraocorticoid activity (locorice, carbenoxole therapy to glucocorticoid receptor resistance syndromes. Clinical presentation includes hypertension with varying severity, hypokalemia, and alkalosis. Ratio of plasma aldosterone concentraion to plasma renin activity remains the best screening tool. Bilateral adrenal venous sampling is the best diagnostic test coupled with a CT scan. Treatment is either surgical (adrenelectomy for unilateral adrenal disease versus medical therapy for idiopathic, ambiguous, or bilateral disease. Medical therapy focuses on blood pressure control and correction of hypokalemia using a combination of anti-hypertensives (calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers and potassium-raising therapies (mineralcorticoid receptor antagonist or potassium sparing diuretics. Direct aldosterone synthetase antagonists represent a promising future therapy.

  15. Differential effects of mineralocorticoid blockade on the hypothalamo-pituitary-adrenal axis in pregnant and nonpregnant ewes

    Science.gov (United States)

    Lingis, Melissa; Richards, Elaine M.

    2011-01-01

    During pregnancy, plasma ACTH and cortisol are chronically increased; this appears to occur through a reset of hypothalamo-pituitary-adrenal (HPA) activity. We have hypothesized that differences in mineralocorticoid receptor activity in pregnancy may alter feedback inhibition of the HPA axis. We tested the effect of MR antagonism in pregnant and nonpregnant ewes infused for 4 h with saline or the MR antagonist canrenoate. Pregnancy significantly increased plasma ACTH, cortisol, angiotensin II, and aldosterone. Infusion of canrenoate increased plasma ACTH, cortisol, and aldosterone in both pregnant and nonpregnant ewes; however, the temporal pattern of these responses differed between these two reproductive states. In nonpregnant ewes, plasma ACTH and cortisol transiently increased at 1 h of infusion, whereas in pregnant ewes the levels gradually increased and were significantly elevated from 2 to 4 h of infusion. MR blockade increased plasma aldosterone from 2 to 4 h in the pregnant ewes but only at 4 h in the nonpregnant ewes. In both pregnant and nonpregnant ewes, the increase in plasma aldosterone was significantly related to the timing and magnitude of the increase in plasma potassium. The results indicate a differential effect of MR activity in pregnant and nonpregnant ewes and suggest that the slow changes in ACTH, cortisol, and aldosterone are likely to be related to blockade of MR effects in the kidney rather than to effects of MR blockade in hippocampus or hypothalamus. PMID:21205934

  16. Regulation of ODC activity in the thymus and liver of rats by adrenal hormones.

    Science.gov (United States)

    Zahner, S L; Prahlad, K V; Mitchell, J L

    1986-01-01

    The activity of L-ornithine decarboxylase (EC 4.1.1.17, ODC) has become a useful indicator of hormone responsiveness. Various regimens of dexamethasone, aldosterone and epinephrine, alone or in combination, were administered to adrenalectomized rats either in acute or chronic doses. In addition, adrenalectomized rats, which were chronically treated with aldosterone and epinephrine, were given a single injection of 50 micrograms dexamethasone and sacrificed at various time intervals after hormone treatment. Hepatic and thymic ODC activity was measured. The expected dexamethasone effect, an increase in hepatic and a decrease in thymic ODC, was observed. This study also revealed that aldosterone induced similar responses in these tissues. Epinephrine had the opposite effect since chronic administration of dexamethasone or aldosterone with epinephrine resulted in control levels of ODC. Furthermore, when aldosterone and epinephrine were chronically administered to adrenalectomized rats, to study the acute effects of dexamethasone on rat thymus and liver, the time course of the response in each tissue was found to be distinct. The influence of the adrenal gland on rat thymus and liver is not restricted only to glucocorticoids, but may also involve other hormones which it secretes.

  17. Regulation of extrarenal potassium homeostasis by adrenal hormones in rats.

    Science.gov (United States)

    Bia, M J; Tyler, K A; DeFronzo, R A

    1982-06-01

    The effect of chronic (7-10 days) adrenal insufficiency on extrarenal potassium tolerance was examined by infusing potassium into rats after acute nephrectomy. The increment in plasma potassium concentration was significantly higher in glucocorticoid-replaced adrenalectomized rats versus controls (max delta PK 3.59 +/-0.11 vs. 2.93 +/- 0.08 meq/liter; P less than 0.001). The impairment in extrarenal potassium tolerance in adrenalectomized rats could not be attributed to acidemia, hypotension, changes in plasma insulin or glucose concentration, or potassium retention prior to study. Acute replacement with aldosterone resulted in significant improvement in the rise in plasma potassium after KCl (max delta PK 3.18 +/- 0.06 meq/liter; P less than 0.005 compared with aldosterone-deficient adrenalectomized rats but higher than in controls, P less than 0.02). If given on a chronic basis, aldosterone replacement led to a complete correction of the defect (max delta PK = 2.89 +/- 0.08 meq/liter). Acute epinephrine replacement in adrenalectomized rats also returned potassium tolerance to normal (max delta PK = 3.02 +/- 0.10 meq/liter). The results demonstrate that extrarenal potassium tolerance is impaired in chronic adrenal insufficiency and suggest that both aldosterone and epinephrine deficiency may contribute to the defect, since replacement with either hormone returns potassium tolerance toward normal. Accordingly, both aldosterone and epinephrine have important extrarenal mechanisms of action.

  18. Secondary hyperaldosteronism, caused by abnormalities of the renal vessels, in clinical endocrinologist

    Directory of Open Access Journals (Sweden)

    Tatjana N. Markova

    2016-03-01

    Full Text Available Aldosterone levels increase in clinical practice may be due to primary or secondary hyperaldosteronism. Secondary hyperaldosteronism (CAA is a clinical syndrome caused by increased synthesis of renin juxtaglomerular apparatus of the kidneys in response to lower perfusion pressure in the afferent glomerular arteriole. This mechanism leads to activation of the renin-angiotensin-aldosterone system with a consequent increase in systemic blood pressure. Clinically manifested CAA secondary (systemic arterial hypertension, the most common form of parenchymal renal disease and renal vascular lesions. Renovascular diseases are a heterogeneous group of pathologies, which includes atherosclerosis of renal arteries, the most common cause; fibromuscular dysplasia (FMD; other more rare diseases, accompanied by a narrowing of the lumen of the renal vessels. Some authors consider the possibility of including a group of renovascular disease presence of multiple renal arteries. Тhe article presents the clinical cases of secondary hyperaldosteronism, caused by FMD and abnormal amounts of the renal arteries, manifested hypertension and increased levels of aldosterone in the blood. Carrying out a detailed search of the diagnostic determination of the ratio of aldosterone to plasma renin helped eliminate endocrine genesis of the disease and to identify the true cause of aldosteronism.

  19. Mechanism of potassium depletion during chronic metabolic acidosis in the rat

    International Nuclear Information System (INIS)

    Scandling, J.D.; Ornt, D.B.

    1987-01-01

    Pair-fed rats on a normal K diet were given either 1.5% NH 4 Cl or water for 4 days. The acid-fed animals developed metabolic acidosis, negative K balance, and K depletion. Urinary Na excretion and urinary flow were not different between the groups beyond the first day. After the 4 days, isolated kidneys from animals in each of these groups were perfused at normal pH and bicarbonate concentrations. Urinary K excretion was similar between the groups despite the potassium depletion in the acid-fed animals. In contrast, isolated kidneys from animals with comparable K depletion induced by dietary K restriction readily conserved K. Sodium excretion and urinary flow were similar among the three groups of isolated kidneys. Plasma aldosterone concentrations were greater in the acid-fed rats after the 4 days of NH 4 Cl ingestion than in the control animals. Adrenalectomized rats were treated with either normal (4 μg/day) or high (22 μg/day) aldosterone replacement while ingesting NH 4 Cl for 4 days. Only in the presence of high aldosterone replacement did the acid-fed adrenalectomized animals develop K depletion. The authors conclude that chronic metabolic acidosis stimulates aldosterone secretion, and that aldosterone maintains the inappropriately high urinary potassium excretion and K depletion seen in this acid-base disorder

  20. Secondary hypertension in adults.

    Science.gov (United States)

    Puar, Troy Hai Kiat; Mok, Yingjuan; Debajyoti, Roy; Khoo, Joan; How, Choon How; Ng, Alvin Kok Heong

    2016-05-01

    Secondary hypertension occurs in a significant proportion of adult patients (~10%). In young patients, renal causes (glomerulonephritis) and coarctation of the aorta should be considered. In older patients, primary aldosteronism, obstructive sleep apnoea and renal artery stenosis are more prevalent than previously thought. Primary aldosteronism can be screened by taking morning aldosterone and renin levels, and should be considered in patients with severe, resistant or hypokalaemia-associated hypertension. Symptoms of obstructive sleep apnoea should be sought. Worsening of renal function after starting an angiotensin-converting enzyme inhibitor suggests the possibility of renal artery stenosis. Recognition, diagnosis and treatment of secondary causes of hypertension lead to good clinical outcomes and the possible reversal of end-organ damage, in addition to blood pressure control. As most patients with hypertension are managed at the primary care level, it is important for primary care physicians to recognise these conditions and refer patients appropriately. Copyright: © Singapore Medical Association.

