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Sample records for aldosterone

  1. Aldosterone and Renin Test

    Science.gov (United States)

    ... are used to treat high blood pressure. Stress, exercise, and pregnancy can also affect the test results. Coffee, tea or cola can affect the 24-hour urine sample test. Your doctor will tell you if you should change the amount of ... routine before aldosterone testing. Licorice may mimic aldosterone ...

  2. Aldosterone blood test

    Science.gov (United States)

    ... Pregnancy High- or low-sodium diet Strenuous exercise Stress How the Test will Feel When the needle is inserted to ... pressure. Aldosterone increases the reabsorption of sodium and water and the release of potassium in the kidneys. ...

  3. Recurrence of adrenal aldosterone-producing adenoma

    OpenAIRE

    Calvo-Romero, J. M.; Ramos-Salado, J. L.

    2000-01-01

    Conn's syndrome (adrenal aldosterone-producing adenoma) and bilateral adrenal hyperplasia are the most common causes of primary aldosteronism. The treatment of choice for patients with aldosterone-producing adenoma is unilateral total adrenalectomy. Recurrence after adequate surgery is exceptional. We present a patient with recurrence of an aldosterone-producing adenoma in the right adrenal gland 9 years after adenomectomy of a aldosterone-producing adenoma in the same adrenal gland. We concl...

  4. Primary aldosteronism and pregnancy.

    Science.gov (United States)

    Landau, Ester; Amar, Laurence

    2016-06-01

    Hypertension (HT) is a complication of 8% of all pregnancies and 10% of HT cases are due to primary aldosteronism (PA). There is very little data on PA and pregnancy. Given the changes in the renin angiotensin system during pregnancy, the diagnosis of PA is difficult to establish during gestation. It may be suspected in hypertensive patients with hypokalemia. A comprehensive literature review identified reports covering 40 pregnancies in patients suffering from PA. Analysis of these cases shows them to be high-risk pregnancies leading to maternal and fetal complications. Pregnancy must be programmed, and if the patient has a unilateral form of PA, adrenalectomy should be performed prior to conception. It is customary to stop spironolactone prior to conception and introduce antihypertensive drugs that present no risk of teratogenicity. When conventional antihypertensive drugs used during pregnancy fail to control high blood pressure, diuretics, including potassium-sparing diuretics may be prescribed. Adrenalectomy can be considered during the second trimester of pregnancy exclusively in cases of refractory hypertension. A European retrospective study is currently underway to collect a larger number of cases. PMID:27156905

  5. Recent Developments in Primary Aldosteronism.

    Science.gov (United States)

    Asbach, E; Williams, T A; Reincke, M

    2016-06-01

    Primary aldosteronism (PA) is the most frequent endocrine cause of secondary arterial hypertension. Sporadic forms of PA caused mainly by an aldosterone producing adenoma (APA) or idiopathic adrenal hyperplasia (IAH) predominate; in contrast, familial forms (familial hyperaldosteronism types I, II and III) affect only a minor proportion of PA patients. Patient based registries and biobanks, international networks and next generation sequencing technologies have emerged over recent years. Somatic hot-spot mutations in the potassium channel GIRK4 (encoded by KCNJ5), in ATPases and a L-type voltage-gated calcium-channel correlate with the autonomous aldosterone production in approximately half of all APAs. The recently discovered form FH III is caused by different germline KCNJ5 mutations with variable clinical presentations and severity. Autoantibodies to the angiotensin II Type 1 receptor have been identified in patients with PA and possibly play a pathophysiological role in the development of PA. Adrenal vein sampling (AVS) represents the gold standard in differentiating unilateral and bilateral forms of PA. Recent consensus papers have tried to implement current guidelines in order to standardise the technique of AVS. New techniques like segmental AVS might allow a finer mapping of the aldosterone production within the adrenal gland. The measurement of the steroids 18-hydroxycortisol and 18-oxocortisol by liquid chromatography tandem mass spectrometry has been shown to be useful to distinguish between unilateral and bilateral forms of PA. PMID:27219889

  6. 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...

  7. 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.

  8. Familial varieties of primary aldosteronism.

    Science.gov (United States)

    Stowasser, M; Gunasekera, T G; Gordon, R D

    2001-12-01

    1. Improved approaches to screening and diagnosis have revealed primary aldosteronism (PAL) to be much more common than previously thought, with most patients normokalaemic. The spectrum of this disorder has been further broadened by the study of familial varieties. 2. Familial hyperaldosteronism type I (FH-I) is a glucocorticoid-remediable form of PAL caused by the inheritance of an adrenocorticotrophic hormone (ACTH)- regulated, hybrid CYP11B1/CYP11B2 gene. Diagnosis has been greatly facilitated by the advent of genetic testing. The severity of hypertension varies widely in FH-I, even among members of the same family, and has demonstrated relationships with gender, degree of biochemical disturbance and hybrid gene crossover point position. Hormone "day curve" studies show that the hybrid gene dominates over wild-type CYP11B2 in terms of aldosterone regulation. This may be due, in part, to a defect in wild-type CYP11B2-induced aldosterone production. Control of hypertension in FH-I requires only partial suppression of ACTH and much smaller glucocorticoid doses than previously recommended. 3. Familial hyperaldosteronism type II (FH-II) is not glucocorticoid remediable and is not associated with the hybrid gene mutation. Familial hyperaldosteronism type II is clinically, biochemically and morphologically indistinguishable from apparently non-familial PAL. Linkage studies in one informative family did not show segregation of FH-II with the CYP11B2, AT1 or MEN1 genes, but a genome-wide search has revealed linkage with a locus in chromosome 7. As has already occurred in FH-I, elucidation of causative mutations is likely to facilitate earlier detection of PAL. PMID:11903322

  9. Aldosterone and type 2 diabetes mellitus.

    Science.gov (United States)

    Zavatta, Guido; Casadio, Elena; Rinaldi, Eleonora; Pagotto, Uberto; Pasquali, Renato; Vicennati, Valentina

    2016-04-01

    Primary hyperaldosteronism (PA) has recently been demonstrated to be strictly associated to metabolic syndrome as compared with essential hypertension (EH). Besides, the characteristics of metabolic syndrome are different in PA compared to EH, as high fasting glucose is more frequent in the former condition. The adverse effect of excess aldosterone on insulin metabolic signaling has generated increasing interest in the role of hyperaldosteronism in the pathogenesis of insulin resistance and resistant hypertension. Moreover, aldosterone receptor antagonist therapy in diabetic and cardiopathic patients improved coronary flow. The aim of this review is to present recent knowledge about the relationship between aldosterone, insulin resistance and diabetes. PMID:26876814

  10. Inflammatory markers in primary aldosteronism.

    Science.gov (United States)

    Šomlóová, Z; Petrák, O; Rosa, J; Štrauch, B; Indra, T; Zelinka, T; Haluzík, M; Zikán, V; Holaj, R; Widimský, J

    2016-06-20

    Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. The unfavorable cardiometabolic profile may be due to aldosterone-mediated activation of inflammatory cells, circulatory cytokines and activation of collagen synthesis in the vessel wall. Aim of our study was to evaluate differences in the levels of hsCRP, IL-6, TNF-alpha and N-terminal propeptide of collagen I (PINP) in patients with PA and essential hypertension (EH) as a control group, and between the subtypes of PA (aldosterone producing adenoma - APA, idiopathic hyperaldosteronism - IHA). We studied 28 patients with PA (IHA - 10 patients, APA - 12 patients, 6 unclassified) and 28 matched patients with EH. There were no differences in the levels of inflammatory markers between the followed groups [EH vs. PA: TNF-alpha (5.09 [3.68-6.32] vs. 4.84 [3.62-6.50] pg/ml), IL-6 (0.94 [0.70-1.13] vs. 0.97 [0.71-1.28] pg/ml), hsCRP (0.53 [0.25-1.54] vs. 0.37 [0.31-0.61] mg/l), leukocytes (6.35+/-1.42 vs. 5.97+/-1.29 10(9) l); APA vs. IHA: TNF-alpha (4.54 [3.62-7.03] vs. 5.19 [4.23-5.27] pg/ml), IL-6 (0.96 [0.63-1.21] vs. 0.90 [0.65-1.06] pg/ml), hsCRP (0.34 [0.29-0.47] vs. 0.75 [0.36-1.11] mg/l), leukocytes (6.37+/-1.41 vs. 5.71+/-1.21 10(9) l)]. Significant differences in the levels of PINP between PA and EH group were observed (35.18 [28.46-41.16] vs. 45.21 [36.95-62.81] microg/l, p

  11. Direct microassay for aldosterone in plasma extracts

    International Nuclear Information System (INIS)

    We previously described an RIA for aldosterone based on highly specific antibodies elicited with aldosterone-3,20 dioxime bovine γ-globulin (Poulsen, K., J. Sancho, and E. Haber, Clin Immunol Immunopathol 2: 373, 1974). We now report the development of higher affinity antibodies of similar specificity that allow the direct measurement of normal aldosterone concentrations in extracts of 100 μl plasma. The detection limit at +-2 SD of mean zero value was 0.2 to 0.3 pg. The assay was validated by (1) zero values in adrenalectomized plasma, (2) parallel displacement plots of aldosterone standards and plasma extracts, (3) 97.7 +- 2.5% recovery of added tracer, (4) a correlation coefficient of 0.992 and a slope of 1.08 in a plot of added vs. recovered unlabeled aldosterone, (5) 10.2% interassay variation and 5.6% intrassay variation, and (6) failure of high concentrations of a variety of steroids added to plasma to perturb the measured aldosterone concentration. The simplicity of the assay results in a high degree of productivity, in that 195 plasma samples may be processed in duplicate, in addition to standard curves, in a single working day

  12. 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; Gammelgaard, P A; Hasner, E; Hesse, B; Tønnesen, K H

    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 adenom...

  13. Aldosterone and the conquest of land.

    Science.gov (United States)

    Colombo, L; Dalla Valle, L; Fiore, C; Armanini, D; Belvedere, P

    2006-04-01

    The sequence of the phylogenetic events that preceded the appearance of aldosterone in vertebrates is described, starting from the ancestral conversion of cytochrome P450s from oxygen detoxification to xenobiotic detoxification and synthesis of oxygenated endobiotics with useful functions in intercellular signalling, such as steroid hormones. At the end of the Silurian period [438-408 million yr ago, (Mya)], a complete set of cytochrome P450s for corticoid synthesis was presumably already available, except for mitochondrial cytochrome P450c18 or aldosterone synthase encoded by CYP11B2. This gene arose by duplication of the CYP11B gene in the sarcopterygian or lobe-finned fish/tetrapod line after its divergence from the actinopterygian or ray-finned fish line 420 Mya, but before the beginning of the colonization of land by tetrapods in the late Devonian period, around 370 Mya. The fact that aldosterone is already present in Dipnoi, which occupy an evolutionary transition between water- and air-breathing but are fully aquatic, suggests that the role of this steroid was to potentiate the corticoid response to hypoxia, rather than to prevent dehydration out of the water. In terrestrial amphibians, there is no differentiation between the secretion rates and gluco- and mineralocorticoid effects of aldosterone and corticosterone. In sauropsids, plasma aldosterone concentrations are much lower than in amphibians, but regulation of salt/water balance is dependent upon both aldosterone and corticosterone, though sometimes with opposed actions. In terrestrial mammals, aldosterone acquires a specific mineralocorticoid function, because its interaction with the mineralocorticoid receptor is protected by the coexpression of the enzyme 11beta-hydroxysteroid dehydrogenase type 2, which inactivates both cortisol and corticosterone. There is evidence that aldosterone can be also synthesized extra-adrenally in brain neurons and cardiac myocytes, which lack this protection and where

  14. Some considerations about evolution of idiopathic primary aldosteronism.

    Science.gov (United States)

    Armanini, D; Fiore, C

    2009-07-01

    The prevalence of primary aldosteronism has increased since many patients who were previously considered as being affected by low renin essential hypertension are actually satisfying the new diagnostic criteria using plasma aldosterone/ plasma renin activity (PRA) ratio. Many of these cases could be classified as subclinical hyperaldosteronism, having normal aldosterone and low PRA, or in alternative the normal range of aldosterone should be revised. Idiopathic hyperaldosteronism can, in many cases, be considered as an evolutive disease: it can be hypothesized that the biochemical picture can be preceded by essential hypertension and that, after several years, primary aldosteronism can evolve back to essential hypertension due to age-related reduced vascular and adrenal sensitivity to angiotensin II. This effect is also evident after longterm treatment with aldosterone receptors blockers and therefore it possible that aldosterone-receptors blockers are able to normalize the sensitivity of glomerulosa to angiotensin II even after long-term withdrawal. The use of aldosterone receptors blockers prevents cardiovascular complications due to local aldosterone effect at the level of endothelium and mononuclear leukocytes; therefore, these drugs should be also considered for therapy of patients with hypertension. It is not excluded that aldosterone receptor blockers could prevent the onset of idiopathic hyperaldosteronism and its complications in patients with hypertension without primary hyperaldosteronism. From all these considerations it follows that the concept of normal range of aldosterone should be revised and the use of aldosterone receptor blockers should be revisited. PMID:19893360

  15. Recent advances in diagnosis and treatment of primary aldosteronism.

    Science.gov (United States)

    Veglio, F; Morello, F; Rabbia, F; Leotta, G; Mulatero, P

    2003-08-01

    Primary aldosteronism is the most common form of secondary hypertension. The use of aldosterone/plasma renin activity ratio (ARR) as a screening test has elevated its prevalence up to 10% of hypertensive patients. Idiopathic bilateral adrenal hyperplasia and aldosterone-producing adrenal adenoma are the leading causes of primary aldosteronism. Most patients with this conditions are normokalemic and clinically undistinguishable from essential hypertensives. However, they suffer from anticipated and more severe target organ damage than other hypertensives. Thus, being primary aldosteronism a common, specifically treatable and sometimes surgically cured form of hypertension, a prompt diagnosis is necessary and cannot be overlooked. The measurement of ambulatory ARR represents the screening test and should be performed in the majority of hypertensive patients. ARR higher than a set cutoff suggests the need of a confirmatory test for primary aldosteronism, such as intravenous saline load or fludrocortisone suppression test. If inability to suppress aldosterone is demonstrated, the disease is confirmed. The subtype evaluation is based on adrenal imaging (CT scan) and selective adrenal venous sampling. The latter is the gold standard for the diagnosis of a lateralized aldosterone secretion, as typically observed in aldosterone-producing adenomas. Microadenomas are frequently overlooked by adrenal image. If lateralization is confirmed, unilateral adrenalectomy is the reasonable therapeutic option, leading to a significant reduction of blood pressure, if not normotension. If bilateral aldosterone excess is demonstrated, an aldosterone receptor antagonist should be administered. This article reviews and discusses the new data about prevalence, diagnosis and treatment of primary aldosteronism. PMID:14605590

  16. Computer tomographic localisation in primary aldosteronism

    International Nuclear Information System (INIS)

    13 patients with verified primary aldosteronism (unilateral adrenal adenoma = 10, bilateral idiopathic hyperplasia = 3) underwent examination by CT and 131J-cholesterol-scintigraphy. CT-scan can be successfully employed for localization of unilateral adenoma exceeding 10 mm in diameter. Small lesions and hyperplasia are rare CT-findings. The value of 131J-cholesterol-scintigraphy for differentiation of the two main subgroups of primary aldosteronism - adenoma and hyperplasia - is limited. In our experience both noninvasive methods are helpful to avoid misleading interpretation. In controversial cases bilateral adrenal venous blood sampling by catheterization is mandatory. (orig.)

  17. Aortic Cell Apoptosis in Rat Primary Aldosteronism Model

    Institute of Scientific and Technical Information of China (English)

    闫永吉; 欧阳金芝; 王超; 吴准; 马鑫; 李宏召; 徐华; 胡争; 李俊; 王保军; 史涛坪; 龚道静; 倪栋; 张旭

    2010-01-01

    This study aimed to determine whether aldosterone could induce vascular cell apoptosis in vivo.Thirty-two male rats were randomly divided into 4 groups:vehicle(control),aldosterone,aldosterone plus eplerenone or hydralazine.They were then implanted with an osmotic mini-pump that infused either aldosterone or the vehicle.Systolic blood pressure(SBP) was measured weekly by the tail-cuff method.After 8 weeks,plasma aldosterone concentration(PAC) and renin activity(PRA) were determined by radioimmunoassay.Aorti...

  18. 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

  19. 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.

  20. 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.

  1. Epicardial Fat Thickness and Primary Aldosteronism.

    Science.gov (United States)

    Iacobellis, G; Petramala, L; Marinelli, C; Calvieri, C; Zinnamosca, L; Concistrè, A; Iannucci, G; De Toma, G; Letizia, C

    2016-04-01

    Primary aldosteronism (PA) is associated with increased cardiovascular risk and left ventricle (LV) changes. Given its peculiar biomolecular and anatomic properties, excessive epicardial fat, the heart-specific visceral fat depot, can affect LV morphology. Whether epicardial fat can be associated with aldosterone and LV mass (LVM) in patients with PA is unknown. We performed ultrasound measurement of the epicardial fat thickness (EAT) in 79 consecutive newly diagnosed patients with PA, 59 affected by bilateral adrenal hyperplasia (IHA), 20 aldosterone-producing adenoma (APA), and 30 patients with essential hypertension (low renin hypertension) (EH). The 3 groups did not differ by age, sex distribution, body mass index (BMI), waist circumference (WC), or blood pressure values. EAT showed a trend of increase in both APA and IHA groups when compared to patients with EH (8.3±1.8 vs. 7.9±1.3 vs. 7.8±2 mm, respectively). EAT was significantly correlated with indexed LVM in the IHA group (r=0.35, p<005), better than BMI or WC were. Interestingly, EAT was highly associated with plasma aldosterone concentrations (PAC) and PAC/plasma renin activity (PRA) (PAC/PRA) in the APA group (p=0.58, p=0.37, p<0.01, for both), whereas BMI and WC were not. EAT was also correlated with PRA in the IHA group (p=-0.28, p<0.05). Our study indicates a novel and interesting interaction of EAT with PA, independent of obesity, abdominal fat and blood pressure control. EAT can locally affect LVM, at least in patients with IHA. Further studies in larger population will be required to confirm these findings. PMID:26983926

  2. Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism.

    Science.gov (United States)

    Mulatero, Paolo; Rabbia, Franco; Milan, Alberto; Paglieri, Cristina; Morello, Fulvio; Chiandussi, Livio; Veglio, Franco

    2002-12-01

    Primary aldosteronism is a specifically treatable and potentially curable form of secondary hypertension. The aldosterone/plasma renin activity ratio (ARR) is routinely used as a screening test. Antihypertensive therapy can interfere with the interpretation of this parameter, but a correct washout period can be potentially harmful. We have investigated the effects of therapy with atenolol, amlodipine, doxazosin, fosinopril, and irbesartan on the ARR in a group of 230 patients with suspected primary aldosteronism. The percent change from control of ARR in patients taking amlodipine was -17%+/-32; atenolol, 62%+/-82; doxazosin, -5%+/-26; fosinopril, -30%+/-24; and irbesartan, -43%+/-27. The ARR change induced by atenolol was significantly higher compared with that induced by all other drugs (P<0.0001), and the ARR change induced by irbesartan was significantly lower than that induced by doxazosin (P<0.0001). One of 55 patients from the group taking amlodipine (1.8%) and 4/17 of the patients taking irbesartan (23.5%) gave a false-negative ARR (<50). None of the patients of the groups taking fosinopril, doxazosin, and atenolol displayed a false-negative ARR. Doxazosin and fosinopril can be used in hypertensive patients who need to undergo aldosterone and PRA measurement for the diagnosis of primary aldosteronism; amlodipine gave a very small percentage of false-negative diagnoses. beta-Blockers also do not interfere with the diagnosis of primary aldosteronism, but they can be responsible for an increased rate of false-positive ARRs. The high rate of false-negative diagnoses in patients undergoing irbesartan treatment requires confirmation in a higher number of patients. PMID:12468576

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

    OpenAIRE

    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 investi...

  4. 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.

  5. 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.

  6. 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.

  7. Increased plasma aldosterone during atrial fibrillation declines following cardioversion

    DEFF Research Database (Denmark)

    Soeby-Land, C; Dixen, U; Therkelsen, S K;

    2011-01-01

    The renin-angiotensin-aldosterone system (RAAS) may be activated during atrial fibrillation (AF); our aim was to evaluate the level of aldosterone in patients with either permanent AF, persistent AF scheduled for cardioversion or patients in sinus rhythm (SR). We hypothesized that an increased...

  8. Primary aldosteronism - recent progress and current concepts.

    Science.gov (United States)

    Kołodziejczyk-Kruk, Sylwia; Januszewicz, Włodzimierz; Pęczkowska, Mariola; Prejbisz, Aleksander; Zgliczyński, Wojciech; Januszewicz, Andrzej

    2013-01-01

    Primary aldosteronism is the commonest form of hormone-related hypertension, with an estimated prevalence of 6-13% in the generalpopulation of hypertensive patients. Among patients with resistant hypertension, the proportion of PA is even higher. Through intensiveresearch in the field of basic science and the creation of large registries of patients with PA, it is possible to understand the effect ofexcess aldosterone not only on the cardiovascular system but also on the morphology and function of the other organs. Recent researchhas highlighted the differences in the regulation of calcium metabolism in patients with adrenal adenomas and PA. A lot of attention hasbeen paid to the improvement of diagnostic methods, with particular emphasis on adrenal vein sampling, which is becoming increasinglyimportant. In recent years there have been many publications on the prevalence of mutations in the potassium channel in patients withadrenal tumours and PA. A new form of familial hyperaldosteronism - FIII, has also been distinguished. Treatment of patients with PAstill relies on the use of mineralocorticoid receptor antagonists or adrenalectomy, preferably preceded by a confirmation of aldosteronesecretion lateralisation by adrenal vein sampling. PMID:24002960

  9. A particular phenotype in a girl with aldosterone synthase deficiency.

    Science.gov (United States)

    Williams, Tracy A; Mulatero, Paolo; Bosio, Maurizio; Lewicka, Sabina; Palermo, Mario; Veglio, Franco; Armanini, Decio

    2004-07-01

    Aldosterone synthase deficiency (ASD) usually presents in infancy as a life-threatening electrolyte imbalance. A 4-wk-old child of unrelated parents was examined for failure to thrive and salt-wasting. Notable laboratory findings were hyperkalemia, high plasma renin, and low-normal aldosterone levels. Urinary metabolite ratios of corticosterone/18-hydroxycorticosterone and 18-hydroxycorticosterone/aldosterone were intermediate between ASD type I and type II. Sequence analysis of CYP11B2, the gene encoding aldosterone synthase (P450c11AS), revealed that the patient was a compound heterozygote carrying a previously described mutation located in exon 4 causing a premature stop codon (E255X) and a further, novel mutation in exon 5 that also causes a premature stop codon (Q272X). The patient's unaffected father was a heterozygous carrier of the E255X mutation, whereas the unaffected mother was a heterozygous carrier of the Q272X mutation. Therefore, the patient's CYP11B2 encodes two truncated forms of aldosterone synthase predicted to be inactive because they lack critical active site residues as well as the heme-binding site. This case of ASD is of particular interest because despite the apparent lack of aldosterone synthase activity, the patient displays low-normal aldosterone levels, thus raising the question of its source. PMID:15240589

  10. Renin and aldosterone at high altitude in man.

    Science.gov (United States)

    Keynes, R J; Smith, G W; Slater, J D; Brown, M M; Brown, S E; Payne, N N; Jowett, T P; Monge, C C

    1982-01-01

    Measurements have been made of hormonal changes relevant to salt and water balance during prolonged exposure to hypoxia to improve our understanding of the syndrome of acute mountain sickness. We have attempted to delineate the detailed inter-relationships between the renin-aldosterone and the vasopressin systems by a metabolically controlled study, involving an orthostatic stress (45 degrees head-up tilt) and an injection of a standard dose of ACTH to test adrenal responsiveness. Three Caucasian medical students underwent a 7-day equilibration at 150 m (Lima, Peru), followed by a 6-day sojourn at 4350 m (Cerro de Pasco, Peru) and a final 7 days at 150 m. Measurements were made of sodium and potassium balance, body weight and the 24-h renal excretion of vasopressin, cortisol and aldosterone 18-glucuronide. These variables showed little change, except for that of aldosterone 18-glucuronide, which fell sharply at altitude and rebounded even more sharply on return to sea level. At altitude, basal plasma levels of renin activity and aldosterone fell, and the response to orthostasis was attenuated, but the fall of plasma renin activity, as compared to plasma aldosterone, was delayed; on return to sea level this dissociation was exacerbated with the return of normal renin responsiveness lagging behind that of aldosterone. We suggest that unknown factors which dissociate the orthodox renin-aldosterone relationship, other than the activity of the angiotensin I-converting enzyme, are operative on exposure to hypoxia. PMID:7057120

  11. History of aldosterone on its 50th birthday.

    Science.gov (United States)

    Fiore, Cristina; Calò, Lorenzo A; Colombo, Lorenzo; Grimm, Clarence E; Armanini, Decio

    2006-01-01

    The paper describes the impact of mineralocorticoid substances on water regulation from Theophrastus (IV century B.C.) to Thomas Addison (1849). It also opens to the missed discovery of aldosterone of I.A. Macchi. PMID:16874725

  12. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism

    Science.gov (United States)

    Scholl, Ute I.; Goh, Gerald; Stölting, Gabriel; de Oliveira, Regina Campos; Choi, Murim; Overton, John D.; Fonseca, Annabelle L.; Korah, Reju; Starker, Lee F.; Kunstman, John W.; Prasad, Manju L.; Hartung, Erum A.; Mauras, Nelly; Benson, Matthew R.; Brady, Tammy; Shapiro, Jay R.; Loring, Erin; Nelson-Williams, Carol; Libutti, Steven K.; Mane, Shrikant; Hellman, Per; Westin, Gunnar; Åkerström, Göran; Björklund, Peyman; Carling, Tobias; Fahlke, Christoph; Hidalgo, Patricia; Lifton, Richard P.

    2013-01-01

    Adrenal aldosterone-producing adenomas (APAs) constitutively produce the salt-retaining hormone aldosterone and are a common cause of severe hypertension. Recurrent mutations in the potassium channel KCNJ5 that result in cell depolarization and Ca2+ influx cause ~40% of these tumors1. We found five somatic mutations (four altering glycine 403, one altering isoleucine 770) in CACNA1D, encoding a voltage-gated calcium channel, among 43 non-KCNJ5-mutant APAs. These mutations lie in S6 segments that line the channel pore. Both result in channel activation at less depolarized potentials, and glycine 403 mutations also impair channel inactivation. These effects are inferred to cause increased Ca2+ influx, the sufficient stimulus for aldosterone production and cell proliferation in adrenal glomerulosa2. Remarkably, we identified de novo mutations at the identical positions in two children with a previously undescribed syndrome featuring primary aldosteronism and neuromuscular abnormalities. These findings implicate gain of function Ca2+ channel mutations in aldosterone-producing adenomas and primary aldosteronism. PMID:23913001

  13. 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.

  14. Rapid actions of aldosterone in vascular health and disease - friend or foe?

    DEFF Research Database (Denmark)

    Skøtt, Ole; Uhrenholt, Torben Rene; Schjerning, Jeppe;

    2006-01-01

    The mineralocorticoid receptor (MR) and the enzyme 11betahydroxysteroid dehydrogenase type 2, which confers aldosterone specificity to the MR, are present in endothelium and vascular smooth muscle. In several pathological conditions aldosterone promotes vascular damage by formation of reactive ox...

  15. Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently.

    Science.gov (United States)

    Lee, Seung Eun; Kim, Jae Hyeon; Lee, You Bin; Seok, Hyeri; Shin, In Seub; Eun, Yeong Hee; Kim, Jung Han; Oh, Young Lyun

    2015-12-01

    A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses. PMID:26248855

  16. Evaluation of aldosterone excretion in very low birth weight infants.

    Science.gov (United States)

    Abdel Mohsen, Abdel Hakeem; Taha, Gamal; Kamel, Bothina A; Maksood, Mohamed Abdel

    2016-01-01

    Data about aldosterone production and excretion in the neonatal period are still few and controversial. Our objectives are to assess urinary aldosterone excretion (UAE) in very low birth weight (VLBW) infants and to identify clinical and biochemical variables that may influence this excretion. Thirty VLBW infants (14 males and 16 females), their gestational age value was 0.176 ± 0.05 μg/24 h and the mean absolute UAE was 1906 ± 271 pg/mL. There was a statistically significant positive correlation between UAE and gestational age and birth weight; also, infants with respiratory distress syndrome had higher urinary aldosterone levels than infants without respiratory distress. Only plasma sodium was a significant independent factor that negatively influenced UAE on linear regression analysis. The renin-angiotensin-aldosterone system of VLBW infants seems to be able, even immediately after birth, to respond to variations of plasma sodium concentrations; measurement of UAE constitutes an interesting method to determine aldosterone production in VLBW infants. PMID:27424689

  17. The Role of Aldosterone in Obesity-Related Hypertension.

    Science.gov (United States)

    Kawarazaki, Wakako; Fujita, Toshiro

    2016-04-01

    Obese subjects often have hypertension and related cardiovascular and renal diseases, and this has become a serious worldwide health problem. In obese subjects, impaired renal-pressure natriuresis causes sodium retention, leading to the development of salt-sensitive hypertension. Physical compression of the kidneys by visceral fat and activation of the sympathetic nervous system, renin-angiotensin systems (RAS), and aldosterone/mineralocorticoid receptor (MR) system are involved in this mechanism. Obese subjects often exhibit hyperaldosteronism, with increased salt sensitivity of blood pressure (BP). Adipose tissue excretes aldosterone-releasing factors, thereby stimulating aldosterone secretion independently of the systemic RAS, and aldosterone/MR activation plays a key role in the development of hypertension and organ damage in obesity. In obese subjects, both salt sensitivity of BP, enhanced by obesity-related metabolic disorders including aldosterone excess, and increased dietary sodium intake are closely related to the incidence of hypertension. Some salt sensitivity-related gene variants affect the risk of obesity, and together with salt intake, its combination is possibly associated with the development of hypertension in obese subjects. With high salt levels common in modern diets, salt restriction and weight control are undoubtedly important. However, not only MR blockade but also new diagnostic modalities and therapies targeting and modifying genes that are related to salt sensitivity, obesity, or RAS regulation are expected to prevent obesity and obesity-related hypertension. PMID:26927805

  18. Effect and mechanism of poly (ADP-ribose) polymerase-1 in aldosterone-induced apoptosis

    OpenAIRE

    Qiao, Weiwei; Zhang, Weili; Shao, Shuhong; GAI, YUSHENG; Zhang, Mingxiang

    2015-01-01

    The present study aimed to investigate the effects of aldosterone on vascular endothelial cells and the viability of poly (ADP-ribose) polymerase 1 (PARP1) in cells, and to examine the molecular mechanisms underlying the effects of aldosterone on vascular endothelial cell injury. Cultured endothelial cells were treated either with different concentrations of aldosterone for the same duration or with the same concentrations of aldosterone for different durations, and the levels of apoptosis an...

  19. Alterations in vascular function in primary aldosteronism: a cardiovascular magnetic resonance imaging study

    OpenAIRE

    Mark, P. B.; Boyle, S; Zimmerli, L U; McQuarrie, E.P.; Delles, C.; Freel, E. M.

    2014-01-01

    Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV). Methods: We studied PA (n=14)...

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

    International Nuclear Information System (INIS)

    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), P450C17) 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)

  1. Severe hypertension in primary aldosteronism and good response to surgery.

    Science.gov (United States)

    Clarke, D; Wilkinson, R; Johnston, I D; Hacking, P M; Haggith, J W

    1979-03-01

    11 patients with primary aldosteronism have been encountered over 11 years and submitted to surgery in a provincial teaching hospital serving a population of 3 million. Contrary to classical teaching, the hypertension has usually been very severe. Precise identification of the site of the lesion preoperatively has been possible by the measurement of adrenal-vein aldosterone levels, and results of surgery have been excellent. The iodocholesterol adrenal scan also correctly identified the site of the adenoma in 5 out of 7 patients in which it was used. Adrenal venography was of little value except in siting catheters. PMID:85065

  2. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism

    OpenAIRE

    Scholl, Ute I; Goh, Gerald; Stölting, Gabriel; de Oliveira, Regina Campos; Choi, Murim; Overton, John D; Fonseca, Annabelle L.; Korah, Reju; Lee F. Starker; Kunstman, John W.; Prasad, Manju L.; Hartung, Erum A.; Mauras, Nelly; Benson, Matthew R.; Brady, Tammy

    2013-01-01

    Adrenal aldosterone-producing adenomas (APAs) constitutively produce the salt-retaining hormone aldosterone and are a common cause of severe hypertension. Recurrent mutations in the potassium channel KCNJ5 that result in cell depolarization and Ca2+ influx cause ~40% of these tumors 1 . We found five somatic mutations (four altering glycine 403, one altering isoleucine 770) in CACNA1D, encoding a voltage-gated calcium channel, among 43 non-KCNJ5-mutant APAs. These mutations lie in S6 segments...

  3. 21 CFR 862.1045 - Aldosterone test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Aldosterone test system. 862.1045 Section 862.1045 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  4. Activating mutations in CTNNB1 in aldosterone producing adenomas.

    Science.gov (United States)

    Åkerström, Tobias; Maharjan, Rajani; Sven Willenberg, Holger; Cupisti, Kenko; Ip, Julian; Moser, Ana; Stålberg, Peter; Robinson, Bruce; Alexander Iwen, K; Dralle, Henning; Walz, Martin K; Lehnert, Hendrik; Sidhu, Stan; Gomez-Sanchez, Celso; Hellman, Per; Björklund, Peyman

    2016-01-01

    Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalence of 5-10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitute a large proportion of PA cases and represent a surgically correctable form of the disease. The WNT signaling pathway is activated in APAs. In other tumors, a frequent cause of aberrant WNT signaling is mutation in the CTNNB1 gene coding for β-catenin. Our objective was to screen for CTNNB1 mutations in a well-characterized cohort of 198 APAs. Somatic CTNNB1 mutations were detected in 5.1% of the tumors, occurring mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. All of the observed mutations altered serine/threonine residues in the GSK3β binding domain in exon 3. The mutations were associated with stabilized β-catenin and increased AXIN2 expression, suggesting activation of WNT signaling. By CYP11B2 mRNA expression, CYP11B2 protein expression, and direct measurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone production. This report provides compelling evidence that aberrant WNT signaling caused by mutations in CTNNB1 occur in APAs. This also suggests that other mechanisms that constitutively activate the WNT pathway may be important in APA formation. PMID:26815163

  5. Activating mutations in CTNNB1 in aldosterone producing adenomas

    Science.gov (United States)

    Åkerström, Tobias; Maharjan, Rajani; Sven Willenberg, Holger; Cupisti, Kenko; Ip, Julian; Moser, Ana; Stålberg, Peter; Robinson, Bruce; Alexander Iwen, K.; Dralle, Henning; Walz, Martin K.; Lehnert, Hendrik; Sidhu, Stan; Gomez-Sanchez, Celso; Hellman, Per; Björklund, Peyman

    2016-01-01

    Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalence of 5–10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitute a large proportion of PA cases and represent a surgically correctable form of the disease. The WNT signaling pathway is activated in APAs. In other tumors, a frequent cause of aberrant WNT signaling is mutation in the CTNNB1 gene coding for β-catenin. Our objective was to screen for CTNNB1 mutations in a well-characterized cohort of 198 APAs. Somatic CTNNB1 mutations were detected in 5.1% of the tumors, occurring mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. All of the observed mutations altered serine/threonine residues in the GSK3β binding domain in exon 3. The mutations were associated with stabilized β-catenin and increased AXIN2 expression, suggesting activation of WNT signaling. By CYP11B2 mRNA expression, CYP11B2 protein expression, and direct measurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone production. This report provides compelling evidence that aberrant WNT signaling caused by mutations in CTNNB1 occur in APAs. This also suggests that other mechanisms that constitutively activate the WNT pathway may be important in APA formation. PMID:26815163

  6. The renaissance of primary aldosteronism: what has it taught us?

    Science.gov (United States)

    Stowasser, Michael; Gordon, Richard Douglas

    2013-06-01

    The growing realisation since the early 1990s that primary aldosteronism (PA) is a much more common cause of hypertension than previously thought, and that aldosterone excess has adverse effects that are at least partly independent of blood pressure, has been the main driving force for a renaissance in clinical and research interest in PA. This has generated a wealth of new knowledge regarding (1) PA's high prevalence, (2) the extent of non-BP dependent cardiovascular and renal organ damage and morbidity and reduced quality of life associated with PA, all of which appear to be at least partly ameliorated by specific treatment (especially surgical) directed against excessive aldosterone action, (3) the diversity of adrenal histopathology associated with PA and the need to subdivide patients based on glucocorticoid remediability (by genetic testing for the hybrid gene mutation causing familial hyperaldosteronism type I, FH-I) and lateralisation on adrenal venous sampling in order to ensure optimal treatment, (4) the value of elucidating genetic bases for PA in terms of improving detection, understanding of pathogenesis and treatment, as illustrated by the determination of the genetic basis of FH-I, and (5) the genetic basis of more common forms including aldosterone-producing adenoma. From the clinical perspective, the principal lesson learnt is that PA, being a common cause of cardiovascular morbidity and reduced quality of life reversible by specific treatment, is worth looking for. PMID:23402683

  7. Reversible heart rhythm complexity impairment in patients with primary aldosteronism

    Science.gov (United States)

    Lin, Yen-Hung; Wu, Vin-Cent; Lo, Men-Tzung; Wu, Xue-Ming; Hung, Chi-Sheng; Wu, Kwan-Dun; Lin, Chen; Ho, Yi-Lwun; Stowasser, Michael; Peng, Chung-Kang

    2015-08-01

    Excess aldosterone secretion in patients with primary aldosteronism (PA) impairs their cardiovascular system. Heart rhythm complexity analysis, derived from heart rate variability (HRV), is a powerful tool to quantify the complex regulatory dynamics of human physiology. We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that underwent adrenalectomy and 25 patients with essential hypertension (EH). The heart rate data were analyzed by conventional HRV and heart rhythm complexity analysis including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We found APA patients had significantly decreased DFAα2 on DFA analysis and decreased area 1-5, area 6-15, and area 6-20 on MSE analysis (all p < 0.05). Area 1-5, area 6-15, area 6-20 in the MSE study correlated significantly with log-transformed renin activity and log-transformed aldosterone-renin ratio (all p < = 0.01). The conventional HRV parameters were comparable between PA and EH patients. After adrenalectomy, all the altered DFA and MSE parameters improved significantly (all p < 0.05). The conventional HRV parameters did not change. Our result suggested that heart rhythm complexity is impaired in APA patients and this is at least partially reversed by adrenalectomy.

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

    International Nuclear Information System (INIS)

    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.)

  9. SFE/SFHTA/AFCE primary aldosteronism consensus: Introduction and handbook.

    Science.gov (United States)

    Amar, Laurence; Baguet, Jean Philippe; Bardet, Stéphane; Chaffanjon, Philippe; Chamontin, Bernard; Douillard, Claire; Durieux, Pierre; Girerd, Xaxier; Gosse, Philippe; Hernigou, Anne; Herpin, Daniel; Houillier, Pascal; Jeunemaitre, Xavier; Joffre, Francis; Kraimps, Jean-Louis; Lefebvre, Hervé; Ménégaux, Fabrice; Mounier-Véhier, Claire; Nussberger, Juerg; Pagny, Jean-Yves; Pechère, Antoinette; Plouin, Pierre-François; Reznik, Yves; Steichen, Olivier; Tabarin, Antoine; Zennaro, Maria-Christina; Zinzindohoue, Franck; Chabre, Olivier

    2016-07-01

    The French Endocrinology Society (SFE) French Hypertension Society (SFHTA) and Francophone Endocrine Surgery Association (AFCE) have drawn up recommendations for the management of primary aldosteronism (PA), based on an analysis of the literature by 27 experts in 7 work-groups. PA is suspected in case of hypertension associated with one of the following characteristics: severity, resistance, associated hypokalemia, disproportionate target organ lesions, or adrenal incidentaloma with hypertension or hypokalemia. Diagnosis is founded on aldosterone/renin ratio (ARR) measured under standardized conditions. Diagnostic thresholds are expressed according to the measurement units employed. Diagnosis is established for suprathreshold ARR associated with aldosterone concentrations >550pmol/L (200pg/mL) on 2 measurements, and rejected for aldosterone concentrationhistory. The patient should be informed of the results expected from medical and surgical treatment of PA before exploration for lateralization is proposed. Lateralization is explored by adrenal vein sampling (AVS), except in patients under 35 years of age with unilateral adenoma on imaging. If PA proves to be lateralized, unilateral adrenalectomy may be performed, with adaptation of medical treatment pre- and postoperatively. If PA is non-lateralized or the patient refuses surgery, spironolactone is administered as first-line treatment, replaced by amiloride, eplerenone or calcium-channel blockers if insufficiently effective or poorly tolerated. PMID:27315757

  10. Zero gravity and cardiovascular homeostasis. The relationship between endogenous hyperprolactinemia and plasma aldosterone

    Science.gov (United States)

    Haber, E.; Re, R. N.; Kourides, I. A.; Weihl, A. C.; Maloof, F.

    1978-01-01

    Prolactin, thyrotropin and aldosterone were measured by radioimmunoassay and plasma renin activity by the radioimmunoassay of angiotensin I in normal women before and after the intravenous injection of 200 micrograms of thyrotropin releasing hormone. Prolactin increased at 15 minutes following thyrotropin releasing hormone. Plasma renin activity was not different from control levels during the first hour following the administration of thyrotropin releasing hormone, nor did the plasma aldosterone concentration differ significantly from the control levels during this period. However, with upright posture, an increase in aldosterone and in plasma renin activity was noted, demonstrating a normal capacity to secrete aldosterone. Similarly, no change in aldosterone was seen in 9 patients with primary hypothyroidism given thyrotropin releasing hormone, despite the fact that the increase in prolactin was greater than normal. These data demonstrate that acutely or chronically elevated serum prolactin levels do not result in increased plasma aldosterone levels in humans.

  11. High prevalence of thyroid ultrasonographic abnormalities in primary aldosteronism.

    Science.gov (United States)

    Armanini, Decio; Nacamulli, Davide; Scaroni, Carla; Lumachi, Franco; Selice, Riccardo; Fiore, Cristina; Favia, Gennaro; Mantero, Franco

    2003-11-01

    The study was performed to evaluate the prevalence of thyroid abnormalities detected by ultrasonography and, in particular, of multinodular nontoxic goiter in primary aldosteronism. We analyzed 80 consecutive of patients with primary hyperaldosteronism (40 with unilateral adenoma and 40 with idiopathic hyperaldosteronism) and 80 normotensive healthy controls, comparable for age, sex, iodine intake, and geographical area. Blood pressure, thyroid palpation, thyroid function, and ultrasonography were evaluated. The prevalence of ultrasonographic thyroid abnormalities was 60% in primary aldosteronism and 27% in controls (p < 0.0001). There was a statistically significant difference in prevalence of these abnormalities in unilateral adenoma and idiopathic hyperaldosteronism with respect to controls (p < 0.05 and p < 0.0001, respectively). The prevalence of multinodular nontoxic goiter in idiopathic hyperaldosteronism was higher than in controls (p < 0.001) and, in particular, in female patients. From these data it seems to be worth considering the existence of primary hyperaldosteronism in patients with multinodular goiter and hypertension. PMID:14665720

  12. Microalbuminuria and hypertension in pregnancy: role of aldosterone and inflammation.

    Science.gov (United States)

    Armanini, Decio; Ambrosini, Guido; Sabbadin, Chiara; Donà, Gabriella; Clari, Giulio; Bordin, Luciana

    2013-09-01

    Women with a history of hypertension in pregnancy are at increased risk of microalbuminuria later in life. Microalbuminuria is a marker of kidney dysfunction frequently related to an inflammatory event. Pregnancy is a dynamic process characterized by immune tolerance, angiogenesis, and hormonal regulation. Menstruation and pregnancy are associated with a physiological inflammation, which is altered in preeclampsia and probably in other hypertensive situations of pregnancy. An imbalance between pro-oxidant factors and the ability to scavenge these factors produces oxidative stress, which has been evaluated in many cells, but leukocytes are the main source of inflammatory cytokines and experimental and clinical evidence support a possible role of aldosterone as a mediator of placental and renal damage mediated by growth factors, reactive oxygen species, and cytokines. Angiotensin-converting enzyme inhibitors and aldosterone receptor blockers are frequently effective in reducing the risk of progression of cardiovascular and renal disease. PMID:24034651

  13. Renin and aldosterone measurements in the management of arterial hypertension.

    Science.gov (United States)

    Viola, A; Monticone, S; Burrello, J; Buffolo, F; Lucchiari, M; Rabbia, F; Williams, T A; Veglio, F; Mengozzi, G; Mulatero, P

    2015-06-01

    Renin-angiotensin-aldosterone system (RAAS) is recognized as the main regulatory system of hemodynamics in man, and its derangements have a key role in the development and maintenance of arterial hypertension. Classification of the hypertensive states according to different patterns of renin and aldosterone levels ("RAAS profiling") allows the diagnosis of specific forms of secondary hypertension and may identify distinct hemodynamic subsets in essential hypertension. In this review, we summarize the application of RAAS profiling for the diagnostic assessment of hypertensive patients and discuss how the pathophysiological framework provided by RAAS profiling may guide therapeutic decision-making, especially in the context of uncontrolled hypertension not responding to multi-therapy. PMID:25993253

  14. Adrenal vein sampling in primary aldosteronism: towards a standardised protocol.

    Science.gov (United States)

    Monticone, Silvia; Viola, Andrea; Rossato, Denis; Veglio, Franco; Reincke, Martin; Gomez-Sanchez, Celso; Mulatero, Paolo

    2015-04-01

    Primary aldosteronism comprises subtypes that need different therapeutic strategies. Adrenal vein sampling is recognised by Endocrine Society guidelines as the only reliable way to correctly diagnose the subtype of primary aldosteronism. Unfortunately, despite being the gold-standard procedure, no standardised procedure exists either in terms of performance or interpretation criteria. In this Personal View, we address several questions that clinicians are presented with when considering adrenal vein sampling. For each of these questions we provide responses based on the available evidence, and opinions based on our experience. In particular, we discuss the most appropriate way to prepare the patient, whether adrenal vein sampling can be avoided for some subgroups of patients, the use of ACTH (1-24) during the procedure, the most appropriate criteria for interpretation of adrenal vein cannulation and lateralisation, the use of contralateral suppression, and strategies to improve success rates of adrenal vein sampling in centres with little experience. PMID:24831990

  15. Overview of the genetic determinants of primary aldosteronism

    Science.gov (United States)

    Al-Salameh, Abdallah; Cohen, Régis; Desailloud, Rachel

    2014-01-01

    Primary aldosteronism is the most common cause of secondary hypertension. The syndrome accounts for 10% of all cases of hypertension and is primarily caused by bilateral adrenal hyperplasia or aldosterone-producing adenoma. Over the last few years, the use of exome sequencing has significantly improved our understanding of this syndrome. Somatic mutations in the KCNJ5, ATP1A1, ATP2B3 or CACNA1D genes are present in more than half of all cases of aldosterone-producing adenoma (~40%, ~6%, ~1% and ~8%, respectively). Germline gain-of-function mutations in KCNJ5 are now known to cause familial hyperaldosteronism type III, and an additional form of genetic hyperaldosteronism has been reported in patients with germline mutations in CACNA1D. These genes code for channels that control ion homeostasis across the plasma membrane of zona glomerulosa cells. Moreover, all these mutations modulate the same pathway, in which elevated intracellular calcium levels lead to aldosterone hyperproduction and (in some cases) adrenal cell proliferation. From a clinical standpoint, the discovery of these mutations has potential implications for patient management. The mutated channels could be targeted by drugs, in order to control hormonal and overgrowth-related manifestations. Furthermore, some of these mutations are associated with high cell turnover and may be amenable to diagnosis via the sequencing of cell-free (circulating) DNA. However, genotype-phenotype correlations in patients harboring these mutations have yet to be characterized. Despite this recent progress, much remains to be done to elucidate the yet unknown mechanisms underlying sporadic bilateral adrenal hyperplasia. PMID:24817817

  16. Physiological techniques in the study of rapid aldosterone effects.

    Science.gov (United States)

    Yusef, Yamil R; Thomas, Warren; Harvey, Brian J

    2014-01-01

    Molecular imaging and electrophysiological techniques are powerful tools to analyze the responses stimulated by aldosterone and other hormones in target tissues. Studies with Ussing-type chambers can be used to measure and characterize changes in transepithelial currents resulting from hormone treatment. Confocal imaging techniques can be used in real time or in fixed preparations to evaluate the localization of receptors, signalling intermediates, and transporters. PMID:25182774

  17. Emergence and evolution of the renin-angiotensin-aldosterone system

    OpenAIRE

    Fournier, D.; Luft, F C; Bader, M.; Ganten, D; Andrade-Navarro, M A

    2012-01-01

    The renin–angiotensin–aldosterone system (RAAS) is not the sole, but perhaps the most important volume regulator in vertebrates. To gain insights into the function and evolution of its components, we conducted a phylogenetic analysis of its main related genes. We found that important parts of the system began to appear with primitive chordates and tunicates and that all major components were present at the divergence of bony fish, with the exception of the Mas receptor. The Mas receptor first...

  18. Cortisol and aldosterone comparisons of cottontail rabbits collected by shooting, trapping, and falconry.

    Science.gov (United States)

    Hamilton, G D; Weeks, H P

    1985-01-01

    Cortisol and aldosterone levels were measured in plasma of eastern cottontail rabbits (Sylvilagus floridanus) collected by three different methods, i.e., shooting, live-trapping and falconry. Cortisol levels ranged from near 0 to 27.5 micrograms/100 ml and aldosterone from near 0 to 220 ng/100 ml. Shot animals had significantly lower cortisol concentrations than those taken by either of the other methods. Trapped cottontails also had significantly lower aldosterone levels. PMID:3981742

  19. Die Rolle von growth arrest specific protein 6 im Aldosteron induzierten Endorganschaden

    OpenAIRE

    Theuer, Stefanie

    2013-01-01

    Growth arrest specific protein 6 (Gas 6) is involved in inflammatory kidney diseases, vascular remodeling, cell adhesion, and thrombus formation. We explored a role for Gas 6 in aldosterone-induced target organ damage. We observed that Gas 6 was upregulated in rats with high aldosterone levels. Mineralocorticoid receptor blockade prevented target organ damage and decreased the elevated Gas 6 expression. Vascular smooth muscle cells given aldosterone increased their Gas 6 expression in vitro. ...

  20. Biological determinants of aldosterone-induced cardiac fibrosis in rats.

    Science.gov (United States)

    Robert, V; Silvestre, J S; Charlemagne, D; Sabri, A; Trouvé, P; Wassef, M; Swynghedauw, B; Delcayre, C

    1995-12-01

    To determine the events leading to cardiac fibrosis in aldosterone-salt hypertensive rats, we studied protein and mRNA accumulation of procollagens I and III for 60 days. After 3 and 7 days of treatment systolic pressure was normal, and no histological or biochemical changes were seen in rat hearts. At day 15 arterial pressure was raised (+40%) and left ventricular hypertrophy was +15%. Cardiac examination after hemalun-eosin staining and immunolabeling with anticollagen I and III antibodies showed no structural alterations, but an 83% increase in right ventricular type III procollagen mRNA levels was found. At 30 and 60 days we found progressive cardiac fibrosis, with inflammatory cells, myocyte necrosis, and elevation of both types I and III procollagen mRNA levels in both ventricles. To determine whether aldosterone had effects on Na,K-ATPase that might lead to ionic disturbances and induce myocyte necrosis, we studied the major cardiac Na,K-ATPase isoform genes. Although Na,K-ATPase alpha 1- and beta 1-subunit mRNA levels were elevated in kidney at day 1, neither of these cardiac transcripts nor the specific alpha 2 isoform was altered between 1 and 15 days. These results show that accumulation of procollagen mRNAs occurs before collagen deposition. Cardiac alterations are late and not preceded by changes in Na,K-ATPase cardiac gene expression, precluding a direct modulation of cardiac collagen synthesis and Na,K-ATPase by aldosterone. PMID:7490157

  1. 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

  2. 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.

  3. Overview of the genetic determinants of primary aldosteronism

    Directory of Open Access Journals (Sweden)

    Al-Salameh A

    2014-04-01

    Full Text Available Abdallah Al-Salameh,1 Régis Cohen,2 Rachel Desailloud3 1Service de Diabétologie, Endocrinologie et Maladies Métaboliques, Centre Hospitalier de Creil, Creil, France; 2Service d'Endocrinologie, Centre Hospitalier de Saint-Denis, Saint-Denis, France; 3Service d'Endocrinologie, Diabétologie et Nutrition, Centre Hospitalier Universitaire d'Amiens, Amiens, France Abstract: Primary aldosteronism is the most common cause of secondary hypertension. The syndrome accounts for 10% of all cases of hypertension and is primarily caused by bilateral adrenal hyperplasia or aldosterone-producing adenoma. Over the last few years, the use of exome sequencing has significantly improved our understanding of this syndrome. Somatic mutations in the KCNJ5, ATP1A1, ATP2B3 or CACNA1D genes are present in more than half of all cases of aldosterone-producing adenoma (~40%, ~6%, ~1% and ~8%, respectively. Germline gain-of-function mutations in KCNJ5 are now known to cause familial hyperaldosteronism type III, and an additional form of genetic hyperaldosteronism has been reported in patients with germline mutations in CACNA1D. These genes code for channels that control ion homeostasis across the plasma membrane of zona glomerulosa cells. Moreover, all these mutations modulate the same pathway, in which elevated intracellular calcium levels lead to aldosterone hyperproduction and (in some cases adrenal cell proliferation. From a clinical standpoint, the discovery of these mutations has potential implications for patient management. The mutated channels could be targeted by drugs, in order to control hormonal and overgrowth-related manifestations. Furthermore, some of these mutations are associated with high cell turnover and may be amenable to diagnosis via the sequencing of cell-free (circulating DNA. However, genotype-phenotype correlations in patients harboring these mutations have yet to be characterized. Despite this recent progress, much remains to be done to

  4. Aldosterone Induces Tissue Inhibitor of Metalloproteinases-1 Expression and Further Contributes to Collagen Accumulation: From Clinical to Bench Studies.

    Science.gov (United States)

    Hung, Chi-Sheng; Chou, Chia-Hung; Liao, Che-Wei; Lin, Yen-Tin; Wu, Xue-Ming; Chang, Yi-Yao; Chen, Ying-Hsien; Wu, Vin-Cent; Su, Ming-Jai; Ho, Yi-Lwun; Chen, Ming-Fong; Wu, Kwan-Dun; Lin, Yen-Hung

    2016-06-01

    Aldosterone induces myocardial fibrosis. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key factor of myocardial fibrosis. This study tested the hypothesis that aldosterone induces TIMP-1 expression and contributes to the fibrotic process. We prospectively enrolled 54 patients with primary aldosteronism, and measured plasma TIMP-1 and echocardiographic parameters. In the cell study, we investigated the possible molecular mechanism by which aldosterone induces TIMP-1 secretion and the effects on collagen accumulation. In the animal study, we measured serum TIMP-1 levels, cardiac TIMP-1 levels, and cardiac structure in an aldosterone infusion mouse model using implantation of aldosterone pellets. In patients with primary aldosteronism, plasma TIMP-1 was correlated with 24-hour urinary aldosterone, left ventricular mass, and impairment of left ventricular diastolic function. In human cardiac fibroblasts, TIMP-1 protein and mRNA expressions were significantly increased by aldosterone through the glucocorticoid receptor/PI3K/Akt/nuclear factor-κB pathway. TIMP-1 small-interfering RNA significantly reduced aldosterone-induced collagen accumulation, and aldosterone did not alter the levels of collagen1a1 or matrix metalloproteinase-1 mRNA. The aldosterone-induced TIMP-1 expression was inversely related to matrix metalloproteinase-1 activity. Furthermore, in the animal model, the serum and cardiac levels of TIMP-1 were significantly elevated in the mice that received aldosterone infusion. This elevation was blocked by RU-486 but not by eplerenone, suggesting that the effect was through glucocorticoid receptors. In a long-term aldosterone infusion model, serum TIMP-1 was associated with serum aldosterone level, cardiac structure, and fibrosis. In conclusion, aldosterone induced TIMP-1 expression in vivo and in vitro. This increased TIMP-1 expression resulted in enhanced collagen accumulation via the suppression of matrix metalloproteinase-1 activity. PMID:27113051

  5. Does aldosterone play a significant role for regulation of vascular tone?

    DEFF Research Database (Denmark)

    Lyngsø, Kristina Sanne; Assersen, Kasper Bostlund; Dalgaard, Emil Geertsen;

    2016-01-01

    formation and vasoconstrictor effects through endothelial contracting cyclooxygenase derived-factors and a changed calcium handling. The response to aldosterone can change within the same blood vessels depending on the exposure time and status of the endothelium. Chronic responses involve changed levels of...... reactive oxygen radicals, endothelia Na-influx and smooth muscle calcium channel expression and perivascular cells, e.g. mast cells, also participate. Moreover, the vascular effect of aldosterone depends on the status of the endothelium which is likely cause of the very different responses to aldosterone...... cells through stimulus-secretion coupling involving depolarization, opening of L- and T-type calcium channels and aldosterone synthase activation. Local formation and release in peripheral tissues such as perivascular fat is recognized. Where does aldosterone affect the vasculature? Mineralocorticoid...

  6. 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.

  7. 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.

  8. Endocrine effects of lithium. III. Hypermagnesaemia and activation of the renin-aldosterone system.

    Science.gov (United States)

    Transbøl, I; Christiansen, C; Baastrup, P C; Nielsen, M D; Giese, J

    1978-07-01

    Hypermagnesaemia is a well-known but as yet unexplained concomitant of lithium treatment. Prior suggestions implicating a role for aldosterone in magnesium homoeostasis prompted this study of plasma renin, plasma aldosterone and serum magnesium in 17 maniodepressive patients on long-term lithium treatment. In addition to hypermagnesaemia (P less than 0.001), this group of patients had raised plasma levels of aldosterone (P less than 0.001) and increased plasma renin concentration (P less than 0.05). Serum magnesium was positively correlated to plasma aldosterone (r = 0.58, P less than 0.02). The relation between activation of the renin-aldosterone system and the presence of hypermagnesaemia during chronic lithium treatment could conceivably be mediated through a lithium-induced hypovolaemic state. PMID:581026

  9. Histamine-dependent prolongation by aldosterone of vasoconstriction in isolated small mesenteric arteries of the mouse

    DEFF Research Database (Denmark)

    Schjerning, Jeppe; Uhrenholt, Torben R; Svenningsen, Per; Vanhoutte, Paul M; Skott, Ole; Jensen, Boye L; Hansen, Pernille B L

    2013-01-01

    In arterioles, aldosterone counteracts the rapid dilatation ("recovery") following depolarization-induced contraction. The hypothesis was tested that this effect of aldosterone depends on COX-derived products and/or NOS inhibition. Recovery of the response to high K(+) was observed in mesenteric...... by aldosterone. Actinomycin-D abolished the effect of aldosterone indicating a genomic effect. The effect was blocked by indomethacin and by the COX-1 inhibitor valeryl salicylate but not by NS-398 (10(-6) mol/L) or the TP-receptor antagonist S18886 (10(-7) mol/L). The effect of aldosterone on...... recovery in arteries from wild type mice and the SNP-mediated dilatation in arteries from eNOS(-/-) mice was inhibited by the histamine H2 receptor antagonist cimetidine. RT-PCR showed expression of mast cell markers in mouse mesenteric arteries. The adventitia displayed granular cells positive for...

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

    International Nuclear Information System (INIS)

    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

  11. Extraordinarily high aldosterone, 901.0 ng/dL, in a patient with primary aldosteronism: an insight into the underlying mechanism.

    Science.gov (United States)

    Okubo, Yosuke; Sato, Yuka; Nakasone, Yasuto; Shirotori, Katsuko; Oguchi, Kazuhiro; Matsushita, Tsuyoshi; Nishikawa, Tetsuo; Yamazaki, Yuto; Sasano, Hironobu; Komatsu, Mitsuhisa; Yamauchi, Keishi; Aizawa, Toru

    2016-02-29

    A 43-yr-old hypertensive male was admitted due to hypokalemia (1.8 mEq/L) and renal dysfunction (eGFR, 20.0 mL/min/1.73 m(2)). His plasma aldosterone was 901.0 ng/dL, plasma renin activity 5.7 ng/mL/hr, and aldosterone/renin activity ratio 158. Angiotensin II (AII) was 0.7 pg/mL, ACTH mass spectrometry analysis showed that aldosterone (104 times the control) as well as its precursors were significantly elevated in the patient's plasma. A left adrenal (4-cm-diameter) tumor with (131)I-Adosterol® uptake was found and removed. Four days later, plasma aldosterone and renin activity had dropped to 7.73 ng/dL and 1.6 ng/mL/hr, respectively. However, they rose to 24.0 ng/dL and 10.9 ng/mL/hr, respectively, by Day 102. Nevertheless, magnetic resonance angiography found no evidence of a renovascular lesion. The tumor was a benign adrenocortical adenoma composed predominantly of clear cells positive for 17α-hydroxylase, [hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerases], and aldosterone synthase. A quantitative real-time polymerase chain reaction analysis of the tumor cells revealed that expression of the gene encoding aldosterone synthase was 85 times the control level. In addition, the tumor cells harbored G151R mutation of the inward rectifying potassium channel subfamily j, member 5 gene. The striking overexpression of aldosterone synthase by the tumor cells was considered the primary mechanism for the extravagant overproduction of aldosterone in this case. This overexpression may have resulted from integration of signals from AII and forced membrane depolarization due to the potassium channel mutation. PMID:26549209

  12. Does Aldosterone Play a Significant Role for Regulation of Vascular Tone?

    Science.gov (United States)

    Lyngsø, Kristina S; Assersen, Kasper; Dalgaard, Emil G; Skott, Ole; Jensen, Boye L; Hansen, Pernille B L

    2016-07-01

    Besides the well-known renal effects of aldosterone, the hormone is now known to have direct vascular effects. Clinical observations underline substantial adverse effects of aldosterone on cardiovascular function. The source of systemic circulating aldosterone is the adrenal gland zona glomerulosa cells through stimulus-secretion coupling involving depolarization, opening of L- and T-type calcium channels and aldosterone synthase activation. Local formation and release in peripheral tissues such as perivascular fat is recognized. Where does aldosterone affect the vasculature? Mineralocorticoid receptors (MRs) are present in endothelial and vascular smooth muscle cells, and MR-independent pathways are also involved. The vascular effects of aldosterone are complex, both concentration and temporal and spatial aspects are relevant. The acute response includes vasodilation through endothelial nitric oxide formation and vasoconstrictor effects through endothelial-contracting cyclooxygenase-derived factors and a changed calcium handling. The response to aldosterone can change within the same blood vessels depending on the exposure time and status of the endothelium. Chronic responses involve changed levels of reactive oxygen radicals, endothelial Na-influx and smooth muscle calcium channel expression. Furthermore, perivascular cells for example mast cells have also been suggested to participate in the chronic response. Moreover, the vascular effect of aldosterone depends on the status of the endothelium which is likely the cause of the very different responses to aldosterone and MR treatment observed in human studies going from increased to decreased flow depending on whether the patient had prior cardiovascular disease with endothelial dysfunction or not. A preponderance of constrictor versus dilator responses to aldosterone could therefore be involved in the detrimental vascular actions of the hormone in the setting of endothelial dysfunction and contribute to explain

  13. Aldosterone-Induced Vascular Remodeling and Endothelial Dysfunction Require Functional Angiotensin Type 1a Receptors.

    Science.gov (United States)

    Briet, Marie; Barhoumi, Tlili; Mian, Muhammad Oneeb Rehman; Coelho, Suellen C; Ouerd, Sofiane; Rautureau, Yohann; Coffman, Thomas M; Paradis, Pierre; Schiffrin, Ernesto L

    2016-05-01

    We investigated the role of angiotensin type 1a receptors (AGTR1a) in vascular injury induced by aldosterone activation of mineralocorticoid receptors inAgtr1a(-/-)and wild-type (WT) mice infused with aldosterone for 14 days while receiving 1% NaCl in drinking water. Aldosterone increased systolic blood pressure (BP) by ≈30 mm Hg in WT mice and ≈50 mm Hg inAgtr1a(-/-)mice. Aldosterone induced aortic and small artery remodeling, impaired endothelium-dependent relaxation in WT mice, and enhanced fibronectin and collagen deposition and vascular inflammation. None of these vascular effects were observed inAgtr1a(-/-)mice. Aldosterone effects were prevented by the AGTR1 antagonist losartan in WT mice. In contrast to aldosterone, norepinephrine caused similar BP increase and mesenteric artery remodeling in WT andAgtr1a(-/-)mice.Agtr1a(-/-)mice infused with aldosterone did not increase sodium excretion in response to a sodium chloride challenge, suggesting that sodium retention could contribute to the exaggerated BP rise induced by aldosterone.Agtr1a(-/-)mice had decreased mesenteric artery expression of the calcium-activated potassium channelKcnmb1, which may enhance myogenic tone and together with sodium retention, exacerbate BP responses to aldosterone/salt inAgtr1a(-/-)mice. We conclude that although aldosterone activation of mineralocorticoid receptors raises BP more inAgtr1a(-/-)mice, AGTR1a is required for mineralocorticoid receptor stimulation to induce vascular remodeling and inflammation and endothelial dysfunction. PMID:27045029

  14. Idiopathic primary hyperaldosteronism: normalization of plasma aldosterone after one month withdrawal of long-term therapy with aldosterone-receptor antagonist potassium canrenoate.

    Science.gov (United States)

    Armanini, D; Scaroni, C; Mattarello, M J; Fiore, C; Albiger, N; Sartorato, P

    2005-03-01

    We have re-evaluated 15 patients with idiopathic primary aldosteronism one month after withdrawal of therapy with aldosterone-receptor antagonist potassium canrenoate. Therapy had lasted for 3 to 24 yr. Median blood pressure (BP) in the sitting position at the time of diagnosis was 160/100 (ranges 150-200/95-110 mmHg); while 1 month after withdrawal of therapy median BP was 145/90 (ranges 125-160/80-100 mmHg). One month after withdrawal, the ratio aldosterone (ng/dl)/plasma renin activity (ng/ml/h) in the upright position was increased only in 3 cases (median 18, range 6.1-125). We found a significant inverse correlation between the upright aldosterone/plasma renin activity (aldo/PRA) ratio, 1 month after withdrawal, and the number of years of therapy with potassium canrenoate. We conclude that long-term therapy with the aldosterone-receptor blocker, potassium canrenoate, can normalize the aldo/PRA ratio in many cases of idiopathic primary hyperaldosteronism after one-month withdrawal of the drug. These data are consistent with possible regression of idiopathic primary hyperaldosteronism after long-term therapy with potassium canrenoate, or in alternative to a persistent effect of potassium canrenoate, on aldosterone synthesis. PMID:15952408

  15. Raised Plasma Aldosterone and Natriuretic Peptides in Atrial Fibrillation

    DEFF Research Database (Denmark)

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

    2006-01-01

    , present AF 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...... log-transformed plasma Nt-proANP. Likewise, present AF at follow-up (p = 0.0008) as well as age (p < 0.0001) were associated with high log-transformed plasma Nt-proBNP. CONCLUSIONS: In patients with earlier AF, AF at long-term follow-up visit was independently associated with raised levels of Nt...... follow-up was related to a high aldosterone level (p = 0.09). For the natriuretic peptides, present AF at follow-up (p < 0.0001), age (p < 0.0001), female gender (p = 0.0047), ischemic heart disease (p = 0.0154), and ongoing treatment with sotalol (p = 0.0003) were all independently associated with high...

  16. Polycystic ovary syndrome: Implications of measurement of plasma aldosterone, renin activity and progesterone.

    Science.gov (United States)

    Armanini, Decio; Bordin, Luciana; Donà, Gabriella; Sabbadin, Chiara; Bakdounes, Leila; Ragazzi, Eugenio; Giorgino, Francesco L; Fiore, Cristina

    2012-05-01

    A positive correlation between aldosterone, inflammatory parameters, blood pressure and metabolic abnormalities in polycystic ovary syndrome (PCOS) has been reported in the early estrogenic phase. The aim of the study was to measure plasma aldosterone, plasma renin activity (PRA) and progesterone on the 21st day of the cycle, in women with PCOS and to consider the interrelationships between these hormones. Sixty-six consecutive normal BMI women with PCOS (median age 24 years, range 21-28 years) and 53 age- and body mass index-matched healthy controls were enrolled in the study. Aldosterone, aldosterone/PRA ratio (ARR) and Homeostasis Model Assessment (HOMA) index were significantly higher (p<0.0001) in PCOS women than controls. Positive correlations were found in PCOS but not in controls between (i) progesterone and aldosterone, (ii) aldosterone and PRA, (iii) PRA and progesterone. Mean blood pressures were within the normal range but significantly higher in PCOS than controls. The increase of plasma aldosterone, ARR and blood pressure in PCOS compared with controls is consistent with an increased mineralocorticoid effector mechanism in PCOS; prolonged therapy with spironolactone could counteract both the hyperandrogenism and reduce future cardiovascular risk. PMID:22387621

  17. TRAF3IP2 mediates aldosterone/salt-induced cardiac hypertrophy and fibrosis.

    Science.gov (United States)

    Sakamuri, Siva S V P; Valente, Anthony J; Siddesha, Jalahalli M; Delafontaine, Patrice; Siebenlist, Ulrich; Gardner, Jason D; Bysani, Chandrasekar

    2016-07-01

    Aberrant activation of the renin-angiotensin-aldosterone system (RAAS) contributes to adverse cardiac remodeling and eventual failure. Here we investigated whether TRAF3 Interacting Protein 2 (TRAF3IP2), a redox-sensitive cytoplasmic adaptor molecule and an upstream regulator of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), mediates aldosterone-induced cardiac hypertrophy and fibrosis. Wild type (WT) and TRAF3IP2-null mice were infused with aldosterone (0.2 mg/kg/day) for 4 weeks along with 1%NaCl in drinking water. Aldosterone/salt, but not salt alone, upregulated TRAF3IP2 expression in WT mouse hearts. Further, aldosterone elevated blood pressure to a similar extent in both WT and TRAF3IP2-null groups. However, TRAF3IP2 gene deletion attenuated aldosterone/salt-induced (i) p65 and c-Jun activation, (ii) extracellular matrix (collagen Iα1 and collagen IIIα1), matrix metalloproteinase (MMP2), lysyl oxidase (LOX), inflammatory cytokine (IL-6 and IL-18), chemokine (CXCL1 and CXCL2), and adhesion molecule (ICAM1) mRNA expression in hearts, (iii) IL-6, IL-18, and MMP2 protein levels, (iv) systemic IL-6 and IL-18 levels, and (iv) cardiac hypertrophy and fibrosis. These results indicate that TRAF3IP2 is a critical signaling intermediate in aldosterone/salt-induced myocardial hypertrophy and fibrosis, and thus a potential therapeutic target in hypertensive heart disease. PMID:27040306

  18. Aldosterone antagonists in monotherapy are protective against streptozotocin-induced diabetic nephropathy in rats.

    Science.gov (United States)

    Banki, Nora F; Ver, Agota; Wagner, Laszlo J; Vannay, Adam; Degrell, Peter; Prokai, Agnes; Gellai, Renata; Lenart, Lilla; Szakal, Dorottya-Nagy; Kenesei, Eva; Rosta, Klara; Reusz, Gyorgy; Szabo, Attila J; Tulassay, Tivadar; Baylis, Chris; Fekete, Andrea

    2012-01-01

    Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers. PMID:22761931

  19. Aldosterone antagonists in monotherapy are protective against streptozotocin-induced diabetic nephropathy in rats.

    Directory of Open Access Journals (Sweden)

    Nora F Banki

    Full Text Available Angiotensin converting enzyme inhibitors (ACEi and angiotensin II receptor blockers (ARB are the standard clinical therapy of diabetic nephropathy (DN, while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers.

  20. Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation

    OpenAIRE

    Fakitsas, P; Adam, G.; Daidié, D; van Bemmelen, M X; Fouladkou, F; Patrignani, A; U. Wagner; Warth, R.; Camargo, S M R; Staub, O.; Verrey, F

    2007-01-01

    The mineralocorticoid hormone aldosterone controls sodium reabsorption and BP largely by regulating the cell-surface expression and function of the epithelial sodium channel (ENaC) in target kidney tubules. Part of the stimulatory effect of aldosterone on ENaC is mediated by the induction of serum- and glucocorticoid-regulated kinase 1 (Sgk1), a kinase that interferes with the ubiquitylation of ENaC by ubiquitin-protein ligase Nedd4-2. In vivo early aldosterone-regulated mRNA now has been ide...

  1. Primary aldosteronism associated with severe rhabdomyolysis due to profound hypokalemia.

    Science.gov (United States)

    Goto, Atsushi; Takahashi, Yoshihiko; Kishimoto, Miyako; Minowada, Shigeru; Aibe, Hitoshi; Hasuo, Kanehiro; Kajio, Hiroshi; Noda, Mitsuhiko

    2009-01-01

    A 55-year-old Japanese man was admitted to our hospital with severe weakness. Without measurement of serum electrolyte concentrations, diuretic therapy for hypertension was started 2 weeks prior to admission. Laboratory findings showed profound hypokalemia (1.4 mEq/L), and extreme elevation of the serum creatinine phosphokinase levels (15,760 IU/L), suggesting that the patient had hypokalemic paralysis and hypokalemia-induced rhabdomyolysis. Further evaluations, including adrenal venous sampling strongly suggested that he had primary aldosteronism. He was treated successfully by laparoscopic adrenalectomy. This case provides an important lesson that serum electrolyte concentrations should be measured in hypertensive patients before the administration of antihypertensive agents. PMID:19218772

  2. UPDATES OF THE RENIN‐ANGIOTENSIN‐ALDOSTERON SYSTEM

    Directory of Open Access Journals (Sweden)

    Minela MĂRĂNDUCA

    2013-07-01

    Full Text Available The renin‐angiotensin‐aldosteron system (RAAS is a hormonal system that contributes to regulation of blood pressure and volume of extracellular fluids, in both nor‐ motensive and hypertensive individuals. Hypertension affects the target organs (kidneys and leads to a vicious circle that contributes to maintaining a high arterial pre‐ ssure. Besides the hemodynamic effects of RAAS/Ang II, Ang II has direct impact on structure/function of kidneys, leading to renal injury. Recently, the proinflammatory effect of Ang II has been discovered. Low renal inflamma‐ tion determined by excessive circulating RAAS, mostly at renal level, promotes and continues the renal disease. This review presents the inflammatory mechanisms initiated by Ang II at renal level, which induce development of renal injury. Identification of such mechanisms might lead to the discovery of new therapeutic approaches for hyperten‐ sion/target organs damage.

  3. Dexamethasone suppresion scintiscan in primary aldosteronism with Scintadren

    International Nuclear Information System (INIS)

    The adrenal uptake of 75Se-selenonorcholesterol (Scintadren) was examined in primary aldosteronism under dexamethasone suppresion to establish the value of the adrenal scintigram in distinguishing aldosteronomas from bilateral hyperplasia and to lateralize adenoma, when present. Twenty-eight patients with Conn's syndrome were studied. The results showed that under dexamethasone suppression there is no difference in the time of visualization between the two adrenals in bilateral hyperplasia; the glands appear simultaneously, even if it is asymmetrical, while adenoma always appears earlier than the normal or hyperplastic other side. Thus comparison of the suppressibility of the two adrenals i.e. the time lag in visualization of the gland, is of diagnostic value. (U.K.)

  4. Rapid effects of aldosterone in primary cultures of cardiomyocytes - do they suggest the existence of a membrane-bound receptor?

    Science.gov (United States)

    Araujo, Carolina Morais; Hermidorff, Milla Marques; Amancio, Gabriela de Cassia Sousa; Lemos, Denise da Silveira; Silva, Marcelo Estáquio; de Assis, Leonardo Vinícius Monteiro; Isoldi, Mauro César

    2016-10-01

    Aldosterone acts on its target tissue through a classical mechanism or through the rapid pathway through a putative membrane-bound receptor. Our goal here was to better understand the molecular and biochemical rapid mechanisms responsible for aldosterone-induced cardiomyocyte hypertrophy. We have evaluated the hypertrophic process through the levels of ANP, which was confirmed by the analysis of the superficial area of cardiomyocytes. Aldosterone increased the levels of ANP and the cellular area of the cardiomyocytes; spironolactone reduced the aldosterone-increased ANP level and cellular area of cardiomyocytes. Aldosterone or spironolactone alone did not increase the level of cyclic 3',5'-adenosine monophosphate (cAMP), but aldosterone plus spironolactone led to increased cAMP level; the treatment with aldosterone + spironolactone + BAPTA-AM reduced the levels of cAMP. These data suggest that aldosterone-induced cAMP increase is independent of mineralocorticoid receptor (MR) and dependent on Ca(2+). Next, we have evaluated the role of A-kinase anchor proteins (AKAP) in the aldosterone-induced hypertrophic response. We have found that St-Ht31 (AKAP inhibitor) reduced the increased level of ANP which was induced by aldosterone; in addition, we have found an increase on protein kinase C (PKC) and extracellular signal-regulated kinase 5 (ERK5) activity when cells were treated with aldosterone alone, spironolactone alone and with a combination of both. Our data suggest that PKC could be responsible for ERK5 aldosterone-induced phosphorylation. Our study suggests that the aldosterone through its rapid effects promotes a hypertrophic response in cardiomyocytes that is controlled by an AKAP, being dependent on ERK5 and PKC, but not on cAMP/cAMP-dependent protein kinase signaling pathways. Lastly, we provide evidence that the targeting of AKAPs could be relevant in patients with aldosterone-induced cardiac hypertrophy and heart failure. PMID:27305962

  5. Does aldosterone play a significant role for regulation of vascular tone?

    DEFF Research Database (Denmark)

    Lyngsø, Kristina Sanne; Assersen, Kasper Bostlund; Dalgaard, Emil Geertsen; Skøtt, Ole; Jensen, Boye L.; Hansen, Pernille B. Lærkegaard

    2016-01-01

    formation and vasoconstrictor effects through endothelial contracting cyclooxygenase derived-factors and a changed calcium handling. The response to aldosterone can change within the same blood vessels depending on the exposure time and status of the endothelium. Chronic responses involve changed levels of...... reactive oxygen radicals, endothelia Na-influx and smooth muscle calcium channel expression and perivascular cells, e.g. mast cells, also participate. Moreover, the vascular effect of aldosterone depends on the status of the endothelium which is likely cause of the very different responses to aldosterone...... and MR treatment observed in human studies going from increased to decreased flow depending on whether the patient had prior cardiovascular disease with endothelial dysfunction or not. A preponderance of constrictor versus dilator responses to aldosterone could therefore be involved in the detrimental...

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

    International Nuclear Information System (INIS)

    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. Impact of aldosterone-producing adenoma on cardiac structures in echocardiography

    OpenAIRE

    Hidaka, Takayuki; Shiwa, Tsuguka; Fujii, Yuichi; Nishioka, Kenji; Utsunomiya, Hiroto; Ishibashi, Ken; Mitsuba, Naoya; Dohi, Yoshihiro; Oda, Noboru; Noma, Kensuke; Kurisu, Satoru; Nakano, Yukiko; Yamamoto, Hideya; Iishida, Takafumi; Higashi, Yukihito

    2013-01-01

    Background Primary aldosteronism (PA) is a most common cause of secondary hypertension. In PA, left ventricular hypertrophy (LVH) is more progressive than in any other cause of hypertension. Aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) are major subtypes of PA. However there is little information concerned with differences of cardiac structures between these two subtypes. Methods We reviewed echocardiographic findings in 46 patients with PA. All patients had a p...

  8. Association of Circulating Renin and Aldosterone With Osteocalcin and Bone Mineral Density in African Ancestry Families.

    Science.gov (United States)

    Kuipers, Allison L; Kammerer, Candace M; Pratt, J Howard; Bunker, Clareann H; Wheeler, Victor W; Patrick, Alan L; Zmuda, Joseph M

    2016-05-01

    Hypertension is associated with accelerated bone loss, and the renin-angiotensin-aldosterone system is a key regulator of blood pressure. Although components of this system are expressed in human bone cells, studies in humans are sparse. Thus, we studied the association of circulating renin and aldosterone with osteocalcin and bone mineral density. We recruited 373 African ancestry family members without regard to health status from 6 probands (mean family size: 62 and relative pairs: 1687). Participants underwent a clinical examination, dual-energy x-ray absorptiometry, and quantitative computed tomographic scans. Renin activity, aldosterone concentration, and osteocalcin were measured in fasting blood samples. Aldosterone/renin ratio was calculated as aldosterone concentration/renin activity. All models were analyzed using pedigree-based variance components methods. Full models included adjustment for age, sex, body composition, comorbidities, lifestyle factors, blood pressure, and antihypertensive medication. Higher renin activity was significantly associated with lower total osteocalcin and with higher trabecular bone mineral density (bothP<0.01). There were also significant genetic correlations between renin activity and whole-body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone/renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biological mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension. PMID:26975710

  9. Evidence for Concerted Effects of Aldosterone On a Target Sodium-transporting Epithelium

    OpenAIRE

    BEAUWENS, R; Crabbé, J.

    1983-01-01

    The sodium-transporting activity of toad skin is stimulated in vitro with aldosterone in the absence of energy-providing substrate; it can be stimulated further upon addition of glucose after prolonged (overnight) incubation. The magnifying effect exerted by glucose in these conditions could be blocked by inhibitors of ribonucleic acid and protein biosynthesis. In addition, exposure to cycloheximide prevented the increase in thermodynamic affinity resulting from aldosterone treatment. A synth...

  10. VLDL-activated cell signaling pathways that stimulate adrenal cell aldosterone production.

    Science.gov (United States)

    Tsai, Ying-Ying; Rainey, William E; Johnson, Maribeth H; Bollag, Wendy B

    2016-09-15

    Aldosterone plays an important role in regulating ion and fluid homeostasis and thus blood pressure, and hyperaldosteronism results in hypertension. Hypertension is also observed with obesity, which is associated with additional health risks, including cardiovascular disease. Obese individuals have high serum levels of very low-density lipoprotein (VLDL), which has been shown to stimulate aldosterone production; however, the mechanisms underlying VLDL-induced aldosterone production are still unclear. Here we demonstrate in human adrenocortical carcinoma (HAC15) cells that submaximal concentrations of angiotensin II and VLDL stimulate aldosterone production in an additive fashion, suggesting the possibility of common mechanisms of action. We show using inhibitors that VLDL-induced aldosterone production is mediated by the PLC/IP3/PKC signaling pathway. Our results suggest that PKC is upstream of the extracellular signal-regulated kinase (ERK) activation previously observed with VLDL. An understanding of the mechanisms mediating VLDL-induced aldosterone production may provide insights into therapies to treat obesity-associated hypertension. PMID:27222295

  11. Regulation of Na+ channels in frog lung epithelium: a target tissue for aldosterone action.

    Science.gov (United States)

    Fischer, H; Clauss, W

    1990-04-01

    Sodium transport across isolated lung tissue of the frog Xenopus laevis was measured in Ussing chambers under voltage-clamp conditions. Perfusing the lungs with NaCl-Ringer's solutions on both sides, a basal distinct amiloride-blockable Na+ current was present. Incubating the lungs with 1 mumol/l aldosterone from the pleural side raised the short circuit current after a 1-h latent period. Maximal values were reached after 4-5 h of aldosterone treatment, at which time the transepithelial Na+ current was more than doubled compared to the control. The stimulatory effect was totally inhibited when the aldosterone treatment was preceded by incubation of the lung tissues with spironolactone in 2000-fold excess. In the presence of amiloride (0.5-8 mumol/l) in the alveolar compartment, a Lorentzian noise component appeared in the power spectrum of the fluctuations in the short circuit current. This enabled the calculation of single Na+ channel current and Na+ channel density under both experimental conditions. Aldosterone stimulation did not change single Na+ channel current. On the other hand, the number of conducting Na+ channels increased in parallel with the transepithelial Na+ transport. This suggests that the alveolar epithelium may be a physiological target tissue for aldosterone. Since fluid absorption in the lung is secondary to active Na+ transport, aldosterone may be a potent regulator for maintaining the relatively fluid-free state of the lumen of the lung in some cases of fluid accumulation. PMID:2162035

  12. The difficulties in differential diagnosis of primary aldosteronism subtypes in women with strokes at a young age

    International Nuclear Information System (INIS)

    In patients with primary aldosteronism (PA), it is fundamental to distinguish between subtypes that benefit from different treatment. The authors describe difficulties in differential diagnosis in a case of 46 year old women with PA and two strokes in the past. Based on high plasma and urine aldosterone concentration, low plasma renin activity (PRA), very high aldosterone/PRA ratio and unilateral macroadenoma detected in computed tomography, aldosterone producing adenoma was diagnosed and the patient was performed unilateral adrenalectomy. Despite the surgical treatment the patient still presented with clinical and biochemical PA symptoms. Moreover, histological examination suggested adrenal hyperplasia, and laboratory tests were typical for glucocorticoid-remediable aldosteronism. Unfortunately, we didn't find a chimeric CYP 11β1/CYP 11βb2 gene. Finally, bilateral adrenal hyperplasia was diagnosed and medical treatment with aldosterone antagonist was initiated. (authors)

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

    OpenAIRE

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

    2013-01-01

    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 if, 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 (BMI) ≥ 25 and <...

  14. Chronic Aldosterone Administration Causes NOX2-Mediated Increases In Reactive Oxygen Species Production and Endothelial Dysfunction in the Cerebral Circulation

    Science.gov (United States)

    CHRISSOBOLIS, Sophocles; DRUMMOND, Grant R.; FARACI, Frank M.; SOBEY, Christopher G.

    2014-01-01

    Objective An elevated plasma aldosterone level is an independent cardiovascular risk factor. Although excess aldosterone promotes cardiovascular disease, no studies have examined the effect of increased plasma aldosterone on the cerebral circulation. A major source of vascular reactive oxygen species (ROS) during cardiovascular disease is the NADPH oxidases. Because NOX2-containing NADPH oxidase (NOX2 oxidase) is highly expressed in cerebral endothelium, we postulated that it might contribute to ROS generation and vascular dysfunction in response to aldosterone. Here we examined the effect of aldosterone and NOX2 oxidase on ROS production and endothelial dysfunction in the cerebral circulation, and whether the effects of aldosterone are exacerbated in aged mice. Methods and Results In adult (average age ~24–25 wk) wild-type (WT) and Nox2-deficient (Nox2−/y) mice, neither vehicle nor aldosterone (0.28 mg/kg/day for 14 days) affected blood pressure (measured using tail-cuff). By contrast, aldosterone treatment reduced dilation of the basilar artery (measured using myography) to the endothelium-dependent agonist acetylcholine in WT mice (P0.05). Aldosterone increased basal and phorbol-dibutyrate stimulated superoxide production (measured using L-012-enhanced chemiluminesence) in cerebral arteries from WT but not Nox2−/y mice. In aged WT mice (average age ~70 wk), aldosterone treatment increased blood pressure, but had a similar effect on cerebral artery superoxide levels as in adult WT mice. Conclusions These data indicate that NOX2 oxidase mediates aldosterone-induced increases in ROS production and endothelial dysfunction in cerebral arteries from adult mice independently of blood pressure changes. Aldosterone-induced hypertension is augmented during aging. PMID:24991871

  15. Aldosterone metabolism in the isolated perfused liver of female and male rats

    International Nuclear Information System (INIS)

    A sex-dependent metabolism of aldosterone has been reported in intact rats. To further characterize the hepatic elimination of aldosterone and its sex dependence, the metabolism of d-[4-14C]aldosterone was studied in isolated perfused liver from male and female Wistar rats, from male rats castrated 3 weeks before experiments, and from younger male rats (same body weight as the female rats). The livers were perfused at a constant flow rate in a recirculating mode with a hemoglobin-free medium containing aldosterone at initially 1 nM. Perfusate aldosterone was measured by a specific RIA. Total 4-14C radio-activity in perfusate and bile was determined. The perfusate [4-14C]aldosterone radiometabolite concentration was calculated. The radiometabolite pattern in additional experiments was studied by HPLC. The male rats exhibited 10% higher systolic blood pressure (P less than 0.05) and 51% higher fasting values of plasma aldosterone (P less than 0.05) compared to those in the female rats. In female rats the hepatic clearance rate of aldosterone per 100 g BW was 72% higher than that in male rats (11.2 +/- 2.7 to 6.5 +/- 1.8 ml/min: P less than 0.01), and that expressed per g liver wet wt was 75% higher (3.5 +/- 1.0 to 2.0 +/- 0.7 ml/min; P less than 0.01). When female rats were compared to younger male rats with the same body weight, 33% higher hepatic aldosterone clearance rates were still found in female rats (21.0 +/- 5.4 to 15.8 +/- 3.2 ml/min; P less than 0.05), and 51% higher values when expressed per g liver wet wt (3.5 +/- 1.0 to 2.3 +/- 0.5 ml/min; P less than 0.01). No difference in the aldosterone clearance rate was observed in castrated male rats compared to that in noncastrated male rats. 4-14C-Labeled radiometabolite levels accumulated similarly in the perfusate of livers of both sexes

  16. Effect of canrenone and amiloride on the prooxidative effect induced by aldosterone in human mononuclear leukocytes in vitro.

    Science.gov (United States)

    Fiore, C; Sartorato, P; Pagnin, E; Ragazzi, E; Calò, L A; Armanini, D

    2009-12-01

    Clinical studies have demonstrated that aldosterone receptor antagonists do improve the survival of patients with chronic heart diseases and in vitro studies have shown that canrenone blocks the proinflammatory effect of aldosterone in mononucler leukocytes (MNL). The aim of the study was to compare, in the model of human MNL, the effect of potassium-sparing diuretics amiloride and canrenone, on the protein expression of p22phox, a NADPH-oxidase system subunit, that is a principal marker of production of superoxide anions. MNL were isolated from 10 informed healthy volunteers (5 males and 5 females, age range 24-36 yr) and the proteins extracted. p22phox protein expression was evaluated by Western blot and quantified using a densitometric semiquantitative analysis. The experiments showed that aldosterone (10(-8) M) enhances the protein expression of p22phox and that its effect is reversed by co-incubation with canrenone (10(-6) M), while incubation with amiloride (10(-6) M) reduced the prooxidative effect of aldosterone at a significantly lower extent than canrenone. Co-incubation with canrenone, amiloride, and aldosterone together produced the same effect as aldosterone plus canrenone. Incubation with cortisol (40(-8) M) was not effective. These data confirm the prooxidative effect of aldosterone in MNL. The addition of aldosterone-receptor antagonist canrenone produced a higher inhibition than sodium channel blocker amiloride on the effect of aldosterone on p22phox protein expression. PMID:19509473

  17. 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.

  18. Aldosterone receptor blockers spironolactone and canrenone: two multivalent drugs.

    Science.gov (United States)

    Armanini, Decio; Sabbadin, Chiara; Donà, Gabriella; Clari, Giulio; Bordin, Luciana

    2014-05-01

    Canrenone is a derivative of spironolactone with lower antiandrogen activity. The drug is used only in few countries and can block all the side effects of aldosterone (ALDO). The drug is effective even in the presence of normal concentrations of ALDO. Mineralcorticoid receptor antagonists block the inflammatory activity of ALDO at the level of target tissues as heart, vessels and mononuclear leukocytes. Canrenone reduces the progression of insulin resistance and of microalbuminuria in type 2 diabetes and other related diseases. Both canrenone and hydrochlorothiazide can enhance the effect of treatment with ACE inhibitors and angiotensin II receptor blockers on microalbuminuria, but ALDO receptor blockers are more active. This different action is due to the fact that only canrenone blocks mineralocorticoid receptors. Serum potassium and renal function should be monitored before and during the treatment. ALDO receptor blockers are recommended in addition to polytherapy for resistant hypertension, but there are no studies on the effect of the drug as first-choice therapy. PMID:24617854

  19. Aldosterone induces fibrosis, oxidative stress and DNA damage in livers of male rats independent of blood pressure changes

    Energy Technology Data Exchange (ETDEWEB)

    Queisser, Nina; Happ, Kathrin; Link, Samuel [Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg (Germany); Jahn, Daniel [Division of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg (Germany); Zimnol, Anna [Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg (Germany); Geier, Andreas [Division of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg (Germany); Schupp, Nicole, E-mail: schupp@uni-duesseldorf.de [Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg (Germany)

    2014-11-01

    Mineralocorticoid receptor blockers show antifibrotic potential in hepatic fibrosis. The mechanism of this protective effect is not known yet, although reactive oxygen species seem to play an important role. Here, we investigated the effects of elevated levels of aldosterone (Ald), the primary ligand of the mineralocorticoid receptor, on livers of rats in a hyperaldosteronism model: aldosterone-induced hypertension. Male Sprague–Dawley rats were treated for 4 weeks with aldosterone. To distinguish if damage caused in the liver depended on increased blood pressure or on increased Ald levels, the mineralocorticoid receptor antagonist spironolactone was given in a subtherapeutic dose, not normalizing blood pressure. To investigate the impact of oxidative stress, the antioxidant tempol was administered. Aldosterone induced fibrosis, detected histopathologically, and by expression analysis of the fibrosis marker, α-smooth muscle actin. Further, the mRNA amount of the profibrotic cytokine TGF-β was increased significantly. Fibrosis could be reduced by scavenging reactive oxygen species, and also by blocking the mineralocorticoid receptor. Furthermore, aldosterone treatment caused oxidative stress and DNA double strand breaks in livers, as well as the elevation of DNA repair activity. An increase of the transcription factor Nrf2, the main regulator of the antioxidative response could be observed, and of its target genes heme oxygenase-1 and γ-glutamylcysteine synthetase. All these effects of aldosterone were prevented by spironolactone and tempol. Already after 4 weeks of treatment, aldosteroneinfusion induced fibrosis in the liver. This effect was independent of elevated blood pressure. DNA damage caused by aldosterone might contribute to fibrosis progression when aldosterone is chronically increased. - Highlights: • Aldosterone has direct profibrotic effects on the liver independent of blood pressure. • Fibrosis is mediated by the mineralocorticoid receptor and

  20. Aldosterone induces fibrosis, oxidative stress and DNA damage in livers of male rats independent of blood pressure changes

    International Nuclear Information System (INIS)

    Mineralocorticoid receptor blockers show antifibrotic potential in hepatic fibrosis. The mechanism of this protective effect is not known yet, although reactive oxygen species seem to play an important role. Here, we investigated the effects of elevated levels of aldosterone (Ald), the primary ligand of the mineralocorticoid receptor, on livers of rats in a hyperaldosteronism model: aldosterone-induced hypertension. Male Sprague–Dawley rats were treated for 4 weeks with aldosterone. To distinguish if damage caused in the liver depended on increased blood pressure or on increased Ald levels, the mineralocorticoid receptor antagonist spironolactone was given in a subtherapeutic dose, not normalizing blood pressure. To investigate the impact of oxidative stress, the antioxidant tempol was administered. Aldosterone induced fibrosis, detected histopathologically, and by expression analysis of the fibrosis marker, α-smooth muscle actin. Further, the mRNA amount of the profibrotic cytokine TGF-β was increased significantly. Fibrosis could be reduced by scavenging reactive oxygen species, and also by blocking the mineralocorticoid receptor. Furthermore, aldosterone treatment caused oxidative stress and DNA double strand breaks in livers, as well as the elevation of DNA repair activity. An increase of the transcription factor Nrf2, the main regulator of the antioxidative response could be observed, and of its target genes heme oxygenase-1 and γ-glutamylcysteine synthetase. All these effects of aldosterone were prevented by spironolactone and tempol. Already after 4 weeks of treatment, aldosteroneinfusion induced fibrosis in the liver. This effect was independent of elevated blood pressure. DNA damage caused by aldosterone might contribute to fibrosis progression when aldosterone is chronically increased. - Highlights: • Aldosterone has direct profibrotic effects on the liver independent of blood pressure. • Fibrosis is mediated by the mineralocorticoid receptor and

  1. Alterations in vascular function in primary aldosteronism: a cardiovascular magnetic resonance imaging study.

    Science.gov (United States)

    Mark, P B; Boyle, S; Zimmerli, L U; McQuarrie, E P; Delles, C; Freel, E M

    2014-02-01

    Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV). We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass. Subjects with PA had significantly lower aortic distensibility and higher PWV compared with EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including ageing. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular ageing. As expected, aortic distensibility and PWV were closely correlated. These results demonstrate that PA patients display increased arterial stiffness compared with EH, independent of vascular ageing. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study. PMID:23884211

  2. Aldosterone and the mineralocorticoid receptor in the cerebral circulation and stroke

    Directory of Open Access Journals (Sweden)

    Dinh Quynh N

    2012-10-01

    Full Text Available Abstract Ischemic stroke is a leading cause of morbidity and mortality worldwide. Elevated plasma aldosterone levels are an independent cardiovascular risk factor and are thought to contribute to hypertension, a major risk factor for stroke. Evidence from both experimental and human studies supports a role for aldosterone and/or the mineralocorticoid receptor (MR in contributing to detrimental effects in the cerebral vasculature and to the incidence and outcome of ischemic stroke. This article reviews the evidence, including the protective effects of MR antagonism. Specifically, the effects of aldosterone and/or MR activation on cerebral vascular structure and on immune cells will be reviewed. The existing evidence suggests that aldosterone and the MR contribute to cerebral vascular pathology and to the incidence and outcome of stroke. We suggest that further research into the signaling mechanisms underlying the effects of aldosterone and MR activation in the brain and its vasculature, especially with regard to cell-specific actions, will provide important insight into causes and potential treatments for cerebrovascular disease and stroke.