  1. RETRACTED: Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population.

    Science.gov (United States)

    Zhong, Weiqiang; Jiang, Zongpei; Zhou, Tian-Biao

    2015-12-01

    This article has been included in a multiple retraction: Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10.1177/1470320314566019 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10

  2. RETRACTED: Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression.

    Science.gov (United States)

    Yang, Chun-Hua; Zhou, Tian-Biao

    2015-12-01

    This article has been included in a multiple retraction: Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression Journal of Renin-Angiotensin-Aldosterone System 1470320314568521, first published on February 3, 2015 doi: 10.1177/1470320314568521 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10.1177/1470320314566019 Tian-Biao Zhou, Xue-Feng Guo, Zongpei

  3. RETRACTED: Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population.

    Science.gov (United States)

    Zhou, Tian-Biao; Guo, Xue-Feng; Jiang, Zongpei; Li, Hong-Yan

    2015-12-01

    The following article has been included in a multiple retraction: Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang, and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population Journal of Renin-Angiotensin-Aldosterone System 1470320314563425, first published on February 1, 2015 doi: 10.1177/1470320314563425 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January

  4. 8C.02

    DEFF Research Database (Denmark)

    Jensen, B L; Frederiksen-Moller, B; Jorgensen, J S

    2015-01-01

    OBJECTIVE: The serine protease prostasin (PRSS8, CAP1) and its activator matriptase and inhibitor nexin-1 are necessary for normal placental development in mice. Prostasin is regulated by aldosterone in the kidney and may activate the epithelial sodium channel (ENaC). Preeclampsia is characterized...... by disturbed placentation, suppression of aldosterone and avid renal sodium retention with hypertension. It was hypothesized that preeclampsia is associated with low prostasin expression in placenta and spillover of prostasin into urine across the defect glomeular barrier. DESIGN AND METHOD: The hypothesis...... or placental weight. In summary, preeclampsia is associated with increased urine but not plasma or tissue prostasin CONCLUSIONS: : It is concluded that placental and plasma prostasin level is not controlled by aldosterone during term pregnancy. In contrast, prostasin is aberrantly filtered and may contribute...

  5. Adrenal scintiphotographic study with 131I-adosterol

    International Nuclear Information System (INIS)

    Sasaki, Tsuneo; Ohno, Akiko; Tanaka, Yoshiaki; Ohshima, Motoo; Matsubara, Kazuhito

    1976-01-01

    Adrenal scintiphotography by Nuclear-Chicago Pho Gamma III or Ohio-Nuclear 100 scinticamera was performed on the 7th, 8th and 9th day following the intravenous administration of 1 mCi of 131 I-adosterol. The cases to studied were 10 cases of primary aldosteronism and 10 suspected, 4 cases of Cushings syndrome and 3 suspected, and 2 cases of pheochromocytoma and 11 suspected. The lesions were clearly demonstrated as hot spots, in all operatively verified cases of primary aldosteronism, Cushings syndrome, and pheochromocytoma, respectively. Normal adrenal glands were either normally visualized or not visualized. In primary aldosteronism, the lesions visualized ranged in size from 13 to 27 mm. In Cushings syndrome, the lesions visualized ranged in size from 20 to 38 mm. In pheochromocytoma, the lesions visualized were 40 mm in diameter. Adrenal scintiphotographic study is useful in detecting lesion and/or determining side of a lesion before the angiographic examination. (J.P.N.)

  6. Prostasin and its regulatory proteins in human placentas from pregnant women with preeclampsia and healthy pregnant controls

    DEFF Research Database (Denmark)

    Frederiksen-Møller, Britta; Jørgensen, Jan Stener; Vogel, Lotte Katrine

    2015-01-01

    for normal placental development in mice. Prostasin is regulated by aldosterone in the kidney and may activate the epithelial sodium channel (ENaC). Preeclampsia is characterized by disturbed placentation, suppression of aldosterone and avid renal sodium retention with hypertension. It was hypothesized...... that preeclampsia is associated with low prostasin expression in placenta and spillover of prostasin into urine across the defect glomerular barrier. METHODS: This hypothesis was addressed in a cross-sectional design with 20 healthy pregnant women and 20 women with new onset of preeclampsia (hypertension and 1......+ for protein on urine dipstick). Blood and urine samples were obtained in relation to delivery and placental biopsies were taken immediately after delivery (control = 39 and preeclampsia 40 weeks). RESULTS: Women with preeclampsia displayed lower levels of aldosterone in plasma (p=0.0475) and in spot urine...

  7. Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity.

    Science.gov (United States)

    Schäfer, Nicola; Lohmann, Christine; Winnik, Stephan; van Tits, Lambertus J; Miranda, Melroy X; Vergopoulos, Athanasios; Ruschitzka, Frank; Nussberger, Jürg; Berger, Stefan; Lüscher, Thomas F; Verrey, François; Matter, Christian M

    2013-12-01

    Aldosterone plays a crucial role in cardiovascular disease. 'Systemic' inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the 'endothelial' MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis. C57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high 'endogenous' aldosterone) and in 'exogenous' aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR. Obesity-induced endothelial dysfunction depends on the 'endothelial' MR and is mediated by an imbalance of oxidative stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complications.

  8. Renal intercalated cells and blood pressure regulation

    Directory of Open Access Journals (Sweden)

    Susan M. Wall

    2017-12-01

    Full Text Available Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl⁻ absorption and HCO₃⁻ secretion largely through pendrin-dependent Cl⁻/HCO₃⁻ exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO₃ administration. In some rodent models, pendrin-mediated HCO₃⁻ secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl⁻ absorption, but also by modulating the aldosterone response for epithelial Na⁺ channel (ENaC-mediated Na⁺ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.

  9. Transient Receptor Potential Canonical (TRPC)/Orai1-dependent Store-operated Ca2+ Channels

    Science.gov (United States)

    Sabourin, Jessica; Bartoli, Fiona; Antigny, Fabrice; Gomez, Ana Maria; Benitah, Jean-Pierre

    2016-01-01

    Store-operated Ca2+ entry (SOCE) has emerged as an important mechanism in cardiac pathology. However, the signals that up-regulate SOCE in the heart remain unexplored. Clinical trials have emphasized the beneficial role of mineralocorticoid receptor (MR) signaling blockade in heart failure and associated arrhythmias. Accumulated evidence suggests that the mineralocorticoid hormone aldosterone, through activation of its receptor, MR, might be a key regulator of Ca2+ influx in cardiomyocytes. We thus assessed whether and how SOCE involving transient receptor potential canonical (TRPC) and Orai1 channels are regulated by aldosterone/MR in neonatal rat ventricular cardiomyocytes. Molecular screening using qRT-PCR and Western blotting demonstrated that aldosterone treatment for 24 h specifically increased the mRNA and/or protein levels of Orai1, TRPC1, -C4, -C5, and stromal interaction molecule 1 through MR activation. These effects were correlated with a specific enhancement of SOCE activities sensitive to store-operated channel inhibitors (SKF-96365 and BTP2) and to a potent Orai1 blocker (S66) and were prevented by TRPC1, -C4, and Orai1 dominant negative mutants or TRPC5 siRNA. A mechanistic approach showed that up-regulation of serum- and glucocorticoid-regulated kinase 1 mRNA expression by aldosterone is involved in enhanced SOCE. Functionally, 24-h aldosterone-enhanced SOCE is associated with increased diastolic [Ca2+]i, which is blunted by store-operated channel inhibitors. Our study provides the first evidence that aldosterone promotes TRPC1-, -C4-, -C5-, and Orai1-mediated SOCE in cardiomyocytes through an MR and serum- and glucocorticoid-regulated kinase 1 pathway. PMID:27129253

  10. Secondary or Transient Pseudohypoaldosteronism Associated With Urinary Tract Anomaly and Urinary Infection: A Case Report

    Directory of Open Access Journals (Sweden)

    Vinod Krishnappa

    2016-09-01

    Full Text Available Hyponatremia with hyperkalemia in infancy is a rare presentation, but may be due to aldosterone deficiency or end organ resistance to its action. There are few cases associating this condition with urinary tract infections or anatomic abnormalities that predispose to infection. Clinicians should have a high index of suspicion in diagnosing secondary pseudohypoaldosteronism (PHA due to its often atypical presentation. We describe ten month-old infant who presented with this condition and was found to have urinary tract infection complicating unilateral urinary tract anomaly, which may have strong association with renal tubular resistance to aldosterone.