  3. Cistrome of the aldosterone-activated mineralocorticoid receptor in human renal cells.

    Science.gov (United States)

    Le Billan, Florian; Khan, Junaid A; Lamribet, Khadija; Viengchareun, Say; Bouligand, Jérôme; Fagart, Jérôme; Lombès, Marc

    2015-09-01

    Aldosterone exerts its effects mainly by activating the mineralocorticoid receptor (MR), a transcription factor that regulates gene expression through complex and dynamic interactions with coregulators and transcriptional machinery, leading to fine-tuned control of vectorial ionic transport in the distal nephron. To identify genome-wide aldosterone-regulated MR targets in human renal cells, we set up a chromatin immunoprecipitation (ChIP) assay by using a specific anti-MR antibody in a differentiated human renal cell line expressing green fluorescent protein (GFP)-MR. This approach, coupled with high-throughput sequencing, allowed identification of 974 genomic MR targets. Computational analysis identified an MR response element (MRE) including single or multiple half-sites and palindromic motifs in which the AGtACAgxatGTtCt sequence was the most prevalent motif. Most genomic MR-binding sites (MBSs) are located >10 kb from the transcriptional start sites of target genes (84%). Specific aldosterone-induced recruitment of MR on the first most relevant genomic sequences was further validated by ChIP-quantitative (q)PCR and correlated with concomitant and positive aldosterone-activated transcriptional regulation of the corresponding gene, as assayed by RT-qPCR. It was notable that most MBSs lacked MREs but harbored DNA recognition motifs for other transcription factors (FOX, EGR1, AP1, PAX5) suggesting functional interaction. This work provides new insights into aldosterone MR-mediated renal signaling and opens relevant perspectives for mineralocorticoid-related pathophysiology. PMID:26054365

  4. 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.

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

    Science.gov (United States)

    McEneaney, Victoria; Dooley, Ruth; Yusef, Yamil R; Keating, Niamh; Quinn, Ursula; Harvey, Brian J; Thomas, Warren

    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. PMID:20434520

  6. Aldosterone induces myofibroblast EGF secretion to regulate epithelial colonic permeability.

    Science.gov (United States)

    Miró, Lluïsa; Pérez-Bosque, Anna; Maijó, Mònica; Amat, Concepció; Naftalin, Richard J; Moretó, Miquel

    2013-05-01

    In vivo studies show that raised aldosterone (Aldo) during low-Na adaptation regulates the growth of pericryptal myofibroblasts and reduces the permeability of the colonic epithelium. The aim of this study was to reproduce in vitro the in vivo condition of increased Aldo using human CCD-18Co myofibroblasts and T84 colonic epithelial cells to measure myofibroblast and epithelial proliferation and the expression of intercellular junction proteins. Proliferation was quantified by measuring 5-bromo-2'-deoxyuridine incorporation. The myofibroblast expression of EGF, VEGFa, and transforming growth factor-β1 (TGF-β1) was measured by real-time PCR and the expression of junctional complex proteins by Western blot. Aldo stimulated the proliferation of myofibroblasts by 70% (P < 0.05) and increased EGF mRNA expression by 30% (P < 0.05) without affecting VEGFa and TGF-β1. EGF concentration in the incubation medium increased by 30% (P < 0.05) 24 h after Aldo addition, and these effects were prevented by the addition of spironolactone. Myofibroblast proliferation in response to Aldo was mediated by EGF receptor (EGFR) and involved both MAPKK and phosphatidylinositol 3-kinase pathways. When T84 cells were incubated with medium from myofibroblasts stimulated with Aldo (conditioned medium), the expression of β-catenin and claudin IV was increased by 30% (P < 0.05) and proliferation by 40% (P < 0.05). T84 proliferation decreased when α-EGF, or the EGFR antagonist AG1478, was present. Results in vivo indicate that rats fed a low-salt diet showed an increased expression of EGF and EGFR in the colonic mucosa. These results support the view that changes in colonic permeability during low-Na adaptation are mediated by the EGF secreted by myofibroblasts in response to raised Aldo. PMID:23467299

  7. Long-term treatment with aldosterone slows the progression of age-related hearing loss.

    Science.gov (United States)

    Halonen, Joshua; Hinton, Ashley S; Frisina, Robert D; Ding, Bo; Zhu, Xiaoxia; Walton, Joseph P

    2016-06-01

    Age-related hearing loss (ARHL), clinically referred to as presbycusis, is one of the three most prevalent chronic medical conditions of our elderly, with the majority of persons over the age of 60 suffering from some degree of ARHL. The progressive loss of auditory sensitivity and perceptual capability results in significant declines in workplace productivity, quality of life, cognition and abilities to communicate effectively. Aldosterone is a mineralocorticoid hormone produced in the adrenal glands and plays a role in the maintenance of key ion pumps, including the Na-K(+)-Cl co-transporter 1 or NKCC1, which is involved in homeostatic maintenance of the endocochlear potential. Previously we reported that aldosterone (1 μM) increases NKCC1 protein expression in vitro and that this up-regulation of NKCC1 was not dose-dependent (dosing range from 1 nM to 100 μM). In the current study we measured behavioral and electrophysiological hearing function in middle-aged mice following long-term systemic treatment with aldosterone. We also confirmed that blood pressure remained stable during treatment and that NKCC1 protein expression was upregulated. Pre-pulse inhibition of the acoustic startle response was used as a functional measure of hearing, and the auditory brainstem response was used as an objective measure of peripheral sensitivity. Long-term treatment with aldosterone improved both behavioral and physiological measures of hearing (ABR thresholds). These results are the first to demonstrate a protective effect of aldosterone on age-related hearing loss and pave the way for translational drug development, using aldosterone as a key component to prevent or slow down the progression of ARHL. PMID:27157488

  8. Diagnosing and Managing Primary Aldosteronism in Hypertensive Patients: a Case-Based Approach.

    Science.gov (United States)

    Carey, Robert M

    2016-10-01

    Primary aldosteronism with a prevalence of 8 % of hypertension and 20 % of pharmacologically resistant hypertension is the most common secondary cause of hypertension. Yet, the diagnosis is missed in the vast majority of patients. Current clinical practice guidelines recommend screening for primary aldosteronism in patients with sustained elevation of blood pressure (BP) ≥150/100 mmHg if possible prior to initiation of antihypertensive therapy, and in patients with resistant hypertension, spontaneous or diuretic-induced hypokalemia, adrenal incidentaloma, obstructive sleep apnea, a family history of early onset of hypertension or cerebrovascular accident management are systematically reviewed and illustrated with a clinical case. PMID:27566330

  9. Independent effects of aldosterone and potassium on induction of potassium adaptation in rat kidney.

    OpenAIRE

    Stanton, B.; Pan, L.; Deetjen, H; Guckian, V; Giebisch, G

    1987-01-01

    We examined the independent effects of a high potassium diet and increased aldosterone levels on the development of renal potassium adaptation. This condition is defined by the increased ability of the kidneys to excrete an acute infusion of potassium. Rats were adrenalectomized (ADX) and received aldosterone at basal levels (0.5 microgram/100 g X d) or at high levels (2.0 micrograms/100 g X d) for 10 d. In each experimental group, animals received either a control diet or a high potassium di...

  10. Antiaging Gene Klotho Regulates Adrenal CYP11B2 Expression and Aldosterone Synthesis.

    Science.gov (United States)

    Zhou, Xiaoli; Chen, Kai; Wang, Yongjun; Schuman, Mariano; Lei, Han; Sun, Zhongjie

    2016-06-01

    Deficiency of the antiaging gene Klotho (KL) induces renal damage and hypertension through unknown mechanisms. In this study, we assessed whether KL regulates expression of CYP11B2, a key rate-limiting enzyme in aldosterone synthesis, in adrenal glands. We found that haplodeficiency of KL(+/-) in mice increased the plasma level of aldosterone by 16 weeks of age, which coincided with spontaneous and persistent elevation of BP. Blockade of aldosterone actions by eplerenone reversed KL deficiency-induced hypertension and attenuated the kidney damage. Protein expression of CYP11B2 was upregulated in adrenal cortex of KL(+/-) mice. KL and CYP11B2 proteins colocalized in adrenal zona glomerulosa cells. Silencing of KL upregulated and overexpression of KL downregulated CYP11B2 expression in human adrenocortical cells. Notably, silencing of KL decreased expression of SF-1, a negative transcription factor of CYP11B2, but increased phosphorylation of ATF2, a positive transcription factor of CYP11B2, which may contribute to upregulation of CYP11B2 expression. Therefore, these results show that KL regulates adrenal CYP11B2 expression. KL deficiency-induced spontaneous hypertension and kidney damage may be partially attributed to the upregulation of CYP11B2 expression and aldosterone synthesis. PMID:26471128

  11. Effect of Salvia Miltiorrhiza on Left Ventricular Hypertrophy and Cardiac Aldosterone in Spontaneously Hypertensive Rats

    Institute of Scientific and Technical Information of China (English)

    韩少杰; 郑智; 任大宏

    2002-01-01

    Summary: Chronic treatment with Salvia Miltiorrhiza preventing left ventricular hypertrophy(LVH) and its possible mechanism-inhibiting the action of cardiac aldosterone in spontaneouslyhypertensive rats (SHR) were investigated. Normotensive Wistar-kyoto (WKY) rats and SHRswere used. Part of SHRs was treated with Salvia Miltiorrhiza for 12 weeks. Systolic blood pres-sure (SBP) and left ventricular mass index were measured. Sections of heart tissue were stainedwith HE method and VanGieson method. Collagen volume fraction was determined in the left ven-tricle by automatically quantitative morphometry. Cardiac aldosterone concentration was measuredby radioimmunoassay. The results indicated that compared with WKY rats, SHRs exhibited high-er SBP, left ventricular collagen volume fraction, and aldosterone concentration (all P<0. 05).After the treatment with Salvia Miltiorrhiza, SBP, left ventricular collagen volume fraction, andaldosterone concentration in SHR were decreased as compared with control group (P<0. 05) ex-cept SBP. It was concluded that chronic treatment with Salvia Miltiorrhiza could prevent left ven-tricular hypertrophy in SHR, significantly inhibit collagen compositions in left ventricle. Themechanism was probably related with the inhibition of the cardiac aldosterone action.

  12. 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 si

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

    Science.gov (United States)

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

    2013-09-01

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

  14. 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. PMID:25631218

  15. Clinical Implication of the Renin-angiotensin-aldosterone Blockers in Chronic Kidney Disease Undergoing Hemodialysis

    OpenAIRE

    Morishita, Yoshiyuki; Kusano, Eiji; Nagata, Daisuke

    2014-01-01

    The renin-angiotensin-aldosterone system (RAAS) blockers have been widely used in chronic kidney disease patients undergoing hemodialysis; however, whether RAAS blockers have beneficial effects for cardiovascular disease in those patients has not been fully defined. This review focuses on the effects of RAAS blockers in chronic kidney disease undergoing hemodialysis for cardiovascular disease.

  16. In vivo left ventricular function and collagen expression in aldosterone/salt-induced hypertension.

    Science.gov (United States)

    Ramirez-Gil, J F; Delcayre, C; Robert, V; Wassef, M; Trouve, P; Mougenot, N; Charlemagne, D; Lechat, P

    1998-12-01

    Cardiac fibrosis is linked to aldosterone-induced hypertension, but the effects on in vivo left ventricular (LV) function are not established. We studied the relations between in vivo LV function and aldosterone/salt cardiac fibrosis. Adult guinea pigs (GPs) were treated for 3 months with an aldosterone infusion and high-salt diet. This treatment induced arterial hypertension (+35%) and moderate LV hypertrophy (LVH; +60%) without right ventricular (RV) hypertrophy. Echo-Doppler LV assessment demonstrated unaltered cardiac output, stroke volume, or LV relaxation. Type I collagen messenger RNA (mRNA) was significantly increased in both ventricles (LV, +48%; RV, +77%) and accompanied by a significant increase in total collagen deposition (LV, from 0.52% in controls to 4.4% in treated GPs; RV, from 0.82 to 5.5% in treated GPs). Plasma norepinephrine levels increased 2.6-fold (p < 0.01) and correlated with the increase in collagen deposition in both ventricles. Collagen content was not correlated with hypertension or LVH. We conclude that aldosterone administration induces cardiac collagen accumulation and a sympathetic stimulation, which might preserve systolic and diastolic function. PMID:9869498

  17. 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 andsodium restriction on vascular health. Body weight, serum aldosterone, 24-h sodium and potassium excretion and obesity-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 Pleptin, insulin, homeostasis assessment of insulin resistance, heart rate, tonic cardiac sympathovagal balance and increases in adiponectin (all Psodium and potassium excretion. Weight loss and reductions in thigh intermuscular fat (intermuscular adipose tissue area; IMAT) were associated with decreases in aldosterone in the subgroup (n=98) with metabolic syndrome (MetS) at baseline (MetS × weight loss, P=0.04; MetS × change in IMAT, P=0.04). Favorable changes in obesity-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. PMID:23657296

  18. Aldosterone-induced oxidative stress and inflammation in the brain are mediated by the endothelial cell mineralocorticoid receptor.

    Science.gov (United States)

    Dinh, Quynh N; Young, Morag J; Evans, Megan A; Drummond, Grant R; Sobey, Christopher G; Chrissobolis, Sophocles

    2016-04-15

    Elevated aldosterone levels, which promote cerebral vascular oxidative stress, inflammation, and endothelial dysfunction, may increase stroke risk, independent of blood pressure and other risk factors. The main target receptor of aldosterone, the mineralocorticoid receptor (MR), is expressed in many cell types, including endothelial cells. Endothelial cell dysfunction is thought to be an initiating step contributing to cardiovascular disease and stroke; however the importance of MR expressed on endothelial cells in the brain is unknown. Here we have examined whether endothelial cell MR mediates cerebral vascular oxidative stress and brain inflammation during aldosterone excess. In male mice, aldosterone (0.72mg/kg/day, 14 days) caused a small increase (~14mmHg) in blood pressure. The MR blocker spironolactone (25mg/kg/d, ip) abolished this increase, whereas endothelial cell MR-deficiency had no effect. Aldosterone increased superoxide production capacity in cerebral arteries, and also mRNA expression of the pro-inflammatory cytokines chemokine (C-C motif) ligand 7 (CCL7), CCL8 and interleukin (IL)-1β in the brain. These increases were prevented by both spironolactone treatment and endothelial cell MR-deficiency; whereas IL-1β expression was blocked by spironolactone only. Endothelial cell MR mediates aldosterone-induced increases in cerebrovascular superoxide levels and chemokine expression in the brain, but not blood pressure or brain IL-1β. Endothelial cell-targeted MR antagonism may represent a novel approach to treat cerebrovascular disease and stroke, particularly during conditions of aldosterone excess. PMID:26923165

  19. Blood pressure in patients with primary aldosteronism is influenced by bradykinin B(2) receptor and alpha-adducin gene polymorphisms.

    Science.gov (United States)

    Mulatero, Paolo; Williams, Tracy A; Milan, Alberto; Paglieri, Cristina; Rabbia, Franco; Fallo, Francesco; Veglio, Franco

    2002-07-01

    Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA is most frequently presented as moderate to severe hypertension, but the clinical and biochemical features vary widely. The aim of our study was to identify genetic variants that influence the phenotype of patients with PA. We hypothesized that genetic variants potentially affecting aldosterone production (aldosterone synthase, CYP11B2), renal proximal tubule reabsorption (alpha-adducin), or the mechanisms of counterbalance leading to vasodilatation and sodium excretion (bradykinin B(2)-receptor, B(2)R) could influence the clinical and biochemical characteristics of patients with PA. We studied three polymorphisms of these genes (C-344T of CYP11B2, G460W of alpha-adducin, and C-58T of B(2)R) in 167 primary aldosteronism patients (56 with aldosterone-producing adenoma and 111 with idiopathic hyperaldosteronism). B(2)R and alpha-adducin genotypes were strong independent predictors of both systolic and diastolic blood pressure levels; plasma renin activity and aldosterone also play a marginal role on BP levels. Body mass index, age, sex, and CYP11B2 genotype displayed no significant effect on the clinical parameters of our population. In particular, alpha-adducin and B(2)R polymorphisms accounted for 13.2% and 11.0% of the systolic and diastolic blood pressure variance, respectively. These data suggest that genetic variants of alpha-adducin and the bradykinin B(2)-R influence the blood pressure levels in patients with primary aldosteronism. PMID:12107246

  20. Progress of Aldosterone Breakthroughs%醛固酮逃逸的研究进展

    Institute of Scientific and Technical Information of China (English)

    郭建淑

    2011-01-01

    Renin-angiotensin-aldosterone system inhibitors have become leading drugs in the treatment of hypertension and chronic heart failure. Angiotensin-converting-enzyme inhibitors( ACEI) and angiotensin-receptor blockers ( ARB) do not, however, uniformly suppress the renin-angiotensin-aldosterone system. After a period of therapy with ACEI or ARB, plasma aldosterone levels are elevated in some patients. This phenomenon, is known as 'aldosterone escape' or 'aldosterone breakthrough'. The key questions of how breakthrough happens , how often breakthrough occurs and whether breakthrough leads, to worse outcomes have yet to be definitively answered. This review summarizes reported research on the incidence and mechanism of aldosterone breakthrough, we also discuss the difference of aldosterone breakthrough during the treatment with ACEI or ARB.%肾素-血管紧张素-醛固酮系统抑制剂已成为治疗高血压及心力衰竭的主要药物,然而血管紧张素转换酶抑制剂与血管紧张素Ⅱ受体拮抗剂并没有充分的阻断过度激活的肾素-血管紧张素-醛固酮系统.在经过血管紧张素转换酶抑制剂或血管紧张素Ⅱ受体拮抗剂治疗一段时间后,一部分患者血浆醛固酮水平有所升高,即"醛固酮逃逸现象".该现象的发生率及机制,对临床治疗的影响等重要问题一直不完全清楚,现就醛固醛逃逸现象的发生率、机制、在血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂治疗中的区别等在近年的研究进展做一概要的综述.

  1. Leptin Induces Hypertension and Endothelial Dysfunction via Aldosterone-Dependent Mechanisms in Obese Female Mice.

    Science.gov (United States)

    Huby, Anne-Cécile; Otvos, Laszlo; Belin de Chantemèle, Eric J

    2016-05-01

    Obesity is a major risk factor for cardiovascular disease in males and females. Whether obesity triggers cardiovascular disease via similar mechanisms in both the sexes is, however, unknown. In males, the adipokine leptin highly contributes to obesity-related cardiovascular disease by increasing sympathetic activity. Females secrete 3× to 4× more leptin than males, but do not exhibit high sympathetic tone with obesity. Nevertheless, females show inappropriately high aldosterone levels that positively correlate with adiposity and blood pressure (BP). We hypothesized that leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in females. Leptin control of the cardiovascular function was analyzed in female mice sensitized to leptin via the deletion of protein tyrosine phosphatase 1b (knockout) and in agouti yellow obese hyperleptinemic mice (Ay). Hypersensitivity to leptin (wild-type, 115±2; protein tyrosine phosphatase 1b knockout, 124±2 mm Hg;Pantagonism restored BP and endothelial function in protein tyrosine phosphatase 1b knockout and Ay mice. Hypersensitivity to leptin and obesity reduced BP response to ganglionic blockade in both strains and plasma catecholamine levels in protein tyrosine phosphatase 1b knockout mice. Hypersensitivity to leptin and obesity significantly increased plasma aldosterone levels and adrenal CYP11B2 expression. Chronic leptin receptor antagonism reduced aldosterone levels. Furthermore, chronic leptin and mineralocorticoid receptor blockade reduced BP and improved endothelial function in both leptin-sensitized and obese hyperleptinemic female mice. Together, these data demonstrate that leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in female mice and suggest that obesity leads to cardiovascular disease via sex-specific mechanisms. PMID:26953321

  2. Effect of Acute Exercise on ANP-Induced Inhibition of Aldosterone Release in Rat Adrenals

    OpenAIRE

    SUDA, Kazuhiro; Hagiwara, Hiromi; Komabayashi, Takao; Izawa, Tetsuya; Imai, Hajime; Hayashi, Tomoya; Era, Seiichi

    2004-01-01

    SUDA, K., HAGIWARA, H., KOMABAYASHI, T., IZAWA, T., IMAI, H., HAYASHI, T. and ERA, s., Effect of Acute Exercise on ANP-Induced Inhibition of Aldosterone Release in Rat Adrenals. Abv. Exerc. Sports Physiol., Vol.10, No.2 pp.43-47, 2004. We intide (ANP)-induced inhibition of aldosterone release in rat adrenals. The rats ran on treadmill for two hours. Immediately after the exercise, the adrenals were excised and used for an aldosterone release experiment, an ANP binding assay, and a guanylate c...

  3. Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three somatic mutations near the KCNJ5 potassium channel selectivity filter.

    Directory of Open Access Journals (Sweden)

    Tobias Åkerström

    Full Text Available BACKGROUND: Aldosterone producing lesions are a common cause of hypertension, but genetic alterations for tumorigenesis have been unclear. Recently, either of two recurrent somatic missense mutations (G151R or L168R was found in the potassium channel KCNJ5 gene in aldosterone producing adenomas. These mutations alter the channel selectivity filter and result in Na(+ conductance and cell depolarization, stimulating aldosterone production and cell proliferation. Because a similar mutation occurs in a mendelian form of primary aldosteronism, these mutations appear to be sufficient for cell proliferation and aldosterone production. The prevalence and spectrum of KCNJ5 mutations in different entities of adrenocortical lesions remain to be defined. MATERIALS AND METHODS: The coding region and flanking intronic segments of KCNJ5 were subjected to Sanger DNA sequencing in 351 aldosterone producing lesions, from patients with primary aldosteronism and 130 other adrenocortical lesions. The specimens had been collected from 10 different worldwide referral centers. RESULTS: G151R or L168R somatic mutations were identified in 47% of aldosterone producing adenomas, each with similar frequency. A previously unreported somatic mutation near the selectivity filter, E145Q, was observed twice. Somatic G151R or L168R mutations were also found in 40% of aldosterone producing adenomas associated with marked hyperplasia, but not in specimens with merely unilateral hyperplasia. Mutations were absent in 130 non-aldosterone secreting lesions. KCNJ5 mutations were overrepresented in aldosterone producing adenomas from female compared to male patients (63 vs. 24%. Males with KCNJ5 mutations were significantly younger than those without (45 vs. 54, respectively; p<0.005 and their APAs with KCNJ5 mutations were larger than those without (27.1 mm vs. 17.1 mm; p<0.005. DISCUSSION: Either of two somatic KCNJ5 mutations are highly prevalent and specific for aldosterone producing

  4. 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...

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

    Science.gov (United States)

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

    2013-12-12

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

  6. 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

  7. Single-port laparoscopic adrenalectomy for a right-sided aldosterone-producing adenoma: a case report

    OpenAIRE

    Sasaki Akira; Baba Shigeaki; Obuchi Toru; Umemura Akira; Mizuno Masaru; Wakabayashi Go

    2012-01-01

    Abstract Introduction Single-port laparoscopic adrenalectomy is one of the most interesting surgical advances. Here, we evaluate the safety and feasibility of single-port laparoscopic adrenalectomy as treatment for a right-sided aldosterone-producing adenoma. Case presentation A 39-year-old Japanese woman presented with hypertension and hypokalemia. Abdominal computed tomography and an endocrinological workup revealed a 19mm right adrenal tumor with primary aldosteronism. Our patient was info...

  8. Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney.

    Science.gov (United States)

    Stowasser, Michael; Gordon, Richard D

    2016-10-01

    In the 60 years that have passed since the discovery of the mineralocorticoid hormone aldosterone, much has been learned about its synthesis (both adrenal and extra-adrenal), regulation (by renin-angiotensin II, potassium, adrenocorticotrophin, and other factors), and effects (on both epithelial and nonepithelial tissues). Once thought to be rare, primary aldosteronism (PA, in which aldosterone secretion by the adrenal is excessive and autonomous of its principal regulator, angiotensin II) is now known to be the most common specifically treatable and potentially curable form of hypertension, with most patients lacking the clinical feature of hypokalemia, the presence of which was previously considered to be necessary to warrant further efforts towards confirming a diagnosis of PA. This, and the appreciation that aldosterone excess leads to adverse cardiovascular, renal, central nervous, and psychological effects, that are at least partly independent of its effects on blood pressure, have had a profound influence on raising clinical and research interest in PA. Such research on patients with PA has, in turn, furthered knowledge regarding aldosterone synthesis, regulation, and effects. This review summarizes current progress in our understanding of the physiology of aldosterone, and towards defining the causes (including genetic bases), epidemiology, outcomes, and clinical approaches to diagnostic workup (including screening, diagnostic confirmation, and subtype differentiation) and treatment of PA. PMID:27535640

  9. An additional child case of an aldosterone-producing adenoma with an atypical presentation of peripheral paralysis due to hypokalemia.

    Science.gov (United States)

    Dinleyici, E C; Dogruel, N; Acikalin, M F; Tokar, B; Oztelcan, B; Ilhan, H

    2007-11-01

    Aldosterone-producing adenoma, which is characterized by hypertension, hypokalemia, and elevated aldosterone levels with suppressed plasma renin activity, is a rare condition during childhood and is also potentially curable. To the best of our knowledge, nearly 25 cases of childhood aldosterone-secreting adenoma have been reported in the literature to date. Here we describe a 13-yr-old girl with primary hyperaldosteronism secondary to aldosterone-secreting adenoma. The patient was admitted to our hospital with the neuromuscular complaints of muscle weakness and inability to walk due to hypokalemia. She had been misdiagnosed as having hypokalemic periodic paralysis 2 months before admission and her symptoms had radically improved with potassium supplementation. However, her blood pressure levels had increased and her symptoms reappeared 2 days prior to being observed during hospitalization in our institution. Laboratory examinations revealed hypokalemia (2.1 mEq/l), and increased serum aldosterone levels with suppressed plasma renin activity. Abdominal ultrasonography and abdominal magnetic resonance imaging revealed left adrenal mass. Laparoscopic adrenalectomy was performed and histopathological examinations showed benign adrenal adenoma. Serum aldosterone levels and blood pressure levels returned to normal after surgical intervention. This case demonstrates the importance of a systemic evaluation including blood pressure monitorization of children with hypokalemia as intermittent hypertension episodes may be seen; cases without hypertension may be misdiagnosed as rheumatological or neurological disorders such as hypokalemic periodic paralysis, as in our case. PMID:18075291

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

    Science.gov (United States)

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

    2016-08-01

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

  11. Zero gravity and cardiovascular homeostasis. The relationship between endogenous hyperprolactinemia and plasma aldosterone. Summary report, 1 February 1977--31 January 1978

    International Nuclear Information System (INIS)

    Prolactin, thyrotropin, and aldosterone were measured by radioimmunoassay and plasma renin activity by the radioimmunoassay of angiotensin I in normal women before and after the intravenous injection of 200 μg of thyrotropin-releasing-hormone. Prolactin increased at 15 min following injection of thyrotropin-releasing-hormone. Plasma renin activity was not different from control levels during the first hour following the administration of thyrotropin-releasing-hormone, nor did the plasma aldosterone concentration differ significantly from the control levels during this period. However, with upright posture, an increase in aldosterone and in plasma renin activity was noted, demonstrating a normal capacity to secrete aldosterone. Similarly, no change in aldosterone was seen in 9 patients with primary hypothyroidism given thyrotropin-releasing hormone, despite the fact that the increase in prolactin was greater than normal. These data demonstrate that acutely or chronically elevated serum prolactin levels do not result in increased plasma aldosterone levels in humans

  12. Zero gravity and cardiovascular homeostasis. The relationship between endogenous hyperprolactinemia and plasma aldosterone. Summary report, 1 February 1977--31 January 1978

    Energy Technology Data Exchange (ETDEWEB)

    Haber, E.; Re, R.N.; Kourides, I.A.; Weihl, A.C.; Maloof, F.

    1978-01-31

    Prolactin, thyrotropin, and aldosterone were measured by radioimmunoassay and plasma renin activity by the radioimmunoassay of angiotensin I in normal women before and after the intravenous injection of 200 ..mu..g of thyrotropin-releasing-hormone. Prolactin increased at 15 min following injection of thyrotropin-releasing-hormone. Plasma renin activity was not different from control levels during the first hour following the administration of thyrotropin-releasing-hormone, nor did the plasma aldosterone concentration differ significantly from the control levels during this period. However, with upright posture, an increase in aldosterone and in plasma renin activity was noted, demonstrating a normal capacity to secrete aldosterone. Similarly, no change in aldosterone was seen in 9 patients with primary hypothyroidism given thyrotropin-releasing hormone, despite the fact that the increase in prolactin was greater than normal. These data demonstrate that acutely or chronically elevated serum prolactin levels do not result in increased plasma aldosterone levels in humans.

  13. The role of aldosterone receptor blocker therapy in hypertension and heart failure

    Directory of Open Access Journals (Sweden)

    Giuseppina Santese

    2015-09-01

    Full Text Available The aldosterone receptor blocker therapy as an “add-on” to hypotensive therapy is an excellent therapeutic strategy that has proved to be particularly effective in treating refractory hypertension, hypertension with organ damage and overweight hypertensive patients. Aldosterone receptor blockers are extremely useful in inhibiting hormonal activation linked with heart failure: they have cardioprotective effects not only during full-blown heart failure, but also in its early stages, and this effect can be observed even more frequently in heart failures with metabolic syndrome. The use of molecules such as canrenone with a favorable tolerability profile ensures a better tolerability ratio by providing benefits linked to fewer drug interactions, lower incidence of side effects and improved therapy adherence.

  14. 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

    Objective: Low salt intake or infusion with the mineralocorticoid hormone aldosterone increases the abundance of proteolytically activated gamma ENaC in rat kidney. Prostasin is a serine proteinase GPI-anchored to the apical membrane of renal principal cells. It was hypothesized that the aldoster......Objective: Low salt intake or infusion with the mineralocorticoid hormone aldosterone increases the abundance of proteolytically activated gamma ENaC in rat kidney. Prostasin is a serine proteinase GPI-anchored to the apical membrane of renal principal cells. It was hypothesized...... and in concentrated urine samples no difference was detected between placebo and spironolactone group by ELISA while western immunoblotting showed correlation of urine prostasin with albumin and a reduction in both with spironolactone. Patients with proteinuria displayed elevated u-prostasin compared to control...

  15. Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation.

    Science.gov (United States)

    Fakitsas, Panagiotis; Adam, Gabriele; Daidié, Dorothée; van Bemmelen, Miguel X; Fouladkou, Fatemeh; Patrignani, Andrea; Wagner, Ulrich; Warth, Richard; Camargo, Simone M R; Staub, Olivier; Verrey, François

    2007-04-01

    The mineralocorticoid hormone aldosterone controls sodium reabsorption and BP largely by regulating the cell-surface expression and function of the epithelial sodium channel (ENaC) in target kidney tubules. Part of the stimulatory effect of aldosterone on ENaC is mediated by the induction of serum- and glucocorticoid-regulated kinase 1 (Sgk1), a kinase that interferes with the ubiquitylation of ENaC by ubiquitin-protein ligase Nedd4-2. In vivo early aldosterone-regulated mRNA now has been identified in microselected mouse distal nephron by microarray. From 22 mRNA that displayed a two-fold or more change, 13 were downregulated and nine were upregulated. Besides Sgk1, the induced mRNA include Grem2 (protein related to DAN and cerebrus [PRDC]), activating transcription factor 3, cAMP responsive element modulator, and the ubiquitin-specific protease Usp2-45. The induction of this last enzyme isoform was verified in mouse distal nephron tubule at the protein level. With the use of Hek293 cells, Xenopus oocytes, and mpkCCD(c14) cells as expression systems, it was shown that Usp2-45 deubiquitylates ENaC and stimulates ENaC-mediated sodium transport, an effect that is not additive to that of Sgk1. A deubiquitylating enzyme that targets ENaC in vitro and thus may play a role in sodium transport regulation was identified within a series of new in vivo early aldosterone-regulated gene products. PMID:17344426

  16. Aldosterone-Induced Inflammation in the Rat Heart : Role of Oxidative Stress

    OpenAIRE

    Sun, Yao; Zhang, Jiakun; Lu, Li; Chen, Sue S.; Quinn, Mark T.; Weber, Karl T.

    2002-01-01

    Heart failure and hypertension have each been linked to an induction of oxidative stress transduced by neurohormones, such as angiotensin II and catecholamines. Herein, we hypothesized that aldosterone (ALDO) likewise induces oxidative stress and accounts for a proinflammatory/fibrogenic phenotype that appears at vascular and nonvascular sites of injury found in both right and left ventricles in response to ALDO/salt treatment and that would be sustained with chronic treatment. Uninephrectomi...

  17. Association of KCNJ5 gene missense mutations with aldosterone-producing adenoma and primary hyperaldosteronism

    Institute of Scientific and Technical Information of China (English)

    邵丹

    2013-01-01

    Objective To detect the KCNJ5 gene variations in aldosterone-producing adenoma (APA) with primary hyperaldosteronism (PA) ,and to investigate the association of the KCNJ5 gene missense mutations with APA and PA.Methods A total of 46 APA tumors and their clinical characteristics were collected from Hypertension Center of the People’s Hospital of Xinjiang Uygur Autonomous Region,and all the tumors were confirmed by pathology.

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

    International Nuclear Information System (INIS)

    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. Enhanced Soluble Serum CD40L and Serum P-Selectin Levels in Primary Aldosteronism.

    Science.gov (United States)

    Petramala, L; Iacobellis, G; Carnevale, R; Marinelli, C; Zinnamosca, L; Concistrè, A; Galassi, M; Iannucci, G; Lucia, P; Pignatelli, P; Ciardi, A; Violi, F; De Toma, G; Letizia, C

    2016-07-01

    Primary aldosteronism (PA) is one of the most frequent forms of secondary hypertension, associated with atherosclerosis and higher risk of cardiovascular events. Platelets play a key role in the atherosclerotic process. The aim of the study was to evaluate the platelet activation by measuring serum levels of soluble CD40L (sCD40L) and P-selectin (sP-selectin) in consecutive PA patients [subgroup: aldosterone-secreting adrenal adenoma (APA) and bilateral adrenal hyperplasia (IHA)], matched with essential hypertensive (EH) patients. The subgroup of APA patients was revaluated 6-months after unilateral adrenalectomy. In all PA group, we measured higher serum levels of both sP-selectin (14.29±9.33 pg/ml) and sCD40L (9.53±4.2 ng/ml) compared to EH patients (9.39±5.3 pg/ml and 3.54±0.94 ng/ml, respectively; pAPA, PA patients showed significant reduction of blood pressure (BP) values, plasma aldosterone (PAC) levels and ARR-ratio, associated with a significant reduction of sP-selectin (16.74±8.9 pg/ml vs. 8.1±3.8 pg/ml; pAPA patients (r=0.54; pAPA patients. PMID:27101095

  20. Ambulatory Blood Pressure Monitoring-Derived Short-Term Blood Pressure Variability in Primary Aldosteronism.

    Science.gov (United States)

    Grillo, Andrea; Bernardi, Stella; Rebellato, Andrea; Fabris, Bruno; Bardelli, Moreno; Burrello, Jacopo; Rabbia, Franco; Veglio, Franco; Fallo, Francesco; Carretta, Renzo

    2015-08-01

    The aim of this study was to investigate the short-term blood pressure (BP) variability (BPV) derived from ambulatory blood pressure monitoring (ABPM) in patients with primary aldosteronism (PA), either idiopathic hyperaldosteronism (IHA) or aldosterone-producing adenoma (APA), in comparison with patients with essential hypertension (EH) and normotensive (NT) controls. Thirty patients with PA (16 with IHA and 14 with APA), 30 patients with EH, and 30 NT controls, matched for sex, age, body mass index, and antihypertensive therapy, were studied. The standard deviation (SD) of 24-hour, daytime, and nighttime BP; 24-hour weighted SD of BP; and 24-hour BP average real variability were not different between patients with PA and those with EH (P=not significant). All BPV indices were higher in patients with PA, either IHA or APA subtypes, and patients with EH, compared with NT controls (P<.001 to P<.05). ABPM-derived short-term BPV is increased in patients with PA, and it may represent an additional cardiovascular risk factor in this disease. The role of aldosterone excess in BPV has to be clarified. PMID:25880017

  1. Primary aldosteronism caused by unilateral adrenal hyperplasia: rethinking the accuracy of imaging studies.

    Science.gov (United States)

    Chen, Su-Yu; Shen, Sjen-Jung; Chou, Chien-Wen; Yang, Chwen-Yi; Cheng, Hon-Mei

    2006-03-01

    A rare type of aldosteronism, known as unilateral adrenal hyperplasia (UAH), is difficult to diagnose, not only because it fails to conform to the typical common subtypes, but also because imaging results are unreliable. We report 2 Taiwanese patients with UAH. Case 1 was a 44-year-old man with 2 episodes of hypokalemic paralysis. Hypertension and suppressed plasma renin activity (PRA) with elevated plasma aldosterone concentration (PAC) were observed. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) showed a right adrenal mass, but adrenal scintigraphy revealed no definite laterality. The patient underwent a laparoscopic right adrenalectomy. Adrenal cortical hyperplasia was discovered from results of the histologic analysis. Case 2 was a 33-year-old woman referred for hypokalemia, hypertension, and a left adrenal mass found on a CT scan. However, MRI revealed normal adrenal glands. The adrenal vein sampling for PAC showed overproduction of PAC from the left adrenal gland. A laparoscopic left adrenalectomy was done. Pathology results revealed micronodular cortical hyperplasia with central hemorrhage. Blood pressure, plasma potassium, aldosterone, and renin activity levels returned to normal after operation in both cases. Both patients have been well for 3 years and 16 months, respectively, after surgery. We review the literature and discuss the limitations of imaging studies. PMID:16599018

  2. A Rare Cause of Hypokalemia: Aldosterone-Secreting Adrenocortical Carcinoma Dear Editor,

    Directory of Open Access Journals (Sweden)

    Ethem Turgay Cerit

    2014-03-01

    Full Text Available Adrenocortical carcinoma (ACC is a rare malignancy accounting for 0.05-0.2% of all cancers (1. Determinants of prognosis are the stage of disease and completeness of resection(2. Approximately 60% of ACCs are hormonally active and glucocorticoids and/or androgens are most frequently over-secreted (2. Rapid development of signs and symptoms of Cushing’s syndrome is the most frequent presentation (3. Aldosterone-secreting ACC is extremely uncommon, comprising 0% to 7% of all functioning ACCs and presents with severe hypertension and profound hypokalemia (4. Here we report a case diagnosed as aldosterone producing adrenocortical carcinoma presented with severe hypokalemia and hypertension. A 32-year-old man referred to our instution because of pain and marked weakness especially in his lower extremities for 2 months. On admission his blood pressure was 180 mmHg systolic and 110 mmHg diastolic. Laboratory investigation revealed severe hypokalemia (2.6 mmol/l (normal: 3.5-5.5 mmol/l, elevated serum aldosterone (39.0 ng/dl (normal: 0.8-13 ng/dl with suppressed plasma renin activity (0.07 ng/ml/h. Serum sodium level was 142 mmol/l (normal: 135-146 mmol/l. Serum aldosterone level was not supressed (38.2 ng/dl after saline infusion test. Serum dehydroepiandrosterone sulfate (DHEA-SO4 was 150 mcg/dl (normal: 80-560, Δ4-androstenedione was 1.91 ng/ml (normal: 0.5-4.8 and total testosterone was 447.3 ng/dl (normal: 229.8-799.8 (Table 1. Suppressed renin levels, increased aldosterone levels with an aldosterone/renin ratio >30 were suggestive findings of aldosterone-producing adenoma of the adrenal gland or bilateral adrenal hyperplasia. Computed tomography demonstrated a large (4.6 cm left-sided adrenal tumour which is heterogeneous and has lobulated margin without a contrasting pattern of adenoma (Figure 1. 24-h urinary catecholamines and low-dose dexamethasone-suppressed plasma cortisol concentrations were all normal. At surgery, an adrenal mass (70

  3. Molecular identity and gene expression of aldosterone synthase cytochrome P450

    International Nuclear Information System (INIS)

    11β-Hydroxylase (CYP11B1) of bovine adrenal cortex produced corticosterone as well as aldosterone from 11-deoxycorticosterone in the presence of the mitochondrial P450 electron transport system. CYP11B1s of pig, sheep, and bullfrog, when expressed in COS-7 cells, also performed corticosterone and aldosterone production. Since these CYP11B1s are present in the zonae fasciculata and reticularis as well as in the zona glomerulosa, the zonal differentiation of steroid production may occur by the action of still-unidentified factor(s) on the enzyme-catalyzed successive oxygenations at C11- and C18-positions of steroid. In contrast, two cDNAs, one encoding 11β-hydroxylase and the other encoding aldosterone synthase (CYP11B2), were isolated from rat, mouse, hamster, guinea pig, and human adrenals. The expression of CYP11B1 gene was regulated by cyclic AMP (cAMP)-dependent signaling, whereas that of CYP11B2 gene by calcium ion-signaling as well as cAMP-signaling. Salt-inducible protein kinase, a cAMP-induced novel protein kinase, was one of the regulators of CYP11B2 gene expression

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

    Science.gov (United States)

    Jin, Ze-Ning; Wei, Yong-Xiang

    2016-01-01

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

  5. Diagnostic performance of CT versus MR in detecting aldosterone-producing adenoma in primary hyperaldosteronism (Conn's syndrome)

    International Nuclear Information System (INIS)

    The aim of the present study is to compare the diagnostic performance of CT and MR imaging in detecting aldosterone-producing adenoma and to compare the interobserver variability in the detection of an aldosterone-producing adenoma on CT and MR. A retrospective study of 34 patients with primary hyperaldosteronism was performed. A total of 17 cases of aldosterone-producing adenoma and 17 cases of bilateral adrenal hyperplasia were included. The final diagnosis of an adenoma was made by surgery with histological confirmation, whereas that of bilateral adrenal hyperplasia was made on adrenal venous sampling or a good biochemical and clinical response following medical treatment alone and in the absence of a unilateral radiological abnormality. The CT (n=30) and MR (n=24) scans were reviewed independently by two radiologists experienced in adrenal imaging, who were unaware of the cause of the primary hyperaldosteronism. The diagnostic performances of both observers in detecting an aldosterone-producing adenoma on CT and MR imaging were compared. The 16 adenomatous nodules that were detected on imaging ranged from 1 to 4.75 cm in diameter. The calculated sensitivity and specificity for detecting aldosterone-producing adenoma were 87 and 93% for one observer and 85 and 82% for the other observer on CT, and 83 and 83% for one observer and 92 and 92% for the other observer on MR, respectively. Receptor operating characteristics curve analysis showed similar performances of both observers in detecting an aldosterone-producing adenoma on CT and MR imaging. There was good interobserver agreement on CT (k=0.71) and on MR (k=0.67). We have demonstrated comparable diagnostic performance and good interobserver agreement on CT and MR imaging for the detection of aldosterone-producing adenoma. (orig.)

  6. Studies on the subcommissural organ area in the rat: the effects aldosterone infused into the central nervous system

    International Nuclear Information System (INIS)

    D-aldosterone (5 ng/μl/hr) was infused for six days into the area of the subcommissural organ (SCO) of conscious rats to test the hypothesis that the SCO and the adrenal zona glomerulosa are related functionally in a negative feedback manner. Aldosterone increased urinary sodium loss and the sodium/potassium ratio. These effects still occurred when cannulae were displaced caudally up to 1 mm from the targeted SCO area. Aldosterone decreased the cross-sectional area of the adrenal medulla without affecting chromaffin cell density. Adrenal content of corticosterone was increased. These effects were highly dependent upon proper cannula placement and were not observed when the tip of the cannula was not in contact with the cerebrospinal fluid of the pineal recess over the rostral two-thirds of the SCO. Aldosterone infused intracerebroventricularly (ivt) into a lateral ventricle had no effect on sodium excretion, adrenal corticosterone concentration or adrenal morphology. After the infusion of radiolabelled aldosterone into the SCO area, the majority of the radioactivity was restricted to an area about 1-2 mm in diameter from the SCO. Iron-dextran injected intraperiotoneally did not accumulate in the SCO; therefore, the blood-brain barrier is intact. It is concluded that the effects of aldosterone were dependent upon the area of the brain in which it was infused. Aldosterone increased sodium excretion by an action in the SCO and/or adjacent structures. A relationship between mineralocorticoids and the adrenal modulla mediated by the SCO is also postulated. With regard to the blood-brain and brain-CSF barriers, the SCO more closely resembles general brain tissue than other circumventricular organs

  7. 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.

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

    Science.gov (United States)

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

    2013-12-01

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

  9. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Yan-Huan Feng; Ping Fu

    2016-01-01

    Objective: To examine the efficacy and safety of dual blockade of the renin-angiotensin-aldosterone system (RAAS) among patients with type 2 diabetic kidney disease.Data Sources: We searched the major literature repositories, including the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE, for randomized clinical trials published between January 1990 and October 2015 that compared the efficacy and safety of the use of dual blockade of the RAAS versus the use ofmonotherapy, 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 evidence-based practice.

  11. Hypokalemic myopathy associated with primary aldosteronism and glycyrrhizine-induced pseudoaldosteronism.

    Science.gov (United States)

    Ishikawa, S; Saito, T; Okada, K; Atsumi, T; Kuzuya, T

    1985-12-01

    Enzymatic and histological features of muscular disorders associated with primary aldosteronism and glycyrrhizine-induced pseudoaldosteronism were studied. Among 10 patients with primary aldosteronism and 3 patients with pseudoaldosteronism, 5 patients were admitted to our hospital because of muscular weakness. The serum potassium (K) level was 1.86 +/- 0.21 mEq/l in a myopathy group on admission, a value significantly less than that of the 2.74 +/- 0.10 mEq/l in a non-myopathy group (p less than 0.01). Serum creatine phosphokinase (CPK), glutamate-oxyloacetate transaminase (GOT), and lactate dehydrogenase (LDH) were increased in the myopathy group compared to the non-myopathy group; serum CPK was 1412.6 +/- 902.6 vs. 22.8 +/- 5.0 mU/ml, serum GOT was 186.4 +/- 75.3 vs. 24.2 +/- 5.4 mU/ml (p less than 0.05), and serum LDH was 1133.4 +/- 377.3 vs. 387.6 +/- 42.5 mU/ml (p less than 0.05) in the groups with and without myopathy. Analysis of CPK isozymes revealed that the MM type exceeded 95%. The elevated serum CPK, GOT and LDH rapidly decreased to the normal range and muscular strength completely improved within 6 to 13 days after hospitalization, when the serum K level remained below than normal. Light microscopic finding of damaged muscle showed the diffuse necrosis and vacuolization of muscle fibers. Electron microscopic study clearly demonstrated complete dissolution of myofilaments with disappearance of sarcoplasmic reticulum and T-tubules in the necrotic muscle fibers. These results indicate that muscular lesions may occur in primary aldosteronism and pseudoaldosteronism when the serum K level is decreased to below 2.0 mEq/l. This myopathy is not periodic paralysis but hypokalemic myopathy. The mechanism by which K deficiency causes muscular damage remains unknown. PMID:3914413

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

    Science.gov (United States)

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

    2015-03-15

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

  13. 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

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

    International Nuclear Information System (INIS)

    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)

  15. The first laparoscopic resection of an aldosterone-secreting adrenocortical oncocytoma in a child

    Directory of Open Access Journals (Sweden)

    Melih Akin

    2014-09-01

    Full Text Available Oncocytomas of the adrenal cortex are usually benign and nonfunctional, consisting of oncocytes in which the cytoplasm becomes eosinophilic due to the accumulation of abnormal mitochondria. Oncocytomas can exist in many organs and are frequently found in the salivary gland, kidneys, thyroid gland, parathyroid gland, and hypophysis. Functioning oncocytomas are very rarely observed in children, and no more than ten cases have been reported in the literature. Here, we present the first report of laparoscopic excision of an aldosterone-secreting adrenocortical oncocytoma in a child.

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

    International Nuclear Information System (INIS)

    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)

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

    Science.gov (United States)

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

    2016-08-01

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

  18. A Rare Presentation of Primary Hyperparathyroidism with Concurrent Aldosterone-Producing Adrenal Carcinoma

    Directory of Open Access Journals (Sweden)

    Mario Molina-Ayala

    2015-01-01

    Full Text Available Aldosterone-producing adrenocortical carcinomas are an extremely rare cause of hyperaldosteronism (<1%. Coexistence of different endocrine tumors warrants additional screening for multiple endocrine neoplasia syndromes, especially in young patients with large or malignant masses. We present the case of a 40-year-old man with a history of hypertension that presented with an incidental left adrenal tumor during an ultrasound performed for nephrolithiasis. Biochemical assessment showed a mildly elevated calcium (11.1 mg/dL, high parathyroid hormone, and a plasma aldosterone concentration/plasma renin activity ratio of 124.5 (normal < 30, compatible with primary hyperparathyroidism with a concomitant primary hyperaldosteronism. A Tc99m-MIBI scintigraphy showed an abnormally increased tracer uptake in the right superior parathyroid and abdominal computed tomography confirmed a left adrenal tumor of 20 cm. The patient underwent parathyroidectomy and adrenalectomy with final pathology reports of parathyroid hyperplasia and adrenal carcinoma with biochemical remission of both endocrinopathies. He was started on chemotherapy, but the patient developed a frontal cortex and an arm metastasis and finally died less than one year later.

  19. Aldosterone-secreting adrenal cortical carcinoma. A case report and review of the literature.

    Science.gov (United States)

    Griffin, Adrienne Carruth; Kelz, Rachel; LiVolsi, Virginia A

    2014-09-01

    Adrenal cortical carcinomas (ACC) are rare, typically aggressive malignant neoplasms with a reported incidence of 1-2 cases per 1 million population and account for 0.05-0.2 % of all malignancies. The majority of these tumors are functional with approximately 60 % of patients experiencing endocrine symptomatology typically characterized by Cushing's syndrome (40 %) or a mixed hormonal picture of Cushing syndrome seen in association with virilization. Rarely, patients present with a pure hormonal syndrome of feminization or hyperaldosteronism, 6 and 2.5 %, respectively. We report a case of a 76-year-old woman presenting with recently diagnosed hypertension secondary to primary hyperaldosteronism. The patient underwent laparoscopic converted to an open adrenalectomy and a diagnosis of adrenocortical carcinoma (aldosteronoma clinical) was rendered. This case and review of the literature highlight that while rare, aldosterone-secreting adrenal cortical carcinomas may occur. In this case report, we discuss the clinical presentation, pathologic findings, and review the literature for adrenal cortical carcinomas and aldosterone-secreting adrenal cortical carcinomas. PMID:24682757

  20. Mineralocorticoid receptor is involved in the aldosterone pathway in human red blood cells.

    Science.gov (United States)

    Bordin, Luciana; Saccardi, Carlo; Donà, Gabriella; Sabbadin, Chiara; Andrisani, Alessandra; Ambrosini, Guido; Plebani, Mario; Brunati, Anna Maria; Ragazzi, Eugenio; Gizzo, Salvatore; Armanini, Decio

    2016-01-01

    We have recently demonstrated that excessive aldosterone (Aldo) secretion in primary aldosteronism (PA) is associated with red blood cells (RBC) senescence. These alterations were prevented/inhibited by cortisol (Cort) or canrenone (Can) raising the hypothesis that Aldo effects in RBC may be mediated by mineralocorticoid receptor (MR), though to date MR has never been demonstrated in human RBC. The aim of this multicenter comparative study was to investigate whether Aldo effects were mediated by MR in these a-nucleated cells. We included 12 healthy controls (HC) and 22 patients with PA. MR presence and activation were evaluated in RBC cytosol by glycerol gradient sedimentation, Western blotting, immuno-precipitation and radioimmunoassay. We demonstrated that RBC contained cytosolic MR, aggregated with HSP90 and other proteins to form multiprotein complex. Aldo induced MR to release from the complex and to form MR dimers which were quickly proteolyzed. Cort induced MR release but not dimers formation while Can was not able to induce MR release. In addition, RBC cytosol from PA patients contained significantly higher amounts of both MR fragments (p<0.0001) and Aldo (p<0.0001) concentrations. In conclusion, in RBC a genomic-like Aldo pathway is proposed involving MR activation, dimerization and proteolysis, but lacking nuclear transcription. In addition, dimers proteolysis may ensure a sort of Aldo scavenging from circulation by entrapping Aldo in MR fragments. PMID:27158328

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

    International Nuclear Information System (INIS)

    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 210C 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 35-420C 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 (P0C 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.

  2. Comparison of eplerenone and spironolactone for the treatment of primary aldosteronism.

    Science.gov (United States)

    Karashima, Shigehiro; Yoneda, Takashi; Kometani, Mitsuhiro; Ohe, Masashi; Mori, Shunsuke; Sawamura, Toshitaka; Furukawa, Kenji; Seta, Takashi; Yamagishi, Masakazu; Takeda, Yoshiyu

    2016-03-01

    The mineralocorticoid receptor (MR) is expressed in the kidneys and in adipose tissue, and primary aldosteronism (PA) is associated with metabolic syndrome. This study assessed the effects of MR blockade by eplerenone (EPL) and spironolactone (SPL) on blood pressure (BP) and metabolic factors in patients with PA. Fifty-four patients with PA were treated with one of two MRAs, EPL (25-100 mg daily, n=27) or SPL (12.5-100 mg daily, n=27) for 12 months. Visceral (VAT) and subcutaneous adipose tissue were quantified using CT and FatScan imaging analysis software. Body mass index, homeostasis model assessment-insulin resistance (HOMA-IR), serum creatinine, potassium and lipids, urinary albumin excretion (UAE) and plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were measured before and after treatment. EPL and SPL decreased BP and increased serum potassium levels to similar degrees. PAC and PRA did not differ between the two groups. Although treatment with the MRAs did not change HOMA-IR or serum lipids, they significantly decreased UAE and VAT (PEPL and SPL are effective and safe for the treatment of PA. The long-term metabolic and renal effects of these MRAs should be further investigated. PMID:26606875

  3. 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

    2003-01-01

    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 a

  4. [A case of primary aldosteronism presenting hypokalemic myopathy induced by benidipine hydrochloride; a dihydropyridine calcium channel blocker].

    Science.gov (United States)

    Sugawara, H; Shiraiwa, H; Otsuka, M; Ueki, A

    2000-05-01

    We report a 46-year-old man with primary aldosteronism presenting hypokalemia, periodic paralysis and hypokalemic myopathy whose clinical course paralleled with the dosage of benidipine hydrochloride, a dihydropyridine calcium channel blocker (DHP-CCB), administered for the treatment of hypertension. To see relations between DHP-CCB and episodes of motor weakness in patients with primary aldosteronism, we surveyed retrospectively the history of motor weakness and anti-hypertensive drugs in 14 consecutive cases with primary aldosteronism in our institute. Five patients out of 11 cases (45.5%) who had received DHP-CCB experienced muscle weakness, however, the rest of three patients receiving other anti-hypertensive drug had not experienced weakness. Though, less attention has been paid as thiazide diuretics, it is reported that DHP-CCB also induces hypokalemia through several mechanisms. However, the occurrence of motor weakness by DHP-CCB is very rare. Our results show that primary aldosteronism should be taken into account when we encounter patients manifesting episodic motor weakness by the use of DHP-CCB. PMID:11002726

  5. Systemic effects of angiotensin III in conscious dogs during acute double blockade of the renin-angiotensin-aldosterone-system

    DEFF Research Database (Denmark)

    Gammelgaard, Iben; Wamberg, Søren; Bie, Peter

    2006-01-01

    increased mean arterial blood pressure (+14 +/- 4 mmHg) and plasma aldosterone by 79% (+149 +/- 17 pg mL(-1)) and reduced plasma renin activity and sodium excretion (-41 +/- 16 mIU L(-1) and -46 +/- 6 micromol min(-1) respectively). AngIII mimicked these effects and the magnitude of AngIII responses was...

  6. The role of the epithelial Na+ channel (ENaC in high AVP but low aldosterone states

    Directory of Open Access Journals (Sweden)

    James D Stockand

    2012-07-01

    Full Text Available Due to the abundance of seminal discoveries establishing a strong causal relation between changes in aldosterone signaling, the activity of the epithelial Na+ channel (ENaC and blood pressure, the role of ENaC in health and disease is understood almost exclusively through the concept that this channel functions (in the distal nephron as a key end-effector controlling renal sodium excretion during feedback regulation of blood pressure by the renin-angiotensin-aldosterone system (RAAS. Recent findings of aldosterone-independent stimulation of ENaC by vasopressin challenge the completeness of dogmatic understanding where ENaC serves solely as an end-effector of the RAAS important for control of sodium balance. Rather the consequences of activating ENaC in the distal nephron appear to depend on whether the channel is activated in the absence (by aldosterone or presence (by AVP of simultaneous activation of aquaporin 2 water channels. Thus, a unifying paradigm has ENaC at the junction of two signaling systems that sometimes must compete: one controlling and responding to changes in sodium balance, perceived as mean arterial pressure, and the other water balance, perceived as plasma osmolality.

  7. Moderate inappropriately high aldosterone/NaCl constellation in mice: cardiovascular effects and the role of cardiovascular epidermal growth factor receptor.

    Science.gov (United States)

    Schreier, Barbara; Rabe, Sindy; Winter, Sabrina; Ruhs, Stefanie; Mildenberger, Sigrid; Schneider, Bettina; Sibilia, Maria; Gotthardt, Michael; Kempe, Sabine; Mäder, Karsten; Grossmann, Claudia; Gekle, Michael

    2014-01-01

    Non-physiological activation of the mineralocorticoid receptor (MR), e.g. by aldosterone under conditions of high salt intake, contributes to the pathogenesis of cardiovascular diseases, although beneficial effects of aldosterone also have been described. The epidermal growth factor receptor (EGFR) contributes to cardiovascular alterations and mediates part of the MR effects. Recently, we showed that EGFR is required for physiological homeostasis and function of heart and arteries in adult animals. We hypothesize that moderate high aldosterone/NaCl, at normal blood pressure, affects the cardiovascular system depending on cardiovascular EGFR. Therefore we performed an experimental series in male and female animals each, using a recently established mouse model with EGFR knockout in vascular smooth muscle cells and cardiomyocytes and determined the effects of a mild-high aldosterone-to-NaCl constellation on a.o. marker gene expression, heart size, systolic blood pressure, impulse conduction and heart rate. Our data show that (i) cardiac tissue of male but not of female mice is sensitive to mild aldosterone/NaCl treatment, (ii) EGFR knockout induces stronger cardiac disturbances in male as compared to female animals and (iii) mild aldosterone/NaCl treatment requires the EGFR in order to disturb cardiac tissue homeostasis whereas beneficial effects of aldosterone seem to be independent of EGFR. PMID:25503263

  8. A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery.

    Science.gov (United States)

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

    2016-06-01

    Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl(-1) and aldosterone renin activity ratio of 90.2 (ng dl(-1) per ng ml(-1 )h(-1)), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl(-1) confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production. PMID:26538381

  9. 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

  10. Primary Aldosteronism

    Science.gov (United States)

    ... Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Glands and Types of Hormones Brainy Hormones What ... Health Hormones and Health Journey Through the Endocrine System Endocrine Glands and Types of Hormones Brainy Hormones What ...

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

    Science.gov (United States)

    Werner, Christian; Pöss, Janine; Böhm, Michael

    2010-07-01

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

  12. Aldosterone and angiotensin II induced protein aggregation in renal proximal tubules

    DEFF Research Database (Denmark)

    Cheema, Muhammad Umar; Poulsen, Ebbe Toftgaard; Enghild, Jan J; Hoorn, Ewout; Fenton, Robert A; Praetorius, Jeppe

    2013-01-01

    systems in the kidney from control rats and rats receiving aldosterone or angiotensin II treatment for 7 days. Control rats formed both aggresomes and autophagosomes specifically in the proximal tubules, indicating a need for these structures even under baseline conditions. Fluorescence sorted aggresomes...... apparent change in the aggresome-autophagosome markers. Angiotensin II induced aggregation of RPL27 specifically in proximal tubules, again without apparent change in antiaggregating proteins or the aggresome-autophagosome markers. Albumin endocytosis was unaffected by the hormone administration. Taken...... together, we find that the renal proximal tubules display aggresome formation and autophagy. Despite an increase in aggregation-prone protein load in these tubules during hormone treatment, renal proximal tubules seem to have sufficient capacity for removing protein aggregates from the cells....

  13. Diastolic heart failure in the elderly and the potential role of aldosterone antagonists.

    Science.gov (United States)

    Kumar, Ashwani; Meyerrose, Gary; Sood, Vineeta; Roongsritong, Chanwit

    2006-01-01

    The overall incidence of heart failure increases with age, affecting up to 10% of people >65 years of age. Diastolic heart failure is also age-dependent, increasing from 40% in patients > or =70 years of age. Elderly patients usually have other co-morbid conditions such as hypertension, diabetes mellitus, coronary artery disease and atrial fibrillation that can adversely affect the diastolic properties of the heart. The clinical manifestations of diastolic heart failure are similar to those of systolic heart failure. In practice, the diagnosis is generally based on the finding of typical symptoms and signs of heart failure with preserved left ventricular ejection fraction and no valvular abnormalities on echocardiography. Altered ventricular relaxation and abnormal ventricular filling are the hallmarks of diastolic heart failure. Cardiac fibrosis and cellular disarray lead to the alterations in the diastolic properties of the heart. Diffuse foci of fibrosis in the myocardium have been reported with advancing age. Aldosterone has been shown to play a crucial role in the development of cardiac fibrosis via a direct effect on the mineralocorticoid receptors within the myocardium. Unlike the situation with treatment of systolic heart failure, few clinical trials are available to guide the management of patients with diastolic heart failure. In the absence of controlled clinical trials, patient management is based on control of the physiological factors (blood pressure, heart rate, blood volume and myocardial ischaemia) that are known to exert important effects on ventricular relaxation. Aldosterone antagonists inhibit the deposition of collagen matrix in the myocardium, thereby targeting the basic pathophysiological mechanism of diastolic dysfunction. Thus, they appear to represent a promising therapeutic approach for this condition. Currently, only small clinical trials supporting this therapy are available and large clinical trials evaluating long-term outcomes in

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

    International Nuclear Information System (INIS)

    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 131I-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, 131I-adosterol scintigraphy, and ACTH-AVS in determining the appropriate therapy. (author)

  15. 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.

  16. Fast Nongenomic Effect of Aldosterone on the Volume of Principal Cells in Collecting Tube and Genetic Heterogeneity of Epithelial Sodium Channel in the Postnatal Ontogenesis of Rat Kidney.

    Science.gov (United States)

    Logvinenko, N S; Gerbek, Yu E; Solenov, E I; Ivanova, L N

    2016-03-01

    The effects of amiloride, epithelial sodium pump inhibitor, on the fast nongenomic effect of aldosterone in principal cells of an isolated segment of the distal portion of renal collecting tubes were studied in 10-day-old and adult rats. Fluorescent staining with Calcein AM showed various effects of amiloride (10(-5) M) on the stabilizing effect of aldosterone (10 nM) in hypotonic shock (280/140 mOsm/kg). Amiloride attenuated by 30% the effect of aldosterone on the amplitude of principal cell swelling in adult animals and almost completely abolished this effect in 10-day rats (p<0.05). These age-specific differences in the contribution of the distal portion of the collecting tube to the nongenomic effect of aldosterone did not depend on genetic heterogeneity of its α-subunit. PMID:27021081

  17. CACNA1H(M1549V) Mutant Calcium Channel Causes Autonomous Aldosterone Production in HAC15 Cells and Is Inhibited by Mibefradil.

    Science.gov (United States)

    Reimer, Esther N; Walenda, Gudrun; Seidel, Eric; Scholl, Ute I

    2016-08-01

    We recently demonstrated that a recurrent gain-of-function mutation in a T-type calcium channel, CACNA1H(M1549V), causes a novel Mendelian disorder featuring early-onset primary aldosteronism and hypertension. This variant was found independently in five families. CACNA1H(M1549V) leads to impaired channel inactivation and activation at more hyperpolarized potentials, inferred to cause increased calcium entry. We here aimed to study the effect of this variant on aldosterone production. We heterologously expressed empty vector, CACNA1H(WT) and CACNA1H(M1549V) in the aldosterone-producing adrenocortical cancer cell line H295R and its subclone HAC15. Transfection rates, expression levels, and subcellular distribution of the channel were similar between CACNA1H(WT) and CACNA1H(M1549V). We measured aldosterone production by an ELISA and CYP11B2 (aldosterone synthase) expression by real-time PCR. In unstimulated cells, transfection of CACNA1H(WT) led to a 2-fold increase in aldosterone levels compared with vector-transfected cells. Expression of CACNA1H(M1549V) caused a 7-fold increase in aldosterone levels. Treatment with angiotensin II or increased extracellular potassium levels further stimulated aldosterone production in both CACNA1H(WT)- and CACNA1H(M1549V)-transfected cells. Similar results were obtained for CYP11B2 expression. Inhibition of CACNA1H channels with the T-type calcium channel blocker Mibefradil completely abrogated the effects of CACNA1H(WT) and CACNA1H(M1549V) on CYP11B2 expression. These results directly link CACNA1H(M1549V) to increased aldosterone production. They suggest that calcium channel blockers may be beneficial in the treatment of a subset of patients with primary aldosteronism. Such blockers could target CACNA1H or both CACNA1H and the L-type calcium channel CACNA1D that is also expressed in the adrenal gland and mutated in patients with primary aldosteronism. PMID:27258646

  18. Clinical significance of renin-angiotensin-aldosterone system, endothelin and nitric oxide in renal hypertension and adrenocorticoadenomas

    International Nuclear Information System (INIS)

    Objective: To investigate the roles of renin-angiotensin system (RAS) and aldosterone (ALD), endothelin (ET), nitric oxide (NO) in patients with renal hypertension (30 cases) and adrenocorticoadenomas (35 cases), 30 normal subjects were included in the study as controls. Methods: Radioimmunoassay (RIA) was used to determine the plasma concentrations of the renin, angiotensin II, aldosterone, endothelin (ET) in the above cases. Enzymic assay was adopted to examine the plasma concentration of the nitric oxide synthase (NOS). Results: The plasma concentrations of renin, angiotensin II, aldosterone, endothelin, NOS in control group were 1.04 +- 0.90 ng/ml/h, 71.06 +- 16.18 pg/ml, 144.77 +- 32.57 pg/ml, 45.86 +- 20.85 pg/ml, 32.2 +- 4.61 U/ml respectively. The concentration in renal hypertension patients were 7.53 +- 2.23 ng/ml/h, 144.77 +- 68.45 pg/ml, 261.07 +- 73.03 pg/ml, 96.72 +- 31.36 pg/ml, 28.8 +- 6.14 U/ml, respectively, all of the above items were significantly higher than those in the control group (p<0.01) except with the concentration of NOS , which were lower than that in controls (p<0.05). The plasma concentrations of the renin, angiotensin II, ALD, ET, NOS in the patients with adrenocorticoadenomas were 0.55 +- 0.47 ng/ml/h, 71.85 +- 17.85 pg/ml, 247.03 +- 84.03 pg/ml, 81.83 +- 28.38 pg/ml, 32.34 +- 9.02 U/ml, respectively the ALD, ET were higher than those in controls (p<0.01) but renin all AII were lower (p<0.05). Conclusion: The plasma concentrations of renin, angiotensin II, aldosterone in the patients with renal hypertension were higher than those in the controls. The patients with adrenocortical adenoma secreted a lot of ALD, thereby feedback inhibited secretion of the renin all AII. The aldosterone played an important role in the renal adenoma and renal hypertension. Determination of the plasma renin, angio-tension, aldosterone and NO might be able to and NO diagnose renal hypertension and adrenocorticoadenoma earlier

  19. 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.......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....

  20. THE ASSOCIATIONS OF ADIPOKINES WITH SELECTED MARKERS OF THE RENIN-ANGIOTENSINOGEN-ALDOSTERONE SYSTEM: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS

    OpenAIRE

    Allison, Matthew A.; Jenny, Nancy Swords; McClelland, Robyn L.; Cushman, Mary; Rifkin, Dena

    2014-01-01

    Among obese individuals, increased sympathetic nervous system activity results in increased renin and aldosterone production, as well as renal tubular sodium reabsorption. This study determined the associations between adipokines and selected measures of the reninangiotensinogen-aldosterone system (RAAS). The sample was 1,970 men and women from the Multi-Ethnic Study of Atherosclerosis who were free of clinical cardiovascular disease at baseline and had blood assayed for adiponectin, leptin, ...

  1. 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

    OpenAIRE

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

    2015-01-01

    Objectives: The present study investigated the effects of aqueous extract of Hibiscus sabdariffa (HS) on the three basic components of renin-angiotensin-aldosterone system: Plasma renin, serum angiotensin-converting enzyme (ACE), and plasma aldosterone (PA) in mild to moderate essential hypertensive Nigerians and compared with that of lisinopril, an ACE inhibitor. Materials and Methods: A double-blind controlled randomized clinical study was used. Seventy-eight newly diagnosed but untreate...

  2. 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.

  3. 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

    International Nuclear Information System (INIS)

    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

  4. The associations of adipokines with selected markers of the renin-angiotensinogen-aldosterone system: the multi-ethnic study of atherosclerosis.

    Science.gov (United States)

    Allison, M A; Jenny, N S; McClelland, R L; Cushman, M; Rifkin, D

    2015-02-01

    Among obese individuals, increased sympathetic nervous system (SNS) activity results in increased renin and aldosterone production, as well as renal tubular sodium reabsorption. This study determined the associations between adipokines and selected measures of the renin-angiotensinogen-aldosterone system (RAAS). The sample consisted of 1970 men and women from the Multi-Ethnic Study of Atherosclerosis who were free of clinical cardiovascular disease at baseline and had blood assayed for adiponectin, leptin, plasma renin activity (PRA) and aldosterone. The mean age was 64.7 years and 50% were female. The mean (s.d.) PRA and aldosterone were 1.45 (0.56) ng ml(-1) and 150.1 (130.5) pg ml(-1), respectively. After multivariable adjustment, a 1-s.d. increment of leptin was associated with a 0.55 ng ml(-1) higher PRA and 8.4 pg ml(-1) higher aldosterone (Pleptin and adiponectin were not materially changed with additional adjustment for PRA. Exclusion of those taking antihypertensive medications modestly attenuated the associations. The associations between leptin and both PRA and aldosterone were not different by gender but were significantly stronger among non-Hispanic Whites and Chinese Americans than African and Hispanic Americans (Pleptin may be relevant to blood pressure regulation via the RAAS, in that the associations appear to be robust to antihypertension medication use and that the associations are likely different by ethnicity. PMID:24919752

  5. Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22(phox) in human mononuclear leukocytes.

    Science.gov (United States)

    Calò, Lorenzo A; Zaghetto, Francesca; Pagnin, Elisa; Davis, Paul A; De Mozzi, Paola; Sartorato, Paola; Martire, Giuseppe; Fiore, Cristina; Armanini, Decio

    2004-04-01

    Aldosterone excess can produce heart and kidney fibrosis, which seem to be related to a direct effect of aldosterone at the level of specific receptors. We report a direct, mineralocorticoid-mediated effect on the protein expression of two markers of oxidative stress after incubation of mononuclear leukocytes with 1 x 10(-8) M aldosterone (p22(phox)/beta-actin = 1.38 +/- 0.05 and PAI-1/beta-actin = 1.80 +/- 0.05). The same effect was also found with 3 x 10(-5) M glycyrrhetinic acid, the principal constituent of licorice root (p22(phox)/beta-actin = 1.37 +/- 0.97 and PAI-1/beta-actin = 1.80 +/- 0.04). The effect of both aldosterone and glycyrrhetinic acid is blocked by incubation with added 1 x 10(-6) M of receptor-antagonist canrenone. Canrenone alone did not show any effect. PAI-1 related protein was also found using 4 x 10(-9) M aldosterone. Incubations with 1 x 10(-9) M for 3 hours as well as 1 x 10(-8) M aldosterone for 5, 10, and 20 minutes were ineffective for both proteins. These data support the previous finding of an involvement of mononuclear leukocytes in the pathogenesis of the oxidative stress induced by hyperaldosteronism. In addition, the results confirm our previous data on a direct effect of glycyrrhetinic acid at the level of mineralocorticoid receptors. PMID:15070972

  6. 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

    Science.gov (United States)

    Zhu, X.Q.; Hong, H.S.; Lin, X.H.; Chen, L.L.; Li, Y.H.

    2014-01-01

    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 (P0.05). 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. PMID:25014176

  7. 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

    Directory of Open Access Journals (Sweden)

    X.Q. Zhu

    2014-08-01

    Full Text Available 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 (P0.05. 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.

  8. 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; Hansen, Pernille B L

    2016-01-01

    AIMS: The aims were to develop a method for real-time detection of histamine release and to test if incubation with aldosterone induces histamine release from isolated, perfused mice mesenteric arteries. METHODS: Fura-2 loaded HEK-293 cells transfected with the histamine H1 receptor was used 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...

  9. 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)

    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.

  10. AB203. The mutational landscapes of adrenal cortex aldosterone-producing adenoma (APA) diversified between different populations

    OpenAIRE

    Wu, Song; Huang, Peide; Zhang, Meng

    2015-01-01

    Objective The genetic determinants of aldosterone-producing adrenal adenoma (APA), one of the most common causes of secondary hypertension, had been studied intensively in European patients but its mutational landscapes in Asian populations remained unclear. We aim to further understand the genetic determinants of APA in East Asian patients. Methods We perform Whole-exome sequencing and comprehensive data analyses in tumors and matched normal tissues from 22 Chinese APA patients. Results Nota...

  11. Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Jae Hee Ahn

    2012-04-01

    Full Text Available BackgroundAldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats.MethodsAnimals were divided into six groups as follows: Otsuka Long-Evans Tokushima Fatty (OLETF rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day, OLETF rats treated with a high dose of eplerenone (200 mg/kg/day, OLETF rats treated with lisinopril (10 mg/kg/day, OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and lisinopril 10 mg/kg/day, and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks.ResultsUrinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-β1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups.ConclusionEplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug.

  12. Renin-angiotensin-aldosterone system in the elderly: rational use of aliskiren in managing hypertension

    Directory of Open Access Journals (Sweden)

    Karl Andersen

    2009-03-01

    Full Text Available Karl AndersenDepartment of Medicine, Division of Cardiology, Landspitali University Hospital, University of Iceland, Reykjavik, IcelandAbstract: The overall purpose of hypertension treatment is 2-fold. First, patients often have symptoms that are related to their high blood pressure and although subtle in many instances may be improved dramatically by blood pressure control. The main reason for blood pressure treatment, however, is to reduce the burden of cardiovascular complications and end organ damage related to the condition. This may be considered the ultimate goal of blood pressure treatment. In this respect, actual blood pressure measurements may be seen as surrogate end points as the organ protective effects of two antihypertensive agents may differ significantly even though their blood pressure lowering effects are similar. Thus beta-blockers, once seen as first-line treatment of hypertension for most patients, now are considered as third- or fourth-line agents according to the latest NICE guidelines (National Institute for Health and Clinical Excellence, www.nice.org.uk/CG034. On the other hand, agents that inhibit the activity of the renin-angiotensin-aldosterone system (RAAS are being established as safe, effective and end organ protective in numerous clinical trials, resulting in their general acceptance as first-line treatment in most patients with stage 2 hypertension. This shift in emphasis from beta-blockers and thiazide diuretics is supported by numerous clinical trials and has proven safe and well tolerated by patients. The impact of this paradigm shift will have to be established in future long-term randomized clinical trials. The optimal combination treatment with respect to end organ protection has yet to be determined. Most combinations will include either a RAAS active agent and calcium channel blocker or two separate RAAS active agents working at different levels of the cascade. In this respect direct renin inhibitors

  13. 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

  14. Gene polymorphisms of renin-angiotensin-aldosterone system components and the progression of chronic kidney diseases

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    Agata Kujawa-Szewieczek

    2010-08-01

    Full Text Available The renin-angiotensin-aldosterone system (RAAS plays an important role in the pathogenesis of hypertension as well as cardiovascular diseases and chronic kidney diseases. Among the most frequently studied RAAS gene polymorphisms are the angiotensin-converting enzyme insertion/deletion (I/D, angiotensinogen M235T and angiotensin II receptor type 1 A1166C polymorphisms.A significant correlation was found between the I/D polymorphism and cardiovascular morbidity and mortality rates. However, there was no significant correlation between I/D, M235T, A1166C polymorphism and arterial hypertension. The role of I/D polymorphism in the development and progression of chronic kidney disease is also non-conclusive. However, DD genotype has been identified as relevant for loss of renal function both in patients with IgA nephropathy and in patients of Asian origin with diabetic nephropathy.The relationship between RAAS gene polymorphism and transplanted kidney function has not been confirmed in large prospective and retrospective studies. Conclusion: there is no clear opinion concerning the influence of RAAS genotypes on the prevalence of post-transplant hypertension or erythrocytosis.Although a role of RAAS gene polymorphism in kidney function deterioration could not be ruled out, it is more likely that a variety of genetic and environmental factors influence the progression of chronic kidney diseases.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

    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

  17. A Rare Case of Subclinical Primary Aldosteronism and Subclinical Cushing's Syndrome without Cardiovascular Complications.

    Science.gov (United States)

    Kitajima, Natsumi; Seki, Toshiro; Yasuda, Atsushi; Oki, Masayuki; Takagi, Atsushi; Hanai, Kazuya; Terachi, Toshiro; Fukagawa, Masafumi

    2016-04-01

    We report a rare case of subclinical primary aldosteronism (PA) and subclinical Cushing's syndrome (CS). A 49-year-old woman was referred to our hospital for the evaluation of an adrenal incidentaloma. The patient had no previous medical history and no family history of notable illness. Her blood pressure was 103/60 mmHg. She had no Cushingoid features. Routine laboratory examinations were within the normal ranges including normokalemia. Based on the endocrinological results and imaging findings, we finally made a diagnosis of subclinical PA caused by both adrenal glands and subclinical CS caused by bilateral adrenal tumors. Interestingly, this patient had no risk factors for cardiovascular disease. In addition, the optimal management of patients with subclinical CS and subclinical PA has not been established. Therefore, we are observing her without medical therapy. Four years after diagnosis, no cardiovascular complications have been detected, including cerebral infarction, chronic kidney disease, cardiomegaly on echocardiography, and atherosclerosis on carotid ultrasonography. One important question is why the excessive hormone secretion did not affect the cardiovascular status of this patient. In this regard, we discuss several possible mechanisms including mineralocorticoid resistance and glucocorticoid sensitivity. PMID:27050894

  18. Advances in Aldosterone Receptor Antagonists on Hypertension%醛固酮受体拮抗剂的降压治疗进展

    Institute of Scientific and Technical Information of China (English)

    黄红娟

    2011-01-01

    The hormone aldosterone is the final product of the renin angiotensin aldosterone system, which contributes significantly to primary and sustained hypertension. Increasingly attention is being given to the role aldosterone has in influencing blood pressure. This review shows the pathophysiology of aldosterone, its classification and mechanism, and clinical uses of aldosterone receptor antagonist.%醛固酮是肾素-血管紧张素-醛固酮系统的终末环节,在原发性高血压、顽固性高血压中起重要作用.醛固酮受体拮抗剂在高血压治疗方面的作用越来越受到重视.现综述醛固酮在高血压中的病理生理作用,醛固酮受体拮抗剂的分类、降压机制及临床应用进展等.

  19. INFLUENCE OF PULSED SHORT WAVE (DIAPULSE TREATMENT ON THE BIOCHEMICAL PARAMETERS CORTISOL AND ALDOSTERONE

    Directory of Open Access Journals (Sweden)

    Dogaru Gabriela

    2015-12-01

    Full Text Available Pulsed short waves are part of high frequency therapy; unlike continuous short waves, where the phenomenon of tissular endothermia occurs, they have therapeutic effects that seem to depend rather on the interaction of electromagnetic waves with biological tissue, as they act only through specific electromagnetic energy. The recommended work technique for the use of the Diapulse device is that regardless of the exposed somatic region, there will be an initial exposure of one of the following regions: prehepatic, epigastric or lumbar (for action on the adrenal glands. Considering the role and the effects of the hormones of the adrenocortical gland, particularly glucocorticoids, on the body, which influence the inflammatory response of the connective tissue, with a role in rheumatoid pathology, we monitored the changes in the function of this gland. The biochemical parameters cortisol and aldosterone were quantitatively assessed in patients with complex regional pain syndrome type I (algoneurodystrophy treated with pulsed short waves, who were initially exposed to radiation of the lumbar region. In the same treatment session, all patients were exposed to radiation of the lumbar region, at a dose of 4/400 impulses/sec., for 10 minutes, followed by radiation of the affected region at a dose of 6/600 impulses/sec., for 10 minutes. There was one treatment session per day, for 14 days. It was demonstrated that radiation of the lumbar region at a dose of 4/400 impulses/sec. caused no changes in the hormonal function of the adrenal gland, i.e. no hypo- or hyperfunction; there was no overstrain or overstress after exposure to pulsed short waves, which is an important aspect, with applicability in clinical practice. Studies demonstrated both the local and the general, systemic influence of pulsed short waves, the induced changes being for the most part strictly dependent on the dose used.

  20. Aldosterone response to sodium deprivation and angiotensin II in patients with hypopituitarism.

    Science.gov (United States)

    Seifert, C; Oelkers, W

    1981-03-01

    Unknown pituitary factor(s) apart from ACTH may participate in the regulation of aldosterone (aldo) secretion in man. We investigated whether the 'sensitization' of the zona glomerulosa against angiotensin II (A II) by sodium deficiency was mediated by the pituitary gland. A II was infused in stepwise increasing doses (2, 4, 8 ng/kg/min) into 5 normal subjects (N) and into 8 patients with hypopituitarism (H) before and after 4 days on low sodium diet. Mean cumulative sodium balance after the low sodium diet was -145mM in N and -165mM in H. Plasma-aldo and aldo-excretion rate on the normal sodium diet were slightly higher in H than in N but rose less than normal during sodium depletion in H. Plasma A II and renin activity on normal sodium were slightly higher in H than in N, but the increase on the low sodium diet was blunted in H. The stimulation of plasma-aldo by A II infusion was similar in both groups on the normal sodium diet. In both groups, the response of P-aldo to A II infusion was greater in the sodium deplete than in the replete state, although 'sensitization' was slightly less marked in H than in N. This may be due to the blunted rise of plasma-A II after sodium loss in H, which may also account for abnormalities in the blood pressure response in the H group. Altogether, the results speak against a direct involvement of the pituitary gland in 'sensitization', but an indirect influence through unexplained abnormalities in renin secretion is possible. PMID:7211097

  1. Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study (Primary Aldosteronism in TOrino-GENetic forms).

    Science.gov (United States)

    Mulatero, Paolo; Tizzani, Davide; Viola, Andrea; Bertello, Chiara; Monticone, Silvia; Mengozzi, Giulio; Schiavone, Domenica; Williams, Tracy Ann; Einaudi, Silvia; La Grotta, Antonio; Rabbia, Franco; Veglio, Franco

    2011-11-01

    Primary aldosteronism (PA) is the most frequent cause of secondary hypertension, and patients display an increased prevalence of cardiovascular events compared with essential hypertensives. To date, 3 familial forms of PA have been described and termed familial hyperaldosteronism types I, II, and III (FH-I to -III). The aim of this study was to investigate the prevalence and clinical characteristics of the 3 forms of FH in a large population of PA patients. Three-hundred consecutive PA patients diagnosed in our unit were tested by long-PCR of the CYP11B1/CYP11B2 hybrid gene that causes FH-I, and all of the available relatives of PA patients were screened to confirm or exclude PA and, thus, FH-II. Urinary 18-hydroxycortisol and 18-oxocortisol were measured in all of the familial PA patients. Two patients were diagnosed with FH-I (prevalence: 0.66%), as well as 21 of their relatives, and clinical phenotypes of the 2 affected families varied markedly. After exclusion of families who refused testing and those who were not informative, 199 families were investigated, of which 12 were diagnosed with FH-II (6%) and an additional 15 individuals had confirmed PA; clinical and biochemical phenotypes of FH-II families were not significantly different from sporadic PA patients. None of the families displayed a phenotype compatible with FH-III diagnosis. Our study demonstrates that familial forms of hyperaldosteronism are more frequent than previously expected and reinforces the recommendation of the Endocrine Society Guidelines to screen all first-degree hypertensive relatives of PA patients. PMID:21876069

  2. Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas.

    Science.gov (United States)

    Åkerström, Tobias; Willenberg, Holger Sven; Cupisti, Kenko; Ip, Julian; Backman, Samuel; Moser, Ana; Maharjan, Rajani; Robinson, Bruce; Iwen, K Alexander; Dralle, Henning; D Volpe, Cristina; Bäckdahl, Martin; Botling, Johan; Stålberg, Peter; Westin, Gunnar; Walz, Martin K; Lehnert, Hendrik; Sidhu, Stan; Zedenius, Jan; Björklund, Peyman; Hellman, Per

    2015-10-01

    Aldosterone-producing adenomas (APAs) are found in 1.5-3.0% of hypertensive patients in primary care and can be cured by surgery. Elucidation of genetic events may improve our understanding of these tumors and ultimately improve patient care. Approximately 40% of APAs harbor a missense mutation in the KCNJ5 gene. More recently, somatic mutations in CACNA1D, ATP1A1 and ATP2B3, also important for membrane potential/intracellular Ca(2) (+) regulation, were observed in APAs. In this study, we analyzed 165 APAs for mutations in selected regions of these genes. We then correlated mutational findings with clinical and molecular phenotype using transcriptome analysis, immunohistochemistry and semiquantitative PCR. Somatic mutations in CACNA1D in 3.0% (one novel mutation), ATP1A1 in 6.1% (six novel mutations) and ATP2B3 in 3.0% (two novel mutations) were detected. All observed mutations were located in previously described hotspot regions. Patients with tumors harboring mutations in CACNA1D, ATP1A1 and ATP2B3 were operated at an older age, were more often male and had tumors that were smaller than those in patients with KCNJ5 mutated tumors. Microarray transcriptome analysis segregated KCNJ5 mutated tumors from ATP1A1/ATP2B3 mutated tumors and those without mutation. We observed significant transcription upregulation of CYP11B2, as well as the previously described glomerulosa-specific gene NPNT, in ATP1A1/ATP2B3 mutated tumors compared to KCNJ5 mutated tumors. In summary, we describe novel somatic mutations in proteins regulating the membrane potential/intracellular Ca(2) (+) levels, and also a distinct mRNA and clinical signature, dependent on genetic alteration. PMID:26285814

  3. Polymorphisms of renin-angiotensin-aldosterone system gene in chinese han patients with nonfamilial atrial fibrillation.

    Directory of Open Access Journals (Sweden)

    Li-Qun Zhao

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

  4. Vitamin D receptor, an important transcription factor associated with aldosterone-producing adenoma.

    Directory of Open Access Journals (Sweden)

    Changlong Bi

    Full Text Available OBJECTIVE: To explore the endocrine mechanisms of aldosterone-producing adenoma (APA by using the microarray expression profiles of normal and APA samples. METHODS: The gene expression profile GSE8514 was downloaded from Gene Expression Omnibus database, including samples from normal adrenals (n = 5 and APAs (n = 10. The differentially expressed genes (DEGs were identified by samr package and endocrine DEGs were obtained according to Clinical Genome Database. Then, functional enrichment analysis of screened DEGs was performed by DAVID (Database for Annotation, Visualization and Integrated Discovery. Finally, a regulatory network was constructed to screen endocrine genes related with adrenal dysfunction and pathway enrichment analysis for the constructed network was performed. RESULTS: A total of 2149 DEGs were identified including 379 up- and 1770 down-regulated genes. And 26 endocrine genes were filtered from the DEGs. Furthermore, the down-regulated DEGs are mainly related to protein kinase cascade, response to molecule of bacterial origin, response to lipopolysaccharide, cellular macromolecule catabolic process and macromolecule catabolic process, while the up-regulated DEGs are related with regulation of ion transport. The target genes of VDR (vitamin D receptor, one of the three endocrine genes differentially expressed in the regulatory network, were endocrine genes including CYP24A1 (25-hydroxyvitamin D-24-hydroxylase and PTH (parathyroid hormone. Three pathways may be associated with APA pathogenesis including cytokine-cytokine receptor interaction, pathways in cancer and autoimmune thyroid disease. CONCLUSION: The VDR is the most significant transcription factor and related endocrine genes might play important roles in the endocrine mechanisms of APA.

  5. 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...... subunit) and ATP2B3 (encoding a Ca2+ ATPase) genes in three and two of the nine APAs, respectively. These ATPases are expressed in adrenal cells and control sodium, potassium and calcium ion homeostasis. Functional in vitro studies of ATP1A1 mutants showed loss of pump activity and strongly reduced...... affinity for potassium. Electrophysiological ex vivo studies on primary adrenal adenoma cells provided further evidence for inappropriate depolarization of cells with ATPase alterations. In a collection of 308 APAs, we found 16 (5.2%) somatic mutations in ATP1A1 and 5 (1.6%) in ATP2B3. Mutation...

  6. 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)

    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

  7. Quinidine-sensitive K+ channels in the basolateral membrane of embryonic coprodeum epithelium: regulation by aldosterone and thyroxine.

    Science.gov (United States)

    Illek, B; Fischer, H; Clauss, W

    1993-01-01

    Basolateral K+ channels and their regulation during aldosterone- and thyroxine-stimulated Na+ transport were studied in the lower intestinal epithelium (coprodeum) of embryonic chicken in vitro. Isolated tissues of the coprodeum were mounted in Ussing chambers and investigated under voltage-clamped conditions. Simultaneous stimulation with aldosterone (1 mumol.l-1) and thyroxine (1 mumol.l-1) raised short-circuit current after a 1- to 2-h latent period. Maximal values were reached after 6-7 h of hormonal treatment, at which time transepithelial Na+ absorption was more than tripled (77 +/- 11 microA.cm-2) compared to control (24 +/- 8 microA.cm-2). K+ currents across the basolateral membrane were investigated after permeabilizing the apical membrane with the pore-forming antibiotic amphotericin B and application of a mucosal-to-serosal K+ gradient. This K+ current could be dose dependently depressed by the K+ channel blocker quinidine. Fluctuation analysis of the short-circuit current revealed a spontaneous and a blocker-induced Lorentzian noise component in the power density spectra. The Lorentzian corner frequencies increased linearly with the applied blocker concentration. This enabled the calculation of single K+ channel current and K+ channel density. Single K+ channel current was not affected by stimulation, whereas the number of quinidine-sensitive K+ channels in the basolateral membrane increased from 11 to 26.10(6).cm-2 in parallel to the hormonal stimulation transepithelial Na+ transport. This suggests that the basolateral membrane is a physiological target during synergistic aldosterone and thyroxine regulation of transepithelial Na+ transport for maintaining intracellular K+ homeostasis. PMID:8151014

  8. 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.

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

    Science.gov (United States)

    Mochel, Jonathan P; Danhof, Meindert

    2015-01-01

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

  10. 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.)

  11. 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)

    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 123I-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. 123I-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.)

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

    International Nuclear Information System (INIS)

    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)

  13. Aldosterone, corticosterone, and thyroid hormone and their influence on respiratory control development in Lithobates catesbeianus: An in vitro study.

    Science.gov (United States)

    Rousseau, Jean-Philippe; Bairam, Aida; Kinkead, Richard

    2016-04-01

    The emergence of air breathing during Lithobates catesbeianus development requires significant changes to the brainstem circuits that generate and regulate breathing; however, the mechanisms responsible for initiating this transformation remain largely unknown. Because amphibian metamorphosis is regulated by hormones such as aldosterone, corticosterone, and thyroid hormone (T3), we tested the hypothesis that exposing the brainstem to these hormones augments the fictive air breathing frequency in pre-metamorphic tadpoles. Brainstems were isolated and were placed either in the recording chamber (acute; 1h+1h recovery) or in a bottle (chronic exposure; 24h) for treatment. Brainstems were exposed to artificial cerebrospinal fluid (aCSF; sham treatment) or one of the following hormones: aldosterone (100nM), corticosterone (100nM), or T3 (100nM). While acute exposure had limited effects on respiratory motor output, chronic incubation with any hormone significantly increased fictive air breathing; the burst frequencies observed following treatment were similar to those observed in adult bullfrogs. We conclude that through their long term effects, hormones regulating metamorphosis can initiate the maturation of the neural circuits that generate and regulate breathing in this species. PMID:25476838

  14. Moderate antiproteinuric effect of add-on aldosterone blockade with eplerenone in non-diabetic chronic kidney disease. A randomized cross-over study

    DEFF Research Database (Denmark)

    Boesby, Lene; Elung-Jensen, Thomas; Klausen, Tobias Wirenfeldt;

    2011-01-01

    Reduction of proteinuria and blood pressure (BP) with blockers of the renin-angiotensin system (RAS) impairs the progression of chronic kidney disease (CKD). The aldosterone antagonist spironolactone has an antiproteinuric effect, but its use is limited by side effects. The present study evaluated...

  15. 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; Zappe, Dion H; Meng, Xiangyi; Parving, Hans-Henrik

    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 i...

  16. 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

    2007-01-01

    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 tot

  17. Renin-angiotensin-aldosterone responsiveness to low sodium and blood pressure reactivity to angiotensin-II are unrelated to cholesteryl ester transfer protein mass in healthy subjects

    NARCIS (Netherlands)

    Krikken, Jan A.; Dallinga-Thie, Geesje M.; Navis, Gerjan; Dullaart, Robin P. F.

    2008-01-01

    Background: The blood pressure increase associated with the cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib is probably attributable to an off-target effect but it is unknown whether activation of the renin-angiotensin-aldosterone system (RAAS) may be related to variation in the pla

  18. Upregulation of the Renin-Angiotensin-Aldosterone-Ouabain System in the Brain Is the Core Mechanism in the Genesis of All Types of Hypertension

    Directory of Open Access Journals (Sweden)

    Hakuo Takahashi

    2012-01-01

    Full Text Available Basic research using animal models points to a causal role of the central nervous system in essential hypertension; however, since clinical research is technically difficult to perform, this connection has not been confirmed in humans. Recently, renal nerve ablation in humans proved to continuously decrease blood pressure in resistant hypertension. Furthermore, when electrical stimulation was continuously applied to the carotid baroreceptor nerve of human adults, their blood pressure lowered. These findings promoted the concept that the central nervous system may actually be involved in the pathogenesis of essential hypertension, which is closely associated with excess sodium intake. We have demonstrated that endogenous digitalis plays a key role in hypertension associated with excess sodium intake via sympathetic activation in rats. Increased sodium concentration inside the brain activates epithelial sodium channels and the renin-angiotensin-aldosterone system in the brain. Aldosterone releases ouabain from neurons in the paraventricular nucleus in the hypothalamus. Angiotensin II and aldosterone of peripheral origin reach the brain to augment sympathetic outflow. Collectively essential hypertension associated with excess sodium intake and obesity, renovascular hypertension, and primary aldosteronism and pseudoaldosteronism all seem to have a common cause originating from the central nervous system.

  19. Blockades of angiotensin and aldosterone reduce osteopontin expression and interstitial fibrosis infiltration in rats with myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yu-ling; ZHOU Shu-xian; LEI Juan; YUAN Gui-yi; WANG Jing-feng

    2008-01-01

    Background It has been reported that osteopontin has an important role in cardiac fibrosis and remodeling.However,its direct mechanisms remain unclear.The purpose of this study was to investigate the role of angiotensin and aldosterone blockades in cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted (MI) rats.Methods Fifty SD rats that survived 24 hours after ligating left anterior descending coronary artery were randomly divided into three groups:Ml-saline group (n=15,5 ml/d),MI-perindopril group (n=18,perindopril 2 mg·kg-1·d-1) and MI-spironolacton (n=17,spironolacton 20 mg·kg-1.d-1).A sham operation group (n=15) was selected as non-infarcted control.At 6 weeks after treatment,hemodynamic pararmeters and left ventricular function were measured with catheterization,interstitial fibrosis infiltration and cardiomyocyte diameters were evaluated histologically.Myocardium osteopontin protein expression level in the non-infarcted myocardium was detected by Western blotting.Results No osteopontin protein was detected in the myocardium of sham-operation rats.High levels of osteopontin protein expression were detected in the MI-saline rats,but the levels were suppressed in the MI-perindopril and MI-spironolacton rats at 6 weeks following MI (P<0.01,respectively).Compared with the sham operation group,all rats in the MI group showed marked interstitial fibrosis infiltration in the non-infarction area,higher ventricular weight]body weight ratio,significantly increased cardiomyocyte diameter (P<0.01,respectively),and developed significant systolic and diastolic dysfunction as indicated by decreased left ventricular systolic pressure (LVSP) and ±dp/dt,as well as increased left ventricular end-diastolic pressure (LVEDP) (P<0.01,respectively).Angiotensin and aldosterone blockades partly prevented cardiac fibrosis and systolic and diastolic dysfunction (P<0.01,respectively).Conclusion Treatment with angiotensin and aldosterone blockades

  20. Utilidad de la relación aldosterona y actividad renina plasmática en el diagnóstico de hiperaldosteronismo primario Aldosterone/renin ratio in the diagnosis of primary aldosteronism

    Directory of Open Access Journals (Sweden)

    María Carolina Ríos

    2011-12-01

    Full Text Available El hiperaldosteronismo primario (HP es la forma más común de hipertensión arterial (HTA secundaria. Recientemente varios estudios sugieren que la prevalencia de esta enfermedad varía entre 5% y 15% entre la población hipertensa, y 20% para hipertensión arterial refractaria. El objetivo de este estudio fue, ante la gran variabilidad de prevalencias sobre HP según las publicaciones internacionales y pocos datos en la Argentina, aportar la prevalencia de HP en un hospital general del interior del país, relacionándolo con el grado de HTA y presencia de normokalemia. En este estudio transversal se realizó dosaje de A/ARP en 123 pacientes hipertensos, suspendiendo toda medicación que interfiriera en los dosajes hormonales; se utilizó como método confirmatorio el test de solución salina (SS para el diagnóstico de HP y la tomografía computarizada (TC de abdomen para el diagnóstico etiológico del HP. Se detectó una relación A/ARP elevada en 20 (16.4% pacientes. En 18 se realizó el test de SS, confirmando el diagnóstico de aldosteronismo en 8 (6.5% del total. En la TC, dos presentaron adenomas, y seis glándulas suprarrenales normales. Todos los pacientes con HP pertenecían al grupo II y III de HTA según el VI Joint National Committee (VI JNC y el 50% fue normokalémico. Encontramos una prevalencia de 6.5% de HP, asociado a grado II y III de hipertensión, y valores de potasio normal en la mitad de los pacientes.Primary aldosteronism (PA is a possible cause of endocrine hypertension. Recent studies have suggested a prevalence ranging between 5% and 15% of all hypertensive patients, and 20% in patients with refractory hypertension.The objective of this transversal study was to establish the prevalence of PA in a hypertensive population using the aldosterone / plasma renin ratio (ARR as a screening method, considering that the prevalence rates for PA among hypertensive people present a wide range and that there are only few reports

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

    Science.gov (United States)

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

    2016-06-01

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

  2. Single-port laparoscopic adrenalectomy for a right-sided aldosterone-producing adenoma: a case report

    Directory of Open Access Journals (Sweden)

    Sasaki Akira

    2012-07-01

    Full Text Available Abstract Introduction Single-port laparoscopic adrenalectomy is one of the most interesting surgical advances. Here, we evaluate the safety and feasibility of single-port laparoscopic adrenalectomy as treatment for a right-sided aldosterone-producing adenoma. Case presentation A 39-year-old Japanese woman presented with hypertension and hypokalemia. Abdominal computed tomography and an endocrinological workup revealed a 19mm right adrenal tumor with primary aldosteronism. Our patient was informed of the details of the surgical procedure and our efforts to reduce the number of incisions needed - ideally, to a single incision - when removing her adrenal gland. A single-port laparoscopic adrenalectomy was attempted. A multichannel port was inserted through a 2.5cm umbilical incision. A 5mm flexible laparoscope, articulating laparoscopic dissector and tissue sealing device were the primary tools used in the operation. The right liver lobe was evaluated using a percutaneous instrument, providing good visualization of the operative field surrounding her right adrenal gland. The single-port laparoscopic adrenalectomy was successfully completed without any intraoperative complications. The operating time was 76 minutes, and her blood loss was 5mL. Oral intake was resumed on the first postoperative day, and the length of her hospital stay was three days. Her postoperative course was uneventful with no morbidity within one month of follow-up, and our patient had excellent cosmetic results. Conclusions Single-port laparoscopic adrenalectomy is a safe and feasible procedure for patients with a right-sided adrenal tumor when performed by a surgeon experienced in laparoscopic and adrenal surgery. However, more surgical experience using this technique is required to confirm our initial impressions.