  11. Steroid radioimmunoassay: contribution of standards to blank values, ch. 4

    International Nuclear Information System (INIS)

    Froelich, M.; Termorshuizen, W.; Kenter, E.; Molenaar, A.J.

    1977-01-01

    The sensitivity of the radioimmunoassay of steroids is considerably reduced by high blank values which may be derived in part from co-chromatographed standards. Blank levels approach the detection limit of the radioimmunoassay of aldosterone, testosterone and androstenedione when 10,000 dpm (30-35 pg) labelled steroids are used as reference standard. When 20 μg aldosterone, testosterone, or androstenedione is used as standard, blank levels of up to 12,800 pg were measured in the radioimmunoassay. Application of the standards on a separate strip does not improve the results. From the experiments it appeared that contamination took place by transport by the solvent

  12. Study of hormonal status of surgical patients with endometrial carcinoma

    International Nuclear Information System (INIS)

    Musina, R.Kh.; Kiseleva, N.S.; Modnikov, O.P.

    1987-01-01

    A radioimmunoassay was conducted in the pituitary-ovary and pituitary-adrenals systems in 37 cases of endometrial carcinoma treatment and 1, 3, 5 and 14 days after extirpation of the uterus and appendages. The levels of follicle - stimulating (FSH) and luteinizing (LH) hormones of the pituitary, prolactin, ACTH, estradiol, progesterone, testosterone, cortisol and aldosterone were studied. Such disturbances as decreased production of FSH, LH, progesterone and testosterone were observed before operation. Surgery was followed by a considerable rise in prolactin production and basal levels of FSH and LH, a decrease in estradiol, progesterone and testosterone concentrations and was accompanied by a sizeable release of cortisol and aldosterone

  13. Primary hyperaldosteronism diagnosed with adrenal vein sampling. Characteristics and follow-up after adrenalectomy in a Danish study

    DEFF Research Database (Denmark)

    Pedersen, Maria; Karlsen, Mona Aarenstrup; Ankjærgaard, Kasper L

    2016-01-01

    BACKGROUND: Primary hyperaldosteronism (PA), known as Mb Conn, is one of the most common forms of secondary hypertension in middle-aged adults. High plasma aldosterone has been associated with severe organ damage. The unilateral aldosterone-producing adenoma (lateralized disease) is a subtype of PA...... had higher blood pressure (BP) and lower serum potassium compared to patients with bilateral hyperplasia. No difference regarding age and gender distribution was detected. Despite lateralized disease diagnosed from AVS, the medical images were normal in 10 patients (28%). Follow-up of 30 patients who...

  14. 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....

  15. [Clinical case of the month. Renovascular arterial hypertension complicated by diabetes insipidus: report of a case and review of the literature].

    Science.gov (United States)

    Feloni, S; Radermacher, L; Remy, C; Jousten, J; Corman, V

    2013-01-01

    Mrs. A, a 62 year old patient with a history of hypertension, polyuria and polydipsia is hospitalized after a malaise. A severe hypokalemia, which is the cause of the polyuria and polydipsia, is discovered. The presence of hypertension and hypokalemia arises suspicion of a primary hyperaldosteronism and the plasma levels of renin and aldosterone are measured. Elevated aldosterone levels are combined with high plasma renin concentrations which permits to rule out primary hyperaldosteronism. Further explorations reveal a subocclusive ostial stenosis of the right renal artery. A treatment by sartan is instaured, which allows arterial pressure control and kalemia normalization. Chronic hypokalemia can be the cause of tubular nephropathy manifested by nephrogenic diabetes insipidus.

  16. Laparoscopic adrenal cortex

    International Nuclear Information System (INIS)

    Peyrolou, A.; Salom, A.; Harguindeguy; Taroco, L.; Ardao, G.; Broli, F. . E mail: andresssss@adinet.com.uy

    2005-01-01

    The paper presents the case of a female patient who carried an aldosterone-secreting tumor of adrenal cortex.In the analysis of diagnosis and para clinical examinations there is particular reference to the laparoscopic surgery mode of treatment.Diagnosis should be established on the basis of clinical and laboratory tests (hypopotassemia and hyperaldosteronism).Tumor topography was confirmed through CT scan, MRI and Scintiscan in left adrenal cortex.Resection was consequently made through laparoscopic surgery.The patients evolution was excellent from the surgical viewpoint,with I levels of blood pressure, potassium and aldosterone returned to normal

  17. A novel method for analysing key corticosteroids in polar bear (Ursus maritimus) hair using liquid chromatography tandem mass spectrometry

    DEFF Research Database (Denmark)

    Weisser, Johan; Hansen, Martin; Björklund, Erland

    2016-01-01

    . This procedure allows for the simultaneous determination of multiple steroids, which is in contrast to previous polar bear studies based on ELISA techniques. Absolute method recoveries were 81%, 75% and 60% for cortisol, corticosterone and aldosterone, respectively. We applied the developed method on a hair......This paper presents the development and evaluation of a methodology for extraction, clean-up and analysis of three key corticosteroids (aldosterone, cortisol and corticosterone) in polar bear hair. Such a methodology can be used to monitor stress biomarkers in polar bears and may provide...

  18. [The effect of a single inhalation of mineral water on the blood hormonal status in healthy volunteers].

    Science.gov (United States)

    Khinchagov, B P; Polushina, N D; Frolkov, V K

    1998-01-01

    Concentrations of ACTH, TTH, STH, LH, PSH, hydrocortisone, insulin, glucagone, triiodthyronine, thyroxine, aldosterone, glucose and unesterified fatty acids (NEFA) were measured in the blood of 23 healthy male volunteers aged 18 to 35 years 15, 30 and 60 min after a single nose inhalation and oral intake of mineral water Essentuki No. 17. Inhalation of Essentuki No. 17 stimulated secretion of the hormones and some parameters of metabolic reactions: the levels of glucose, NEFA, hydrocortisone, aldosterone, TTH, PSH and LH rose while those of insulin and growth hormone decreased. Oral intake of this water brought about the same changes in the hormone status except blood insulin the levels of which went up.

  19. Cardiovascular, endocrine, and renal effects of urodilatin in normal humans

    DEFF Research Database (Denmark)

    Bestle, M H; Olsen, Niels Vidiendal; Christensen, P

    1999-01-01

    highest doses. The renin-angiotensin-aldosterone system was inhibited by the three lowest doses but activated by the hypotensive dose of 40 ng. kg-1. min-1. Plasma vasopressin increased by factors of up to 5 during infusion of the three highest doses. Atrial natriuretic peptide immunoreactivity (including...

  20. 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,

  1. 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...

  2. Pulsatility index of renal artery in patients with liver cirrhosis

    International Nuclear Information System (INIS)

    Baik, Soon Koo; Kim, Kwan Hyun; Jeong, Yon Soo; Kim, Hyun Soo; Lee, Dong Ki; Kwon, Sang Ok

    2000-01-01

    As one of non-invasive methods evaluating disorders of renal perfusion using Doppler ultrasonography, PI represents the characteristics of the Doppler waveform more accurately than RI, and even when renal perfusion is severely impaired, objective estimation is possible because of using the mean velocity in its calculation. The purpose of this study is to find out the clinical usefulness of PI for evaluating disorder of renal function in patients with liver cirrhosis. The subjects were 167 patients including 89 of Child A and B groups, 39 of Child C group, and 39 of control group. We compared PI, RI, creatinine, serum renin activity and aldosterone level between each groups, and investigated the relationships of PI with creatinine clearance, serum renin activity, and aldosterone level. Meal PI was 1.00 ± 0.15 in control group, 1.17 ± 0.22 in Child A and B groups, and 1.30 ± 0.28 in Child C group, which showed significant difference between each groups (p<0.05). Also RI, creatinine clearance, serum renin activity and aldosterone level revealed significant difference between each groups (p<0.05). PI showed significant negative relationships with creatinine clearance (p=0.009), serum renin activity (p=0.06), and aldosterone level (p=0.001). Measurement of PI by Doppler ultrasonography is a useful non-invasive method for evaluation renal dysfunction in patients with liver cirrhosis.

  3. Lectin-like receptor for alpha 1-acid glycoprotein in the epithelium of the rat prostate gland and seminal vesicles

    DEFF Research Database (Denmark)

    Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

    1996-01-01

    by mannose and N-Acetyl-D-glucosamine. RESULTS: In vitro the receptor was also inhibited by the steroid hormones cortisone, aldosterone, progesterone, and estradiol, but not by testosterone. A significant regional variation in the expression of AGP-lectin receptor and in the localization of AGP was seen...