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

    Directory of Open Access Journals (Sweden)

    Zohreh Rahimi

    2014-01-01

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

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

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    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.

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

    Science.gov (United States)

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

    2016-09-01

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

  6. Genomic and proteomic analysis of the inhibition of synthesis and secretion of aldosterone hormone induced by quinocetone in NCI-H295R cells.

    Science.gov (United States)

    Wang, Xu; Bai, Yijie; Cheng, Guyue; Ihsan, Awais; Zhu, Feng; Wang, Yulian; Tao, Yanfei; Chen, Dongmei; Dai, Menghong; Liu, Zhengli; Yuan, Zonghui

    2016-03-28

    Quinoxaline 1,4-dioxides (QdNOs) are widely used as a kind of antibacterial growth promoter in animal husbandry. The adrenal cortex was found to be one of the main toxic targets of QdNOs, accompanied by a decreased aldosterone level. However, the way in which QdNOs decrease production of the hormone aldosterone is far from clear. To illustrate the mechanism by which QdNOs damage the adrenal cortex and decrease aldosterone hormone levels, the QdNOs were screened to choose the drug with most toxic effects on aldosterone production, and then to reveal the mechanism between the gene and protein profiles in human adrenocortical cells (NCI-H295R cells). The results found that quinocetone (QCT) showed the highest adrenal toxic effect among QdNOs. After exposing H295R cells to 10 and 20μM QCT for 24h, compared with blank cells, the gene and protein expression profiles obtained were analyzed by microarray and MALDI TOF/TOF mass spectrometry, respectively. The results of microarray analysis suggested that ABCG1 and SREBF1, which were involved in the cholesterol biosynthetic and metabolic processes, and CYP17A1, NR4A2 and G6PD, which were related to aldosterone biosynthesis, were important molecular targets. It has been speculated that PKC and ERK pathways might be involved in the reduction of aldosterone production caused by QCT, through enhanced mRNA expression of CYP17A1. Additionally, JNK and p38MAPK signal transduction pathways might participate in apoptosis induced by QCT. Twenty-nine and 32 protein spots were successfully identified when cells were treated with 10 and 20μM QCT, respectively. These identified proteins mainly included material synthesis and energy metabolism-related proteins, transcription/translation processing-related proteins, signal transduction proteins, cytoskeletal proteins, molecular chaperones, proteins related to response to stress, and transport proteins. Further investigations suggested that oxidative stress caused by QCT was exacerbated

  7. Effect of chronic oral administration of a low dose of captopril on sodium appetite of hypothyroid rats: Influence of aldosterone treatment

    OpenAIRE

    Ventura R.R.; Olivares E.L.; Passos Junior D.B.; Ramalho M.J.; Antunes-Rodrigues J.; Reis L.C.

    2001-01-01

    Rats rendered hypothyroid by treatment with methimazole develop an exaggerated sodium appetite. We investigated here the capacity of hypothyroid rats (N = 12 for each group) to respond to a low dose of captopril added to the ration, a paradigm which induces an increase in angiotensin II synthesis in cerebral areas that regulate sodium appetite by increasing the availability of circulating angiotensin I. In addition, we determined the influence of aldosterone in hypothyroid rats during the exp...

  8. PVN adenovirus-siRNA injections silencing either NOX2 or NOX4 attenuate aldosterone/NaCl-induced hypertension in mice

    OpenAIRE

    Xue, Baojian; Beltz, Terry G.; Johnson, Ralph F.; GUO Fang; Hay, Meredith; Johnson, Alan Kim

    2011-01-01

    Mineralocorticoid excess increases superoxide production by activating NADPH oxidase (NOX), and intracerebroventricular infusions of NADPH oxidase inhibitors attenuate aldosterone (Aldo)/salt-induced hypertension. It has been hypothesized that increased reactive oxygen species (ROS) in the brain may be a key mechanism in the development of hypertension. The present study investigated the brain regional specificity of NADPH oxidase and the role of NOX2 and NOX4 NADPH oxidase subunits in the hy...

  9. Long-term results of adrenalectomy in patients with aldosterone-producing adenomas: multivariate analysis of factors affecting unresolved hypertension and review of the literature.

    Science.gov (United States)

    Lumachi, Franco; Ermani, Mario; Basso, Stefano M M; Armanini, Decio; Iacobone, Maurizio; Favia, Gennaro

    2005-10-01

    The long-term surgical cure rate of patients with primary aldosteronism varies widely, and causes of persistent hypertension are not completely established. We reviewed retrospectively charts from 98 patients (range, 19-70 years old) with aldosterone-producing adenomas who underwent unilateral adrenalectomy. At a median follow-up of 81 months (range, 18-186 months), the mean blood pressure values improved in 95 out of 98 (96.9%) patients, although hypertension was cured only in 71 out of 98 (72.4%) patients. Multivariate analysis using a logistic regression model adjusted for duration of follow-up showed that only age of the patients and duration of the disease independently correlated with unresolved hypertension. The cumulative odds ratio (OR), obtained using the logistic regression function, was 5.38 (95% CI 1.78-16.22), and the OR of single variables were 1.32 (95% CI 0.36-19.83) and 4.56 (95% CI 1.41-14.78), respectively. By using discriminant analysis to derive a classification function for the prediction of unresolved hypertension, a maximum predictive power of 75 per cent was achieved. In conclusion, in patients with an aldosterone-producing adenoma undergoing surgery, the combination of age and duration of hypertension gave the best predictive power of a linear classification function and represented the main independent risk factors affecting hypertension cure rate. PMID:16468537

  10. 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.

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

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

    2007-10-01

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

  13. 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

  14. 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)

    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)

  15. Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury.

    Science.gov (United States)

    Ding, Wei; Guo, Honglei; Xu, Chengyan; Wang, Bin; Zhang, Minmin; Ding, Feng

    2016-04-01

    Aldosterone (Aldo) is an independent risk factor for chronic kidney disease (CKD), and although Aldo directly induces renal tubular cell injury, the underlying mechanisms remain unclear. NLRP3 inflammasome and mitochondrial reactive oxygen species (ROS) have recently been implicated in various kinds of CKD. The present study hypothesized that mitochondrial ROS and NLRP3 inflammasome mediated Aldo-induced tubular cell injury. The NLRP3 inflammasome is induced by Aldo in a dose- and time-dependent manner, as evidenced by increased NLRP3, ASC, caspase-1, and downstream cytokines, such as interleukin (IL)-1β and IL-18. The activation of the NLRP3 inflammasome was significantly prevented by the selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL) (P < 0.01). Mice harboring genetic knock-out of NLRP3 (NLRP3(-/-)) showed decreased maturation of renal IL-1β and IL-18, reduced renal tubular apoptosis, and improved renal epithelial cell phenotypic alternation, and attenuated renal function in response to Aldo-infusion. In addition, mitochondrial ROS was also increased in Aldo-stimulated HK-2 cells, as assessed by MitoSOXTM red reagent. Mito-Tempo, the mitochondria-targeted antioxidant, significantly decreased HK-2 cell apoptosis, oxidative stress, and the activation of NLRP3 inflammasome. We conclude that Aldo induces renal tubular cell injury via MR dependent, mitochondrial ROS-mediated NLRP3 inflammasome activation. PMID:27014913

  16. Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury

    Science.gov (United States)

    Ding, Wei; Guo, Honglei; Xu, Chengyan; Wang, Bin; Zhang, Minmin; Ding, Feng

    2016-01-01

    Aldosterone (Aldo) is an independent risk factor for chronic kidney disease (CKD), and although Aldo directly induces renal tubular cell injury, the underlying mechanisms remain unclear. NLRP3 inflammasome and mitochondrial reactive oxygen species (ROS) have recently been implicated in various kinds of CKD. The present study hypothesized that mitochondrial ROS and NLRP3 inflammasome mediated Aldo–induced tubular cell injury. The NLRP3 inflammasome is induced by Aldo in a dose- and time-dependent manner, as evidenced by increased NLRP3, ASC, caspase-1, and downstream cytokines, such as interleukin (IL)-1β and IL-18. The activation of the NLRP3 inflammasome was significantly prevented by the selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL) (P < 0.01). Mice harboring genetic knock-out of NLRP3 (NLRP3−/−) showed decreased maturation of renal IL-1β and IL-18, reduced renal tubular apoptosis, and improved renal epithelial cell phenotypic alternation, and attenuated renal function in response to Aldo-infusion. In addition, mitochondrial ROS was also increased in Aldo-stimulated HK-2 cells, as assessed by MitoSOXTM red reagent. Mito-Tempo, the mitochondria-targeted antioxidant, significantly decreased HK-2 cell apoptosis, oxidative stress, and the activation of NLRP3 inflammasome. We conclude that Aldo induces renal tubular cell injury via MR dependent, mitochondrial ROS-mediated NLRP3 inflammasome activation. PMID:27014913

  17. Ventricular repolarization before and after treatment in patients with secondary hypertension due to renal-artery stenosis and primary aldosteronism.

    Science.gov (United States)

    Maule, Simona; Bertello, Chiara; Rabbia, Franco; Milan, Alberto; Mulatero, Paolo; Milazzo, Valeria; Papotti, Grazia; Veglio, Franco

    2011-10-01

    A prolonged QT interval is a risk factor for ischemic heart disease in hypertensive subjects. Patients with renal-artery stenosis and primary aldosteronism (PA) are at increased risk of cardiovascular events. The objective of the present study was to evaluate the QT interval in patients with renovascular hypertension (RV) and PA before and after treatment. A total of 24 patients with RV and 38 with PA were studied; 89 patients with essential hypertension (EH) served as control group. Corrected QT intervals (QTcH) were measured from a 12-lead ECG. Basal QTcH was longer in RV (429±30 ms) and PA (423±23 ms) compared with EH controls (407±18 ms; P440 ms was higher in RV (29%) and PA patients (29%) compared with EH controls (4%; P<0.001). QTcH interval was evaluated after treatment in 19 RV and 15 PA patients. QTcH was reduced after renal-artery angioplasty in RV patients (419±14 ms; P=0.02), and after spironolactone or adrenalectomy in PA (403±12 ms; P=0.01). In conclusion, QT interval was prolonged in patients with RV and PA compared with controls with EH. After angioplasty of renal-artery stenosis in RV, and treatment with spironolactone or adrenalectomy in PA, the cardiovascular risk of such patients may be reduced by concomitant blood pressure lowering and QT duration shortening. PMID:21677661

  18. 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.

  19. Aldosterone-induced ENaC and basal Na+/K+-ATPase trafficking via protein kinase D1-phosphatidylinositol 4-kinaseIIIβ trans Golgi signalling in M1 cortical collecting duct cells.

    Science.gov (United States)

    Dooley, Ruth; Angibaud, Emmanuelle; Yusef, Yamil R; Thomas, Warren; Harvey, Brian J

    2013-06-15

    Aldosterone regulates Na(+) transport in the distal nephron through multiple mechanisms that include the transcriptional control of epithelial sodium channel (ENaC) and Na(+)/K(+)-ATPase subunits. Aldosterone also induces the rapid phosphorylation of Protein Kinase D1 (PKD1). PKD isoforms regulate protein trafficking, by the control of vesicle fission from the trans Golgi network (TGN) through activation of phosphatidylinositol 4-kinaseIIIβ (PI4KIIIβ). We report rapid ENaCγ translocation to the plasma membrane after 30 min aldosterone treatment in polarized M1 cortical collecting duct cells, which was significantly impaired in PKD1 shRNA-mediated knockdown cells. In PKD1-deficient cells, the ouabain-sensitive current was significantly reduced and Na(+)/K(+)-ATPase α and β subunits showed aberrant localization. PKD1 and PI4KIIIβ localize to the TGN, and aldosterone induced an interaction between PKD1 and PI4KIIIβ following aldosterone treatment. This study reveals a novel mechanism for rapid regulation of ENaC and the Na(+)/K(+)-ATPase, via directed trafficking through PKD1-PI4KIIIβ signalling at the level of the TGN. PMID:23541637

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

    Science.gov (United States)

    Komers, Radko; Plotkin, Horacio

    2016-05-15

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

  1. A systematic review on randomized control trials on rennin angiotensin aldosterone system inhibitors role in managing hypertension among hemodialysis patients.

    Science.gov (United States)

    Aftab, Raja Ahsan; Khan, Amer Hayat; Adnan, Azreen Syazril; Jannah, Nurul

    2016-01-01

    Randomized control trials (RCTs) are considered as most rigors way of determining the cause-effect relationship of a treatment and outcome. Activation of rennin angiotensin aldosterone system (RAAS) is an important contributor to hypertension in hemodialysis patients. The prevalence of hypertension in hemodialysis patients varies from 60% to 80% and hypertension management alone with conventional hemodialysis is insufficient. Hence, the current review was aimed to investigate the effect of RAAS inhibitors in managing hypertension among hemodialysis patients in a randomized control trial. Using PUBMED and EMBASE databases, randomized control trial with primary or secondary outcomes related to the effect of RAAS inhibitors on blood pressure among hemodialysis patients were included for analysis. The current review also assessed the quality of reporting of RCT. A total of eight RCT met inclusion criteria for current review. According to modified jaded scale, one (12.5%) study scored four points for quality reporting, whereas two (25%) studies scored one point that was the least score. The mean score for all included studies was 2.25. Six (75%) of the eight RCT included, involved ARB in hypertension management among hemodialysis patients, whereas two (25%) studies involved angiotensin-converting enzyme (ACE) inhibitors. Of the siz RCT involving ARB, two (33.3%) RCT also included ACE inhibitors comparison group. Altogether six (75%) studies report a reduction in blood pressure with the use of RAAS inhibitors compared to control group; however, of the six studies, two (33.3%) reported that the reduction in blood pressure was not significant. Whereas, two (25%) studies reported no reduction in blood pressure compared to the control group. The findings from current review do not indicate a clear pattern for a role of RAAS inhibitors for hypertension control among hemodialysis patients. PMID:26853680

  2. Acutely elevated vasopressin increases circulating concentrations of cortisol and aldosterone in fasting northern elephant seal (Mirounga angustirostris) pups

    Science.gov (United States)

    Ortiz, Rudy M.; Wade, Charles E.; Ortiz, C. Leo; Talamantes, Frank

    2003-01-01

    The physiological actions of vasopressin (VP) in marine mammals are not well defined. To help elucidate its hormonal and renal effects in this group of mammals, northern elephant seal (Mirounga angustirostris) pups (N=7; 99+/-4 kg) were first infused with 0.9% saline (control; 220 ml), followed 24 h later with VP (as a 20 ng kg(-1) bolus, then 2 ng kg(-1) min(-1) for approximately 35 min in 225+/-16 ml saline). During both control and VP periods, blood samples were collected prior to infusion, and 15, 30, 60, 120 min and 24 h after infusion to examine the hormonal responses of the pups to VP. Renal responses were quantified from 24 h urine samples obtained prior to infusion (control) and 24 h post-infusion. Compared to the control period, infusion of VP increased plasma concentrations of cortisol over a 120 min period and aldosterone over 30 min, while plasma renin activity (PRA) was decreased for a 120 min period. The plasma urea:creatinine ratio was elevated following infusion of VP. Urine output and osmotic clearance were increased by 69+/-18% (mean +/- S.E.M.) and 36+/-10%, respectively, but free water clearance and glomerular filtration rate were not significantly altered 24 h post-infusion of VP. Solute (osmolality, Na(+), K(+) and Cl(-)) excretion and fractional excretion of electrolytes were also increased when compared to control values. The increase in cortisol concentration suggests that VP may possess corticotropin releasing hormone-like activity in elephant seals. If osmotic diuresis and natriuresis are typical consequences of elevated [VP] in fasting pups, then not increasing VP normally during the fast may serve as a protective mechanism to avoid the potential loss of Na(+) induced by elevated [VP]. Therefore, under natural fasting conditions, pups may be highly sensitive to small changes in [VP], resulting in the maintenance of water and electrolyte balance.

  3. Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Chiao-Yin Sun

    Full Text Available BACKGROUND: Uremic toxins are considered to have a determinant pathological role in the progression of chronic kidney disease. The aim of this study was to define the putative pathological roles of the renal renin-angiotensin-aldosterone system (RAAS and renal tubular epithelial-to-mesenchymal transition (EMT in kidney fibrosis induced by (indoxyl sulfate IS and (p-cresol sulfate PCS. METHODS: Mouse proximal renal tubular cells (PKSV-PRs treated with IS or PCS were used. Half-nephrectomized B-6 mice were treated with IS or PCS for 4 weeks. In the losartan treatment study, the study animal was administrated with IS+losartan or PCS+losartan for 4 weeks. RESULTS: IS and PCS significantly activated the intrarenal RAAS by increasing renin, angiotensinogen, and angiotensin 1 (AT1 receptor expression, and decreasing AT2 receptor expression in vitro and in vivo. IS and PCS significantly increased transforming growth factor-β1 (TGF-β1 expression and activated the TGF-β pathway by increasing Smad2/Smad2-P, Smad3/Smad3-P, and Smad4 expression. The expression of the EMT-associated transcription factor Snail was increased by IS and PCS treatment. IS and PCS induced the phenotype of EMT-like transition in renal tubules by increasing the expression of fibronectin and α-smooth muscle actin and decreasing the expression of E-cadherin. Losartan significantly attenuated the expression of TGF-β1 and Snail, and decreased kidney fibrosis induced by IS and PCS in vivo. CONCLUSION: Activating the renal RAAS/TGF-β pathway has an important pathological role in chronic kidney injury caused by IS and PCS. IS and PCS may increase Snail expression and induce EMT-like transition.

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

    Science.gov (United States)

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

    2016-01-01

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

  5. 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.

  6. 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; Giese, J; Christensen, N J; Bent-Hansen, L; Nielsen, M D

    1987-01-01

    We studied 73 Type 1 (insulin-dependent) diabetic patients, 18 to 50 years of age, with a diabetes duration of more than five years. Group 1: normal urinary albumin excretion below 30 mg per 24 h (n = 19); group 2: microalbuminuria, 30-300 mg per 24 h (n = 36); and group 3: diabetic nephropathy...... = 0.41, p less than 0.01). Extracellular volume was increased in patients (p less than 0.05), whereas plasma volume wasnormal. 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...

  7. Review of Current Research on Aldosterone and Left Ventricular Remodeling after Acute Myocardial Infarction%醛固酮对急性心肌梗死后左心室重构影响的研究进展

    Institute of Scientific and Technical Information of China (English)

    吴春涛

    2011-01-01

    心力衰竭已经成为影响人们生命和生活质量的主要疾病,心肌梗死后心室重构是其重要原因之一,急性心肌梗死后神经内分泌系统的过度激活对心室重构的影响已成为共识.作为肾素-血管紧张素-醛固酮系统的重要组成部分,醛固酮对于心血管系统的病理生理作用以及醛固酮逃逸现象确定了醛固酮受体拮抗剂在心力衰竭治疗中的决定性地位.现就醛固酮对于急性心肌梗死后左心室重构影响的研究进展作一综述.%Heart failure is a disease that affects people's quality of life, and ventricular remodeling after myocardial infarction is one of the major reasons. There is a consensus on the effect of over-activation of the neuroendocrine system after acute myocardial infarction ( AMI) on ventricular remodeling. Aldosterone acts as an important part of the renin-angiotensin-aldosterone system, and the aldosterone receptor antagonist plays a crucial role in the modern therapeutic regimen for heart failure attributed to aldosterone's pathophysiological effects on the cardiovascular system and aldosterone escape phenomenon. This article reviews the effects of aldosterone on left ventricular remodeling of AMI.

  8. Bcl-2 Expression in the Aortas of Model Rats with Aldosterone-Producing Adenomas%Bcl-2在醛固酮腺瘤模型大鼠主动脉中的表达

    Institute of Scientific and Technical Information of China (English)

    闫永吉; 陈戬; 刘建和; 张劲松; 姜永明; 王光; 张海燕

    2011-01-01

    目的:观察醛固酮对主动脉Bcl-2表达的影响.方法:32只SD大鼠随机均分为4组:①空白溶剂设为对照(60%丙二醇+10%乙醇+30%双蒸水);②醛固酮腺瘤:泵入醛固酮(1μg/h);③醛固酮腺瘤+依普利酮组:依普利酮(100 mg·kg-1·d-1);④醛固酮腺瘤+肼苯哒嗪组:肼苯哒嗪(25 mg·kg-1·d-1).渗透泵内分别注入醛固酮或空白溶剂,然后将其埋植于大鼠背部皮下.8周后,免疫组织化学和免疫印迹检测主动脉Bcl-2的表达.结果:与对照组相比,腺瘤组大鼠主动脉Bcl-2表达显著减少(P<0.05);依普利酮能够拮抗醛固酮对Bcl-2表达的抑制作用(P<0.05).结论:醛固酮通过抑制Bcl-2表达,调节细胞凋亡状态,可能是醛固酮诱导主动脉重构的机制之一.%Objective: To observe the effect of aldosterone on Bcl-2 expression in the aorta. Methods: Thirtytwo male rats were randomly divided into 4 groups; vehicle (control), aldosterone-producing adenoma, aldosterone-producing adenoma plus eplerenone or hydralazine. They were then implanted with an osmotic mini-pump that infused either aldosterone or the vehicle. After 8 weeks, Bcl-2 was examined by immunohistochemistry and Western blotting. Results:Compared with controls, the model rats with aldosterone-producing adenoma exhibited decreased aortic expression of Bcl-2. This effect of aldosterone was significantly reversed after co-treatment with eplerenone but not with hydralazine. Conclusions:This study's findings suggest that aldosterone directly suppresses aortic expression of Bcl-2 that may play an important role in aldosterone-induced aortic remodeling.

  9. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension.

    Science.gov (United States)

    Aghamohammadzadeh, Reza; Zhang, Ying-Yi; Stephens, Thomas E; Arons, Elena; Zaman, Paula; Polach, Kevin J; Matar, Majed; Yung, Lai-Ming; Yu, Paul B; Bowman, Frederick P; Opotowsky, Alexander R; Waxman, Aaron B; Loscalzo, Joseph; Leopold, Jane A; Maron, Bradley A

    2016-07-01

    Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10(-9) to 10(-7) M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor-small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.-Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth

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

    Science.gov (United States)

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

    2016-07-27

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

  11. Diagnostic Value of I-131 NP-59 SPECT/CT Scintigraphy in Patients with Subclinical or Atypical Features of Primary Aldosteronism

    Directory of Open Access Journals (Sweden)

    Yi-Chun Chen

    2011-01-01

    Full Text Available Accumulating evidence has shown the adverse effect of long-term hyperaldosteronism on cardiovascular morbidity that is independent of blood pressure. However, the diagnosis of primary aldosteronism (PA remains a challenge for patients who present with subtle or atypical features or have chronic kidney disease (CKD. SPECT/CT has proven valuable in the diagnosis of a number of conditions. The aim of this study was to determine the usefulness of I-131 NP-59 SPECT/CT in patients with atypical presentations of PA and in those with CKD. The records of 15 patients with PA were retrospectively analyzed. NP-59 SPECT/CT was able to identify adrenal lesion(s in CKD patients with suspected PA. Patients using NP-59 SPECT/CT imaging, compared with those not performing this procedure, significantly featured nearly normal serum potassium levels, normal aldosterone-renin ratio, and smaller adrenal size on CT and pathological examination and tended to feature stage 1 hypertension and non-suppressed plasma renin activity. These findings show that noninvasive NP-59 SPECT/CT is a useful tool for diagnosis in patients with subclinical or atypical features of PA and those with CKD.

  12. Incidence and influencing factors of aldosterone breakthrough during therapy with angiotensin Ⅱ receptor bockers alone,or combined with angiotensin-converting enzyme inhibitors in patients with non-diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    梁敏

    2013-01-01

    Objective To investigate the incidence and influen-cing factors of aldosterone breakthrough during therapy with angiotensin Ⅱ receptor blockers(ARB) alone,or combined with angiotensin-converting enzyme inhibitors(ACEI) in Chinese patients with non-diabetic

  13. 肾上腺醛固酮腺瘤大鼠模型的建立%Establishment of a Rat Model of Aldosterone-Producing Adenoma

    Institute of Scientific and Technical Information of China (English)

    闫永吉; 陆义芹; 王保军; 史涛坪; 王光; 张海燕

    2012-01-01

    目的 构建肾上腺醛固酮腺瘤大鼠模型.方法 16只SD大鼠随机分对照组合醛固酮腺瘤组,在ALZET2004的微量渗透泵储药仓内分别注入醛固酮溶液或空白溶剂,然后将其埋于大鼠背部皮下.ALZET2004微量渗透泵可以持续灌注4周,为使醛固酮作用时间达到8周,4周后更换渗透泵1次,同时尾套法测量大鼠尾动脉收缩压;8周后,放免法检测血浆醛固酮浓度和肾素活性.结果 3周后,与对照大鼠相比,腺瘤组大鼠收缩压开始升高,第7周达到顶峰,之后维持在高水平;腺瘤组大鼠血浆醛固酮的浓度显著升高 (P<0.01),肾素活性被抑制 (P<0.01).结论 大鼠皮下埋植微量渗透泵灌注醛固酮,可以成功构建大鼠醛固酮腺瘤模型.%Objective To establish a rat model of aldosterone-producing adenoma (APA). Methods 16 Sprague- Dawley rats subcutaneously implanted with an osmotic mini- pump, were randomly divided into 2 groups: control group (vehicle) and APA (1 μg/h) group. Because the mini- pump (ALZET 2004) could continuously infuse test substance for 4 weeks, another minipump was replaced after the fourth week to make the duration of aldosterone infusion for 8 weeks. Systolic blood pressure (SBP) was measured weekly by the tail-cuff method. At the termination of the study, blood was collected for measurements of plasma renin activity (PRA) and aldosterone concontration (PAC) with radioimmunoassay kits. Results After 3 weeks, APA rats showed significantly and progressively increased SBP compared with controls (P<0.05) , and the SBP level reached peak on 7th week and remained high levels. PRA was substantially depressed and PAC was significantly raised in APA rats (P<0.01) . Conclusion By implanting osmotic minipumps subcutaneously, the rat models of APA can be successfully established, which provide a good platform for investigating the pathogenesis of APA.

  14. A detailed physiologically-based model to simulate the pharmacokinetics and hormonal pharmacodynamics of enalapril on the circulating endocrine renin-angiotensin-aldosterone system

    Directory of Open Access Journals (Sweden)

    MichaelBlock

    2013-02-01

    Full Text Available The renin-angiotensin-aldosterone system (RAAS plays a key role in the pathogenesis of cardiovascular disorders including hypertension and is one of the most important targets for drugs. A whole body physiologically-based pharmacokinetic (wb PBPK model integrating this hormone circulation system and its inhibition can be used to explore the influence of drugs that interfere with this system, and thus to improve the understanding of interactions between drugs and the target system. In this study, we describe the development of a mechanistic RAAS model and exemplify drug action by a simulation of enalapril administration. Enalapril and its metabolite enalaprilat are potent inhibitors of the angiotensin-converting enzyme (ACE. To this end, a coupled dynamic parent-metabolite PBPK model was developed and linked with the RAAS model that consists of seven coupled PBPK models for aldosterone, ACE , angiotensin 1, angiotensin 2, angiotensin 2 receptor type 1, renin and prorenin. The results indicate that the model represents the interactions in the RAAS in response to the pharmacokinetics (PK and pharmacodynamics (PD of enalapril and enalaprilat in an accurate manner. The full set of RAAS hormone profiles and interactions are consistently described at pre- and post-administration steady state as well as during their dynamic transition and show a good agreement to literature data. The model allows a simultaneous representation of the parent-metabolite conversion to the active form as well as the effect of the drug on the hormone levels, offering a detailed mechanistic insight into the hormone cascade and its inhibition. This model constitutes a first major step to establish a PBPK-PD model including the PK and the mode of action (MoA of a drug acting on a dynamic RAAS that can be further used to link to clinical endpoints such as blood pressure.

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

    Science.gov (United States)

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

    2016-03-01

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

  16. 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.

    Science.gov (United States)

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

    2016-02-01

    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 formulation of safety controls for animal products and the design of new QdNOs with less harmful effects. PMID:26802905

  17. Renin-aldosterone and kallikrein-kinin systems in the patients with arterial hypertension who took part in elimination of aftereffects of the accident at Chernobyl Atomic Power Station

    International Nuclear Information System (INIS)

    The study involved 290 patients with arterial hypertension (borderline arterial hypertension, stage 1 and 2 hypertensive disease) who took part in elimination of the aftereffects of the accident at Chernobyl Atomic Power Station (liquidators). The values of pressor renin-aldosterone system and depressor kallikrein-kinin system were determined in the patients. Some peculiarities of vasoactive regulation in these patients were established. Low-renin forms of arterial hypertension are characteristic for the examined liquidators.Irrespective of the stage of hypertension development and renin activity level, increased amount of plasma aldosterone was observed in the liquidators, which can suggest of primary aldosteronism in some patients with low level of renin. Absence of activation and even exhaustion of depressor system (kallikrein-kinin) was revealed in the examined liquidators, which is not characteristic for the patients of the same age who were not exposed to ionizing radiation. The revealed changes of vasoactive regulation in the liquidators with arterial hypertension of comparatively young age have already been described for elderly and old persons and can suggest of aging rate increase in this group of patients

  18. 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

    Indian Academy of Sciences (India)

    Manisha Patnaik; Pallabi Pati; Surendra N. Swain; Manoj K. Mohapatra; Bhagirathi Dwibedi; Shantanu K. Kar; Manoranjan Ranjit

    2014-12-01

    Essential hypertension which accounts 90–95% of the total hypertension cases is affected by both genetic and environmental factors. This study was undertaken to investigate the association of aldosterone synthase C-344T, angiotensin II type I receptor A1166C and 11- hydroxysteroid dehydrogenase type 2 G534A polymorphisms with essential hypertension in the population of Odisha, India. A total of 246 hypertensive subjects (males, 159; females, 87) and 274 normal healthy individuals (males, 158; females, 116) were enrolled in this study based on the inclusion and exclusion criteria. Analysis of genetic and biochemical data revealed that in this population the CT and TT genotypes of aldosterone synthase C-344T polymorphism, frequency of alcohol consumption and aldosterone levels were significantly high among the total as well as male hypertensives, while the AC and CC genotypes of angiotensin II type I receptor A1166C polymorphism were significantly high among the total as well as female hypertensives. High density lipoprotein levels were higher in male hypertensives.

  19. 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

    Indian Academy of Sciences (India)

    Manisha Patnaik; Pallabi Pati; Surendra N. Swain; Manoj K. Mohapatra; Bhagirathi Dwibedi; Shantanu K. Kar; Manoranjan Ranjit

    2015-06-01

    Essential hypertension which accounts 90–95% of the total hypertension cases is affected by both genetic and environmental factors. This study was undertaken to investigate the association of aldosterone synthase C-344T, angiotensin II type I receptor A1166C and 11- hydroxysteroid dehydrogenase type 2 G534A polymorphisms with essential hypertension in the population of Odisha, India. A total of 246 hypertensive subjects (males, 159; females, 87) and 274 normal healthy individuals (males, 158; females, 116) were enrolled in this study based on the inclusion and exclusion criteria. Analysis of genetic and biochemical data revealed that in this population the CT and TT genotypes of aldosterone synthase C-344T polymorphism, frequency of alcohol consumption and aldosterone levels were significantly high among the total as well as male hypertensives, while the AC and CC genotypes of angiotensin II type I receptor A1166C polymorphism were significantly high among the total as well as female hypertensives. High density lipoprotein levels were higher in male hypertensives.

  20. Moderate antiproteinuric effect of add-on aldosterone blockade with eplerenone in non-diabetic chronic kidney disease. A randomized cross-over study.

    Directory of Open Access Journals (Sweden)

    Lene Boesby

    Full Text Available BACKGROUND: Reduction of proteinuria and blood pressure (BP with blockers of the renin-angiotensin system (RAS impairs the progression of chronic kidney disease (CKD. The aldosterone antagonist spironolactone has an antiproteinuric effect, but its use is limited by side effects. The present study evaluated the short-term antiproteinuric effect and safety of the selective aldosterone antagonist eplerenone in non-diabetic CKD. STUDY DESIGN: Open randomized cross-over trial. SETTING AND PARTICIPANTS: Forty patients with non-diabetic CKD and urinary albumin excretion greater than 300 mg/24 hours. INTERVENTION: Eight weeks of once-daily administration of add-on 25-50 mg eplerenone to stable standard antihypertensive treatment including RAS-blockade. OUTCOMES & MEASUREMENTS: 24 hour urinary albumin excretion, BP, p-potassium, and creatinine clearance. RESULTS: The mean urinary albumin excretion was 22% [CI: 14,28], P < 0.001, lower during treatment with eplerenone. Mean systolic BP was 4 mmHg [CI: 2,6], P = 0.002, diastolic BP was 2 mmHg [CI: 0,4], P = 0.02, creatinine clearance was 5% [CI: 2,8], P = 0.005, lower during eplerenone treatment. After correction for BP and creatinine clearance differences between the study periods, the mean urinary albumin excretion was 14% [CI: 4,24], P = 0.008 lower during treatment. Mean p-potassium was 0.1 mEq/L [CI: 0.1,0.2] higher during eplerenone treatment, P<0.001. Eplerenone was thus well tolerated and no patients were withdrawn due to hyperkalaemia. LIMITATIONS: Open label, no wash-out period and a moderate sample size. CONCLUSIONS: In non-diabetic CKD patients, the addition of eplerenone to standard antihypertensive treatment including RAS-blockade caused a moderate BP independent fall in albuminuria, a minor fall in creatinine clearance and a 0.1 mEq/L increase in p-potassium. TRIAL REGISTRATION: Clinicaltrials.gov NCT00430924.

  1. 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.

  2. 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

    Science.gov (United States)

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

    2015-01-01

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

  3. 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; Pavenstädt, Hermann; Narumiya, Shuh; Jensen, Boye L; Nüsing, Rolf M

    2012-01-01

    (+/+), EP4(-/-), and in wild-type mice treated with EP4 receptor antagonist. After 2 wk of a low-salt diet (0.02% wt/wt NaCl), EP4(+/+) mice showed diminished Na(+) excretion, unchanged K(+) excretion, and reduced Ca(2+) excretion. Diuresis and plasma electrolytes remained unchanged. EP4(-/-) exhibited a......, 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......Increased cyclooxygenase-2 (COX-2) expression and PGE(2) synthesis have been shown to be prerequisites for renal renin release after Na(+) deprivation. To answer the question of whether EP4 receptor type of PGE(2) mediates renin regulation under a low-salt diet, we examined renin regulation in EP4...

  4. MITOCHONDRIAL REACTIVE OXYGEN SPECIES (ROS AS SIGNALLING MOLECULES OF INTRACELLULAR PATHWAYS TRIGGERED BY THE CARDIAC RENIN-ANGIOTENSIN II-ALDOSTERONE SYSTEM (RAAS.

    Directory of Open Access Journals (Sweden)

    Verónica Celeste De Giusti

    2013-05-01

    Full Text Available Mitochondria represent major sources of basal reactive oxygen species (ROS production of the cardiomyocyte. The role of ROS as signalling molecules that mediate different intracellular pathways has gained increasing interest among physiologists in the last years. In our lab, we have been studying the participation of mitochondrial ROS in the intracellular pathways triggered by the renin-angiotensin II-aldosterone system (RAAS in the myocardium during the past few years. We have demonstrated that acute activation of cardiac RAAS induces mitochondrial ATP-dependent potassium channel (mitoKATP opening with the consequent enhanced production of mitochondrial ROS. These oxidant molecules, in turn, activate membrane transporters, as sodium/hydrogen exchanger (NHE-1 and sodium/bicarbonate cotransporter (NBC via the stimulation of the ROS-sensitive MAPK cascade. The stimulation of such effectors leads to an increase in cardiac contractility. In addition, it is feasible to suggest that a sustained enhanced production of mitochondrial ROS induced by chronic cardiac RAAS, and hence, chronic NHE-1 and NBC stimulation, would also result in the development of cardiac hypertrophy.

  5. Acute mechanical sensitization of peripheral nociceptors by aldosterone through non-genomic activation of membrane bound mineralocorticoid receptors in naive rats.

    Science.gov (United States)

    Shaqura, Mohammed; Li, Xiongjuan; Al-Madol, Mohammed A; Tafelski, Sascha; Beyer-Koczorek, Antje; Mousa, Shaaban A; Schäfer, Michael

    2016-08-01

    Recently, there is increasing interest in the role of peripheral mineralocorticoid receptors (MR) to modulate pain, but their localization in neurons and glia of the periphery and their distinct involvement in pain control remains elusive. In naive Wistar rats our double immunofluorescence confocal microscopy of the spinal cord, dorsal root ganglia, sciatic nerve and innervated skin revealed that MR predominantly colocalized with calcitonin-gene-related peptide (CGRP)- and trkA-immunoreactive (IR) nociceptive neurons and only marginally with myelinated trkB-IR mechanoreceptive and trkC-IR proprioreceptive neurons underscoring a pivotal role for MR in the modulation of pain. MR could not be detected in Schwann cells, satellite cells, and astrocytes and only scarcely in spinal microglia cells excluding a relevant functional role of glia-derived MR at least in naïve rats. Intrathecal (i.t.) and intraplantar (i.pl.) application of increasing doses of the MR selective agonist aldosterone acutely increased nociceptive behavior which was reversible by a MR selective antagonist and most likely due to non-genomic effects. This was further substantiated by the first identification of membrane bound MR specific binding sites in sensory neurons of dorsal root ganglia and spinal cord. Therefore, a crucial role of MR on nociceptive neurons but not on glia cells and their impact on nociceptive behavior most likely due to immediate non-genomic effects has to be considered under normal but more so under pathological conditions in future studies. PMID:27016023

  6. 醛固酮对肾小球系膜细胞凋亡的影响%Effect of aldosterone on glomerular mesangial cells apoptosis bothin vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    任志龙; 梁伟; 丁国华; 胡凤琪; 杨红霞

    2011-01-01

    Objective To evaluate the effect of aldosterone (Ald) on glomerular mesangial cells apoptosis and to explore the possible mechanisms.Methods Twenty-four Sprngue-Dawley rats were subcutaneously embedded with osmotic mini-pumps and randomly divided into 3 groups.Aldosterone (1.5 μg/h) was administrated subcutaneouly by osmotic mini-pumps in Ald group,eplerenone (Epl,100 mg·kg-1·d-1) and Ald (1.5 μg/h) was given to Epl group.And normal saline was used in control group (Con group).Systolic blood pressure and urinary albumin excretion rate (UAER) were detected on day 0,7,14,21,28.Blood and kidney samples were harvested on day 28.Plasma creatinine,potassium and aldosterone were measured.Renal paraffin sections were stained by PAS and the morphological changes were evaluated by light microscopy.Apoptosis index of mesangial cells were detected by TUNEL assay.The glomerular mesangial cells (MCs) were cultured in a DMEM-F12 media.MCs apoptosis was evaluated by staining cells with Annexin V and propidium iodide (PI) using flow cytometer.Expression of Bcl-2 and Bax mRNA was examined by RT-PCR.The protein level of Bad or phospho-Bad was measured by Western blotting.Results Ald-infused rats developed hyperaldosteronemia and hypokalemia.Rats in Ald group exhibited significant hypertension and marked albuminuria.Ald group rats showed increased number of TUNEL-positive mesangial cells when compared with control rats (P<0.05).Aldosterone induced mesangial cells apoptosis in a time-dependent manner.Expression of Bcl-2 mRNA was decreased but Bax mRNA was increased in aldosterone treated MCs compared to that in Con group (P<0.05).Aldosterone promoted dephosphorylation of cytosolic phospho-Bad compared with vehicle treated cells (P< 0.05).However,eplerenone attenuated these effects of aldosterone.Conclusion Aldosterone directly promotes mesangial cells apoptosis,and eplerenone can attenuate this effect of aldosterone.Dephosphorylation of cytosolic phospho-Bad may be the key

  7. 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

  8. 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.

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

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    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.

  10. Progress in the associated G-protein-coupled receptors (GPCRs) of aldosterone-producing adenoma (APA) pathogenesis%醛固酮瘤(APA)发病相关的G蛋白耦联受体(GPCRs)研究进展

    Institute of Scientific and Technical Information of China (English)

    徐曦

    2014-01-01

    醛固酮瘤(aldosterone-producing adenoma,APA)是原发性醛固酮增多症的一个重要亚型,约占30%~60%,是引起继发性高血压的重要病因.有关APA的发病机制,可见不同水平与角度的研究,但是对于APA的具体发病机制仍不清楚.本文就已知的与发病相关的G蛋白耦联受体(G-protein-coupled receptors,GPCRs)进行论述.

  11. Mechanism of renin-angiotensin-aldosterone system inhibitors%肾素-血管紧张素-醛固酮系统抑制剂的作用机制

    Institute of Scientific and Technical Information of China (English)

    朱凌倜; 周京敏

    2013-01-01

    Renin-angiotensin-aldosterone system (RAAS) is a complex network system in regulating cardiovascular and renal function. RAAS activation plays an extremely important role in the development and prognosis of hypertension, myocardial remodeling after acute myocardial infarction, acute and chronic heart failure and renal insufifciency. The symptoms and prognosis of patients with above-mentioned diseases can be signiifcantly improved by blocking different levels of RAAS. This article reviews the mechanism of several RAAS inhibitors which are commonly used in clinic.%肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system, RAAS)是一种调控心血管和肾功能的复杂的网络系统。RAAS的激活在高血压、急性心肌梗死后的心肌重塑、急性和慢性心力衰竭以及肾功能不全等多种疾病的进展中起着重要的作用,而RAAS抑制剂能够显著延缓上述疾病的进展和改善患者的预后。本文就目前临床常用的几类RAAS抑制剂的作用机制作一概述。

  12. Inverting Notions of the Biological Role of the Renin → Angiotensin-II → Aldosterone System and the Function of Arterial Pressure as a Metabolism Regulator

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    Vladimir N. Titov

    2014-09-01

    Full Text Available The phylogenetic theory of general pathology postulates that notions of the biological role of arterial pressure (AP in physiology and pathology have been subjected to inversion. The nephron’s activation of the synthesis of the components renin → angiotensin-II (A-II and the augmentation of aldosterone secretion are directed not at an increase in AP but at preserving the volume of the piece of the third world ocean, privatized by each species, - the pool of the intercellular milieu in which, just like millions of years before, there continue to live all cells. Phylogenetically earlier organs cannot regulate the action of a later one in AP phylogenesis – a physical factor in metabolism regulation. It is not the kidneys that increase AP but the vasomotor center, which, increasing AP in the proximal segment and further hydrodynamic pressure in the distal segment of the arterial bed, seeks to reanimate the function of nephrons, the biological function of endoecology and the biological reaction of excretion. In addition to playing a major role in the biological function of locomotion, AP is a physical factor in compensating for impairments in the biological functions of homeostasis, trophology, endoecology, and adaptation. There have formed sequentially three levels of metabolic regulation in phylogenesis. At an autocrine level, there occurs a specific regulation of biochemical reactions. Within paracrinally regulated communities of cells, in the distal segment of the arterial bed, metabolism is regulated by millions of local peristaltic pumps through compensating for the biological reaction of endothelium-dependent vasodilation, microcirculation, and the action of humoral mediators and hormonal principles. In vivo from the level of the vasomotor center metabolism is non-specifically, systemically regulated by the physical factor – AP – through sympathetic activation of the heart; in the proximal segment of the arterial bed and the distal

  13. The Effect of Renin-Angiotensin-Aldosterone System Blockade Medications on Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography: A Meta-Analysis.

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    Zhijun Wu

    Full Text Available Contrast-induced nephropathy (CIN is the main complication of contrast media administration (CM in patients undergoing coronary angiography (CAG and percutaneous coronary intervention (PCI. There are inconsistent results in the literature regarding the effect of renin-angiotensin-aldosterone system (RAAS blockers (angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs] on CIN. We evaluated the association between the administration of ACEI/ARBs and CIN, as well as the effect of ACEI/ARBs on post-procedural changes in renal function index, in patients undergoing CAG.We searched Pubmed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for relevant studies. The primary search generated 893 potentially relevant articles. A total of 879 studies were excluded because they did not meet the selection criteria. Finally, 14 studies were eligible for inclusion. There were 7,288 patients that received ACEI/ARBs and 8,159 patients that received placebo or naive to ACEI/ARBs in the study. A random or a fixed effect model was used to calculate the pooled odd ratios (ORs.The risk of CIN was significantly increased in the ACEI/ARBs group compared to the control group (OR= 1.50, 95%CI: 1.03-2.18, P =0.03. The magnitude of association was significantly reinforced in the observational studies (OR=1.84, 95%CI 1.19-2.85, P=0.006 but not in the randomized controlled trials (OR=0.88, 95%CI 0.41-1.90 P=0.74. The summary adjusted OR of 4 observational studies was 1.56 (95%CI 1.25-1.94, P<0.0001 and was weaker than the unadjusted OR.Although there is some evidence to suggest that the administration of RAAS blockers was associated with the increased risk of CIN in patients undergoing CAG, the robustness of our study remains weak. The results are based on small observational studies and need further validation.

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

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    Yu-Wei Chen

    2016-05-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  16. Effects of eplerenone, amlodipine and telmisartan on podocyte injury in aldosterone-infused rats%不同降压药对醛固酮输注大鼠足细胞损伤的影响

    Institute of Scientific and Technical Information of China (English)

    粱伟; 陈铖; 丁国华; 石明; 石晶; 任志龙; 胡凤琪; 杨红霞

    2008-01-01

    Objective To investigate whether aldosterone infusion induces glomerular or podocyte injury in rats and to evaluate the effects of eplerenoen (EPL), andodipine (CCB) and telmisartan (ARB) on aldosterone- induced injury. Methods Thirty male Sprague-Dawley rats were divided into 5 groups: control, subcutaneous infusion of aldosterone (1.5 μg/h, ALD group) and aldosterone infusion plus eplerenone (100 mg·kg-1·d-1, EPL group), amlodipine(10 nag·kg-1·d-1 CCB group), telmisartan (3 mg·kg-1·d-1, ARB group), respectively. Systolic blood pressure(SBP) and urinary albumin excretion ratio(UAER) were measured at day 0, 7, 14, 21, 28. Blood samples were harvested to detect plasma angiotensin Ⅱ, plasma aldosterone, serum sodium, serum potassium and serum creatinine at day 28. Glomerular damge was quantified by morphological glomerular injury score (GIS). Immunohistochemistry and RT-PCR were performed to evaluate podocyte lesion, and apoptosis ratio of pedocyte (ARP) in a glomerular cross section was analyzed by TUNEL. Results ALD infusion progressively increased SBP and UAER compared with CTL (P<0.01). SBP was significantly reduced in EPL, CCB or ARB-treated animals, meanwhile, UAER was decreased in EPL and ARB group, but not in CCB group. The ALD-infused rats exibited hypernatremia and hypopotassaemia, which were blocked by EPL adminstration but not by CCB or ARB treatment. ARB group had a significant increase in plasma angiotensin Ⅱ compared with ALD, CCB and EPL groups(P<0.01). The ALD-infused animals developed hyperaldosteronemia compared with CTL, but with no difference of plasma aldosterone among ALD, EPL, CCB and ARB-treated rats. Treatment with EPL prevented an increase of GIS and ARP compared with CCB and ARB (P<0.05, P<0.01). Protein and mRNA expression of nephfin was up-regulated in ALD group (P< 0.01), but was significantly prevented by EPL treatment(P<0.01), whereas CCB and ARB therapy had no such effect. Conclusion ALD infusion significantly

  17. Local aldosterone system mediated "hyperglycaemic memory" in human mesangial cells%局部醛固酮系统介导高糖致人系膜细胞损伤记忆效应

    Institute of Scientific and Technical Information of China (English)

    杜超; 熊勤攀; 周波; 苏红

    2012-01-01

    Objective To investigate the effect of hyperglycaemic memory on the local aldosterone system, reactive oxygen species (ROS) and expression of oncofetal fibronectin (oncofetal FN) mRNA in human mesangial cells (HMCs) ,and to further understand the role of local aldosterone system in the process. Methods In this study HMCs were divided into the following groups:normal glucose group (NG, 5 mmol/L D-glucose for 2 days),high glucose group (HG, 25 mmol/L D-glucose for 2 days), memory group (M, 25 mmol/L D-glucose for 2 days-* 5 mmol/L D-glucose for 4 days) , memory + eplerenone group (MY,25 mmol/L D-glucose for 2 days^-5 mmol/L D-glucose+10 //mol/L eplerenone for 4 days), normal glucose + eplerenone group (NY,5 mmol/L D-glucose for 2 days —- 5 mmol/L D-glucose+10 (imol/L eplerenone for 4 days),and persistent normal glucose group (SN, 5 mmol/L D-glucose for 6 days). ROS levels were tested by fluorescence microscope and fluorescence microplate reader. Aldosterone synthase (CYP11B2) protein expression was detected by Western blotting analysis. The mRNA expressions of llphydroxysteroid dehydrogenase type 2,CYP11B2 and oncofetal FN were detected by RT-PCR. The expression and translocation of mineralocorticoid receptor (MR) was observed by laser scanning confocal microscope (LSCM). Aldosterone level in cell culture supernatant was detected by radioimmunoassay. Results (DCYP11B2 mRNA and protein expression in group HG and in group M were all significantly increased, being 3. 45 , 2. 09 and 3. 14, 2. 06 folds of those in group NG, respectively (all F<0. 05). The aldosterone levels in HMCs culture supernatant were significantly increased in group HG and group M, being 2. 01 and 1. 81 folds of that in group NG. respectively (P

  18. Beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine, diuretics, aldosterone antagonist, ivabradine, devices and digoxin (BANDAID(2) ): an evidence-based mnemonic for the treatment of systolic heart failure.

    Science.gov (United States)

    Chia, N; Fulcher, J; Keech, A

    2016-06-01

    Heart failure causes significant morbidity and mortality, with recognised underutilisation rates of guideline-based therapies. Our aim was to review current evidence for heart failure treatments and derive a mnemonic summarising best practice, which might assist physicians in patient care. Treatments were identified for review from multinational society guidelines and recent randomised trials, with a primary aim of examining their effects in systolic heart failure patients on mortality, hospitalisation rates and symptoms. Secondary aims were to consider other clinical benefits. MEDLINE and EMBASE were searched using a structured keyword strategy and the retrieved articles were evaluated methodically to produce an optimised reference list for each treatment. We devised the mnemonic BANDAID (2) , standing for beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine (or potentially neprilysin inhibitor), diuretics, aldosterone antagonist, ivabradine, devices (automatic implantable cardioverter defibrillator, cardiac resynchronisation therapy or both) and digoxin as a representation of treatments with strong evidence for their use in systolic heart failure. Treatment with omega-3 fatty acids, statins or anti-thrombotic therapies has limited benefits in a general heart failure population. Adoption of this mnemonic for current evidence-based treatments for heart failure may help improve prescribing rates and patient outcomes in this debilitating, high mortality condition. PMID:26109136

  19. The role of renin-angiotensin-aldosterone system in salty taste and sodium intake regulation%肾素-血管紧张素-醛固酮系统在咸味觉功能及摄钠调控中的作用

    Institute of Scientific and Technical Information of China (English)

    吕波; 闫剑群

    2011-01-01

    咸味觉感受功能对摄钠行为的引导和调控至关重要,体钠平衡失调将引起一系列神经内分泌变化以产生钠欲,并伴有咸味觉感受功能的变化.肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system,RAAS)的多个成分在体钠平衡失调对咸味觉功能的调控中扮演重要角色.外周及脑源性血管紧张素II(angiotensin II,ANG II)和醛固酮(aldosterone,ALD)可协同作用于中枢相应敏感神经元,调控动物咸味觉喜好及敏感性,进而调控摄钠行为,并帮助机体维持体钠平衡.

  20. 24-hour urinary aldosterone excretion rate

    Science.gov (United States)

    ... RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods . 22nd ed. Philadelphia, PA: Elsevier Saunders; ... by: Brent Wisse, MD, Associate Professor of Medicine, Division of Metabolism, Endocrinology & Nutrition, University ...

  1. Renin-Angiotensin-Aldosteron-System und Linksventrikelfunktion

    Directory of Open Access Journals (Sweden)

    Stanek B

    2002-01-01

    Full Text Available Der ungünstige Einfluß der neurohumoralen Systeme auf die Hämodynamik bei Patienten mit Herzinsuffizienz ist seit langem bekannt. Neueren Studien zufolge ist das Reninsystem auch an den pathologischen Strukturveränderungen des Herz-Kreislauf-Systems wesentlich beteiligt. Daher sind es nicht unbedingt die vasodilatierenden Wirkungen der Antagonisten im Reninsystem, die zu den Langzeiterfolgen bei der Behandlung kardiovaskulärer Erkrankungen, insbesondere der chronischen Herzinsuffizienz, führen. Vielmehr dürfte die Verzögerung oder die Regression der ungünstigen Umbauvorgänge des linken Ventrikels ursächlich beteiligt sein. Sequentielle Blockade des Reninsystems mit ACE-Hemmern in Kombination mit Angiotensinrezeptorblockern scheint noch weitere günstige Effekte auf die Progression der Herzinsuffizienz, gemessen an der verbesserten Linksventrikelfunktion, zu erbringen. Über die Wertigkeit der Angiotensinrezeptorblocker in Hinblick auf die Lebensverlängerung - insbesondere bei gleichzeitiger Betablockade - herrscht noch keine endgültige Klarheit. Zukünftige Vergleichsstudien werden zeigen, ob Angiotensinrezeptorblocker bei der Herzinsuffizienz ihr Potential als eigenständige Therapieklasse gegenüber den ACE-Hemmern behaupten können.

  2. Relationship of gene polymorphisms of angiotensin convertion enzyme, aldosterone synthase and α-adducin with subclinical renal lesion%血管紧张素转换酶醛固酮合酶α-内收蛋白基因多态性与肾损害的关系

    Institute of Scientific and Technical Information of China (English)

    陈慧; 林慧中; 陈燕; 骆杰伟; 吴小盈; 李德育; 伍延安; 沈晓丽

    2008-01-01

    Objective To investigate the relationship of gene polymorphisms of angiotensin eonvertion enzyme (ACE), aldosterone synthase (CYP11B2)and α-adducin with subclinical renal lesion. Methods I/D polymorphism of ACE gene, -344T/C polymorphism of CYP11B2 gene and 460G/T polymorphism of α-adduein gene were detected by polymerase chain reaction (PCR) and restrictive fragment length polymorphism(RFLP) in 604 normotensive subjects and 1081 primary hypertensive patients whose creatinine (Cr) were less than 2mg/L. The primary hypertensive and normotensive subjects were divided respectively into normal group (Ccr≥60ml/min) and subclinical renal lesion (Ccr<60 ml/min) group, according to creatinine clearance rate (Ccr) calculated by Cockcroft-Gault equation. Results ANOVA, contingency X2 and partition of chi-square were selected. The frequencies of different genotypes of ACE, CYP11B2, and α-adducin were in agreement with Hardy-Weinberg equilibrium in our study. Normal renal function group (A group, n=512) and subclinical renal lesion group (B group, n=92) in normotensive subjects, and normal renal function group (C group, n=828) and subclinical renal lesion group (D group, n=252) in hypertensive patients were compared. The patients in B and D groups were older than those in A and C groups (P0.05).ACE-DD基因型分布频率在高血压肾损害组最高为22.6%(57/252),α-adducin-TT基因型分布频率在血压肾功能正常组最低为13.3%(68/512),分别与其他3组比较,差异有统计学意义(均为P0.05).CYP11B2各基因型的分布频率4组比较,差异无统计学意义(均为P>0.05). 结论 随增龄,肾功能异常增加,ACE-DD基因型与高血压肾损害相关,α-adducin-TT基因型与高血压和肾损害均相关,但未发现CYP11B2基因多态性与肾损害的关系.

  3. Haemochromatosis and aldosterone deficiency presenting with Yersinia pseudotuberculosis septicaemia.

    OpenAIRE

    Conway, S. P.; Dudley, N; Sheridan, P.; Ross, H.

    1989-01-01

    A 50 year old man presented with a pyrexial illness following a holiday abroad. Yersinia pseudotuberculosis was isolated from blood culture. Response to appropriate antibiotic therapy was prompt and complete, but full recovery was complicated by an episode of hyperkalaemia, hyponatraemia and the passing of large volumes of dilute urine. Three years previously he had developed diabetes mellitus and hypogonadotrophic hypogonadism. Investigation on recovery showed underlying haemochromatosis and...

  4. Influence of PCI on levels of brain natriuretic peptide and aldosterone and short-term prognosis in patients with acute myocardial infarction%冠脉介入治疗对急性心梗患者脑利钠肽、醛固酮水平和近期预后的影响

    Institute of Scientific and Technical Information of China (English)

    林佩璜

    2015-01-01

    目的:探讨冠脉介入治疗(PCI)对急性左室下壁和前壁心肌梗死患者血浆脑利钠肽(BNP)、醛固酮(Ald)水平及近期预后的影响。方法:分析治疗前212例急性下壁(140例)、前壁(72例)心肌梗死患者血浆BNP、Ald水平及与冠脉病变的关系;比较两组患者直接、延迟PCI治疗后血浆BNP、Ald水平的变化及对近期预后的影响。结果:PCI治疗前,与急性下壁梗死组比较,急性前壁梗死组患者血浆 BNP[(642.06±235.08) ng/L比(856.54±223.50) ng/L]、Ald[(50.26±5.23) ng/dl比(88.34±8.52) ng/dl ]水平、冠脉狭窄程度[(82.28±7.65)%比(90.64±7.54)%]及3支病变发生率(22.52%比39.66%)均明显升高(P均<0.05);直接和延迟PCI治疗后,血浆BNP、Ald水平明显下降(P均<0.01),且直接PCI组较延迟PCI组血浆BNP[急性下壁梗死组:(216.93±119.86) ng/L比(453.75±107.54) ng/L ,急性前壁梗死组:(245.754±121.52) ng/L比(483.04±164.65) ng/L]、Ald[急性下壁梗死组:(40.09±6.55) ng/dl比(45.34±8.15) ng/dl ,急性前壁梗死组:(43.65±3.50) ng/dl比(50.43±9.21) ng/dl]水平下降更显著(P均<0.01);未行PCI治疗的患者近期死亡发生率明显高于行直接 PCI及延迟PCI治疗的患者(11.63%比2.78%比3.28%,P均<0.05)。结论:急性前壁心肌梗死患者血浆BNP、Ald水平高,冠脉病变严重;直接PCI较延迟PCI治疗血浆BNP、Ald浓度下降幅度更大,未行PCI治疗的患者死亡率较高。%Objective:To explore the influence of percutaneous coronary intervention (PCI) on plasma levels of brain natri‐uretic peptide (BNP) and aldosterone (Ald) and short‐term prognosis in patients with acute left ventricular inferior and an‐terior wall myocardial infarction .Methods:A total of 212 patients were divided into acute inferior myocardial infarction

  5. Determination of the Aldosterone/Plasma Renin Activity Ratio for the Screening of Primary Hyperaldosteronism in Essential Hypertension: a Multicentric Study Determinación del valor de corte de la relación aldosterona/actividad de renina plasmática para la detección de hiperaldosteronismo primario en hipertensión arterial esencial: estudio multicéntrico

    Directory of Open Access Journals (Sweden)

    E Pardes

    2010-06-01

    Full Text Available Primary hyperaldosteronism (PHA or Conn's disease was classically suspected in the presence of hypertension (H and hypokalemia. It was previously considered as a rare cause of H, being reported in only 1% of hypertensive patients. It can be caused by an adrenal adenoma (the former usual presentation or by adrenal hyperplasia. But since the use of the aldosterone/plasma renin activity ratio (AAR as the screening method in the last years, it is currently considered as almost the most frequent cause of secondary H., accounting for 5-10% of essential H. Plasma rennin activity (PRA determination is a laborious procedure with low reproducibility and it directly affects the AAR; thus each laboratory must assess its own cut-off value. Therefore, in the Adrenal Department of the Argentine Society of Endocrinology and Metabolism (SAEM, we performed this multicentric prospective study of a population of Argentina with the aim of assessing our own AAR cut-off level in normotensive controls in order to apply it for PHA screening in essential hypertensive patients. We studied 353 adult subjects: 104 controls, aged 45,18 ± 13,78 years-old ( X±SD, with no history of arterial hypertension in their first-degree relatives and with two separate day-registry of blood pressure≤ 139/85 mmHg and 249 hypertensive patients, aged 51± 13,6 years-old ( X ± SD, with arterial blood pressure≥ 140/90 mmHg in the sitting position. Subjects with cardiac, renal, hepatic and neurological diseases were excluded as well as those with Cushing´s syndrome, hyperthyroidism, untreated hypothyroidism, diabetes mellitus and patients under glucocorticoids, oral contraceptive pills or estrogen therapy. A normal sodium diet was indicated and potassium was supplemented when needed. Blood was withdrawn between 8 and 10:00 a.m. with the subjects in the upright position. Aldosterone (A was determined by DPC radioimmunoassay (RIA and PRA, by DIA-Sorin RIA. The A normal levels are 4-30 ng

  6. INFLUENCE OF PULSED SHORT WAVE (DIAPULSE) TREATMENT ON THE BIOCHEMICAL PARAMETERS CORTISOL AND ALDOSTERONE

    OpenAIRE

    Dogaru Gabriela

    2015-01-01

    Pulsed short waves are part of high frequency therapy; unlike continuous short waves, where the phenomenon of tissular endothermia occurs, they have therapeutic effects that seem to depend rather on the interaction of electromagnetic waves with biological tissue, as they act only through specific electromagnetic energy. The recommended work technique for the use of the Diapulse device is that regardless of the exposed somatic region, there will be an initial exposure of one of the following r...

  7. The renin–angiotensin–aldosterone-system and right heart failure in congenital heart disease

    OpenAIRE

    Stine Andersen; Asger Andersen; Jens Erik Nielsen-Kudsk

    2016-01-01

    Adults with congenital heart disease represent a rapidly growing patient group. Dysfunction of the right ventricle is often present, and right heart failure constitutes the main cause of death. Heart failure therapies used in acquired left heart failure are often initiated in adults with right heart failure due to congenital heart disease, but the right ventricle differs substantially from the left ventricle, and the clinical evidence for this treatment strategy is lacking. In this review,...

  8. The first laparoscopic resection of an aldosterone-secreting adrenocortical oncocytoma in a child

    OpenAIRE

    Melih Akin; Basak Erginel; Canan Tanik; Nurver Akinci; Abdullah Yildiz; Bahar Beker; Cetin Ali Karadag; Nihat Sever; Sebnem Turk; Ali Ihsan Dokucu

    2014-01-01

    Oncocytomas of the adrenal cortex are usually benign and nonfunctional, consisting of oncocytes in which the cytoplasm becomes eosinophilic due to the accumulation of abnormal mitochondria. Oncocytomas can exist in many organs and are frequently found in the salivary gland, kidneys, thyroid gland, parathyroid gland, and hypophysis. Functioning oncocytomas are very rarely observed in children, and no more than ten cases have been reported in the literature. Here, we present the first report of...

  9. Advances in the Renin-Angiotensin-Aldosterone System: Relevance to Diabetic Nephropathy

    OpenAIRE

    Audrey Koitka; Christos Tikellis

    2008-01-01

    Hypertension is now recognized as a key contributory factor to the development and progression of kidney disease in both type 1 and type 2 diabetes. The renin angiotensin system (RAS) and its effector molecule angiotensin II, in particular, have a range of hemodynamic and nonhemodynamic effects that contribute not only to the development of hypertension, but also to renal disease. As a result, therapeutic inhibition of the RAS with angiotensin-converting enzyme inhibitors and/or selective ang...

  10. Renal Type A Intercalated Cells Contain Albumin in Organelles with Aldosterone-Regulated Abundance

    OpenAIRE

    Jensen, Thomas Buus; Cheema, Muhammad Umar; Szymiczek, Agata; Damkier, Helle Hasager; Praetorius, Jeppe

    2015-01-01

    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 i...

  11. 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...

  12. New perspectives in the renin-angiotensin-aldosterone system (RAAS I: endogenous angiotensin converting enzyme (ACE inhibition.

    Directory of Open Access Journals (Sweden)

    Miklós Fagyas

    Full Text Available Angiotensin-converting enzyme (ACE inhibitors represent the fifth most often prescribed drugs. ACE inhibitors decrease 5-year mortality by approximately one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors, which endogenous inhibitory effects are much less characterized than that for the clinically administered ACE inhibitors. Here we aimed to investigate this endogenous ACE inhibition in human sera. It was hypothesized that ACE activity is masked by an endogenous inhibitor, which dissociates from the ACE when its concentration decreases upon dilution. ACE activity was measured by FAPGG hydrolysis first. The specific (dilution corrected enzyme activities significantly increased by dilution of human serum samples (23.2 ± 0.7 U/L at 4-fold dilution, 51.4 ± 0.3 U/L at 32-fold dilution, n = 3, p = 0.001, suggesting the presence of an endogenous inhibitor. In accordance, specific enzyme activities did not changed by dilution when purified renal ACE was used, where no endogenous inhibitor was present (655 ± 145 U/L, 605 ± 42 U/L, n = 3, p = 0.715, respectively. FAPGG conversion strongly correlated with angiotensin I conversion suggesting that this feature is not related to the artificial substrate. Serum samples were ultra-filtered to separate ACE (MW: 180 kDa and the hypothesized inhibitor. Filtering through 50 kDa filters was without effect, while filtering through 100 kDa filters eliminated the inhibiting factor (ACE activity after <100 kDa filtering: 56.4 ± 2.4 U/L, n = 4, control: 26.4 ± 0.7 U/L, n = 4, p<0.001. Lineweaver-Burk plot indicated non-competitive inhibition of ACE by this endogenous factor. The endogenous inhibitor had higher potency on the C-terminal active site than N-terminal active site of ACE. Finally, this endogenous ACE inhibition was also present in mouse, donkey, goat, bovine sera besides men (increasing of specific ACE activity from 4-fold to 32-fold dilution: 2.8-fold, 1.7-fold, 1.5-fold, 1.8-fold, 2.6-fold, respectively. We report here the existence of an evolutionary conserved mechanism suppressing circulating ACE activity, in vivo, similarly to ACE inhibitory drugs.

  13. In Utero Exposure to the Antiandrogen Di-(2-Ethylhexyl) Phthalate Decreases Adrenal Aldosterone Production in the Adult Rat1

    OpenAIRE

    Martinez-Arguelles, Daniel B.; Guichard, Theodore; Culty, Martine; Zirkin, Barry R.; Papadopoulos, Vassilios

    2011-01-01

    We previously reported that in utero exposure of the male fetus to the plasticizer di-(2-ethylhexyl) phthalate (DEHP) resulted in decreased circulating levels of testosterone in the adult without affecting Leydig cell numbers, luteinizing hormone levels, or steroidogenic enzyme expression. Fetal exposure to DEHP resulted in reduced mineralocorticoid receptor (MR; NR3C2) expression in adult Leydig cells. In the present studies, treatment of pregnant Sprague-Dawley dams from Gestational Day 14 ...

  14. Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction

    DEFF Research Database (Denmark)

    Rossignol, Patrick; Cleland, John G F; Bhandari, Sunil; Tala, Stéphane; Gustafsson, Finn; Fay, Renaud; Lamiral, Zohra; Dobre, Daniela; Pitt, Bertram; Zannad, Faiez

    2012-01-01

    We evaluated the effect of the selective mineralocorticoid receptor antagonist eplerenone on renal function and the interaction between changes in renal function and subsequent cardiovascular outcomes in patients with heart failure and left ventricular systolic dysfunction after an acute myocardial...... infarction in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS)....

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

    International Nuclear Information System (INIS)

    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.)

  16. 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 Henrik

    2006-01-01

    dysfunction and splanchnic and systemic haemodynamics (r = - 0.56-0.55), but only weakly with CBV (r = - 0.25, p < 0.02). In a multivariate regression analysis, plasma renin was determined by serum sodium, alkaline phosphatases and systolic blood pressure (p < 0.04 to p < 0.001). CONCLUSIONS: CBV correlates...... RAAS, including the CBV. Circulating plasma renin concentrations were measured using an immunoradiometric assay. RESULTS: Arterial renin concentrations were significantly higher in the patients than in the controls (p < 0.003). Plasma renin correlated significantly with several indicators of liver...

  17. RU28318, an Aldosterone Antagonist, in Combination with an ACE Inhibitor and Angiotensin Receptor Blocker Attenuates Cardiac Dysfunction in Diabetes

    Science.gov (United States)

    Benter, Ibrahim F.; Babiker, Fawzi; Al-Rashdan, Ibrahim; Yousif, Mariam; Akhtar, Saghir

    2013-01-01

    Aims. We evaluated the effects of RU28318 (RU), a selective mineralocorticoid receptor (MR) antagonist, Captopril (Capt), an angiotensin converting enzyme inhibitor, and Losartan (Los), an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R-) induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I) followed by a period of 30 min of reperfusion (R). Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple). Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving −dP/dt (a measure of diastolic function) when administered to diabetic hearts after ischemia. PMID:24066305

  18. RU28318, an Aldosterone Antagonist, in Combination with an ACE Inhibitor and Angiotensin Receptor Blocker Attenuates Cardiac Dysfunction in Diabetes

    Directory of Open Access Journals (Sweden)

    Ibrahim F. Benter

    2013-01-01

    Full Text Available Aims. We evaluated the effects of RU28318 (RU, a selective mineralocorticoid receptor (MR antagonist, Captopril (Capt, an angiotensin converting enzyme inhibitor, and Losartan (Los, an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R- induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I followed by a period of 30 min of reperfusion (R. Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple. Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving -dP/dt (a measure of diastolic function when administered to diabetic hearts after ischemia.

  19. 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

    trial, with randomised double-masked placebo-controlled intervention and a prospective observational study. We aim to include 3280 type 2 diabetic participants with normoalbuminuria. The CKD273 classifier will be assessed in all participants. Participants with high-risk pattern are randomised to......INTRODUCTION: Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment in...... normoalbumuric patients have given mixed results. This might reflect that the large fraction of normoalbuminuric patients are not at risk of progression, thereby reducing power in previous studies. A specific risk classifier based on urinary proteomics (chronic kidney disease (CKD)273) has been shown to identify...

  20. 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)

    S A Savelyeva

    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.

  1. Human in vivo study of the renin-angiotensin-aldosterone system and the sympathetic activity after 8 weeks daily intake of fermented milk

    DEFF Research Database (Denmark)

    Usinger, Lotte; Ibsen, Hans; Linneberg, Allan; Azizi, Michel; Flambard, Bénédicte; Jensen, Lars T

    2010-01-01

    Milk fermented by lactic acid bacteria is suggested to have antihypertensive effect in humans. In vitro and animal studies have established an angiotensin-converting enzyme (ACE) inhibitor effect of peptides in fermented milk. However, other modes of action must be considered, because until today...... no human studies have confirmed an ACE inhibition in relation to the intake of fermented milk....

  2. New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) IV: Circulating ACE2 as a Biomarker of Systolic Dysfunction in Human Hypertension and Heart Failure

    Science.gov (United States)

    Úri, Katalin; Fagyas, Miklós; Mányiné Siket, Ivetta; Kertész, Attila; Csanádi, Zoltán; Sándorfi, Gábor; Clemens, Marcell; Fedor, Roland; Papp, Zoltán; Édes, István; Tóth, Attila; Lizanecz, Erzsébet

    2014-01-01

    Background Growing evidence exists for soluble Angiotensin Converting Enzyme-2 (sACE2) as a biomarker in definitive heart failure (HF), but there is little information about changes in sACE2 activity in hypertension with imminent heart failure and in reverse remodeling. Methods, Findings Patients with systolic HF (NYHAII-IV, enrolled for cardiac resynchronisation therapy, CRT, n = 100) were compared to hypertensive patients (n = 239) and to a healthy cohort (n = 45) with preserved ejection fraction (EF>50%) in a single center prospective clinical study. The status of the heart failure patients were checked before and after CRT. Biochemical (ACE and sACE2 activity, ACE concentration) and echocardiographic parameters (EF, left ventricular end-diastolic (EDD) and end-systolic diameter (ESD) and dP/dt) were measured. sACE2 activity negatively correlated with EF and positively with ESD and EDD in all patient's populations, while it was independent in the healthy cohort. sACE2 activity was already increased in the hypertensive group, where signs for imminent heart failure (slightly decreased EF and barely increased NT-proBNP levels) were detected. sACE2 activities further increased in patients with definitive heart failure (EF<50%), while sACE2 activities decreased with the improvement of the heart failure after CRT (reverse remodeling). Serum angiotensin converting enzyme (ACE) concentrations were lower in the diseased populations, but did not show a strong correlation with the echocardiographic parameters. Conclusions Soluble ACE2 activity appears to be biomarker in heart failure, and in hypertension, where heart failure may be imminent. Our data suggest that sACE2 is involved in the pathomechanism of hypertension and HF. PMID:24691269

  3. 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.

  4. Human in vivo study of the renin-angiotensin-aldosterone system and the sympathetic activity after 8 weeks daily intake of fermented milk

    DEFF Research Database (Denmark)

    Usinger, Lotte; Ibsen, Hans; Linneberg, Allan;

    2010-01-01

    Milk fermented by lactic acid bacteria is suggested to have antihypertensive effect in humans. In vitro and animal studies have established an angiotensin-converting enzyme (ACE) inhibitor effect of peptides in fermented milk. However, other modes of action must be considered, because until today...

  5. Oxidative and nitrosative stress induced by the mineralocorticoid aldosterone - Mechanism of induction and role of signal transduction pathways and transcription factors

    OpenAIRE

    Queisser, Nina

    2010-01-01

    Several epidemiological studies found that hypertensive patients have an increased risk to develop kidney cancer. Hyperaldosteronism frequently results in arterial hypertension and contributes to the development and progression of kidney injury, with reactive oxygen species (ROS) playing an important role. ROS are thought to be associated with many pathological conditions such as cancer and other disorders, like cardiovascular complications , which often go along with hypertension. The aim of...

  6. Protektive kardiovaskuläre Effekte weiblicher Sexualsteroide - Estrogenrezeptoren reduzieren den Aldosteron-induzierten oxidativen Stress in glatten Gefäßmuskelzellen

    OpenAIRE

    Mühlfelder, Melanie

    2011-01-01

    Reaktive Sauerstoffspezies (ROS, engl. reactive oxygen species) sind hochreaktive Biomoleküle, die in geringen Konzentrationen ubiquitär als Produkte des normalen zellulären Metabolismus entstehen. Zum Schutz vor irreversiblen oxidativen Schädigungen durch diese Moleküle, besitzt der Organismus antioxidative Enzyme und nicht-enzymatische Antioxidantien, die ROS neutralisieren. Eine pathophysiologische Zunahme der Generierung und Freisetzung von ROS und/oder verminderte zelluläre Abwehrmechani...

  7. New perspectives in the renin-angiotensin-aldosterone system (RAAS III: endogenous inhibition of angiotensin converting enzyme (ACE provides protection against cardiovascular diseases.

    Directory of Open Access Journals (Sweden)

    Miklós Fagyas

    Full Text Available ACE inhibitor drugs decrease mortality by up to one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors. Here we investigated the clinical significance of this potential endogenous ACE inhibition. ACE concentration and activity was measured in patient's serum samples (n = 151. ACE concentration was found to be in a wide range (47-288 ng/mL. ACE activity decreased with the increasing concentration of the serum albumin (HSA: ACE activity was 56 ± 1 U/L in the presence of 2.4 ± 0.3 mg/mL HSA, compared to 39 ± 1 U/L in the presence of 12 ± 1 mg/mL HSA (values are mean ± SEM. Effects of the differences in ACE concentration were suppressed in human sera: patients with ACE DD genotype exhibited a 64% higher serum ACE concentration (range, 74-288 ng/mL, median, 155.2 ng/mL, n = 52 compared to patients with II genotype (range, 47-194 ng/mL, median, 94.5 ng/mL, n = 28 while the difference in ACE activities was only 32% (range, 27.3-59.8 U/L, median, 43.11 U/L, and range 15.6-55.4 U/L, median, 32.74 U/L, respectively in the presence of 12 ± 1 mg/mL HSA. No correlations were found between serum ACE concentration (or genotype and cardiovascular diseases, in accordance with the proposed suppressed physiological ACE activities by HSA (concentration in the sera of these patients: 48.5 ± 0.5 mg/mL or other endogenous inhibitors. Main implications are that (1 physiological ACE activity can be stabilized at a low level by endogenous ACE inhibitors, such as HSA; (2 angiotensin II elimination may have a significant role in angiotensin II related pathologies.

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

    OpenAIRE

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

    2016-01-01

    Hemodialysis (HD) is the most commonly-used renal replacement therapy for patients with end-stage renal disease worldwide. Arterio-venous fistula (AVF) is the vascular access of choice for HD patients with lowest risk of infection and thrombosis. In addition to environmental factors, genetic factors may also contribute to malfunction of AVF. Previous studies have demonstrated the effect of genotype polymorphisms of angiotensin converting enzyme on vascular access malfunction. We conducted a m...

  9. Upregulation of the Renin-Angiotensin-Aldosterone-Ouabain System in the Brain Is the Core Mechanism in the Genesis of All Types of Hypertension

    OpenAIRE

    Hakuo Takahashi

    2012-01-01

    Basic research using animal models points to a causal role of the central nervous system in essential hypertension; however, since clinical research is technically difficult to perform, this connection has not been confirmed in humans. Recently, renal nerve ablation in humans proved to continuously decrease blood pressure in resistant hypertension. Furthermore, when electrical stimulation was continuously applied to the carotid baroreceptor nerve of human adults, their blood pressure lowered....

  10. 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 that...

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

    International Nuclear Information System (INIS)

    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)

  12. 醛固酮瘤患者术前和术后高血糖患病率观察%Observation on the prevalence of hyperglycemia in patients with aldosterone-producing adenoma before and after operation

    Institute of Scientific and Technical Information of China (English)

    张炜; 张征; 徐尔理

    2013-01-01

    目的 探讨醛固酮瘤(APA)患者高血糖患病率及其术后变化. 方法 检测APA组血压、血醛固酮(S-Ald)、尿醛固酮(U-Ald)、血浆肾素活性(PRA)基础和激发值,与原发性高血压(EH)和对照组比较.APA组行肾上腺肿瘤摘除术后随访激素及糖代谢指标,与术前比较. 结果 APA组葡萄糖及胰岛素曲线下面积(AUCg,AUCi)高于EH、对照组,胰岛素抵抗指数(HOMA-IR)高于对照组.APA组高血糖者44.6%,高于EH、对照组.根据OGTT结果将APA组分为APA合并高血糖(A)亚组和APA未合并高血糖(B)亚组,A亚组S-Ald高于B亚组.APA患者08:00 S-Ald与2hPG、AUCg呈正相关,血钾与2 hPG、AUCg呈负相关.APA组术后S-Ald、U-Ald、FPG、2hPG、AUCg及AUCi均较术前下降,血钾升高.术后患者高血糖患病率35.4%. 结论 APA患者高血糖患病率升高,其原因与醛固酮高分泌有关.

  13. The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin–angiotensin–aldosterone system, oxidative stress and endogenous digitalis in the brain

    OpenAIRE

    Takahashi, Hakuo; Yoshika, Masamichi; Komiyama, Yutaka; Nishimura, Masato

    2011-01-01

    The central nervous system has a key role in regulating the circulatory system by modulating the sympathetic and parasympathetic nervous systems, pituitary hormone release, and the baroreceptor reflex. Digoxin- and ouabain-like immunoreactive materials were found >20 years ago in the hypothalamic nuclei. These factors appeared to localize to the paraventricular and supraoptic nuclei and the nerve fibers at the circumventricular organs and supposed to affect electrolyte balance and blood press...

  14. Effects of Eplerenone on Renal Expression of Renin Receptor in Aldosterone-Infused Rats%依普利酮对醛固酮输注大鼠肾脏肾素受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    易家志; 梁伟; 丁国华; 杨红霞

    2009-01-01

    目的:探讨依普利酮(Epl)对醛固酮(ALD)输注大鼠肾脏肾素受体表达的影响.方法:18只SD大鼠随机分为3组:对照组、ALD输注组、Epl治疗组,均皮下埋置渗透性微泵,其中ALD输注组、Epl治疗组持续输注ALD(1.5μg·h-1),Epl治疗组同时给予依普利酮(100mg·kg-1·d-1)灌胃,对照组、ALD输注组以等量生理盐水灌胃.隔周测量尾动脉压,收集24h尿液测定尿白蛋白排泄率(UAER),于第28天处死动物.PAS染色观察肾组织病理改变,RT-PCR法检测肾素受体表达,免疫组化染色检测肾素受体表达.结果:ALD输注组大鼠血压、UAER较对照组显著升高(P<0.05),Epl治疗组大鼠血压、UAER显著低于ALD输注组(P<0.05);ALD输注组大鼠肾小球系膜细胞增殖伴系膜外基质增多,Epl治疗组肾小球病理变化较ALD输注组显著减轻;肾素受体主要分布于肾小球系膜细胞,Epl治疗组肾素受体mRNA显著低于ALD输注组(P<0.05).结论:依普利酮能显著减少ALD榆注大鼠肾脏肾素受体表达,减轻ALD诱导的大鼠肾脏损伤.

  15. PF-03882845, a non-steroidal mineralocorticoid receptor antagonist, prevents renal injury with reduced risk of hyperkalemia in an animal model of nephropathy

    OpenAIRE

    CarineMBoustany-Kari; TristanMaurer; RenaEudy; StephenOrena

    2013-01-01

    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 ...

  16. APAとIHAの頻度(第3回副腎静脈サンプリング研究会プロシーディングス)

    OpenAIRE

    西川, 哲男; 齋藤, 淳; 大村, 昌夫; NISHIKAWA, Tetsuo; SAITO, Jun; OMURA, Masao

    2006-01-01

    Hypertension caused by primary aldosteronism (PA) due to aldosterone-producing adenoma (APA) is curable by surgically removing the lesion. Differential diagnosis of APA from idiopathic hyperaldosteronism (IHA) is critical before a clinician can decide how to treat each of the condition, since APA is treated by resection of the adrenal lesion while IHA is treated by administration of aldosterone blockades. Clinical records of 65 PA patients, who visited our hospitals from 1995 to 1999, were an...

  17. 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...

  18. Laparoscopic Adrenalectomy for Bilateral Metachronous Aldosteronomas

    OpenAIRE

    Rizek, Philippe; Gorecki, Piotr; Lindenmayer, Aristid; Moktan, Sabita

    2011-01-01

    Introduction: Primary aldosteronism affects 5% to 13% of patients with hypertension. Idiopathic bilateral hyperplasia (IHA) and unilateral aldosterone-producing adenoma (APA) are the most common types of primary aldosteronism. Bilateral APA is a very rare entity with only a few reports in the literature. We present the case of a patient with metachronous bilateral APA treated with metachronous bilateral total and near total adrenalectomy. Case Report: A 66-year-old female was evaluated for hy...

  19. Hypertension

    Science.gov (United States)

    ... or adrenal-gland disorders. Conditions that can cause secondary hypertension may include: Cushing syndrome Primary aldosteronism Pheochromocytoma Hyperthyroidism Hyperparathyroidism Hypothyroidism Narrowing of the arteries that carry ...

  20. 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; Meng, Xiangyi; Parving, Hans-Henrik; Viberti, Giancarlo; Remuzzi, Giuseppe

    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...

  1. 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; Meng, Xiangyi; Parving, Hans-Henrik; Viberti, Giancarlo; Remuzzi, Giuseppe

    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-American...

  2. Prostaglandin synthetase inhibitor in an infant with congenital chloride diarrhoea.

    OpenAIRE

    Minford, A M; Barr, D G

    1980-01-01

    Hyper-reninaemia, hypokaluria, and hypokalaemia in an infant with congenital chloride diarrhoea improved during treatment with a prostaglandin synthetase inhibitor, ketoprofen. There was evidence of increased activity of therenin-aldosterone system when ketoprofen was stopped. It is suggested that prostaglandins may be involved in stimulating the renin-aldosterone system in congenital chloride diarrhoea.

  3. Postnatal adrenalectomy impairs urinary concentrating ability by increased COX-2 and leads to renal medullary injury

    DEFF Research Database (Denmark)

    Stubbe, Jane; Madsen, Kirsten; Nielsen, Finn T; Bonde, Rasmus K; Skøtt, Ole; Jensen, Boye L

    2007-01-01

    We hypothesized that aldosterone promotes development of the renal medulla in the postnatal period and that cyclooxygenase-2 (COX-2) activity contributes to renal dysfunction after impaired aldosterone signaling. To test these hypotheses, rat pups underwent either sham operation or adrenalectomy at...

  4. Mineralocorticoid receptor antagonists: emerging roles in cardiovascular medicine

    Directory of Open Access Journals (Sweden)

    Funder JW

    2013-10-01

    Full Text Available John W FunderPrince Henry's Institute, Clayton, Victoria, AustraliaAbstract: Spironolactone was first developed over 50 years ago as a potent mineralocorticoid receptor (MR antagonist with undesirable side effects; it was followed a decade ago by eplerenone, which is less potent but much more MR-specific. From a marginal role as a potassium-sparing diuretic, spironolactone was shown to be an extraordinarily effective adjunctive agent in the treatment of progressive heart failure, as was eplerenone in subsequent heart failure trials. Neither acts as an aldosterone antagonist in the heart as the cardiac MR are occupied by cortisol, which becomes an aldosterone mimic in conditions of tissue damage. The accepted term “MR antagonist”, (as opposed to “aldosterone antagonist” or, worse, “aldosterone blocker”, should be retained, despite the demonstration that they act not to deny agonist access but as inverse agonists. The prevalence of primary aldosteronism is now recognized as accounting for about 10% of hypertension, with recent evidence suggesting that this figure may be considerably higher: in over two thirds of cases of primary aldosteronism therapy including MR antagonists is standard of care. MR antagonists are safe and vasoprotective in uncomplicated essential hypertension, even in diabetics, and at low doses they also specifically lower blood pressure in patients with so-called resistant hypertension. Nowhere are more than 1% of patients with primary aldosteronism ever diagnosed and specifically treated. Given the higher risk profile in patients with primary aldosteronism than that of age, sex, and blood pressure matched essential hypertension, on public health grounds alone the guidelines for first-line treatment of all hypertension should mandate inclusion of a low-dose MR antagonist.Keywords: spironolactone, eplerenone, primary aldosteronism, public health, inverse agonists

  5. 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.

  6. 组织醛固酮对自发性高血压大鼠心脏靶器官的损害和伊普利酮的保护作用%Damage of Aldosterone on the Heart of the Rat with Spontaneously Hypertensive and Protective Effect of Eplerenone

    Institute of Scientific and Technical Information of China (English)

    王清; 万征; 孙跃民; 王鹏

    2010-01-01

    目的 观察自发性高血压大鼠(Spontaneously hypertensive rats,SHR)中醛固酮和心室重构与心肌细胞凋亡的关系以及选择性盐皮质激素受体拮抗剂--依普利酮(Eplerenone,Epl)对心室重构和心肌细胞凋亡的抑制作用.方法 20只8周龄雄性SHR随机分为2组,SHR-Epl组(Epl 50 mg/Kg)和SHR-C组(高血压对照组),10只雄性Wistar Kyoto大鼠(WKY)作为正常血压对照组.用放射免疫方法检测血浆和心肌组织醛固酮浓度;通过检测天狼星红染色组织切片的胶原蛋白沉积分数来评价心肌纤维化;应用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测心肌细胞凋亡;应用RT-PCR和Western-Blotting法检测Bcl-2和Bax mRNA和蛋白表达.结果 SHR-Epl组和SHR-C组较WKY组收缩压升高(P<0.01),但此两组间无差别.SHR-Epl组、SHR-C组和WKY组的心重,体重分别是(3.48±0.56),(4.04±0.27)和(2.78±0.12)mg/s;心肌细胞直径是(15.15±0.14),(17.24±0.36)和(14.31±0.20)μm;胶原蛋白沉积分数是(3.81±0.30),(4.39±0.23)和(3.48±0.23)%;凋亡指数是(0.36±0.21),(1.95±0.17)和(0.21±0.05)%,SHR-C组均高于WKY组(P<0.01)和SHR-Epl组(p<005),且SHR-Epl组高于WKY组(P<0.05).SHR-Epl组的Bcl-2/bax mRNA和蛋白表达比值高于SHR-C组(P<0.05).结论 SHR心肌组织可以分泌醛固酮,且在心室重构和心肌细胞凋亡过程中起到重要的促进作用,Epl对SHR心室重构和心肌细胞凋亡有一定抑制作用.

  7. 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

    OpenAIRE

    Hindalis Ballesteros Epifanio; Leonardo Antonio Mamede Zornoff; Beatriz Bojikian Matsubara; Sergio Alberto Rupp de Paiva; Roberto Minoru Tani Inoue; Luiz Shiguero Matsubara

    2005-01-01

    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...

  8. 缬沙坦及其与培哚普利合用对慢性心力衰竭患者醛固酮代谢的影响%The Effects of Valsartan and Combination With Perindopril on Metabolism of Aldosterone in Patients With Chronic Heart Failure

    Institute of Scientific and Technical Information of China (English)

    张道华; 牛文堂; 王克志

    2005-01-01

    目的:观察慢性心力衰竭(心衰)患者长期应用缬沙坦及缬沙坦与培哚普利联合治疗是否存在醛固酮逃逸.方法:120例慢性心衰患者随机分为缬沙坦组、培哚普利组及联合治疗组,每组40例,疗程24周.测定治疗前、治疗后12周及24周血浆血管紧张素Ⅱ(AngⅡ)及醛固酮变化.对照组40例为健康查体者.结果:120例慢性心衰患者血浆AngⅡ、醛固酮水平较对照组健康查体者升高(P<0.01).缬沙坦组治疗后12周及24周醛固酮水平较治疗前降低(P<0.01), AngⅡ水平治疗后12周升高(P<0.05);24周与12周比较醛固酮及AngⅡ水平均无显著差异(P>0.05).培哚普利组治疗后12周及24周醛固酮、AngⅡ水平均较治疗前降低(P<0.01),治疗后24周较12周时又明显升高(P<0.05).联合治疗组治疗后12周及24周醛固酮水平下降(P<0.01),而AngⅡ水平无显著性改变(P>0.05);治疗后24周与12周比较差异均无显著性(P>0.05).结论:缬沙坦及培哚普利与缬沙坦联合长期治疗慢性心衰患者不产生明显的醛固酮逃逸.

  9. Treatment and Management

    Science.gov (United States)

    ... benefits found on adults, other medications such as beta-blockers and aldosterone may also be used in children. ... of blood flow out of the heart. Instead, beta blockers and calcium channel blockers are prescribed to patients ...

  10. Rationale and trial design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes

    DEFF Research Database (Denmark)

    de Zeeuw, Dick; Akizawa, Tadao; Agarwal, Rajiv;

    2013-01-01

    Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic...

  11. SNPs in microRNA binding sites in 3'-UTRs of RAAS genes influence arterial blood pressure and risk of myocardial infarction

    DEFF Research Database (Denmark)

    Nossent, Anne Yaël; Hansen, Jakob Liebe; Doggen, Carine;

    2011-01-01

    We hypothesized that single nucleotide polymorphisms (SNPs) located in microRNA (miR) binding sites in genes of the renin angiotensin aldosterone system (RAAS) can influence blood pressure and risk of myocardial infarction....

  12. Eplerenone

    Science.gov (United States)

    ... works by blocking the action of aldosterone, a natural substance in the body that raises blood pressure. ... Eplerenone controls high blood pressure but does not cure it. It may take 4 weeks or longer ...

  13. Insulin resistance and associated dysfunction of resistance vessels and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2005-01-01

    vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counterregulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin...

  14. Effects of cilazapril on endothelial cell function and fibrinolysis system in atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    HAN Wei; LI Wei-min; XIE Bao-dong; LI Yue; ZHAO Ji-yi; HUANG Yong-lin

    2005-01-01

    @@ Recently, it has been found that atrial fibrillation (AF) is associated with renin angiotensin aldosterone system (RAAS) activation and that angiotensin converting enzyme inhibition (ACEI) reduces incidence of AF in hypertensive patients.

  15. Hyponatremia and brain injury: absence of alterations of serum brain natriuretic peptide and vasopressin Hiponatremia e traumatismo cranioencefálico: ausência de alteração sanguínea do peptídeo natriurético cerebral e hormônio antidiurético

    OpenAIRE

    Karina Nascimento Costa; Helen Mayumi Nakamura; Leonardo Rodrigues da Cruz; Lucas Sampaio Valente Fernandes de Miranda; Rubens Carneiro dos Santos-Neto; Susyanne Lavor Cosme; Luiz Augusto Casulari

    2009-01-01

    OBJECTIVE: To study any possible relation between hyponatremia following brain injury and the presence of cerebral salt-wasting syndrome (CSWS) or the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and if vasopressin, brain natriuretic peptide (BNP) and aldosterone have a role in its mechanism. METHOD: Patients with brain injury admitted to the intensive care unit were included and had their BNP, aldosterone and vasopressin levels dosed on day 7. RESULTS: Twenty six adul...

  16. Hyperkalaemia induced by carbonic anhydrase inhibitor.

    OpenAIRE

    Wakabayashi, Y.

    1991-01-01

    An 81-year-old man developed hyperkalaemic and hyperchloraemic metabolic acidosis following treatment with a carbonic anhydrase inhibitor for his glaucoma. He had mild renal failure and selective aldosterone deficiency was confirmed. In this case the treatment did not lead to hypokalaemia because of the limited potassium secretory capacity in the renal tubules from selective aldosterone deficiency; rather, it may have led to hyperkalaemia because metabolic acidosis induced by the carbonic anh...

  17. Smooth Muscle Cell Mineralocorticoid Receptors Are Mandatory for Aldosterone–Salt to Induce Vascular Stiffness

    OpenAIRE

    Galmiche, Guillaume; Pizard, Anne; Gueret, Alexandre; El Moghrabi, Soumaya; Ouvrard-Pascaud, Antoine; Berger, Stefan; Challande, Pascal; Jaffe, Iris Z.; Labat, Carlos; Lacolley, Patrick; Jaisser, Frédéric

    2013-01-01

    Arterial stiffness is recognized as a risk factor for many cardiovascular diseases. Aldosterone via its binding to and activation of the mineralocorticoid receptors (MRs) is a main regulator of blood pressure by controlling renal sodium reabsorption. Although both clinical and experimental data indicate that MR activation by aldosterone is involved in arterial stiffening, the molecular mechanism is not known. In addition to the kidney, MR is expressed in both endothelial and vascular smooth m...

  18. Urinary Kallikrein Excretion in Essential and Mineralocorticoid Hypertension

    OpenAIRE

    Holland, O. Bryan; Chud, James M.; Braunstein, Helen

    1980-01-01

    Urinary kallikrein excretion has been reported to be decreased in patients with essential hypertension and elevated in patients with primary aldosteronism as a reflection of mineralocorticoid activity. Low renin essential hypertension (LREH) has been postulated to result from excess production of an unknown mineralocorticoid(s). Urinary kallikrein excretion was compared in outpatients with essential hypertension, mineralocorticoid hypertension (primary aldosteronism and 17α-hydroxylase defici...

  19. Targeted Skin Overexpression of the Mineralocorticoid Receptor in Mice Causes Epidermal Atrophy, Premature Skin Barrier Formation, Eye Abnormalities, and Alopecia

    OpenAIRE

    Sainte Marie, Yannis; Toulon, Antoine; Paus, Ralf; Maubec, Eve; Cherfa, Aicha; Grossin, Maggy; Descamps, Vincent; Clemessy, Maud; Gasc, Jean-Marie; Peuchmaur, Michel; Glick, Adam; Farman, Nicolette; Jaisser, Frederic

    2007-01-01

    The mineralocorticoid receptor (MR) is a transcription factor of the nuclear receptor family, activation of which by aldosterone enhances salt reabsorption in the kidney. The MR is also expressed in nonclassical aldosterone target cells (brain, heart, and skin), in which its functions are incompletely understood. To explore the functional importance of MR in mammalian skin, we have generated a conditional doxycycline-inducible model of MR overexpression, resulting in double-transgenic (DT) mi...

  20. 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.......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....

  1. Urinary serine proteases and activation of ENaC in kidney-implications for physiological renal salt handling and hypertensive disorders with albuminuria

    DEFF Research Database (Denmark)

    Svenningsen, Per; Andersen, Henrik; Nielsen, Lise H; Jensen, Boye L.

    2015-01-01

    in acute conditions with proteinuria, like nephrotic syndrome and preeclampsia, and in chronic diseases, such as diabetes with microalbuminuria. A vast literature on renin-angiotensin-aldosterone system and volume homeostasis from the last four decades show a number of common characteristics for...... conditions with albuminuria compatible with impaired renal Na(+) excretion: hypertension and volume retention is secondary to proteinuria in, e.g., preeclampsia and nephrotic syndrome; plasma concentrations of renin, angiotensin II, and aldosterone are frequently suppressed in proteinuric conditions, e...