  4. Sodium intake, RAAS-blockade and progressive renal disease

    NARCIS (Netherlands)

    de Borst, Martin H; Navis, Gerjan

    Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors or angiotensin receptor blockers is the current standard treatment to prevent progressive renal function loss in patients with chronic kidney disease. Yet in many patients the

  5. Effects of sodium restriction and hydrochlorothiazide on RAAS blockade efficacy in diabetic nephropathy : a randomised clinical trial

    NARCIS (Netherlands)

    Kwakernaak, Arjan J.; Krikken, Jan A.; Binnenmars, S. Heleen; Visser, Folkert W.; Hemmelder, Marc H.; Woittiez, Arend-Jan; Groen, Henk; Laverman, Gozewijn D.; Navis, Gerjan

    Background Reduction of dietary sodium intake or diuretic treatment increases renin-angiotensin-aldosterone system (RAAS) blockade efficacy in non-diabetic nephropathy. We aimed to investigate the effect of sodium restriction and the diuretic hydrochlorothiazide, separately and in combination, added

  6. Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Afzelius, Pia; Bazeghi, Nassim; Bie, Peter

    2011-01-01

    Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development of this ...

  7. Chronic heart failure

    African Journals Online (AJOL)

    enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs) and aldosterone ... It has a predictive power of 90% in this situation (c-statistic. 0.90). It is a useful rule-out ... Psychosocial support and the treatment of depression are becoming ...

  8. Does SGLT2 inhibition with dapagliflozin overcome individual therapy resistance to RAAS inhibition?

    NARCIS (Netherlands)

    Petrykiv, Sergei; Laverman, Gozewijn D.; de Zeeuw, Dick; Heerspink, Hiddo J. L.

    Individual patients show a large variation in their response to renin-angiotensin-aldosteron system (RAAS) inhibition (RAASi), both in surrogates such as albuminuria and in hard renal outcomes. Sodium-glucose co-transporter 2 inhibitors (SGLT2) have been shown to lower albuminuria and to confer

  9. [Is this the end for double RAAS inhibition?

    NARCIS (Netherlands)

    Deinum, J.

    2014-01-01

    Recently, the VA NEPHRON-D study was stopped early due to insignificant effects and increased adverse events. This was the last in a series of trials on the value of dual versus single blockade of the renin-angiotensin-aldosterone system in patients at risk for renal or cardiovascular complications.

  10. New nonabsorbable potassium-exchange resins in hyperkalaemia

    NARCIS (Netherlands)

    Roscioni, Sara S.; Lambers Heerspink, Hiddo

    New data suggest that treatment with patiromer or sodium zirconium cyclosilicate for up to 8 weeks reduces plasma potassium levels in hyperkalaemic patients. If proven safe and effective for long-term use, these therapies might be administered together with intensive renin-angiotensin-aldosterone

  11. Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients : results from a phase 3 randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Anker, Stefan D.; Kosiborod, Mikhail; Zannad, Faiez; Pina, Ileana L.; McCullough, Peter A.; Filippatos, Gerasimos; van der Meer, Peter; Ponikowski, Piotr; Rasmussen, Henrik S.; Lavin, Philip T.; Singh, Bhupinder; Yang, Alex; Deedwania, Prakash

    2015-01-01

    AimsHyperkalaemia in heart failure patients limits use of cardioprotective renin-angiotensin-aldosterone system inhibitors (RAASi). Sodium zirconium cyclosilicate (ZS-9) is a selective potassium ion trap, whose mechanism of action may allow for potassium binding in the upper gastrointestinal tract

  12. [Acute renal failure due to RAAS-inhibitors combined with dehydration].

    NARCIS (Netherlands)

    Scherpbier-de Haan, N.D.; Grauw, W.J.C. de; Wetzels, J.F.M.; Vervoort, G.M.M.

    2010-01-01

    Two men (61 and 81 years old) with mild impaired kidney function developed acute renal failure due to dehydration combined with the use of inhibitors of the renin-angiotensin-aldosterone system (RAAS). After rehydration, correction of hyperkalaemia and stopping RAAS-inhibition and diuretics, they

  13. Hjertestop associeret med syndrome of apparent mineralocorticoid excess

    DEFF Research Database (Denmark)

    Meldgaard-Nielsen, Anne; Laugesen, Esben; Poulsen, Per Løgstrup

    2014-01-01

    Ventricular fibrillation is an unknown complication to the syndrome of apparent mineralocorticoid excess (SAME). This case report describes a young woman admitted with hypo-kalaemia and hypertension. Concentrations of both P-renin and P-aldosterone were low and urinary steroid metabolites revealed...

  14. Steroid hormone excretion is enhanced by sucrose feeding to rats

    International Nuclear Information System (INIS)

    Kruger, T.C.; Hsu, H.; Saunders, J.P.; Kim, S.S.; Given-Proctor, J.; Ahrens, R.A.

    1986-01-01

    The hypothesis tested was that feeding rats sucrose rather than invert sugar (50:50 mixture of glucose and fructose) or cornstarch would result in a more rapid excretion of intravenously injected 1,2- 3 H aldosterone or 1,2,6,7- 3 H cortisol. The three carbohydrate sources provided 45% of dietary energy when fed, respectively, to one of three groups of 10 male, Sprague Dawley rats. After 4 or 8 weeks of ad lib feeding of the three diets 5 μCI of 3 H-labeled hormones were injected intravenously and % recovery in urine and feces was measured for 4 days by liquid scintillation counting. Nearly 90% of the 3 H injected as 1,2- 3 H aldosterone was recovered over 4 days in the excreta of the sucrose fed rats. This recovery of 3 H from aldosterone was significantly greater (P 3 H from intravenously injected 1,2,6,7- 3 H cortisol followed a similar pattern. The authors anticipate that the excretion of all metabolic end products and xenobiotics excreted as glucuronides would be enhanced by sucrose feeding. Oxocarbonium ions from the glucose portion of sucrose digestion in the mammalian small intestine are thought to compete with oxocarbonium ions from the glucuronic acid portion of glucuronide hydrolysis. Such competition may slow glucuronide hydrolysis and promote glucuronide excretion, including the glucuronides derived from aldosterone and cortisol

  15. Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy

    NARCIS (Netherlands)

    Siwy, Justyna; Schanstra, Joost P.; Argiles, Angel; Bakker, Stephan J. L.; Beige, Joachim; Boucek, Petr; Brand, Korbinian; Delles, Christian; Duranton, Flore; Fernandez-Fernandez, Beatriz; Jankowski, Marie-Luise; Al Khatib, Mohammad; Kunt, Thomas; Lajer, Maria; Lichtinghagen, Ralf; Lindhardt, Morten; Maahs, David M.; Mischak, Harald; Mullen, William; Navis, Gerarda; Noutsou, Marina; Ortiz, Alberto; Persson, Frederik; Petrie, John R.; Roob, Johannes M.; Rossing, Peter; Ruggenenti, Piero; Rychlik, Ivan; Serra, Andreas L.; Snell-Bergeon, Janet; Spasovski, Goce; Stojceva-Taneva, Olivera; Trillini, Matias; von der Leyen, Heiko; Winklhofer-Roob, Brigitte M.; Zuerbig, Petra; Jankowski, Joachim

    Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system

  16. The influence of the ACE (I/D) polymorphism on systemic and renal vascular responses to angiotensins in normotensive, normoalbuminuric Type 1 diabetes mellitus

    NARCIS (Netherlands)

    Luik, PT; Hoogenberg, K; Kerstens, MN; Beusekamp, BJ; de Jong, PE; Dullaart, RPF; Navis, GJ

    Aim/hypothesis. The renin-angiotensin-aldosterone system is important in diabetic nephropathy, with the angiotensin-converting-enzyme DD-genotype being a renal risk factor. The D-allele is associated with higher ACE concentrations, but functional consequences in diabetes mellitus are not known. To

  17. Plasma metanephrine for assessing the selectivity of adrenal venous sampling

    NARCIS (Netherlands)

    Dekkers, T.; Deinum, J.; Schultze Kool, L.J.; Blondin, D.; Vonend, O.; Hermus, A.R.M.M.; Peitzsch, M.; Rump, L.C.; Antoch, G.; Sweep, F.C.; Bornstein, S.R.; Lenders, J.W.M.; Willenberg, H.S.; Eisenhofer, G.

    2013-01-01

    Adrenal vein sampling is used to establish the origins of excess production of adrenal hormones in primary aldosteronism. Correct catheter positioning is confirmed using adrenal vein measurements of cortisol, but this parameter is not always reliable. Plasma metanephrine represents an alternative

  18. Adrenal scintigraphy

    International Nuclear Information System (INIS)

    Beierwaltes, W.H.

    1979-01-01

    The following items are discussed:anatomy and physiology of adrenal glands, clinical indications of scintigraphy, radiobiology and radiochemistry, scintigraphic imaging, adrenocortical hyperfunction, aldosteronism and hypertension associated with low renin level, excess of androgen, adrenocortical hyperfunction and future perspectives of adrenal scintigraphy. (M.A.) [pt

  19. The effect of RAAS blockade on markers of renal tubular damage in diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, Stine; Rossing, Kasper; Hess, Georg

    2012-01-01

    Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid......-binding protein (LFABP)....

  20. 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...