  2. Percutaneous ablation of functioning adenoma in a patient with a single adrenal gland

    OpenAIRE

    Nunes, Thiago Franchi; Szejnfeld, Denis; Xavier, Ana Carolina Wanderley; Goldman, Suzan Menasce

    2013-01-01

    The conventional treatment of functioning adrenal adenomas is laparoscopic resection. Since the 1990s, radiofrequency ablation has been increasingly applied to the treatment of tumours of the liver, lungs and musculoskeletal system. However, the use of radiofrequency ablation to treat adrenal nodules is still an uncommon procedure, particularly in aldosterone-producing adenomas. We report the case of a 35-year-old male patient with resistant hypertension, hypokalaemia and aldosterone-producin...

  3. Adrenal scanning with 131I-19-cholesterol

    International Nuclear Information System (INIS)

    The purpose of this paper is to describe our clinical experience of adrenal scanning with 131I-19-cholesterol and discuss its clinical usefulness. Adrenal scanning was performed for 21 patients with hypertension. One millicurie of 131I-19-cholesterol was injected intravenously and adrenal scannings were taken 6 to 11 days after injection with a rectilinear scanner or a gamma camera. No patient had an untoward reaction to the radiopharmaceutical. Confirmed diagnosis was obtained in 7 of 21 patients, i.e., 3 cases of primary aldosteronism, 1 idiopathic aldosteronism, 1 Cushing's syndrome and 2 cases of the essential hypertension. Among all of the primary aldosteronism and Cushing's syndrome, adrenal scanning gave clear evidence of concentration of radioactivity at the site of tumor. In the idiopathic aldosteronism of our study, uptake of radioactivity was brightly visible on the right, while uptake by the left gland was inhibited, so this case was diagnosed incorrectly as primary aldosteronism. The kidney scan with 203Hg-chlormerodrin obtained without moving the patient after an adrenal scan was very useful for getting information of anatomical site of the activity. The effective half-life was calculated as 1.83 days by means of sequential profile whole-body scannings, and the total-body absorbed radiation dose was estimated as 0.65 rad/mCi by using MIRD pamphlets. Our conclusion is that the adrenal scanning with 131I-19-cholesterol is very useful for localization of the functional adrenal cortical tumor. (author)

  4. Autoradiographic evidence of nuclear binding of spironolactone in rabbit cortical collecting tubule

    International Nuclear Information System (INIS)

    Previous biochemical studies indicated that the spirolactone-mineralocorticoid receptor complexes are unable to translocate into the nucleus. The present study was designed to reinvestigate the intracellular distribution of spirolactone-binding sites, using autoradiography. For this purpose, rabbit kidney pyramids were incubated at 30 C with tritiated SC9420 or aldosterone. Thereafter, aldosterone-sensitive cortical collecting tubules were microdissected and processed for dry film autoradiography. The concentration was 2 nM for both steroids. Non-specific labeling was determined by incubations with tritiated steroids plus a 100-fold excess of unlabeled steroids. Results show the presence of specific nuclear labeling for both [3H] aldosterone and [3H]SC9420. Specific cytoplasmic labeling was very low for both [3H]aldosterone and [3H]SC9420. The nuclear labeling by [3H]SC9420 was equally and almost completely displaced by a 100-fold excess of unlabeled aldosterone or SC9420 (91% and 87%, respectively). We conclude that spironolactone-receptor complexes migrate into the nucleus. The difference between these results and those of previous studies with biochemical techniques, which failed to detect specific nuclear binding of spirolactone, may be due to methodological reasons

  5. Role of Per1 and the Mineralocorticoid Receptor in the Coordinate Regulation of αENaC in Renal Cortical Collecting Duct Cells

    Directory of Open Access Journals (Sweden)

    Jacob eRichards

    2013-09-01

    Full Text Available Renal function and blood pressure exhibit a circadian pattern of variation, but the molecular mechanism underlying this circadian regulation is not fully understood. We have previously shown that the circadian clock protein Per1 positively regulates the basal and aldosterone-mediated expression of the alpha subunit of the renal epithelial sodium channel (αENaC. The mechanism of this regulation has not been determined however. To further elucidate the mechanism of Mineralocorticoid Receptor (MR and Per1 action, site-directed mutagenesis, DNA pull-down assays and chromatin immunoprecipitation methods were used to investigate the coordinate regulation of αENaC by Per1 and MR. Mutation of two circadian response E-boxes in the human αENaC promoter abolished both basal and aldosterone-mediated promoter activity. DNA pull down assays demonstrated the interaction of both MR and Per1 with the E-boxes from the αENaC promoter. These observations were corroborated by chromatin immunopreciptation experiments showing increased occupancy of MR and Per1 on an E-box of the αENaC promoter in the presence of aldosterone. This is the first report of an aldosterone-mediated increase in Per1 on a target gene promoter. Taken together, these results demonstrate the novel finding that Per1 and MR mediate the aldosterone response of αENaC through DNA/protein interaction in renal collecting duct cells.

  6. Mechanism of potassium depletion during chronic metabolic acidosis in the rat

    International Nuclear Information System (INIS)

    Pair-fed rats on a normal K diet were given either 1.5% NH4Cl 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 NH4Cl 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 NH4Cl 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

  7. YPEL4 modulates HAC15 adrenal cell proliferation and is associated with tumor diameter.

    Science.gov (United States)

    Oki, Kenji; Plonczynski, Maria W; Gomez-Sanchez, Elise P; Gomez-Sanchez, Celso E

    2016-10-15

    Yippee-like (YPEL) proteins are thought to be related to cell proliferation because of their structure and location in the cell. The aim of this study was to clarify the effects of YPEL4 on aldosterone production and cell proliferation in the human adrenocortical cell line (HAC15) and aldosterone producing adenoma (APA). Basal aldosterone levels in HAC15 cells over-expressing YPEL4 was higher than those of control HAC15 cells. The positive effects of YPEL4 on cell proliferation were detected by XTT assay and crystal violet staining. YPEL4 levels in 39 human APA were 2.4-fold higher compared to those in 12 non-functional adrenocortical adenomas, and there was a positive relationship between YPEL4 levels and APA diameter (r = 0.316, P APA in humans. PMID:27333825

  8. 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...... delivery (control = 39 and preeclampsia 40 weeks). Prostasin, matriptase, nexin-1 and HAIs were measured by qPCR and western immunoblotting (prostasin, matriptase, nexin-1) and ELISA (prostasin). Aldosterone was measured in plasma and urine by ELISA. RESULTS: Women with preeclampsia displayed lower levels...... of aldosterone in plasma and in spot urine normalized for creatinine (p = 0.0001). Placental weight was not different between groups. Prostasin, matriptase, HAI 1 and 2, and nexin mRNA abundances were not different in placental tissue between groups. Prostasin and nexin protein level in placental...

  9. [Hypokalemia, a key clinical data for diagnosing primary hyperaldosteronism].

    Science.gov (United States)

    Rodríguez Maya, B; Rodríguez Goncer, I; Diego Hernández, C

    2016-01-01

    We report a case of a 37 year-old man with a long history of hypertension under treatment, who was admitted at our institution with intense fatigue and weakness of lower limbs. The laboratory results at Emergency Department showed severe hypokalemia. A study of secondary hypertension was carried out. With the initial suspicion of primary hyperaldosteronism, complete blood test was done including plasma renine activity, which was completely suppressed, and plasma aldosterone concentration, which resulted normal. Likewise, an abdomen CT was performed and revealed a left adrenal mass consistent of suprarrenal adenoma. Therefore, a salt loading suppression test was done with subsequent measure of plasmatic renine activity, which was still suppressed, plasma aldosterone concentration, that persisted normal, and a 24-h urinary aldosterone excretion rate, which was clearly high, supporting the suspected diagnosis. After the adrenalectomy, the patient remained asymptomatic with normal blood pressure without treatment and with normal serum potassium levels. PMID:26869044

  10. Cellular Pathophysiology of an Adrenal Adenoma-Associated Mutant of the Plasma Membrane Ca(2+)-ATPase ATP2B3.

    Science.gov (United States)

    Tauber, Philipp; Aichinger, B; Christ, C; Stindl, J; Rhayem, Y; Beuschlein, F; Warth, R; Bandulik, S

    2016-06-01

    Adrenal aldosterone-producing adenomas (APAs) are a main cause for primary aldosteronism leading to arterial hypertension. Physiologically, aldosterone production in the adrenal gland is stimulated by angiotensin II and high extracellular potassium. These stimuli lead to a depolarization of the plasma membrane and, as a consequence, an increase of intracellular Ca(2+). Mutations of the plasma membrane Ca(2+)-ATPase ATP2B3 have been found in APAs with a prevalence of 0.6%-3.1%. Here, we investigated the effects of the APA-associated ATP2B3(Leu425_Val426del) mutation in adrenocortical NCI-H295R and human embryonic kidney (HEK-293) cells. Ca(2+) measurements revealed a higher basal Ca(2+) level in cells expressing the mutant ATP2B3. This rise in intracellular Ca(2+) was even more pronounced under conditions with high extracellular Ca(2+) pointing to an increased Ca(2+) influx associated with the mutated protein. Furthermore, cells with the mutant ATP2B3 appeared to have a reduced capacity to export Ca(2+) suggesting a loss of the physiological pump function. Surprisingly, expression of the mutant ATP2B3 caused a Na(+)-dependent inward current that strongly depolarized the plasma membrane and compromised the cytosolic cation composition. In parallel to these findings, mRNA expression of the cytochrome P450, family 11, subfamily B, polypeptide 2 (aldosterone synthase) was substantially increased and aldosterone production was enhanced in cells overexpressing mutant ATP2B3. In summary, the APA-associated ATP2B3(Leu425_Val426del) mutant promotes aldosterone production by at least 2 different mechanisms: 1) a reduced Ca(2+) export due to the loss of the physiological pump function; and 2) an increased Ca(2+) influx due to opening of depolarization-activated Ca(2+) channels as well as a possible Ca(2+) leak through the mutated pump. PMID:27035656

  11. Vasodilatation with captopril and prazosin in chronic heart failure: double blind study at rest and on exercise.

    Science.gov (United States)

    Bayliss, J; Canepa-Anson, R; Norell, M S; Poole-Wilson, P; Sutton, G

    1986-03-01

    A double blind cross over study was performed to compare the long term hormonal, haemodynamic, and clinical responses to specific inhibition of the renin-angiotensin-aldosterone system (captopril) and of the alpha 1 adrenoceptors of the sympathetic system (prazosin) both at rest and during upright exercise in patients with chronic heart failure. Sixteen patients completed one month's treatment with each drug. During conventional diuretic treatment (control) plasma renin activity, aldosterone, and noradrenaline were increased at rest and on exercise. Control left ventricular filling pressures were raised, and correlated significantly with plasma renin activity both at rest and on exercise. Systemic vascular resistance was increased at rest, and its reduction during exercise correlated inversely with the increase in plasma renin activity and plasma noradrenaline. After one month's treatment with captopril there were reductions in plasma aldosterone, weight, left ventricular filling pressure, and systemic vascular resistance at rest and on exercise. Dyspnoea was relieved and exercise capacity increased. The greater fall in systemic vascular resistance on exercise no longer correlated with the increase in plasma renin activity. During treatment with prazosin there were increases in plasma noradrenaline and, transiently, in plasma aldosterone. Fluid retention occurred, and left ventricular filling pressure was unchanged. Compared with control values systemic vascular resistance was reduced at rest but not on exercise. Dyspnoea and exercise capacity did not improve. In chronic heart failure, vasodilatation by inhibition of the alpha adrenergic system with prazosin causes compensatory stimulation of the renin-angiotensin-aldosterone system and does not result in clinical benefit. Inhibition of the renin-angiotensin-aldosterone system with captopril causes secondary vasodilatation at rest and on exercise and results in improvement in symptoms and exercise capacity. PMID

  12. Isolation and identification of urine constituents showing affinity to highly specific mineralocoid antibodies

    International Nuclear Information System (INIS)

    Isolation and identification of urine constituents showing affinity to highly specific mineralocoid antibodies. Owing to the combined use of reversed-phase high pressure liquid chromatography (HPLC) and radioimmunoassays containing specific aldosterone antibodies as well as 3α, 5β-tetrahydroaldosterone antibodies it was possible to detect the metabolites and/or precursors of aldosterone in the urine of humans. Untreated urine samples of healthy volunteers and patients showing certain shifts in the aldosterone balance were separated using an acetonitrile-water gradient and the immunological activity was subsequently measured in fractions of the column eluate. Slightly polar peaks ascribed to immunologically active TH-ALDO were predominantly observed for patients showing primary aldosteronism and reduced levels of hydroxylase 21, whereas those peaks were not or only to a minor degree seen to occur in the control patients. In order to isolate larger quantities of this unpolar ligand urine samples of 30 to 2200 ml were extracted using organic solvents and partially subjected to glucuronide cleavage. Competitive binding studies using different antisera suggested the presence of a 3α, 5β structure. HPLC fractions showing immunological activity were then subjected to derivation procedures and examined using the GC/MS technique. This permitted a relatively unpolar metabolite of aldosterone, 11β, 18(S); 18, 20α-diepoxy-3α-hydroxy-5β-pregnane, to be identified, which is referred to as M 1 and was first described by Kelly et al. (1962). These investigations, however, have revealed the previously unknown fact that this metabolite arises from endogenous aldosterone and shows significant increases in certain pathological conditions. (orig.)

  13. Mechanisms of renal NaCl retention in proteinuric disease

    DEFF Research Database (Denmark)

    Svenningsen, Per; Friis, Ulla G; Versland, Jostein B;

    2013-01-01

    In diseases with proteinuria, for example nephrotic syndrome and pre-eclampsia, there often are suppression of plasma renin-angiotensin-aldosterone system components, expansion of extracellular volume and avid renal sodium retention. Mechanisms of sodium retention in proteinuria are reviewed. In...... animal models of nephrotic syndrome, the amiloride-sensitive epithelial sodium channel ENaC is activated while more proximal renal Na(+) transporters are down-regulated. With suppressed plasma aldosterone concentration and little change in ENaC abundance in nephrotic syndrome, the alternative modality of...

  14. The metabolic and hemodynamic effects of prolonged bed rest in normal subjects

    Science.gov (United States)

    Chobanian, A. V.; Lille, R. D.; Tercyak, A.; Blevins, P.

    1974-01-01

    Investigation in six normal subjects of the effects of chronic bed rest on the interrelationships between cardiovascular hemodynamics, catecholamine metabolism, vascular reactivity, renin and aldosterone activity, and electrolyte and fluid balance. Negative sodium and potassium balances and reductions in plasma volume were observed in all subjects, but plasma renin activity and aldosterone secretory rate showed no significant change. Other findings included the observation that major decreases in sodium balance and plasma volume occurred in the early bed rest period and did not correlate closely with the degree of orthostatic intolerance.

  15. Steroid radioimmunoassay: contribution of standards to blank values, ch. 4

    International Nuclear Information System (INIS)

    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

  16. Retraction notice.

    Science.gov (United States)

    2015-12-01

    The following articles have 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 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 Chun-Hua Yang and Tian

  17. SARTANS AND ANGIOTENSIN CONVERTING ENZYME INHIBITORS: A DUEL BETWEEN TWO LEADERS OF PHARMACOTHERAPY OF CARDIOVASCULAR DISEASES

    OpenAIRE

    K. A. Gyamdzhyan; M. L. Maksimov

    2015-01-01

    Topical issues of cardiovascular disease pharmacotherapy influencing function of the renin-angiotensin-aldosterone system are discussed. Efficacy and safety of two major cardiovascular drug classes, angiotensin converting enzyme inhibitors and sartans, are compared. Data from evidence base of the both drug classes are presented.

  18. Adrenal scintigraphy

    International Nuclear Information System (INIS)

    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.)

  19. The scintigraphic assessment of adrenocortical function

    International Nuclear Information System (INIS)

    The adrenal gland uptake of the radiopharmaceutical 131I-6#betta#-iodomethylnorcholesterol (NP-59) was used to localize diseases of the adrenal cortex and to functionally characterize abnormal cortisol secretion in Cushing's syndrome, adrenal hyperandrogenism and aldosterone secretion in an animal model

  20. A steroid metabolizing gene variant in a polyfactorial model improves risk prediction in a high incidence breast cancer population

    Directory of Open Access Journals (Sweden)

    Eldon R. Jupe

    2014-12-01

    Conclusions and general significance: Since the optimized PFRM consistently outperformed BCRAT in all Caucasian study populations, it represents an improved personalized risk assessment tool. The finding of higher Marin County risk linked to a CYP11B2 aldosterone synthase SNP associated with essential hypertension offers a new genetic clue to sporadic breast cancer predisposition.

  1. Nuclear medicine imaging in the evaluation of endocrine hypertension

    OpenAIRE

    Punit Sharma; Rakesh Kumar

    2012-01-01

    Endocrine hypertension forms a small (< 5%) but curable subset of patients with hypertension. Common endocrine causes of hypertension include pheochromocytoma, Cushing's syndrome, primary hyperaldosteronism, and thyroid disorders. Nuclear medicine imaging plays an important role in evaluation of patients with endocrine hypertension. It has established role in patients of pheochromocytoma/paraganglioma, Cushing's syndrome, aldosteronism, and thyroid disorders. We present a brief overview of ro...

  2. Recombinant human erythropoietin in humans down-regulates proximal renal tubular reabsorption and causes a fall in glomerular filtration rate

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Aachmann-Andersen, Niels Jacob; Oturai, Peter;

    2010-01-01

    rHuEPO elevates hemoglobin concentration both by increasing red blood cell volume and by a decrease in plasma volume. This study delineates the association of rHuEPO-induced changes in blood volumes with changes in the renin-aldosterone system and renal function. 16 healthy males were given rHuEP...

  3. Disease: H00242 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00242 Liddle syndrome Liddle syndrome (LS) is a rare form of autosomal dominant hypertension ch ... e channels at the cell surface, leading persistent absorption ... of Na+ and resulting in large blood volume and hig ... hsa04960(6338+6340) Aldosterone-regulated sodium reabsorption ... SCNN1B [HSA:6338] [KO:K04825] SCNN1G [HSA:6340] [K ...

  4. Disease: H00258 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available .4 I15.2 OMIM: 203400 610600 PMID:15134805 White PC Aldosterone synthase deficiency and related disorders. M...n the CYP11B2 gene. Eur J Endocrinol 144:59-62 (2001) PMID:10559665 Peter M, Dubuis JM, Sippell WG Disorders

  5. Effectiveness of 131I nor-cholesterol uptake per unit volume of adrenal adenoma in the diagnosis of aldosteronoma

    International Nuclear Information System (INIS)

    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, 131I nor-cholesterol uptake of the adrenocortical adenomas, and 131I 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 p131I nor-cholesterol uptake of adrenocortical adenoma. The 131I 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 p131I nor-cholesterol uptake per unit volume of adenoma obtained from adrenocortical scintigraphy without dexamethasone suppression can be useful in the diagnosis of aldosteronoma. (author)

  6. Long-term L-Triiodothyronine (T3) treatment in stable systolic heart failure patients

    DEFF Research Database (Denmark)

    Holmager, Pernille; Schmidt, Ulla; Mark, Peter;

    2015-01-01

    -SPECT). Neurohormonal stimulation was evaluated by plasma measurements of natriuretic peptides, aldosterone, renin, noradrenalin and copeptin levels. The patients were monitored for potential cardiac arrhythmias at the start of each treatment period. RESULTS: Thirteen patients completed the protocol. Mean LVEF was 43...

  7. Molecular mechanism of Na+,K+-ATPase malfunction in mutations characteristic of adrenal hypertension

    DEFF Research Database (Denmark)

    Kopec, Wojciech; Loubet, Bastien; Poulsen, Hanne; Khandelia, Himanshu

    2014-01-01

    Mutations within ion-transporting proteins may severely affect their ability to traffic ions properly and thus perturb the delicate balance of ion gradients. Somatic gain-of-function mutations of the Na(+),K(+)-ATPase α1-subunit have been found in aldosterone-producing adenomas that are among the...

  8. Renin release

    DEFF Research Database (Denmark)

    Schweda, Frank; Friis, Ulla; Wagner, Charlotte;

    2007-01-01

    The aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in salt, volume, and blood pressure homeostasis of the body. Renin is mainly produced and released into circulation by the so-called juxtaglomerular epithelioid cells, located...

  9. Growth arrest specific protein 6 participates in DOCA-induced target-organ damage.

    Science.gov (United States)

    Park, Joon-Keun; Theuer, Stefanie; Kirsch, Torsten; Lindschau, Carsten; Klinge, Uwe; Heuser, Arnd; Plehm, Ralph; Todiras, Mihai; Carmeliet, Peter; Haller, Hermann; Luft, Friedrich C; Muller, Dominik N; Fiebeler, Anette

    2009-08-01

    Growth arrest-specific protein 6 (Gas 6) is involved in inflammatory kidney diseases, vascular remodeling, cell adhesion, and thrombus formation. We explored a role for Gas 6 in aldosterone-induced target organ damage. We observed that Gas 6 was upregulated in rats with high aldosterone levels. Mineralocorticoid receptor blockade prevented target organ damage and decreased the elevated Gas 6 expression. Vascular smooth muscle cells given aldosterone increased their Gas 6 expression in vitro. To test the pathophysiological relevance, we investigated the effects of deoxycorticosterone acetate (DOCA) on Gas 6 gene-deleted ((-/-)) mice. After 6 weeks DOCA, Gas 6(-/-) mice developed similar telemetric blood pressure elevations compared to wild-type mice but were protected from cardiac hypertrophy. Cardiac expression of interleukin 6 and collagen IV was blunted in Gas 6(-/-) mice, indicating reduced inflammation and fibrosis. Gas 6(-/-) mice also had an improved renal function with reduced albuminuria, compared to wild-type mice. Renal fibrosis and fibronectin deposition in the kidney were also reduced. Gas 6 deficiency reduces the detrimental effects of aldosterone on cardiac and renal remodeling independent of blood pressure reduction. Gas 6 appears to play a role in mineralocorticoid receptor-mediated target organ damage. Furthermore, because warfarin interferes with Gas 6 protein expression, the findings could be of clinical relevance for anticoagulant choices. PMID:19564549

  10. Study of the components of renin-angiotensinaldosterone system and KalliKrein -Kinin system in normal pregnancy

    International Nuclear Information System (INIS)

    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.)

  11. SARTANS AND ANGIOTENSIN CONVERTING ENZYME INHIBITORS: A DUEL BETWEEN TWO LEADERS OF PHARMACOTHERAPY OF CARDIOVASCULAR DISEASES

    Directory of Open Access Journals (Sweden)

    K. A. Gyamdzhyan

    2015-12-01

    Full Text Available Topical issues of cardiovascular disease pharmacotherapy influencing function of the renin-angiotensin-aldosterone system are discussed. Efficacy and safety of two major cardiovascular drug classes, angiotensin converting enzyme inhibitors and sartans, are compared. Data from evidence base of the both drug classes are presented.

  12. Alcohol-induced hypertension: Mechanism and prevention

    OpenAIRE

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

    2014-01-01

    Epidemiological, preclinical and clinical studies established the association between high alcohol consumption and hypertension. However the mechanism through which alcohol raises blood pressure remains elusive. Several possible mechanisms have been proposed such as an imbalance of the central nervous system, impairment of the baroreceptors, enhanced sympathetic activity, stimulation of the renin-angiotensin-aldosterone system, increased cortisol levels, increased vascular reactivity due to i...

  13. Clinical Case of the Month: PERSISTENT HYPERTENSION IN A YOUNG WOMAN: A CLASSIC PRESENTATION OF CONN'S SYNDROME.

    Science.gov (United States)

    Yandle Md, Gretchen; Vonderhaar Md, Derek J; Thayalakulasingam Md, Theepha; Zieske Md, Arthur; Smith Md, David; Engel Md Phd, Lee S; Richards Md, Robert; Lopez Md, Fred A

    2016-01-01

    Primary aldosteronism PA is a secondary cause of hypertension that is often missed due to inadequate clinical evaluation and the lack of classically described laboratory abnormalities. Based on guidelines from the Endocrine Society, primary aldosteronism should be suspected in young patients with moderate to severe hypertension, patients with hypertension and coexisting hypokalemia, any patient with hypertension and an incidental adrenal adenoma, and hypertension in the setting of a significant family history of early onset hypertension or cerebral vascular accident in a first degree relative less than 40 years of age.1 In previous years, primary aldosteronism was attributed to less than one percent of all causes of secondary hypertension. However, recent research and increased utilization of aldosterone plasma renin ratio ARR as a method for screening has led to the understanding that majority of patients with PA are not hypokalemic, and the current literature now places the incidence of PA between 5-13 percent. Additionally, a growing body of evidence has demonstrated inflammatory, fibrotic, and remodeling effects on the cardiovascular and renal tissue that appear to be independent of PA- induced hypertension. Therefore a high suspicion for PA must be incorporated into evaluation of hypertensive patients, as diagnosis and subsequent treatment not only improves blood pressure control, but also acts to diminish cardiovascular morbidity and mortality. Here we present a case of a young woman with a seven-year history of hypertension prior to receiving a diagnosis of Conn's Syndrome. PMID:26986864

  14. Cardiorenal-endocrine dynamics during and following volume expansion

    International Nuclear Information System (INIS)

    The relationship between atrial pressure, atrial natriuretic peptide (ANP), the renin-angiotensin-aldosterone system, and renal hemodynamic and excretory function was examined during and following acute 10% body weight saline volume expansion and measurements were made at 3.3, 6.6, and 10% body weight volume expansion in pentobarbital anesthetized dogs. Right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), fractional excretion of Na (FE/sub Na/), and ANP all increased in parallel during volume expansion. Plasma renin activity (PRA) and aldosterone decreased in parallel during 10% volume expansion. ANP, PRA and aldosterone were measured by radioimmunoassay. Following 10% volume expansion, saline was infused at the peak urine flow rate to maintain peak volume expansion. Despite continued saline infusion, RAP, PCWP, and ANP decreased in parallel. In contrast, FE/sub Na/ remained increased, and aldosterone and PRA remained depressed. These studies demonstrate that atrial pressures, ANP, and FE/sub Na/ increase in parallel during volume expansion; this suggests a role for ANP in modulating acute atrial volume overload. During stable volume expansion periods, however, despite a decrease in ANP levels, Na excretion remains elevated, suggesting that non-ANP mechanisms may be important in maintaining natriuresis during stable volume expansion

  15. Cardiovascular, endocrine, and renal effects of urodilatin in normal humans

    DEFF Research Database (Denmark)

    Bestle, M H; Olsen, Niels Vidiendal; Christensen, P; Jensen, B V; Bie, P

    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...

  16. 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.

    2012-01-01

    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 t

  17. Responses to dehydration in the one-humped camel and effects of blocking the renin-angiotensin system.

    Directory of Open Access Journals (Sweden)

    Mahmoud Alhaj Ali

    Full Text Available Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP.

  18. Local Angiotensin Pathways in Human Carotid Atheroma: Towards a Systems Biology Approach

    OpenAIRE

    Bricca, Giampiero; Legedz, Liliana; Nehme, Ali; Ayari, Hanène; Paultre, Christian; Hodroj, Wassim; Li, Jacques-Yuan; Randon, Jacques; Lohez, Olivier; Dhaouadi, Nedra; Gustin, Marie Paule; Cerutti, Catherine

    2015-01-01

    We will summarize the data we have obtained in human carotid artery concerning the organization of an extended local renin angiotensin aldosterone system and its variations at different stages of atheroma. In a system view, we propose a model where concomitant increase in angiotensin and glucocorticoid signaling is induced and amplified in VSMC while vascular smooth muscle cells transdifferentiate toward a lipid storing phenotype.

  19. Potassium secretion in mammalian distal colon

    DEFF Research Database (Denmark)

    Sørensen, Mads Vaarby

    2009-01-01

    -/- and the CFTR-/- mouse, we could functionally isolate the cAMP-activated K+ conductance as the BK channel. In addition we found the cAMP-activated K+ conductance to be further up-regulated by aldosterone. Taken together, these results show cAMP-activated K+ secretion occurs via a regulated specific...

  20. Sub-chronic dietary tryptophan depletion--an animal model of depression with improved face and good construct validity.

    Science.gov (United States)

    Franklin, M; Bermudez, I; Murck, H; Singewald, N; Gaburro, S

    2012-02-01

    Sub-chronic tryptophan depletion (SCTD) is proposed as an animal model for depression. Aims were to test the hypothesis and optimise the time of SCTD-induced depression-related behaviour and associated biochemical changes. Sprague Dawley rats were treated with a low tryptophan (TRP) containing diet for 0, 7 or 14 days. Peripheral and central neurochemical markers were measured. SCTD-induced depression-related behaviour was assessed by the forced swim test (FST). Model sensitivity to antidepressants was tested by concomitant treatment with paroxetine. SCTD-induced significant reductions in weight gain and measures of peripheral and central TRP. Corticosterone, aldosterone and kynurenine (K), increased whilst kynurenic acid (KA), an NMDA antagonist decreased. 5-HT(2) receptor binding Bmax was enhanced but was reversed by paroxetine. Corticosterone and aldosterone were significantly negatively-correlated to weight gain. SCTD increased floating time and reduced swimming time in the FST but were reversed by paroxetine. Aldosterone was increased at 7 and 14 days, whereas other changes maximised at 14 days. Aldosterone may be an early marker or causal link for depression development. Increased corticosterone and brain tissue 5-HT-receptor density may be correlates of depressive behaviour. Consequential increases in NMDA signalling through increased K/KA ratios suggest the model may be useful for testing novel antidepressants. PMID:22074993

  1. 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)....

  2. Bed rest and increased diuretic treatment in chronic congestive heart failure

    DEFF Research Database (Denmark)

    Abildgaard, U; Aldershvile, J; Ring-Larsen, H;

    1985-01-01

    .1), respectively. Plasma concentrations of adrenaline, noradrenaline, renin and aldosterone were increased, as measured in the supine position. No significant differences were found between the two groups. Plasma concentrations of antidiuretic hormone were within normal limits. In conclusion, continuous bed rest...

  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

    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 in...

  4. Influences of 3-methylcholanthrene, phenobarbital and dexamethasone on xenobiotic metabolizing-related cytochrome P450 enzymes and steroidogenesis in human fetal adrenal cortical cells

    Institute of Scientific and Technical Information of China (English)

    Hui WANG; Min HUANG; Ren-xiu PENG; Jiang LE

    2006-01-01

    Aim: To explore the influence and possible mechanism of xenobiotics on adrenal steroidogenesis during fetal development. Methods: Primary human fetal adrenal cortical cells were prepared, cultured and treated with 3-methylcholanthrene, phenobarbital and dexamethasone. The activities of 7-ethoxyresorufin 0-dealkylase, benzphetamine, aminopyrine and erythromycin N-demethylases were measured by enzyme assays. At the same time, quantitative analysis of steroid hormones cortisol, aldosterone, testosterone and progesterone were carried out in cultural medium by radioimmunoassays. Results: The activities of benzphetamine and aminopyrine Ar-demethylase were increased in the cultural fetal adrenal cells treated with phenobarbital (0.25-1 mmol/L) for 24 h. Dexamethasone (25-100 μmol/L) also increased the activity of erythromycin W-demethylase. The activity of 7-ethoxyresorufin 0-dealkylase was undetected in the cells treated without and with 3-methylcholanthrene (0.5-2 μmol/L). Meanwhile, the contents of medium cortisol, aldosterone and progesterone were decreased after treatment with 3-methylcholanthrene. Cortisol, aldosterone and progesterone concentrations were also slightly decreased with phenobarbital. Dexamethasone enhanced the productions of cortisol and progesterone remarkably. The trend of testosterone concentration was uncertain after 3-methylcholanthrene, phenobarbital or dexamethasone treatment. Conclusion: 3-Methylcholanthrene, phenobarbital or dexamethasone could interfere with the synthesis of cortisol, aldosterone and progesterone in primary human fetal adrenal cortical cells, which likely act through xenobiotic metabolizing-related cytochrome P450 isoform activation.

  5. Disease: H00243 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available erited cause of type 4 RTA includes hyperkalaemia associated with hypertension and low or normal levels of p...f tubulointerstitial renal diseases. Finally, a great number of drugs may induce hyperkalemic RTA. Endocrine disea...se; Urinary system disease hsa04960(6337+6338+6340+4306) Aldosterone-regulated sodium reabsorption SCN

  6. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan

    NARCIS (Netherlands)

    Vogt, Liffert; Waanders, Fernke; Boornsma, Frans; de Zeeuw, Dick; Navis, Gerjan

    2008-01-01

    There is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these intervention

  7. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan

    NARCIS (Netherlands)

    L. Vogt (Liffert); F. Waanders (Femke); F. Boomsma (Frans); D. de Zeeuw (Dick); G. Navis (Gerjan)

    2008-01-01

    textabstractThere is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these

  8. Between-patient differences in the renal response to renin-angiotensin system intervention: clue to optimising renoprotective therapy?

    NARCIS (Netherlands)

    Laverman, Ger Jan; Navis, Ger Jan; de Zeeuw, Dick

    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, promp

  9. [Laboratory Medicine Learned Through Research on the Pathogenesis of Hypertension].

    Science.gov (United States)

    Takahashi, Hakuo

    2015-05-01

    Laboratory tests used in clinical practice to assess hypertension include a differential diagnosis, the assessment of complications, and detection of adverse events with medication, which cover a variety of fields of laboratory medicine. I learned laboratory medicine through basic and clinical studies on the pathogenesis of hypertension, and summarized those findings and my interpretations. Basic research using animal models points to a causal role of the central nervous system in essential hypertension; however, since clinical research is technically difficult to perform, this connection has not been confirmed in humans. Recently, renal nerve ablation in humans proved to continuously decrease the blood pressure in the presence of resistant hypertension. Furthermore, when electrical stimulation was continuously applied to the carotid baroreceptor nerve of human adults, their blood pressure lowered. These findings promoted the concept that the central nervous system may actually be involved in the pathogenesis of essential hypertension, which is closely associated with excess sodium intake. We demonstrated that endogenous digitalis plays a key role in hypertension associated with excess sodium intake via sympathetic activation in rats. An increased sodium concentration inside the brain activates epithelial sodium channels and the renin-angiotensin-aldosterone system in the brain. Aldosterone releases ouabain from neurons in the paraventricular nucleus in the hypothalamus. Angiotensin II and aldosterone of peripheral origin reach the brain to augment sympathetic outflow. Collectively essential hypertension associated with excess sodium intake and obesity, renovascular hypertension, and primary aldosteronism and pseudoaldosteronism are all suggested to have a common cause originating from the central nervous system. PMID:26524901

  10. 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, promp

  11. 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

  12. 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

  13. Gender differences in endocrine responses to posture and 7 days of 6 deg head down bed rest

    Science.gov (United States)

    Vernikos, J.; Dallman, M. F.; Keil, L. C.; Ohara, D.; Convertino, V. A.

    1993-01-01

    Endocrine regulation of fluids and electrolytes during seven days of 6 deg head down bed rest (HDBR) was compared in male (n = 8) and, for the first time, female (n = 8) volunteers. The subjects' responses to quiet standing for 2 hr before and after HDBR were also tested. In both sexes, diuresis and natriuresis were evident during the first 2-3 days of HDBR, resulting in a marked increase in the urinary Na/K ratio and significant Na retention on reambulation. After the first day of HDBR, plasma renin activity (PRA) was increased relative to aldosterone, plasma volume was decreased, and the renal response to aldosterone appeared to be appropriate. Circulating levels of arginine vasopressin (AVP), cortisol, and ACTH were unchanged during HDBR. Plasma testosterone decreased slightly on day 2 of HDBR in males. The ratio of AM ACTH to cortisol was lower in females than in males because ACTH was lower in females. Urinary cortisol increased and remained elevated throughout the HDBR in males only. There were no gender differences in the responses to 7 day HDBR, except those in the pituitary-adrenal system; those differences appeared unrelated to the postural change. The provocative cardiovascular test of quiet standing before and after bed rest revealed both sex differences and effects of HDBR. There were significant sex differences in cardiovascular responses to standing, before and after HDBR. Females had greater PRA and aldosterone responses to standing before bedrest and larger aldosterone responses to standing after HDBR than males. Cardiovascular responses to standing before and after bedrest differed markedly: arterial pressure and heart rates increased with standing before HDBR, by contrast, arterial pressure decreased, with greater increases in heart rates after HDBR. In both sexes, all hormonal responses to standing were greater after HDBR. The results show clearly that similar responses to standing as well as to HDBR occur in both sexes, but that females exhibit

  14. 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.

  15. Osmoregulation in wild and captive West Indian manatees (Trichechus manatus).

    Science.gov (United States)

    Ortiz, R M; Worthy, G A; MacKenzie, D S

    1998-01-01

    The ability of West Indian manatees (Trichechus manatus latirostris and Trichechus manatus manatus) to inhabit both freshwater and marine habitats presents an interesting model to study osmoregulation in sirenians. Blood samples were analyzed from manatees held in fresh- and saltwater and from wild animals captured in fresh-, brackish, and saltwater for concentrations of aldosterone, arginine vasopressin, plasma renin activity, Na+, K+, Cl-, and osmolality. Two separate experiments were also conducted on captive animals to evaluate osmoregulatory responses to acute saltwater exposure and freshwater deprivation. Spurious differences were observed in plasma electrolyte and osmolality among the captive and wild groups. Wild brackish water animals exhibited the highest vasopressin concentrations, while wild freshwater manatees had the highest aldosterone levels. A significant correlation between mean vasopressin and osmolality was demonstrated for captive and wild animals. When freshwater animals were acutely exposed to saltwater, osmolality, Na+, and Cl- increased 5.5%, 8.0%, and 14%, respectively, while aldosterone decreased 82.6%. Saltwater animals deprived of freshwater exhibited an almost twofold increase in aldosterone during the deprivation period and a fourfold decrease when freshwater was again provided. Within this group, osmolality increased significantly by 3.4% over the course of the study; however, electrolytes did not change. The lack of consistent differences in electrolyte and osmolality among wild and captive groups suggests that manatees are good osmoregulators regardless of the environment. The high aldosterone levels in wild freshwater animals may indicate a need to conserve Na+, while the high vasopressin levels in wild brackish-water manatees suggest an antidiuretic state to conserve water. Vasopressin levels appear to be osmotically mediated in manatees as in other mammals. PMID:9678505

  16. Dopamine receptor expression and function in human normal adrenal gland and adrenal tumors.

    Science.gov (United States)

    Pivonello, Rosario; Ferone, Diego; de Herder, Wouter W; de Krijger, Ronald R; Waaijers, Marlijn; Mooij, Diana M; van Koetsveld, Peter M; Barreca, Antonina; De Caro, Maria Laura del Basso; Lombardi, Gaetano; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J

    2004-09-01

    Dopamine is known to play a role in the modulation of aldosterone and catecholamine secretion from the adrenal gland, where dopamine receptors (DR), in particular the DR type 2 (D(2)), have been found to be expressed. DR expression has also been demonstrated in some types of benign adrenal tumors. The aims of the current study were to evaluate DR expression and D(2) localization in the normal adrenal gland and in different types of benign and malignant adrenal tumors, as well as to evaluate the in vitro effects of the dopamine agonists bromocriptine and cabergoline on hormone secretion in nontumoral adrenal cells. Adrenal tissues from 25 patients, subjected to adrenal surgery for different diseases, were studied. These included three normal adrenals; five adrenal hyperplasias; four aldosterone-secreting, two cortisol-secreting, and two clinically nonfunctioning adrenal adenomas; two aldosterone-secreting, two cortisol-secreting, and two androgen-secreting adrenal carcinomas; and three pheochromocytomas. In all tissues, DR and D(2) isoform (D(2long) and D(2short)) expression was evaluated by RT-PCR. D(2) localization was also evaluated by immunohistochemistry using a specific polyclonal antibody, whereas D(2)-like receptor expression was evaluated by receptor-ligand binding study, using the radiolabeled D(2) analog (125)I-epidepride. The effects of bromocriptine and cabergoline on baseline and ACTH and/or angiotensin II-stimulated aldosterone, cortisol, and androstenedione secretion were evaluated in cell cultures derived from five different adrenal hyperplasia. At RT-PCR, both D(1)-like and D(2)-like receptors were expressed in all normal and hyperplastic adrenals. D(2) and D(4) were expressed in aldosterone- and cortisol-secreting adenomas, cortisol-secreting carcinomas, and clinically nonfunctioning adenomas, whereas no DR was expressed in aldosterone- and androgen-secreting carcinomas. D(2), D(4), and D(5) were expressed in pheochromocytomas. In all D(2

  17. Resistant hypertension with adrenal nodule: are we removing the right gland?

    Science.gov (United States)

    Taylor, Peter N; Tabasum, Arshiya; Rao Bondugulapati, L N; Parker, Danny; Baglioni, Piero; Okosieme, Onyebuchi E; Scott Coombes, David

    2015-01-01

    Summary Resistant hypertension is often difficult to treat and may be associated with underlying primary aldosteronism (PA). We describe the case of an elderly gentleman who presented with severe and resistant hypertension and was found to have a left adrenal incidentaloma during evaluation but had aldosterone excess secondary to unilateral adrenal hyperplasia (UAH) of the contralateral gland, which needed surgical intervention. A 65-year-old gentleman was evaluated for uncontrolled high blood pressure (BP) in spite of taking four antihypertensive medications. The high BP was confirmed on a 24-h ambulatory reading, and further biochemical evaluation showed an elevated serum aldosterone renin ratio (ARR) (1577 pmol/l per ng per ml per h). Radiological evaluation showed an adrenal nodule (15 mm) in the left adrenal gland but an adrenal vein sampling demonstrated a lateralization towards the opposite site favouring the right adrenal to be the source of excess aldosterone. A laparoscopic right adrenalectomy was performed and the histology of the gland confirmed nodular hyperplasia. Following surgery, the patient's BP improved remarkably although he remained on antihypertensives and under regular endocrine follow-up. PA remains the most common form of secondary and difficult-to-treat hypertension. Investigations may reveal incidental adrenal lesions, which may not be the actual source of excess aldosterone, but UAH may be a contributor and may coexist and amenable to surgical treatment. An adrenal vein sampling should be undertaken for correct lateralization of the source, otherwise a correctable diagnosis may be missed and the incorrect adrenal gland may be removed. Learning points Severe and resistant hypertension can often be associated with underlying PA. ARR is an excellent screening tool in patients with suspected PA. Lateralization with adrenal venous sampling is essential to isolate the source and differentiate between unilateral and bilateral causes of

  18. A case of liddle′s syndrome; unusual presentation with hypertensive encephalopathy

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota

    2014-01-01

    Full Text Available Liddle′s syndrome is a rare cause of secondary hypertension. Identification of this disorder is important because treatment differs from other forms of hypertension. We report an interesting case of a 35-year-old lady, a known diabetic and hypertensive patient, who presented with features of hypertensive encephalopathy. The family history was unremarkable. Past treat-ment with various combinations of antihypertensive medications including spironolactone, all at high doses, failed to control her blood pressure. Upon evaluation, the patient had hypokalemic alkalosis, low 24-h urine potassium and suppressed plasma renin activity. Although these findings were similar to hyperaldosteronism, plasma aldosterone was lower than the normal range. Blood pressure decreased markedly after administration of amiloride. Along with hyporeninemic hypo-aldosteronism, the non-responsiveness to spironolactone and good response to amiloride esta-blished the diagnosis of Liddle′s syndrome.

  19. The role of computed tomography in the localization of adrenal cortex tumors

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate the usefulness of computed tomography in the localisation of adrenal tumors producing aldosterone and cortisol. One case each of Conn's and Cushing's syndrome are described. The diagnosis of Conn's syndrome was established by demonstrating an elevated plasma aldosterone level 'at rest' and its decrease after stimulation, the absence of plasma renin activity and a lowered plasma potassium level. The diagnosis of Cushing's syndrome due to adrenal adenoma was established by demonstrating the typical clinical features, an abnormal diurnal rhythm of cortisol and ACTH secretion and an increased urine excretion of 17-OHCS without suppression by large doses of dexamethasone. The localisation and the size of the tumors as determined by computed tomography were confirmed during surgery. (orig.)

  20. Adrenal incidentalomas. Primary hyperaldosteronism

    International Nuclear Information System (INIS)

    Adrenal incidentalomas are masses incidentally discovered at X rays, ultrasound or MRI examination of the abdomen. In 100 CT scans, one can expect to find two incidentalomas on average. The article by Murat and Dupas is dealing with the strategy of biological, morphological and scintigraphic examinations to be performed in such patients, to assess whether the tumor is of a benign or a malignant nature. Zenatti et al propose a detailed exploration of the aldosterone pathways, since adrenal carcinoma may be responsible for a specific profile of the serum concentrations of mineralo-steroids, compatible with a blockade of the last step of the aldosterone synthesis. The exploration of primary hyperaldosteronism requires biological and imaging techniques. Tabarin et al summarize the main biological parameters and tests available for the diagnosis of this condition and delineate the indications of imaging techniques, associated to hormonal tests to distinguish between adenoma and bilateral adrenal hyperplasia. (author). 104 refs

  1. Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

    Directory of Open Access Journals (Sweden)

    Costas Tsioufis

    2011-01-01

    Full Text Available Resistant hypertension (RH is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH.

  2. Percutaneous ablation of functioning adenoma in a patient with a single adrenal gland

    Science.gov (United States)

    Nunes, Thiago Franchi; Szejnfeld, Denis; Xavier, Ana Carolina Wanderley; Goldman, Suzan Menasce

    2013-01-01

    The conventional treatment of functioning adrenal adenomas is laparoscopic resection. Since the 1990s, radiofrequency ablation has been increasingly applied to the treatment of tumours of the liver, lungs and musculoskeletal system. However, the use of radiofrequency ablation to treat adrenal nodules is still an uncommon procedure, particularly in aldosterone-producing adenomas. We report the case of a 35-year-old male patient with resistant hypertension, hypokalaemia and aldosterone-producing adenoma in a single adrenal gland. The patient underwent CT-guided percutaneous radiofrequency ablation. Clinical, laboratory and MRI follow-up data indicated excellent response to treatment. This case report is the first in the literature to describe the use of CT-guided percutaneous radiofrequency ablation in the treatment of a functioning adrenal adenoma in a patient with a single adrenal gland. PMID:23737584

  3. Alpha-human atrial natriuretic polypeptide (. cap alpha. -hANP) specific binding sites in bovine adrenal gland

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, K.; Nawata, H.; Kato, K.I.; Ibayashi, H.; Matsuo, H.

    1986-06-13

    The effects of synthetic ..cap alpha..-human atrial natriuretic polypeptide (..cap alpha..-hANP) on steroidogenesis in bovine adrenocortical cells in primary monolayer culture were investigated. ..cap alpha..-hANP did not inhibit basal aldosterone secretion. ..cap alpha..-hANP induced a significant dose-dependent inhibition of basal levels of cortisol and dehydroepiandrosterone (DHEA) secretion and also of aCTH (10/sup -8/M)-stimulated increases in aldosterone, cortisol and DHEA secretion. Visualization of (/sup 125/I) ..cap alpha..-hANP binding sites in bovine adrenal gland by an in vitro autoradiographic technique demonstrated that these sites were highly localized in the adrenal cortex, especially the zona glomerulosa. These results suggest that the adrenal cortex may be a target organ for direct receptor-mediated actions of ..cap alpha..-hANP.

  4. Alpha-human atrial natriuretic polypeptide (α-hANP) specific binding sites in bovine adrenal gland

    International Nuclear Information System (INIS)

    The effects of synthetic α-human atrial natriuretic polypeptide (α-hANP) on steroidogenesis in bovine adrenocortical cells in primary monolayer culture were investigated. α-hANP did not inhibit basal aldosterone secretion. α-hANP induced a significant dose-dependent inhibition of basal levels of cortisol and dehydroepiandrosterone (DHEA) secretion and also of aCTH (10-8M)-stimulated increases in aldosterone, cortisol and DHEA secretion. Visualization of [125I] α-hANP binding sites in bovine adrenal gland by an in vitro autoradiographic technique demonstrated that these sites were highly localized in the adrenal cortex, especially the zona glomerulosa. These results suggest that the adrenal cortex may be a target organ for direct receptor-mediated actions of α-hANP

  5. Transient Pseudohypoaldosteronism due to Urinary Tract Infection in Infancy: A Report of 4 Cases

    OpenAIRE

    Kaplowitz Paul; Vaidyanathan Priya; Nandagopal Radha

    2009-01-01

    Hyponatremia with hyperkalemia in infancy is an uncommon but life-threatening occurrence. In the first weeks of life, this scenario is often associated with aldosterone deficiency due to salt-wasting congenital adrenal hyperplasia. However, alternative diagnoses involving inadequate mineralocorticoid secretion or action must be considered, particularly for infants one month of age or older. We report four infants who presented with profound hyponatremia accompanied by urinary tract infection...

  6. Transient Pseudohypoaldosteronism due to Urinary Tract Infection in Infancy: A Report of 4 Cases

    OpenAIRE

    Radha Nandagopal; Priya Vaidyanathan; Paul Kaplowitz

    2009-01-01

    Hyponatremia with hyperkalemia in infancy is an uncommon but life-threatening occurrence. In the first weeks of life, this scenario is often associated with aldosterone deficiency due to salt-wasting congenital adrenal hyperplasia. However, alternative diagnoses involving inadequate mineralocorticoid secretion or action must be considered, particularly for infants one month of age or older. We report four infants who presented with profound hyponatremia accompanied by urinary tract infection,...