  1. Angiotensin II type 1 receptor (A1166C) gene polymorphism in ...

    African Journals Online (AJOL)

    H. El-banawy

    2015-01-05

    Jan 5, 2015 ... sure and body fluids, via renin-angiotensin–aldosterone system ... the most studied one is the A1166C variant.2–5,8,10–14 It is a ... polymorphism on the development of ESRD in adult Egyptian ... teaching hospital, Alexandria University. ..... important part of the clinical process of renal risk identifica- tion.

  2. Common Secondary Causes of Resistant Hypertension and Rational for Treatment

    OpenAIRE

    Faselis, Charles; Doumas, Michael; Papademetriou, Vasilios

    2011-01-01

    Resistant hypertension is defined as uncontrolled blood pressure despite the use of three antihypertensive drugs, including a diuretic, in optimal doses. Treatment resistance can be attributed to poor adherence to antihypertensive drugs, excessive salt intake, physician inertia, inappropriate or inadequate medication, and secondary hypertension. Drug-induced hypertension, obstructive sleep apnoea, primary aldosteronism, and chronic kidney disease represent the most common secondary causes of ...

  3. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency in ...

    African Journals Online (AJOL)

    was measured by Cisbio radioimmunoassay (Cisbio, France), and serum aldosterone and 17-OHP were measured by .... Compared with SV patients, notably more CSW patients (62.1%, n=18) had severe acute malnutrition. SV patients were more likely to be obese (n=5, 45.5%) or overweight (n=6, 54.5%) at presentation ...

  4. Clinical characteristics and causes of heart failure, adherence to ...

    African Journals Online (AJOL)

    ... of AHF are cardiomyopathy, IHD and RHD. AHF affects a young population and is associated with a high rate of rehospitalisation and mortality. There is serious under-use of beta-blockers, aldosterone antagonists and digoxin. Emphasis on the rigorous application of treatment guidelines is needed to reduce readmission ...

  5. CASE REPORT CASE CASE Conned by Conn's syndrome

    African Journals Online (AJOL)

    2008-01-08

    Jan 8, 2008 ... ing of the aldosterone-producing adenoma (APA) can prove challenging but is nonetheless very important for surgical planning and cure. We present two patients with MRI (magnetic resonance imaging) confirma- tion of APA with negative and equivocal CT (computed tomography) scans. Case 1.

  6. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    The rennin–angiotensin–aldosterone system (RAAS) is a critical pathway in regulating blood pressure and salt/water homeostasis, possessing an intimate relationship with the development of systemic artery hypertension (SAH). Once hypertension is considered a risk factor for coronary artery disease (CAD), the RAAS is ...

  7. RAAS and stress markers in acute ischemic stroke

    DEFF Research Database (Denmark)

    Back, C.; Thiesen, K L; Olsen, Karsten Skovgaard

    2015-01-01

    . MATERIALS AND METHODS: Blood from a jugular and cubital vein was collected within 48 h of stroke onset, after 24 and 48 h, and renin, angiotensin I, angiotensin II, aldosterone, norepinephrine, epinephrine, and cortisol were measured. Post-stroke cubital vein samples were collected after 8 (4.7-10) months...

  8. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial

    DEFF Research Database (Denmark)

    de Zeeuw, Dick; Agarwal, Rajiv; Amdahl, Michael

    2010-01-01

    Despite treatment with renin–angiotensin–aldosterone system (RAAS) inhibitors, patients with diabetes have increased risk of progressive renal failure that correlates with albuminuria. We aimed to assess whether paricalcitol could be used to reduce albuminuria in patients with diabetic nephropathy....

  9. DTNSRDC Library Subject Thesaurus.

    Science.gov (United States)

    1980-03-01

    FORMALDEHYDE SURFACE PROPERTIES FURALDEHYDES ALUEDU(ASINUNUMY) ALUUht BT ASTRONOMY BT MONOSACCHARIDES ALBERTA ALDOSTERONE ST CANADA BT ADRENAL CORTEX...CARBOHYDRATES BT TUBES NT DEXTP* GLYCCSIDESCAPILLARY WAVES * POLYSACCHARIDES . SGARSCAPPING TRISACCHARIDES CAPROLACTONES CARBON BT CYCLOHEXANONES UF...BRADO:ARDIA CARBOXYMETHYLCELLULOSE CORONARY DISEASE BT POLYSACCHARIDES * EMBOLISM HEMATOoAS CARBURETOR AIR SCOOPS PULMONARY EDEMA ST AIR INTAKES * RHEUMATIC

  10. Elevated N-terminal pro-brain natriuretic peptide levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of dietary sodium restriction and diuretics, but not angiotensin receptor blockade, in proteinuric renal patients

    NARCIS (Netherlands)

    Slagman, Maartje C. J.; Waanders, Femke; Vogt, Liffert; Damman, Kevin; Hemmelder, Marc; Navis, Gerjan; Laverman, Gozewijn D.

    Background. Renin angiotensin aldosterone system (RAAS) blockade only partly reduces blood pressure, proteinuria and renal and cardiovascular risk in chronic kidney disease (CKD) but often requires sodium targeting [i.e. low sodium diet (LS) and/or diuretics] for optimal efficacy. However, both

  11. Elevated N-terminal pro-brain natriuretic peptide levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of dietary sodium restriction and diuretics, but not angiotensin receptor blockade, in proteinuric renal patients

    NARCIS (Netherlands)

    Slagman, Maartje C. J.; Waanders, Femke; Vogt, Liffert; Damman, Kevin; Hemmelder, Marc; Navis, Gerjan; Laverman, Gozewijn D.

    2012-01-01

    Background. Renin angiotensin aldosterone system (RAAS) blockade only partly reduces blood pressure, proteinuria and renal and cardiovascular risk in chronic kidney disease (CKD) but often requires sodium targeting [i.e. low sodium diet (LS) and/or diuretics] for optimal efficacy. However, both

  12. Effects of short-term addition of NSAID to diuretics and/or RAAS-inhibitors on blood pressure and renal function

    NARCIS (Netherlands)

    Nygard, Peder; Jansman, Frank G. A.; Kruik-Kolloffel, Willemien J.; Barnaart, Alex F. W.; Brouwers, Jacobus R. B. J.

    Background The combined post-operative use of diuretics and/or renin-angiotensin-aldosterone system (RAAS) inhibitors may increase the risk of nonsteroidal anti-inflammatory drug (NSAID) associated renal failure because of a drug-drug interaction. Objective The aim of this study was to investigate

  13. CARDIOVASCULAR ENDOCRINOLOGY Dual RAAS blockade has dual effects on outcome

    NARCIS (Netherlands)

    Heerspink, Hiddo J. Lambers; de Zeeuw, Dick

    Makani and colleagues report that dual blockade of the renin-angiotensin-aldosterone system is associated with harm despite previous studies showing that this approach decreases blood pressure and albuminuria. Do these results imply that we should abandon surrogate markers? Or should we become more

  14. Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease

    DEFF Research Database (Denmark)

    Currie, Gemma; Taylor, Alison H M; Fujita, Toshiro

    2016-01-01

    BACKGROUND: Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemi...... pressure and urinary protein/albumin excretion with a quantifiable risk of hyperkalaemia above predefined study upper limit....

  15. Effectiveness of 131I nor-cholesterol uptake per unit volume of adrenal adenoma in the diagnosis of aldosteronoma

    International Nuclear Information System (INIS)

    Kita, Tamotsu; Tomita, Hiroko; Sakaguchi, Chiharu

    2010-01-01

    Diagnosis of adrenal adenomas for patients with primary aldosteronism is sometimes difficult only by referring to the visualization pattern in adrenocortical scintigraphy without regards to standard scintigraphy or suppression scintigraphy with dexamethasone. We studied if quantitative evaluation of the standard scintigraphy without dexamethasone suppression can be useful to diagnose aldosteronomas. Twenty-nine patients who had undergone adrenalectomy with different clinical manifestations (16 patients with primary aldosteronism, 6 patients with Cushing's syndrome and 7 patients without hormonal abnormality) were included in the study. Volume of the adrenocortical adenomas, 131 I nor-cholesterol uptake of the adrenocortical adenomas, and 131 I nor-cholesterol uptake per unit volume of the adrenocortical adenomas were compared between the 3 groups. The volume of adrenocortical adenomas in the patients with primary aldosteronism was significantly lower than those in the other two groups (Cushing's syndrome p 131 I nor-cholesterol uptake of adrenocortical adenoma. The 131 I nor-cholesterol uptake per unit volume of adrenocortical adenomas was significantly higher in the patients with primary aldosteronism than those in the other two groups (Cushing's syndrome p 131 I nor-cholesterol uptake per unit volume of adenoma obtained from adrenocortical scintigraphy without dexamethasone suppression can be useful in the diagnosis of aldosteronoma. (author)

  16. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    One such candidate gene is angiotensin convertingenzyme (ACE) for various cardiovascular mechanisms. ACE is the key enzyme of the renin angiotensin aldosterone systempathway which maintains homeostasis blood pressure in the body and any variation in the levels is reported to be associatedwith various complex ...

  17. Inhibition of cGMP-specific phosphodiesterase type 5 reduces sodium excretion and arterial blood pressure in patients with NaCl retention and ascites

    DEFF Research Database (Denmark)

    Thiesson, Helle C; Jensen, Boye L; Jespersen, Bente

    2005-01-01

    ANG II, and aldosterone concentrations significantly after 60 min. Plasma cGMP concentration was increased after 120 and 180 min, and urinary sodium excretion and mean arterial blood pressure were decreased significantly at 120 and 180 min. Plasma ANP concentration, GFR, and RBF did not change after...

  18. Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons

    Science.gov (United States)

    Zhu, Xiaoxia; Walton, Joseph P.

    2016-01-01

    Age-related hearing loss (ARHL) -presbycusis - is the most prevalent neurodegenerative disease and number one communication disorder of our aged population; and affects hundreds of millions of people worldwide. Its prevalence is close to that of cardiovascular disease and arthritis, and can be a precursor to dementia. The auditory perceptual dysfunction is well understood, but knowledge of the biological bases of ARHL is still somewhat lacking. Surprisingly, there are no FDA-approved drugs for treatment. Based on our previous studies of human subjects, where we discovered relations between serum aldosterone levels and the severity of ARHL, we treated middle age mice with aldosterone, which normally declines with age in all mammals. We found that hearing thresholds and suprathreshold responses significantly improved in the aldosterone-treated mice compared to the non-treatment group. In terms of cellular and molecular mechanisms underlying this therapeutic effect, additional experiments revealed that spiral ganglion cell survival was significantly improved, mineralocorticoid receptors were upregulated via post-translational protein modifications, and age-related intrinsic and extrinsic apoptotic pathways were blocked by the aldosterone therapy. Taken together, these novel findings pave the way for translational drug development towards the first medication to prevent the progression of ARHL. PMID:27667674

  19. Kaempferol inhibits the production of ROS to modulate OPN-αvβ3 integrin pathway in HUVECs.

    Science.gov (United States)

    Xiao, Hong-Bo; Lu, Xiang-Yang; Liu, Zi-Kui; Luo, Zhi-Feng

    2016-06-01

    In the present study, we tested the hypothesis that aldosterone regulates osteopontin (OPN)-related signaling pathways to promote nuclear factor κB (NF-κB) activation in primary human umbilical vein endothelial cells (HUVECs) and that kaempferol, a flavonoid compound, blocks those changes. Aldosterone induced productions of reactive oxygen species (ROS), OPN, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) and expression of nicotinamide adenine dinucleotide phosphate-oxidase 4 (Nox4), NF-κB, OPN, alphavbeta3 (αvβ3) integrin, and inhibitor of NF-κB alpha phosphorylation (P-IκBα) in HUVEC. HUVECs were pretreated with kaempferol (0, 1, 3, or 10 μM) for 1 h and exposed to aldosterone (10(-6) M) for 24 h. Kaempferol reduced ROS, OPN, NF-κB, IL-6, and TNF-α levels; Nox4, αvβ3 integrin; and P-IκBα expressions. The effect of aldosterone was also abrogated by spironolactone (10(-6) M). In addition, vitamin C (20 mmol/L) reduced ROS production. Vitamin C and LM609 (10 μg/mL) treatment decreased expressions of OPN, αvβ3 integrin, and NF-κB (P kaempferol may modulate OPN-αvβ3 integrin pathway to inhibit NF-κB activation in HUVECs.

  20. Study of the components of renin-angiotensinaldosterone system and KalliKrein -Kinin system in normal pregnancy

    International Nuclear Information System (INIS)

    Abreu Fagundes, V.G. de.

    1984-01-01

    The alterations in the renin-angiotensin-aldosterone system and Kallikrein-Kinin system were studied. The possible interferences of these systems on the arterial pressure and on the evolution of normal pregnancy were presented in the following situations: when the pregnant change from dorsal decumbency to left lateral decumbency and to orthostatic position. (M.A.C.) [pt

  1. Synthesis of hydroxyeicosatetraenoic acids (HETE's) by adrenal glomerulosa cells and incorporation into cellular lipids

    International Nuclear Information System (INIS)

    Campbell, W.B.; Richards, C.F.; Brady, M.T.; Falck, J.R.

    1986-01-01

    The role of lipoxygenase metabolites of arachidonic acid (AA) in the regulation of aldosterone secretion was studied in isolated rat adrenal glomerulosa cells. Cells were incubated with 14 C-AA in the presence of angiotensin (AII). The media was extracted, metabolites isolated by HPLC, and structures of the metabolites determined by UV absorbance and mass spectrometry. The major products were 12- and 15-HETE with lesser amounts of 11- and 5-HETE. When adrenal cells were incubated with 15-, 12- or 5-HPETE or their respective HETE's (0.03-300nM), there was no significant change in basal or AII-stimulated aldosterone release. Cells were incubated with [ 3 H]-AA, -5-HETE, -15-HETE, -12-HETE or -LTB. The cellular lipids were extracted and analyzed by TLC. AA was incorporated into phospholipids (22%), cholesterol esters (50%) and triglycerides (21%). Neither the HETE's or LTB 4 were incorporated into phospholipids. 5-HETE was taken up into di- and mono-glycerides. The rates of incorporation of AA and 5-HETE were similar (+ 1/2 = 10 min). The incorporation of 5-HETE into glycerol esters did not modify the release of aldosterone by the cells. Thus, while adrenal cells synthesize HETE's, these eicosanoids do not appear to alter the synthesis of aldosterone

  2. Effect of hypoxaemia on water and sodium homeostatic hormones and renal function

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1995-01-01

    , a hypoxic ventilatory response produces hypocapnia and respiratory alkalosis. Acute hypoxaemia depresses aldosterone secretion secondary to a direct effect on adrenal cells. Also plasma renin is decreased in resting hypoxaemic conditions, but the mechanism remains unknown. These hormonal changes may have...

  3. Download this PDF file

    African Journals Online (AJOL)

    User

    cigarette smoking. The heart failure responded satisfactorily to anti-heart failure medications including loop diuresis, angiotensin converting enzyme and aldosterone inhibition, and low dose beta blockade with carvidilol. Blood sugar was adequately controlled using metformin and glibenclamide. Blood pressure control was ...

  4. The secretory KCa1.1 channel localises to crypts of distal mouse colon: functional and molecular evidence

    DEFF Research Database (Denmark)

    Sørensen, Mads Vaarby; Strandsby, Anne Bystrup; Larsen, Casper Kornbech

    2011-01-01

    The colonic epithelium absorbs and secretes electrolytes and water. Ion and water absorption occurs primarily in surface cells, whereas crypt cells perform secretion. Ion transport in distal colon is regulated by aldosterone, which stimulates both Na+ absorption and K+ secretion. The electrogenic...

  5. Changes of endocrine hormones in simple obese females

    International Nuclear Information System (INIS)

    Wei Tao; Duan Wenruo; Ma Yongxiu; Chen Yanping

    2005-01-01

    To study the relationship between plasma leptin, adiponectin, insulin, cortisol, aldosterone and BMI in simple obese females, leptin, adiponectin, insulin, cortisol and aldosterone were tested in 48 fat women with BMI ranging 23-24.9 kg/m 2 and another 40 with BMI≥ 25 kg/m 2 by radioimmunoassay and immunoradiometric assay. Besides, 42 healthy women(BMI ranging 18-22.9 kg/m 2 )were also tested as controls. Pearson's correlation and other statistic methods were used in data processing. The results showed that the levels of leptin, insulin, cortisol and aldosterone were linearily postively correlated with BMI in obesity groups, and were higher than those in controls remarkably (P<0.01). Meanwhile, the levels of adiponectin were linearily nagatively correlated with BMI in obesity groups. Our conclusion is that along with increase of BMI, the plasma levels of insulin and leptin increase in obese women, whereas the level of adiponectin decreases. The increasing levels of leptin, insulin, cortisol, aldosterone and decreasing level of adiponectin may be partly indicative of the etiology of diabetes, hyper- tension and nephrosis in obese females. (authors)

  6. Radioimmunoassay reagent and its use in a radioimmunoassay

    International Nuclear Information System (INIS)

    Polito, A.J.; Knight, W.S.

    1977-01-01

    A radioimmunoassay to detect or determine a steroid of the cortisone and aldosterone group has been developed. The invention particularly concerns a steroid derivative containing imidazole group which is radioactively labelled. The invented reagents are labelled with iodine 125. (VJ) [de

  7. Radioimmunoassays of tetrahydroaldosterone (TH-Aldo) in human urine

    International Nuclear Information System (INIS)

    Kohl, K.-H.; Vecsei, P.; Abdelhamid, S.

    1978-01-01

    Specific antisera against tetrahydroaldosterone (TH-Aldo) were raised in two white New Zealand rabbits. 3α,5β-TH-aldo-20-oxime-bovine-serum albumin commplex was used as antigen. The resulting titers were 1:18 000 and 1:16 000. Except tetrahydrocortisol (THF) (0.23%) and tetrahydro-18-hydroxy-11-dehydrocorticosterone (18-OH-THA) (3.2%), all steroids and steroid metabolites gave negligible cross-reactions. Immunograms of the paper chromatograms made from the n-butanol-extract of the urines, as well as after β-glucuronidase treatment and dichlormethane extraction, were studied to further define the specificity of the antiserum. Antibody H 1 (used in this study) reacted with aldosterone-18-gluc., a TH-aldosterone-glucuronide (probably the 21-glucuronide) and an unidentified less polar material. Two methods were developed: a) TH-Aldo-glucuronide(s) estimation after ethylacetate pre-extraction as a rapid screening test of endogenous aldosterone production. b) estimation of TH-aldosterone using one chromatographic system. The results of method a) showed a significant correlation with the values obtained by technique b). Normal values (method b) were 25.88 plus minus 16.50 μg/24 h (range 9.5 - 64.8 μg/24 h). A significant correlation was also shown between the TH-aldo (technique b) and 18-gluc. values. (author)

  8. Renal graft failure after addition of an angiotensin II receptor antagonist to an angiotensin-converting enzyme inhibitor

    DEFF Research Database (Denmark)

    Kamper, Anne-Lise; Nielsen, Arne Høj; Baekgaard, Niels

    2002-01-01

    Combined treatment with an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor blocker (ARB) has been suggested in order to achieve a more complete blockade of the renin-angiotensin-aldosterone system in cardiovascular and renal disease. The present report descri...

  9. Adrenal scan in 17-alpha-hydroxylase deficiency: false indication of adrenal adenoma

    International Nuclear Information System (INIS)

    Shore, R.M.; Lieberman, L.M.; Newman, T.J.; Friedman, A.; Bargman, G.J.

    1981-01-01

    A patient who was thought to have testicular feminization syndrome and primary aldosteronism had an adrenal scan that suggested an adrenal adenoma. After later diagnosis of 17-alpha-hydroxylase deficiency, she was treated with glucocorticoids rather than surgery. Her clinical course and a repeat adrenal scan confirmed she did not have a tumor

  10. Hydronephrosis is associated with elevated plasmin in urine in pediatric patients and rats and changes in NCC and γ-ENaC abundance in rat kidney

    DEFF Research Database (Denmark)

    Zachar, Rikke; Al-Mashhadi, Ammar; Dimke, Henrik

    2018-01-01

    , and with a stimulated renin-angiotensin-aldosterone system (RAAS) in rodent models. This study aimed at investigating the hypothesis that i) in pediatric patients with UPJO the RAAS is activated prior to surgical relief of the obstruction; ii) in rats with UPJO the RAAS activation is reflected by increased abundance...

  11. Corticosteroid effect on Caco-2 cell lipids depends on cell differentiation

    Czech Academy of Sciences Publication Activity Database

    Jindřichová, Šárka; Nováková, O.; Bryndová, Jana; Tvrzická, E.; Lisá, Věra; Novák, F.; Pácha, Jiří

    2003-01-01

    Roč. 87, 2-3 (2003), s. 157-165 ISSN 0960-0760 R&D Projects: GA ČR GA305/01/0281 Institutional research plan: CEZ:AV0Z5011922 Keywords : aldosterone * dexamethasone * phospholipids Subject RIV: CE - Biochemistry Impact factor: 2.596, year: 2003

  12. CHRONIC KIDNEY DISEASE RAAS blockade and diastolic heart failure in chronic kidney disease

    NARCIS (Netherlands)

    Franssen, Casper F. M.; Navis, Gerjan

    New data from Ahmed et al. show that discharge prescriptions for renin-angiotensin-aldosterone inhibitor therapy are associated with a significant reduction in all-cause mortality in elderly patients with diastolic heart failure and chronic kidney disease (CKD). These observational data support the

  13. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    High density lipoprotein levels were higher in male hypertensives. Volume 94 Issue 2 June 2015 pp 363-363 Erratum. Aldosterone synthase C-344T, angiotensin II type 1 receptor A1166C and 11- hydroxysteroid dehydrogenase G534A gene polymorphisms and essential hypertension in the population of Odisha, India.

  14. Adrenal Hormones in Common Bottlenose Dolphins (Tursiops truncatus: Influential Factors and Reference Intervals.

    Directory of Open Access Journals (Sweden)

    Leslie B Hart

    Full Text Available Inshore common bottlenose dolphins (Tursiops truncatus are exposed to a broad spectrum of natural and anthropogenic stressors. In response to these stressors, the mammalian adrenal gland releases hormones such as cortisol and aldosterone to maintain physiological and biochemical homeostasis. Consequently, adrenal gland dysfunction results in disruption of hormone secretion and an inappropriate stress response. Our objective herein was to develop diagnostic reference intervals (RIs for adrenal hormones commonly associated with the stress response (i.e., cortisol, aldosterone that account for the influence of intrinsic (e.g., age, sex and extrinsic (e.g., time factors. Ultimately, these reference intervals will be used to gauge an individual's response to chase-capture stress and could indicate adrenal abnormalities. Linear mixed models (LMMs were used to evaluate demographic and sampling factors contributing to differences in serum cortisol and aldosterone concentrations among bottlenose dolphins sampled in Sarasota Bay, Florida, USA (2000-2012. Serum cortisol concentrations were significantly associated with elapsed time from initial stimulation to sample collection (p<0.05, and RIs were constructed using nonparametric methods based on elapsed sampling time for dolphins sampled in less than 30 minutes following net deployment (95% RI: 0.91-4.21 µg/dL and following biological sampling aboard a research vessel (95% RI: 2.32-6.68 µg/dL. To examine the applicability of the pre-sampling cortisol RI across multiple estuarine stocks, data from three additional southeast U.S. sites were compared, revealing that all of the dolphins sampled from the other sites (N = 34 had cortisol concentrations within the 95th percentile RI. Significant associations between serum concentrations of aldosterone and variables reported in previous studies (i.e., age, elapsed sampling time were not observed in the current project (p<0.05. Also, approximately 16% of

  15. Adrenal Hormones in Common Bottlenose Dolphins (Tursiops truncatus): Influential Factors and Reference Intervals.

    Science.gov (United States)

    Hart, Leslie B; Wells, Randall S; Kellar, Nick; Balmer, Brian C; Hohn, Aleta A; Lamb, Stephen V; Rowles, Teri; Zolman, Eric S; Schwacke, Lori H

    2015-01-01

    Inshore common bottlenose dolphins (Tursiops truncatus) are exposed to a broad spectrum of natural and anthropogenic stressors. In response to these stressors, the mammalian adrenal gland releases hormones such as cortisol and aldosterone to maintain physiological and biochemical homeostasis. Consequently, adrenal gland dysfunction results in disruption of hormone secretion and an inappropriate stress response. Our objective herein was to develop diagnostic reference intervals (RIs) for adrenal hormones commonly associated with the stress response (i.e., cortisol, aldosterone) that account for the influence of intrinsic (e.g., age, sex) and extrinsic (e.g., time) factors. Ultimately, these reference intervals will be used to gauge an individual's response to chase-capture stress and could indicate adrenal abnormalities. Linear mixed models (LMMs) were used to evaluate demographic and sampling factors contributing to differences in serum cortisol and aldosterone concentrations among bottlenose dolphins sampled in Sarasota Bay, Florida, USA (2000-2012). Serum cortisol concentrations were significantly associated with elapsed time from initial stimulation to sample collection (p<0.05), and RIs were constructed using nonparametric methods based on elapsed sampling time for dolphins sampled in less than 30 minutes following net deployment (95% RI: 0.91-4.21 µg/dL) and following biological sampling aboard a research vessel (95% RI: 2.32-6.68 µg/dL). To examine the applicability of the pre-sampling cortisol RI across multiple estuarine stocks, data from three additional southeast U.S. sites were compared, revealing that all of the dolphins sampled from the other sites (N = 34) had cortisol concentrations within the 95th percentile RI. Significant associations between serum concentrations of aldosterone and variables reported in previous studies (i.e., age, elapsed sampling time) were not observed in the current project (p<0.05). Also, approximately 16% of Sarasota Bay

  16. Effect of laparotomy on the pituitary-adrenal axis in dogs.

    Science.gov (United States)

    Skovira, Emily J; Behrend, Ellen N; Martin, Linda G; Palmer, Lee E; Kemppainen, Robert J; Lee, Hollie P

    2017-08-01

    OBJECTIVE To assess effects of major abdominal surgery on serum cortisol and aldosterone and plasma canine ACTH (cACTH) concentrations. ANIMALS 39 healthy dogs undergoing laparotomy during veterinary student surgical laboratories. PROCEDURES Blood samples were obtained before and at completion of surgery. Serum cortisol and aldosterone and plasma cACTH concentrations were measured by use of validated radioimmunoassays. Changes in concentrations (postoperative concentration minus preoperative concentration) were calculated. Data were analyzed by use of the Wilcoxon signed rank test, Pearson correlation analysis, and Mann-Whitney rank sum test. RESULTS Cortisol, aldosterone, and cACTH concentrations increased significantly from before to after surgery. Although cortisol and aldosterone concentrations increased in almost all dogs, cACTH concentrations decreased in 6 of 32 (19%) dogs. All dogs had preoperative cortisol concentrations within the reference range, but 24 of 39 (62%) dogs had postoperative concentrations above the reference range. A correlation between the change in cACTH concentration and the change in cortisol concentration was not detected. CONCLUSIONS AND CLINICAL RELEVANCE Laparotomy caused a significant increase in serum cortisol and aldosterone concentrations. In most dogs, but not all dogs, plasma cACTH concentrations increased. Lack of correlation between the change in cACTH concentration and the change in cortisol concentration suggested that increased postoperative cortisol concentrations may have been attributable to ACTH-independent mechanisms, an early ACTH increase that caused a sustained cortisol release, or decreased cortisol clearance. Further studies are indicated to evaluate the effects of various anesthetic protocols and minimally invasive surgical techniques on the stress response.

  17. PF-03882845, a non-steroidal mineralocorticoid receptor antagonist, prevents renal injury with reduced risk of hyperkalemia in an animal model of nephropathy

    Directory of Open Access Journals (Sweden)

    Stephen eOrena

    2013-10-01

    Full Text Available The mineralocorticoid receptor (MR antagonists PF 03882845 and eplerenone were evaluated for renal protection against aldosterone mediated renal disease in uninephrectomized Sprague Dawley (SD rats maintained on a high salt diet and receiving aldosterone by osmotic mini pump for 27 days. Serum K+ and the urinary albumin to creatinine ratio (UACR were assessed following 14 and 27 days of treatment. Aldosterone induced renal fibrosis as evidenced by increases in UACR, collagen IV staining in kidney cortex, and expression of pro fibrotic genes relative to sham operated controls not receiving aldosterone. While both PF 03882845 and eplerenone elevated serum K+ levels with similar potencies, PF 03882845 was more potent than eplerenone in suppressing the rise in UACR. PF 03882845 prevented the increase in collagen IV staining at 5, 15 and 50 mg/kg BID while eplerenone was effective only at the highest dose tested (450 mg/kg BID. All doses of PF 03882845 suppressed aldosterone induced increases in collagen IV, transforming growth factor 1 (Tgf 1, interleukin 6 (Il-6, intermolecular adhesion molecule 1 (Icam-1 and osteopontin gene expression in kidney while eplerenone was only effective at the highest dose. The therapeutic index (TI, calculated as the ratio of the EC50 for increasing serum K+ to the EC50 for UACR lowering, was 83.8 for PF 03882845 and 1.47 for eplerenone. Thus the TI of PF 03882845 against hyperkalemia was 57 fold superior to that of eplerenone indicating that PF 03882845 may present significantly less risk for hyperkalemia compared to eplerenone.

  18. Regulation of renal Na+-K-ATPase in the rat: role of increased potassium transport

    International Nuclear Information System (INIS)

    Mujais, S.K.; Chekal, M.A.; Hayslett, J.P.; Katz, A.I.

    1986-01-01

    The purpose of this study was to characterize the alterations in collecting tubule Na + -K + -ATPase activity produced by sustained increments in dietary potassium in the rat and to evaluate the role of aldosterone in their generation. In adrenal-intact animals, feeding a high-potassium diet or administration of a high physiological dose of aldosterone, which simulates the delivery rate of this hormone during potassium loading, caused marked increments in Na + -K + -ATPase activity in the cortical collecting tubule (CCT) but had no effect on the enzyme in the inner stripe of the medullary collecting tubule (MCT). A significant increase in enzyme activity was also observed after smaller dietary potassium increments and after 4 days of dietary potassium load. In adrenalectomized rats provided with physiological replacement doses of corticosterone and aldosterone, Na + -K + -ATPase activity in both CCT and MCT was similar to that of adrenal-intact controls but remained unchanged after 7 days on the potassium-enriched (10-fold) diet. In contrast, adrenalectomized animals receiving the high physiological dose of aldosterone displayed an increase in Na + -K + -ATPase activity of CCT comparable with that of adrenal-intact animals, whereas the enzyme activity in the MCT was unaffected. In conclusion, 1) following chronic potassium loading Na + -K + -ATPase activity increases significantly in the CCT with no change in its activity in the inner stripe of the MCT; 2) this increase in enzyme activity occurs in a time-dependent fashion and in proportion to the potassium load; and 3) the stimulation of Na + -K + -ATPase activity in adrenal-replaced rats is facilitated by augmented levels of aldosterone, such as those actually observed in adrenal-intact rats subjected to chronic potassium loading

  19. Regulation of renal Na -K-ATPase in the rat: role of increased potassium transport

    Energy Technology Data Exchange (ETDEWEB)

    Mujais, S.K.; Chekal, M.A.; Hayslett, J.P.; Katz, A.I.

    1986-08-01

    The purpose of this study was to characterize the alterations in collecting tubule Na -K -ATPase activity produced by sustained increments in dietary potassium in the rat and to evaluate the role of aldosterone in their generation. In adrenal-intact animals, feeding a high-potassium diet or administration of a high physiological dose of aldosterone, which simulates the delivery rate of this hormone during potassium loading, caused marked increments in Na -K -ATPase activity in the cortical collecting tubule (CCT) but had no effect on the enzyme in the inner stripe of the medullary collecting tubule (MCT). A significant increase in enzyme activity was also observed after smaller dietary potassium increments and after 4 days of dietary potassium load. In adrenalectomized rats provided with physiological replacement doses of corticosterone and aldosterone, Na -K -ATPase activity in both CCT and MCT was similar to that of adrenal-intact controls but remained unchanged after 7 days on the potassium-enriched (10-fold) diet. In contrast, adrenalectomized animals receiving the high physiological dose of aldosterone displayed an increase in Na -K -ATPase activity of CCT comparable with that of adrenal-intact animals, whereas the enzyme activity in the MCT was unaffected. In conclusion, 1) following chronic potassium loading Na -K -ATPase activity increases significantly in the CCT with no change in its activity in the inner stripe of the MCT; 2) this increase in enzyme activity occurs in a time-dependent fashion and in proportion to the potassium load; and 3) the stimulation of Na -K -ATPase activity in adrenal-replaced rats is facilitated by augmented levels of aldosterone, such as those actually observed in adrenal-intact rats subjected to chronic potassium loading.

  20. Patterns and predictors of evidence-based medication continuation among hospitalized heart failure patients (from Get With the Guidelines-Heart Failure).

    Science.gov (United States)

    Krantz, Mori J; Ambardekar, Amrut V; Kaltenbach, Lisa; Hernandez, Adrian F; Heidenreich, Paul A; Fonarow, Gregg C

    2011-06-15

    Hospitalized patients with heart failure and decreased ejection fraction are at substantial risk for mortality and rehospitalization, yet no acute therapies are proven to decrease this risk. Therefore, in-hospital use of medications proved to decrease long-term mortality is a critical strategy to improve outcomes. Although endorsed in guidelines, predictors of initiation and continuation of angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), β blockers, and aldosterone antagonists have not been well studied. We assessed noncontraindicated use patterns for the 3 medications using the Get With the Guidelines-Heart Failure (GWTG-HF) registry from February 2009 through March 2010. Medication continuation was defined as treatment on admission and discharge. Multivariable logistic regression using generalized estimating equations was used to determine factors associated with discharge use. In total 9,474 patients were enrolled during the study period. Of those treated before hospitalization, overall continuation rates were 88.5% for ACE inhibitors/ARBs, 91.6% for β blockers, and 71.9% for aldosterone-antagonists. Of patients untreated before admission, 87.4% had ACE inhibitors/ARBs and 90.1% had β blocker initiated during hospitalization or at discharge, whereas only 25.2% were started on an aldosterone antagonist. In multivariate analysis, admission therapy was most strongly associated with discharge use (adjusted odds ratios 7.4, 6.0, and 20.9 for ACE inhibitors/ARBs, β blockers, and aldosterone antagonists, respectively). Western region, younger age, and academic affiliation were also associated with higher discharge use. Although ACE inhibitor/ARB and β-blocker continuation rates were high, aldosterone antagonist use was lower despite potential eligibility. In conclusion, being admitted on evidence-based medications is the most powerful, independent predictor of discharge use. Copyright © 2011 Elsevier Inc. All rights reserved.