  7. MicroRNA and Heart Failure

    OpenAIRE

    Lee Lee Wong; Juan Wang; Oi Wah Liew; Arthur Mark Richards; Yei-Tsung Chen

    2016-01-01

    Heart failure (HF) imposes significant economic and public health burdens upon modern society. It is known that disturbances in neurohormonal status play an important role in the pathogenesis of HF. Therapeutics that antagonize selected neurohormonal pathways, specifically the renin-angiotensin-aldosterone and sympathetic nervous systems, have significantly improved patient outcomes in HF. Nevertheless, mortality remains high with about 50% of HF patients dying within five years of diagnosis ...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    sodium excretion. The results are com-patible with the notion that at constant arterial pressure, a volume-receptor elicited reduction in RSNA, via receptors other than beta1-adrenoceptors, decreases renal tubular sodium reabsorption proximal to the macula densa leading to increased NaCl concentration at...... the macula densa and subsequent inhibition of renin secretion. Key words: Blood pressure, angiotensin, aldosterone, natriuresis....

  9. EXERCISE CAPACITY IN HEALTHY PERIMENOPAUSAL WOMEN

    OpenAIRE

    Isayeva, Ganna

    2014-01-01

    The work studies a relationship between the levels of endogenous sex hormones and exercise capacity in healthy women during their perimenopause. Seventy-one healthy perimenopausal women were included in the study. Mod BRUCE protocol has been used to assess exercise capacity. An effect of the follicle-stimulating hormone level on METs values has been detected. No similar effects have been found for estradiol, testosterone, aldosterone, and prolactin.

  10. Pengaruh Pemberian Ekstrak Etanol Buah Mengkudu terhadap Aktivitas Angiotensin Converting Enzyme (ACE) pada Tikus Wistar yang Mendapat Diet Natrium

    OpenAIRE

    Syahreza, Adri

    2012-01-01

    Hypertension is now a global problem because of the prevalence continues to increase in line with lifestyle changes. One of hypertension cause is excess intake of sodium thus will increase the fluid volume in the body. One of regulates the fluid balance in the body is mechanism of renin angiotensin aldosterone system (RAAS). Increasing activity of angiotensin converting enzyme (ACE) in the body will lead to hypertension through RAAS. ACE activation can be inhibited by ACE In...

  11. Glucocorticoids increase salt appetite by promoting water and sodium excretion

    OpenAIRE

    Thunhorst, Robert L.; Beltz, Terry G.; Johnson, Alan Kim

    2007-01-01

    Glucocorticoids [e.g., corticosterone and dexamethasone (Dex)], when administered systemically, greatly increase water drinking elicited by angiotensin and sodium ingestion in response to mineralocorticoids [e.g., aldosterone and deoxycorticosterone acetate (DOCA)], possibly by acting in the brain. In addition, glucocorticoids exert powerful renal actions that could influence water and sodium ingestion by promoting their excretion. To test this, we determined water and sodium intakes, excreti...

  12. Spironolactone treatment attenuates vascular dysfunction in type 2 diabetic mice by decreasing oxidative stress and restoring NO/GC signaling

    OpenAIRE

    Silva, Marcondes A. B.; Bruder-Nascimento, Thiago; Cau, Stefany B. A.; Lopes, Rheure A. M.; Mestriner, Fabiola L. A. C.; Fais, Rafael S.; Touyz, Rhian M.; Tostes, Rita C.

    2015-01-01

    Type 2 diabetes (DM2) increases the risk of cardiovascular disease. Aldosterone, which has pro-oxidative and pro-inflammatory effects in the cardiovascular system, is positively regulated in DM2. We assessed whether blockade of mineralocorticoid receptors (MR) with spironolactone decreases reactive oxygen species (ROS)-associated vascular dysfunction and improves vascular nitric oxide (NO) signaling in diabetes. Leptin receptor knockout [LepRdb/LepRdb (db/db)] mice, a model of DM2, and their ...

  13. Spironolactone treatment attenuates vascular dysfunction in type 2 diabetic mice by decreasing oxidative stress and restoring NO/GC signaling

    OpenAIRE

    Marcondes Alves Barbosa Da Silva; Thiago eBruder-Nascimento; Stêfany Bruno Assis Cau; Rheure AM Lopes; Fabiola LAC Mestriner; Fais, Rafael S.; Touyz, Rhian M.; Tostes, Rita C.

    2015-01-01

    Type 2 diabetes (DM2) increases the risk of cardiovascular disease. Aldosterone, which has pro-oxidative and pro-inflammatory effects in the cardiovascular system, is positively regulated in DM2. We assessed whether blockade of mineralocorticoid receptors (MR) with spironolactone decreases ROS-associated vascular dysfunction and improves vascular NO signaling in diabetes. Leptin receptor knockout [LepRdb/LepRdb (db/db)] mice, a model of DM2, and their counterpart controls [LepRdb/LepR+, (db/+...

  14. PPARγ Agonist Beyond Glucose Lowering Effect

    OpenAIRE

    Sugawara, Akira; Uruno, Akira; Kudo, Masataka; Matsuda, Ken; Yang, Chul Woo; Ito, Sadayoshi

    2011-01-01

    The nuclear hormone receptor PPARγ is activated by several agonists, including members of the thiazolidinedione group of insulin sensitizers. Pleiotropic beneficial effects of these agonists, independent of their blood glucose-lowering effects, have recently been demonstrated in the vasculature. PPARγ agonists have been shown to lower blood pressure in animals and humans, perhaps by suppressing the renin-angiotensin (Ang)-aldosterone system (RAAS), including the inhibition of Ang II type 1 re...

  15. Arterial Ageing

    OpenAIRE

    Lee, Seung-Jun; Park, Sung-Ha

    2013-01-01

    Arterial ageing is characterized by age associated degeneration and sclerosis of the media layer of the large arteries. However, besides ageing, clinical conditions, which enhance oxidative stress and inflammation act to accelerate the degree of arterial ageing. In this review, we summarized the pathophysiology and contributing factors that accelerate arterial ageing. Among them, we focused on hypertension, the renin-angiotensin-aldosterone system and vascular inflammation which are modifiabl...

  16. Cosegregation of the renin allele of the spontaneously hypertensive rat with an increase in blood pressure.

    OpenAIRE

    Kurtz, T. W.; Simonet, L; Kabra, P M; Wolfe, S; Chan, L; Hjelle, B L

    1990-01-01

    The spontaneously hypertensive rat (SHR) exhibits alterations in the renin-angiotensin-aldosterone system which are similar to those that characterize patients with "nonmodulating" hypertension, a common and highly heritable form of essential hypertension. Accordingly, we determined whether the inheritance of a DNA restriction fragment length polymorphism (RFLP) marking the renin gene of the SHR was associated with greater blood pressure than inheritance of a RFLP marking the renin gene of a ...

  17. Pharmacokinetic interactions and pharmacogenetics of aliskiren

    OpenAIRE

    Tapaninen, Tuija

    2012-01-01

    Aliskiren is an antihypertensive drug approved for clinical use in 2007. It acts by inhibiting renin, the first enzyme in the renin-angiotensin-aldosterone system. Marked interindividual variability exists in the pharmacokinetics of aliskiren. Interestingly, the pharmacokinetic properties of aliskiren suggest an important role for drug transporters in its pharmacokinetics. Aliskiren is poorly absorbed, and therefore, its oral bioavailability is only 2-3%. The elimination of aliskiren occurs m...

  18. Adrenal scanning in children

    International Nuclear Information System (INIS)

    Adrenal scanning with 131I-Adosterol is very useful and rather non-invasive than adrenal angiography in children. It is possible to diagnose various diseases of the adrenal glands not only structural but also functional abnormalities. In patients with adrenogenital syndromes, we are able to demonstrate hyperplasia of the adrenal glands, and in patients with aldosteronism or Cushing's syndrome differential diagnosis between bilateral hyperplasia and functional adenoma of the adrenal gland can be made. (author)

  19. Adrenal adenomas: relationship between histologic lipid-rich cells and CT attenuation number

    International Nuclear Information System (INIS)

    Objective: To evaluate the relationship between lipid-rich cells of the adrenal adenoma and precontrast computed tomographic (CT) attenuation numbers in three clinical groups. Materials and Methods: Thirty-five surgically resected adrenal adenomas were used. The clinical diagnoses of the patients included 13 cases of primary aldosteronism, 15 cases of Cushing's syndrome, and 7 non-functioning tumors. The number of lipid-rich clear cells was counted using a microscopic eyepiece grid that contained 100 squares. The results were expressed as the percentages of lipid-rich areas. Results: There was a strong inverse linear relationship between the percentage of lipid-rich cells and the precontrast CT attenuation number (R2=0.724, P<0.0001). There were significantly more lipid-rich cells in the primary aldosteronism and non-functioning tumor cases compared to cases of Cushing's syndrome (P=0.007 and 0.015, respectively). The CT attenuation numbers of the primary aldosteronism cases were significantly lower than those of Cushing's syndrome (P=0.0052). Furthermore, the CT attenuation numbers of the non-functioning tumor cases were lower than those of Cushing's syndrome cases. Conclusion: We showed that adrenal adenomas in primary aldosteronism and non-functioning tumors contain significantly more lipid-rich cells than those in Cushing's syndrome. They also showed significantly lower attenuation than that in Cushing's syndrome on CT scans. Our results suggest that precontrast CT attenuation numbers may be helpful in the differentiation of adenomas from non-adenomatous lesions, which include malignancies

  20. Adrenal adenomas: relationship between histologic lipid-rich cells and CT attenuation number

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Takayuki E-mail: yamataka@rad.med.tohoku.ac.jp; Ishibashi, Tadashi; Saito, Haruo; Matsuhashi, Toshio; Majima, Kazuhiro; Tsuda, Masashi; Takahashi, Shoki; Moriya, Takuya

    2003-11-01

    Objective: To evaluate the relationship between lipid-rich cells of the adrenal adenoma and precontrast computed tomographic (CT) attenuation numbers in three clinical groups. Materials and Methods: Thirty-five surgically resected adrenal adenomas were used. The clinical diagnoses of the patients included 13 cases of primary aldosteronism, 15 cases of Cushing's syndrome, and 7 non-functioning tumors. The number of lipid-rich clear cells was counted using a microscopic eyepiece grid that contained 100 squares. The results were expressed as the percentages of lipid-rich areas. Results: There was a strong inverse linear relationship between the percentage of lipid-rich cells and the precontrast CT attenuation number (R{sup 2}=0.724, P<0.0001). There were significantly more lipid-rich cells in the primary aldosteronism and non-functioning tumor cases compared to cases of Cushing's syndrome (P=0.007 and 0.015, respectively). The CT attenuation numbers of the primary aldosteronism cases were significantly lower than those of Cushing's syndrome (P=0.0052). Furthermore, the CT attenuation numbers of the non-functioning tumor cases were lower than those of Cushing's syndrome cases. Conclusion: We showed that adrenal adenomas in primary aldosteronism and non-functioning tumors contain significantly more lipid-rich cells than those in Cushing's syndrome. They also showed significantly lower attenuation than that in Cushing's syndrome on CT scans. Our results suggest that precontrast CT attenuation numbers may be helpful in the differentiation of adenomas from non-adenomatous lesions, which include malignancies.

  1. Obesity-related hypertension: epidemiology, pathophysiology, treatments, and the contribution of perivascular adipose tissue.

    Science.gov (United States)

    Aghamohammadzadeh, Reza; Heagerty, Anthony M

    2012-06-01

    The advent of the obesity epidemic has highlighted the need to re-assess more closely the pathophysiology of obesity-related hypertension with the aim of identifying new therapies. In this article, we review the role of the renin-angiotensin-aldosterone system, sympathetic nervous system, and inflammation in relation to the pathophysiology of this condition. We also discuss the potential role of the perivascular adipose tissue in the context of obesity-related hypertension. PMID:22713152

  2. ELEVATION OF SERUM POTASSIUM AND ITS OUTCOME IN CHRONIC RENAL FAILURE PATIENTS

    OpenAIRE

    Punam Yadav; Dinkar Malik; Sandeep Kumar; Vijai Malik

    2014-01-01

    Potassium is the principal metallic ion inside the cells. During physical activity potassium ion leaves muscle cells and this leads to fatigue. When aldosteron instructs the kidney to retain sodium ion, they generally excrete more potassium ion. The kidneys are the principal organ of excretion for potassium, not only potassium is filtered by the kidneys in the glomeruli but it is also secreted by the tubules. Chronic renal failure does not cause severe or progressive hyperkala...

  3. Ocular and skin manifestations in systemic pseudohypoaldosteronism

    OpenAIRE

    Eliwa, Mahmoud Salah; El-Emmawie, Aymen Hussein; Saeed, Mahmood Ahmad

    2014-01-01

    Pseudohypoaldosteronism type-1 is a rare disorder characterised by end-organ resistance to aldosterone resulting in salt-losing crisis with hyponatraemic dehydration, hyperkalaemia and metabolic acidosis. We report two siblings with pseudohypoaldosteronism type-1 who presented early in neonatal period with hyponatraemia, severe hyperkalaemia and metabolic acidosis. Both babies had miliaria like skin rash which flared up during episodes of hyperkalaemia and hyponatraemia. They had visible dila...

  4. Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial

    OpenAIRE

    Pitt, Bertram; Anker, Stefan D.; Bushinsky, David A; Dalane W Kitzman; Zannad, Faiez; Huang, I-Zu

    2011-01-01

    Aims To evaluate efficacy and safety of RLY5016 (a non-absorbed, orally administered, potassium [K+]-binding polymer) on serum K+ levels in patients with chronic heart failure (HF) receiving standard therapy and spironolactone. Methods and results One hundred and five patients with HF and a history of hyperkalaemia resulting in discontinuation of a renin–angiotensin–aldosterone system inhibitor/blocker and/or beta-adrenergic blocking agent or chronic kidney disease (CKD) with an estimated glo...

  5. Amiloride inhibits mammalian renal kallikrein and a kallikrein-like enzyme from toad bladder and skin.

    OpenAIRE

    Margolius, H S; Chao, J.

    1980-01-01

    Renal kallikrein is localized in luminal plasma membranes of the mammalian distal nephron and gains access to urine from this site. Its activity is regulated, in part, by aldosterone. These facts led us to study the effects of amiloride, a drug known to inhibit sodium reabsorption and potassium secretion at this site, on kallikrein activity. Amiloride inhibited the esterolytic activity of purified rat or human urinary kallikrein or of rat renal cortical cells upon a synthetic substrate (ID50 ...

  6. Syndromes that Mimic an Excess of Mineralocorticoids.

    Science.gov (United States)

    Sabbadin, Chiara; Armanini, Decio

    2016-09-01

    Pseudohyperaldosteronism is characterized by a clinical picture of hyperaldosteronism with suppression of renin and aldosterone. It can be due to endogenous or exogenous substances that mimic the effector mechanisms of aldosterone, leading not only to alterations of electrolytes and hypertension, but also to an increased inflammatory reaction in several tissues. Enzymatic defects of adrenal steroidogenesis (deficiency of 17α-hydroxylase and 11β-hydroxylase), mutations of mineralocorticoid receptor (MR) and alterations of expression or saturation of 11-hydroxysteroid dehydrogenase type 2 (apparent mineralocorticoid excess syndrome, Cushing's syndrome, excessive intake of licorice, grapefruits or carbenoxolone) are the main causes of pseudohyperaldosteronism. In these cases treatment with dexamethasone and/or MR-blockers is useful not only to normalize blood pressure and electrolytes, but also to prevent the deleterious effects of prolonged over-activation of MR in epithelial and non-epithelial tissues. Genetic alterations of the sodium channel (Liddle's syndrome) or of the sodium-chloride co-transporter (Gordon's syndrome) cause abnormal sodium and water reabsorption in the distal renal tubules and hypertension. Treatment with amiloride and thiazide diuretics can respectively reverse the clinical picture and the renin aldosterone system. Finally, many other more common situations can lead to an acquired pseudohyperaldosteronism, like the expansion of volume due to exaggerated water and/or sodium intake, and the use of drugs, as contraceptives, corticosteroids, β-adrenergic agonists and FANS. In conclusion, syndromes or situations that mimic aldosterone excess are not rare and an accurate personal and pharmacological history is mandatory for a correct diagnosis and avoiding unnecessary tests and mistreatments. PMID:27251484

  7. The story of spironolactones from 1957 to now: from sodium balance to inflammation.

    Science.gov (United States)

    Sabbadin, Chiara; Calò, Lorenzo A; Armanini, Decio

    2016-02-01

    After the discovery of aldosterone (1953), many synthetic steroids were tested for their ability to block the sodium retaining and potassium excreting effect of synthetic mineralocorticoids in adrenalectomized rats. In the same years Kagawa discovered that 17-spirolactone steroids were effective to block mineralocorticoid effects, but when used alone they did not produce any effect in adrenalectomized rats. After the description of the first case of primary aldosteronism (1955), spironolactone (SP) was considered the main treatment before surgery to control blood pressure and kaliemia and for long-term treatment in patients with bilateral adrenal hyperplasia. SP was further used for various clinical situations, such as liver cirrhosis, idiopathic oedema, nephrosis and congestive heart failure. SP also shows an antiandrogen action, effective in polycystic ovary syndrome. In 1985 we demonstrated that human mononuclear leukocytes (MNL) possess mineralocorticoid receptors (MR) and lately we demonstrated that coincubation of MNL with canrenone blocked aldosterone mediated inflammatory, reducing the expression of PAI-1 and p22phox. It is well known that MNL and macrophages are mainly involved in vascular inflammation and atherosclerosis and we have hypothesized that the tissue invasion of MNL brings MR in the site of inflammation starting the process. Recently, aldosterone has been associated with the promotion of many organ-specific autoimmune diseases, inducing Th17 polarization of CD4+ T cells and suggesting new possible therapeutic targets for anti-mineralocorticoid drugs. In conclusion, considering all the benefits of MR-antagonists, their use should be reconsidered not only for the treatment but also for the prevention of many clinical situations. PMID:26913880

  8. Furosemide and 11beta-hydroxysteroid dehydrogenase activity, in man.

    Science.gov (United States)

    Palermo, M; Armanini, D; Shackleton, C H L; Sorba, G; Cossu, M; Roitman, E; Scaroni, C; Delitala, G

    2002-09-01

    Mineralocorticoid receptors possess the same affinity for aldosterone and for cortisol and preferential binding of aldosterone is modulated by the 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) enzyme, which converts cortisol to its inactive metabolite cortisone. Several endogenous or exogenous compounds able to inhibit the enzyme have been described and, as a consequence, produce the syndrome of apparent mineralocorticoid excess (AME) characterized by hypertension, hypokalemia, volume repletion and suppression of the renin-angiotensin-aldosterone system. High doses of furosemide, a diuretic that works in the luminal surface of the thick ascending limb of Henle's loop, have been reported to inhibit 11 beta-OHSD activity to the same extent as licorice in vivo and in vitro, in rat. The aim of our study was to verify the effect of the drug on 11 beta-OHSD activity in man at the doses currently used in clinical practice. We tested the activity of 11 beta-OHSD following both acute and protracted administration of furosemide. In the acute study, the drug was administered at low (40 mg i.v. in bolo) and high doses (infusion of 10 mg/kg bw i.v for six hours); the protracted furosemide administration consisted in 50 mg/day for 20 days, by mouth. The ratios between the cortisol metabolites tetrahydrocortisol plus allo-tetrahydrocortisol to tetra-hydrocortisone and urinary free cortisol to urinary free cortisone were used to measure the activity of 11 beta-OHSD. Urinary cortisol, cortisone and their metabolites were tested by a gas-chromatographic/mass spectrometric method. Neither acute nor prolonged administration of furosemide did affect the activity of 11 beta-OHSD although the drug was able to modify plasma aldosterone and PRA secretion and to determine hypokalemia. Our results suggest that furosemide does not play a significant role in 11 beta-OHSD modulation in humans, at least at the dosage used in clinical practice. PMID:12373630

  9. URINARY PROSTASIN: A POSSIBLE BIOMARKER FOR RENAL PRESSURE NATRIURESIS IN BLACK ADOLESCENTS

    OpenAIRE

    Zhu, Haidong; Chao, Julie; Guo, Dehuang; Li, Ke; Huang, Ying; Hawkins, Kimberly; Wright, Nikki; Stallmann-Jorgenson, Inger; Yan, Weili; Harshfield, Gregory A.; Dong, Yanbin

    2009-01-01

    Prostasin is a membrane-bound/secretive serine protease interacting with aldosterone and the epithelial sodium channel in the kidney. We and others have previously proposed the concept of stress-induced pressure natriuresis (SIPN) where increased urinary sodium excretion (UNaV) is coupled with elevated blood pressure (BP) in response to behavioral stress in normotensive adolescents. This study thus aimed to test the relationship between prostasin and pressure natriuresis using the SIPN model....

  10. Angiotensin Converting Enzyme Activity in Alopecia Areata

    OpenAIRE

    Mohammad Reza Namazi; Armaghan Ashraf; Farhad Handjani; Ebrahim Eftekhar; Amir Kalafi

    2014-01-01

    Background. Alopecia areata (AA) is a chronic inflammatory disease of the hair follicle. The exact pathogenesis of AA remains unknown, although recent studies support a T-cell mediated autoimmune process. On the other hand, some studies have proposed that the renin-angiotensin-aldosterone system (RAAS) may play a role in autoimmunity. Therefore, we assessed serum activity of angiotensin converting enzyme (ACE), a component of this system, in AA. Methods. ACE activity was measured in the sera ...

  11. Congenital adrenal hyperplasia, CYP21 deficiency, screening and clinical aspects

    OpenAIRE

    Nordenström, Anna

    2001-01-01

    Congenital adrenal hyperplasia (CAH) is a group of recessively inherited disorders. More than 90% of all cases of CAB are caused by 21-hydroxylase deficiency. This enzyme deficiency results in reduced ability to synthesize cortisol and aldosterone and at the same time increased secretion of androgens. There is a wide spectrum of severity of the disease. The most severe forms of CAH are life-threatening, with the risk of a salt crisis in the neonatal period. CAH has special i...

  12. A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient

    OpenAIRE

    Ash, Stephen R.; Singh, Bhupinder; Lavin, Philip T; Stavros, Fiona; Rasmussen, Henrik S.

    2015-01-01

    Hyperkalemia contributes to significant mortality and limits the use of cardioprotective and renoprotective renin–angiotensin–aldosterone blockers. Current therapies are poorly tolerated and not always effective. Here we conducted a phase 2 randomized, double-blind, placebo-controlled dose-escalation study to assess safety and efficacy of ZS-9. This oral selective cation exchanger that preferentially entraps potassium in the gastrointestinal tract was given to patients with stable Stage 3 chr...

  13. Impaired homeostatic mechanism of potassium handling after acute oral potassium load in diabetes mellitus.

    OpenAIRE

    H.J. Kim; Ahn, Y. H.; Park, C H; Kang, C M; Park, H C; Bae, H. Y.; Choi, S. D.

    1993-01-01

    Chronic stable diabetic patients (n = 6) were compared with healthy control subjects (n = 5) after acute oral intake of 50 mEq of potassium chloride (KCl) to investigate for possible derangements of homeostatic responses for acute term (3 hrs) to acute potassium load. Plasma renin activity (PRA), plasma aldosterone (PA), and transtubular potassium concentration gradient (TTKG) known as a useful semiquantative index of distal nephron potassium secretion were measured. All the baseline paramete...

  14. Genetics of intracerebral hemorrhage: Insights from candidate gene approaches

    OpenAIRE

    Baoqiong Liu; Le Zhang; Qidong Yang

    2012-01-01

    Intracerebral hemorrhage (ICH) is a heterogeneous disease with genetic factors playing an important role. Association studies on a wide range of candidate pathways suggest a weak but significant effect for several alleles with ICH risk. Among the most widely investigated genes are those involved in the renin-angiotensin-aldosterone system (e.g., angiotensin-converting enzyme), coagulation pathway (e.g., Factor XIII, Factor VII, platelet-activating factor acetylhydrolase, Factor V Leiden, and ...

  15. Research effects of Testosterone undecanoate administration on metabolic and hormonal parameters at men with an obesity and a chronic heart failure

    Directory of Open Access Journals (Sweden)

    N. P. Goncharov

    2013-01-01

    Full Text Available The ATP III criteria of the metabolic syndrome (MS comprise impaired fasting glucose (> 5.6 nmol/L, waist circumference > 102 cm, hypertension (> 130/85 mm Hg, high triglycerides (> 1.7 nmol/L and low HDL-cholesterol (≤1.03 nmol/L. Aldosterone is currently recognized as a key factor in pathogenesis of cardiovascular diseases and insulin resistance, linking hypertension to MS and obesity. Those results prompted us to study the effects of testosterone administration on metabolic and hormonal parameters, including the effects on serum aldosterone on men with MS, lower-than-normal serum testosterone and chronic heart failure. Patients were included in research is older than 40 years.The study group received two injections with Testosterone undecanoate (1000 mg with three month interval. After 24 weeks of testosterone treatment, there were significant declines of insulin and homeostatic model assessment and of serum aldosterone (but no changes in blood pressure. Serum glucose declined but not significantly. There was a slight increase in LDL-cholesterol and a decrease in triglycerides. Other variables of MS and other biochemical variables did not change. Echocardiographical variables did not change. The AMS showed improvements over the first 3 months after testosterone administration but, while sustained, there was no further improvement. Thus, short-term introduction of Testosterone undecanoate within 24 weeks leads to improvement of some markers of MS, but the most expressed and low-studied effect is inhibitory action of testosterone on the increased concentration of aldosterone in serum.

  16. Research effects of Testosterone undecanoate administration on metabolic and hormonal parameters at men with an obesity and a chronic heart failure

    Directory of Open Access Journals (Sweden)

    N. P. Goncharov

    2014-11-01

    Full Text Available The ATP III criteria of the metabolic syndrome (MS comprise impaired fasting glucose (> 5.6 nmol/L, waist circumference > 102 cm, hypertension (> 130/85 mm Hg, high triglycerides (> 1.7 nmol/L and low HDL-cholesterol (≤1.03 nmol/L. Aldosterone is currently recognized as a key factor in pathogenesis of cardiovascular diseases and insulin resistance, linking hypertension to MS and obesity. Those results prompted us to study the effects of testosterone administration on metabolic and hormonal parameters, including the effects on serum aldosterone on men with MS, lower-than-normal serum testosterone and chronic heart failure. Patients were included in research is older than 40 years.The study group received two injections with Testosterone undecanoate (1000 mg with three month interval. After 24 weeks of testosterone treatment, there were significant declines of insulin and homeostatic model assessment and of serum aldosterone (but no changes in blood pressure. Serum glucose declined but not significantly. There was a slight increase in LDL-cholesterol and a decrease in triglycerides. Other variables of MS and other biochemical variables did not change. Echocardiographical variables did not change. The AMS showed improvements over the first 3 months after testosterone administration but, while sustained, there was no further improvement. Thus, short-term introduction of Testosterone undecanoate within 24 weeks leads to improvement of some markers of MS, but the most expressed and low-studied effect is inhibitory action of testosterone on the increased concentration of aldosterone in serum.

  17. Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination

    OpenAIRE

    Cagnoni, Francesca

    2010-01-01

    Francesca Cagnoni1, Christian Achiri Ngu Njwe1, Augusto Zaninelli4, Alessandra Rossi Ricci1, Diletta Daffra2, Antonio D’Ospina1, Paola Preti3, Maurizio Destro11Internal Medicine, Ospedale Unificato Broni-Stradella, Stradella (PV), Italy; 2Internal Medicine, S.S. Annunziata Hospital, Varzi (PV), Italy; 3Internal Medicine, University of Pavia, Pavia, Italy; 4School of Medicine, University of Florence, Florence, ItalyAbstract: The renin–angiotensin–aldosterone syste...

  18. Raised plasma concentrations of atrial natriuretic peptide are independent of left atrial dimensions in patients with chronic atrial fibrillation.

    OpenAIRE

    Berglund, H; Boukter, S; Theodorsson, E; Vallin, H; Edhag, O

    1990-01-01

    The aim of the present study was to determine whether left atrial size--a likely indicator of atrial stretching--correlates with the plasma concentration of atrial natriuretic peptide and whether this relation is different in patients in sinus rhythm and in those with atrial fibrillation. Arterial plasma concentrations of immunoreactive atrial natriuretic peptide (ir-ANP), adrenaline, noradrenaline, aldosterone, and vasopressin were measured in 13 patients in sinus rhythm without apparent hea...

  19. Charakterisierung der Wirkung von Angiotensin II auf die elektrophysiologischen Eigenschaften reninsezernierenden Zellen der Rattenniere

    OpenAIRE

    Stehle, Alexander

    2006-01-01

    Das Renin-Angiotensin-Aldosteron System (RAAS) ist ein rückgekoppeltes Hormonsystem zur Aufrechterhaltung und Regulation von Plasmavolumen, Plasmaosmolarität und Blutdruck. Die Aspartylprotease Renin wird aus reninsezernierenden Zellen (RSZ) der Vasa afferentia der Nieren freigesetzt. Die Sekretion wird gesteuert durch den Sympathikus, den Blutdruck in den Vasa afferentia, die NaCl-Konzentration an der Macula densa und zirkulierende Hormone, insbesondere Angiotensin II (ANGII). Diese Faktoren...

  20. Complex therapeutic approach in a child with syndromic morbid obesity and acute heart failure

    Directory of Open Access Journals (Sweden)

    Lenuţa Popa

    2011-11-01

    Full Text Available We report a case of a three years old child, a boy with acute heart failure associated at a rarecomplex genetic disorders characterized by severe obesity and hypotonia. The treatment consisted ofacute phase diuretics and cardiotonic drugs, followed by chronic angiotensin-converting-enzyme (ACEinhibitor (Enalapril and an aldosterone inhibitor. The child recovered within a few days and remainedclinically stable, with improvement of clinical, EKG and echocardiographic parameters at 2 and 6 - monthfollow-up.

  1. The role of neuromedin B in the regulation of rat pituitary-adrenocortical function

    OpenAIRE

    Malendowicz, L.K.; Macchi, C; Nussdorfer, G G; Nowak, M.

    1996-01-01

    The effects of a 7-day administration of neuromedin B (NMB) andlor ( ~ ~D-rphe~12,)-b ornbesin, an NMB-receptor antagonist (NMB-A) on the function of pituitary-adrenocortical axis were investigated in the rat. NMB raised the plasma concentration of aldosterone, without affecting that of ACTH or corticosterone; the simultaneous administration of NMB-A prevented the effect of NMB. Neither NMB nor NMB-A treatments induced significant changes in adenohypophysis...

  2. Changes in cardiovascular risk factors and hormones during a comprehensive residential three month kriya yoga training and vegetarian nutrition.

    Science.gov (United States)

    Schmidt, T; Wijga, A; Von Zur Mühlen, A; Brabant, G; Wagner, T O

    1997-01-01

    In participants of a comprehensive residential three month yoga and mediation training programme living on a low fat lacto-vegetarian diet changes in cardiovascular risk factors and hormones were studied. Substantial risk factor reduction was found. Body mass index, total serum and LDL cholesterol, fibrinogen, and blood pressure were significantly reduced especially in those with elevated levels. Urinary excretion of adrenaline, noradrenaline, dopamine, aldosterone, as well as serum testosterone and luteinizing hormone levels were reduced, while cortisol excretion increased significantly. PMID:9401632

  3. Functioning adrenal myelolipoma: A rare cause of hypertension

    OpenAIRE

    Nagendar Jakka; J Venkateshwarlu; Naga Satyavani; Neelaveni, K.; Jayanthy Ramesh

    2013-01-01

    Co-occurrence of adrenal incidentaloma with hypertension calls for evaluation of endocrine causes including pheochromocytoma, Cushing′s disease, and primary aldosteronism. We are reporting 40-years-old man who presented with hypertension and adrenal mass. He had elevated metanephrines, histology of resected adrenal mass revealed adrenal myelolipoma, and immuno-histochemistry was positive for chromogranin A. Both his blood pressure and urinary metanephrines returned to normal after surgery. Th...

  4. The renoprotective effects of sulodexide

    OpenAIRE

    Olde Engberink RH; Vogt L

    2016-01-01

    Rik HG Olde Engberink, Liffert Vogt Department of Internal Medicine, Section of Nephrology, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsIn their meta-analysis, Li et al1 reported a renoprotective benefit of sulodexide in patients with diabetic nephropathy. This was the first meta-analysis to evaluate the potential anti-albuminuric effects of sulodexide in such patients. Albuminuria reduction with renin–angiotensin–aldosterone system inhibit...

  5. Addition of Angiotensin Receptor Blockade or Mineralocorticoid Antagonism to Maximal Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy

    OpenAIRE

    Mehdi, Uzma F.; Adams-Huet, Beverley; Raskin, Philip; Vega, Gloria L.; Toto, Robert D.

    2009-01-01

    Aldosterone promotes glomerular and tubular sclerosis independent of angiotensin II in animal models of diabetic nephropathy. Most human studies testing the renoprotective benefit of adding an angiotensin receptor blocker or a mineralocorticoid receptor antagonist to a regimen based on inhibition of angiotensin-converting enzyme (ACE) used relatively low doses of ACE inhibitors. Furthermore, these studies did not determine whether antiproteinuric effects were independent of BP lowering. We co...

  6. Ciblage Tissu-Spécifique des Cascades Enzymatiques de l’Angiotensinogène dans l’Athérome Humain

    OpenAIRE

    Nehme, Ali

    2015-01-01

    Atherosclerosis remains and continues to be the leading cause of death and disability in the world. The implication of Renin-angiotensin-aldosterone system (RAAS) in the development of the disease is well experimentally and clinically documented. However, due to the complexity of the system, these studies remain dispersed and give no clear global view of the association between the system and the disease. In this regard, we studied the functional organization of a set of 37 genes encoding cla...

  7. Percutaneous computed tomography-guided ethanol injection in adrenal benign functioning tumors

    International Nuclear Information System (INIS)

    Objective: To evaluate the effects of percutaneous computed tomography-guided ethanol injection (PEI-CT) in adrenal benign functioning tumors. Methods: Twenty cases of adrenal benign functioning tumors were treated by the therapy of PEI-CT. Among them, 5 cases were pheochromocytomas, and 15 cases were aldosteronomas. After the treatment, the change of blood pressure, aldosterone plasma levels, potassium plasma levels, and catecholamines urine levels was investigated. Both plain and enhanced CT scans were performed before and after the treatment to evaluate the changes of the size and necrosis in the tumors. Results: Normalization of blood pressure and catecholamines urine levels was observed in 5 cases of pheochromocytoma during 6-19 months' follow up after the treatment. In the 15 cases of aldosteronoma, aldosterone plasma levels reduced with potassium plasma levels increasing to the normal range within 5-7 days after the treatment. Aldosterone plasma levels increased with potassium plasma levels reduced again in 7 months after the treatment in one cases, aldosterone plasma levels and potassium plasma levels returned to the normal range after the second treatment. Hypertension returned to normal in 13 cases of aldosteronoma, and one case maintained normal blood pressure (BP) only under the condition of taking lower dosage of spironolactone within 7-15 days after the treatment, and one month later, the blood pressure of the case become normal without taking any antihypertensive drugs. The other case maintained normal blood pressure in the need of taking lower dosage of antihypertensive after the treatment. CT scan showed total necrosis of tumors in 15 cases and majority necrosis in 5 case within 7-15 days after the treatment. Conclusion: The therapy of percutaneous computed tomography-guided ethanol injection in adrenal benign functioning tumors shows satisfactory effects with the advantages of easy manipulation, safety, less injury and cost

  8. Pathophysiologie und therapeutische Modulation der T-Helferzellenfunktion bei der Herzinsuffizienz

    OpenAIRE

    Savvatis, Konstantinos

    2016-01-01

    Chronic heart failure belongs to commenest cardiovascular diseases in the modern world which is associated with high morbidity and mortality. Despite the development of modern therapeutic options, treatment of heart failure remains unchanged over the past 30 years without any improvement in the prognosis of the patients. Blockade of the renin-angiotensin-aldosterone-system and the beta-adrenergic system remains the mainstream medical therapy. Therefore, it is of utmost importance to further e...

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

    LENUS (Irish Health Repository)

    Collier, Patrick

    2012-04-01

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

  10. CT localisation of an aldosteronoma in a 10-year-old boy

    International Nuclear Information System (INIS)

    An adrenal adenoma is a rare cause of primary aldosteronism in children but very important to diagnose as the cure rate is 100% by surgery. The advent of high resolution CT scanners should facilitate very much the role of the radiologist and diminish the delay of diagnosis. We report the case of a 10-year-old boy with such an entity where the aldosteronoma was shown by CT pre-operatively. (orig.)

  11. Fistular onion stalk extract exhibits anti-atherosclerotic effects in rats

    OpenAIRE

    He, Benhong; Hao, Jianjun; Sheng, Weiwei; XIANG, YUANCAI; ZHANG, JIEMEIA; Zhu, Hao; TIAN, JINGCHENG; Zhu, Xu; Feng, Yunxia; XIA, HAO

    2014-01-01

    Fistular onion stalk is used as a traditional herbal medicine, and its extract exhibits certain beneficial effects on cardiovascular disease. In this study, the effects of fistular onion stalk extract on the pathological features, circulating inflammatory cytokines, local renin-angiotensin-aldosterone system (RAAS) and signaling pathway activities were examined using an in vivo model of atherosclerosis. Atherosclerosis of the aorta was induced by loading Sprague Dawley rats with a high-fat di...

  12. Lack of an Association between CYP11B2 C-344T Gene Polymorphism and Ischemic Stroke: A Meta-Analysis of 7,710 Subjects

    OpenAIRE

    Pi, Yan; Zhang, Li-li; Chang, Kai; Guo, Lu; Liu, Yun; Li, Bing-Hu; Cao, Xiao-Jie; Liao, Shao-Qiong; Chang-yue GAO; Li, Jing-Cheng

    2013-01-01

    Background The association between aldosterone synthase (CYP11B2) C-344T gene polymorphism and ischemic stroke remains controversial and ambiguous. To better explain the association between CYP11B2 polymorphism and ischemic stroke risk, a meta-analysis was performed. Methods Based on comprehensive searches of Medline, Embase, Web of Science, CNKI and CBM databases, we identified and abstracted outcome data from all articles to evaluate the association between CYP11B2 polymorphism and ischemic...

  13. Effects of intravenous endralazine in essential hypertension.

    OpenAIRE

    Hoffmann, J J; Thien, T.; van t'Laar, A

    1983-01-01

    The effects of endralazine, administered intravenously, on blood pressure, heart rate, forearm blood flow, plasma renin activity, aldosterone, adrenaline and noradrenaline were studied in five patients with essential hypertension. Endralazine reduced peripheral vascular resistance, resulting in decrease in mean arterial pressure from 141 to 116 mm Hg and increase in heart rate from 67 to 92 beats/min. Plasma renin activity, adrenaline and noradrenaline increased significantly after endralazin...

  14. L’hypertension artérielle et les désordres vasculaires induits par l'érythropoïétine recombinante humaine et le système rénine-angiotensine-aldostérone : Effet de l’exercice et des cellules T régulatrices

    OpenAIRE

    Barhoumi, Tlili,

    2011-01-01

    Hypertension (HTN) is one of the most frequent disease and is of greatest concern in Western countries.HTN is often associated with overweight, kidney, heart and endocrine system disease. Vasculardisorders, associated with HTN induced by erythropoietin (r-HuEPO) treatment in chronic kidneydisease or in case of disruption of the renin-angiotensin-aldosterone system (RAAS), associated increasein arterial stiffness, endothelial dysfunction, unbalanced endothelin-1/nitric oxide ratio (ET-1/NO) an...

  15. Effect of angiotensin receptor blockade on endothelial function: focus on olmesartan medoxomil

    OpenAIRE

    Carlos Ferrario

    2009-01-01

    Carlos FerrarioHypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC, USAAbstract: Endothelial dysfunction is the common link between cardiovascular disease risk factors and the earliest event in the cascade of incidents that results in target organ damage. Angiotensin II, the terminal pressor effector arm of the renin-angiotensin-aldosterone system, increases blood pressure (BP) by vasoconstriction and sodium and fluid retention, and has a pro...

  16. Hormonal and Thirst Modulated Maintenance of Fluid Balance in Young Women with Different Levels of Habitual Fluid Consumption

    OpenAIRE

    Johnson, Evan C.; Colleen X. Muñoz; Liliana Jimenez; Laurent Le Bellego; Brian R Kupchak; Kraemer, William J.; Casa, Douglas J.; Maresh, Carl M.; Armstrong, Lawrence E.

    2016-01-01

    Background: Surprisingly little is known about the physiological and perceptual differences of women who consume different volumes of water each day. The purposes of this investigation were to (a) analyze blood osmolality, arginine vasopressin (AVP), and aldosterone; (b) assess the responses of physiological, thirst, and hydration indices; and (c) compare the responses of individuals with high and low total water intake (TWI; HIGH and LOW, respectively) when consuming similar volumes of water...

  17. The neprilysin pathway in heart failure: a review and guide on the use of sacubitril/valsartan

    OpenAIRE

    Jhund, Pardeep S; McMurray, John J V

    2016-01-01

    Inhibition of neurohumoural pathways such as the renin angiotensin aldosterone and sympathetic nervous systems is central to the understanding and treatment of heart failure (HF). Conversely, until recently, potentially beneficial augmentation of neurohumoural systems such as the natriuretic peptides has had limited therapeutic success. Administration of synthetic natriuretic peptides has not improved outcomes in acute HF but modulation of the natriuretic system through inhibition of the enzy...

  18. Spirolactone provides protection from renal fibrosis by inhibiting the endothelial–mesenchymal transition in isoprenaline-induced heart failure in rats

    OpenAIRE

    Zhou, Hao; Xi, Dan; Liu, Jichen; Zhao, Jinjin; Chen, Si; Guo, Zhigang

    2016-01-01

    Background Fibrosis results in excessive accumulation of extracellular matrix proteins, collagen component alteration, and abnormalities in structure and is partly derived from a process called the endothelial–mesenchymal transition involving transforming growth factor β (TGF-β). We investigated whether spironolactone, an aldosterone receptor blocker, attenuated isoprenaline (Iso)-induced heart failure in rats and also studied the mechanism for the same. Methods Sprague–Dawley rats were subcu...

  19. Effects of felodipine on atrial natriuretic peptide in hypertensive non-insulin dependent diabetes mellitus.

    OpenAIRE

    Jeffrey, R F; Capewell, S; Brown, J.; Collier, A.; Hajducka, C; Lee, M R

    1990-01-01

    Eighteen patients with non-insulin dependent diabetes mellitus and hypertension were treated during two 4 week periods with the calcium antagonist felodipine or placebo in a double-blind, randomised, cross-over study. Mean systemic blood pressure was significantly lower on felodipine, without producing a deleterious effect on diabetic control. Felodipine was associated with an increment in plasma renin concentration but plasma aldosterone and the renal outputs of sodium and dopamine were simi...

  20. HISTORY OF THE ENDOCRINE SURGERY (II)

    OpenAIRE

    E. Tarcoveanu; A. Vasilescu; Oana Epure

    2005-01-01

    The history of the endocrine surgery is recent, with the discovery of glands and hormones at the beginning of the twentieth century. Most of the major endocrine glands were described anatomically around 1900. The hormones were identified during the first decades of the twentieth century. In 1922 a Romanian doctor, Paulescu, discovered a hypoglycemiant hormone, the insulin. Other hormones like aldosterone and cortisol were discovered after a few years. The diffuse gastrointestinal glandular sy...

  1. Outcomes Of Neoadjuvant Chemoradiotherapy In Patients With Locally Advanced Rectal Cancer: A Single Institution Experience.

    OpenAIRE

    Morcalı, Hasan; Figen, Metin; Okumus, Ayşe; Arslan, Nazmiye Deniz; Kızılkaya, Hazım Orhan

    2015-01-01

    Diabetes is a problem of public health that increases due to changes of life and eating habits. One of the most important complications of this disease is cardiomyopathy. Reasons that bring out diabetic cardiomyopathy include hyperglycemia, reaktive oksigen species (ROS), activation of DAG/PKC (diachyl glicerol/protein kinase C) pathway, upregulation of reninangiotensin-aldosteron system, fail of response to hypoxia , endothelial disfunction and otonomic neuropathy. This review aims to develo...

  2. Autosomal dominant polycystic kidney disease: New insights into treatment

    OpenAIRE

    Imed Helal

    2013-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the world′s most common inherited kidney disease. An increasing number of animal and human studies have enhanced our understanding of the molecular and cellular pathology of ADPKD. New treatment options are being tested in clinical trials in spite of the failure of mammalian target of rapamycin inhibitor therapy. The main and most effective therapy remains control of hypertension by renin-angiotensin-aldosterone system (RAAS) blockade. T...

  3. Role of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in hypertension of chronic kidney disease and renoprotection. Study results

    OpenAIRE

    Baltatzi, M; Savopoulos, Ch; Hatzitolios, A

    2011-01-01

    Chronic kidney disease (CKD) is a global health problem associated with considerable morbidity and mortality and despite advances in the treatment of end stage renal disease (ESRD) mechanisms to prevent and delay its progression are still being sought. The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in many of the pathophysiologic changes that lead to progression of renal disease. Traditionally RAAS was considered as an endocrine system and its principal role was to maint...

  4. Smooth muscle cell mineralocorticoid receptors: role in vascular function and contribution to cardiovascular disease

    OpenAIRE

    McCurley, Amy; McGraw, Adam; Pruthi, Dafina; Jaffe, Iris Z.

    2013-01-01

    The mineralocorticoid receptor (MR), a member of the steroid receptor family, regulates blood pressure by mediating the effects of the hormone aldosterone on renal sodium handling. In recent years, it has become clear that MR is expressed in vascular smooth muscle cells (SMC) and interest has grown in understanding the direct role of SMC MR in regulating vascular function. This interest stems from multiple clinical studies where MR inhibitor treatment reduced the incidence of cardiovascular e...

  5. Hyperaldosteronism and cardiovascular risk in patients with autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Lai, Silvia; Petramala, Luigi; Mastroluca, Daniela; Petraglia, Emanuela; Di Gaeta, Alessandro; Indino, Elena; Panebianco, Valeria; Ciccariello, Mauro; Shahabadi, Hossein H; Galani, Alessandro; Letizia, Claudio; D'Angelo, Anna Rita

    2016-07-01

    Hypertension is commonly associated with autosomal dominant polycystic kidney disease (ADPKD), often discovered before the onset of renal failure, albeit the pathogenetic mechanisms are not well elucidated. Hyperaldosteronism in ADPKD may contribute to the development of insulin resistance and endothelial dysfunction, and progression of cardiorenal disease. The aim of study was to evaluate the prevalence of primary aldosteronism (PA) in ADPKD patients and identify some surrogate biomarkers of cardiovascular risk.We have enrolled 27 hypertensive ADPKD patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, evaluating the renin-angiotensin-aldosterone system (RAAS), inflammatory indexes, nutritional status, homocysteine (Hcy), homeostasis model assessment-insulin resistance (HOMA-IR), mineral metabolism, microalbuminuria, and surrogate markers of atherosclerosis [carotid intima media thickness (cIMT), ankle/brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI) and left ventricular mass index (LVMI)]. Furthermore, we have carried out the morpho-functional magnetic resonance imaging (MRI) with high-field 3 T Magnetom Avanto.We have divided patients into group A, with normal plasma aldosterone concentration (PAC) and group B with PA, present in 9 (33%) of overall ADPKD patients. Respect to group A, group B showed a significant higher mean value of LVMI, HOMA-IR and Hcy (P = 0.001, P = 0.004, P = 0.018; respectively), and a lower value of FMD and 25-hydroxyvitamin D (25-OH-VitD) (P = 0.037, P = 0.019; respectively) with a higher prevalence of non-dipper pattern at Ambulatory Blood Pressure Monitoring (ABPM) (65% vs 40%, P FMD, and 25-OH-VitD, considered as surrogate markers of atherosclerosis, compared to ADPKD patients with normal PAC values. Our results indicate a higher overall cardiovascular risk in ADPKD patients with inappropriate aldosterone secretion, and a screening for PA in all patients with

  6. Effects of Ramiprilat-Coated Stents on Neointimal Hyperplasia, Inflammation, and Arterial Healing in a Porcine Coronary Restenosis Model

    OpenAIRE

    Hong, Young Joon; Jeong, Myung Ho; Song, Sun-Jung; Sim, Doo Sun; Kim, Jung Ha; Lim, Kyung Seob; Hachinohe, Daisuke; Ahmed, Khurshid; Hwang, Seung Hwan; Lee, Min Goo; Ko, Jum Suk; Park, Keun-Ho; Yoon, Hyun Ju; Yoon, Nam Sik; Kim, Kye Hun

    2011-01-01

    Background and Objectives The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of neointimal hyperplasia, and a role for angiotensin II in the migration and proliferation of vascular smooth muscle cells in restenotic lesions has been proposed. The aim of this study was to determine the anti-proliferative and anti-inflammatory effects of ramiprilat-coated stents in a porcine coronary overstretch restenosis model. Subjects and Methods Pigs were randomized into two gr...

  7. Hierarchical study of Guyton Circulatory Model

    OpenAIRE

    Assar, Rodrigo; Soueidan, Hayssam; Sherman, David James

    2009-01-01

    This article presents an initial study of the Guyton Circulatory Model using BioRica. This model consists of 18 connected modules, each of which caracterise a separate physiological subsystem. We have focused the present analysis in the Renin- Angiotensin-Aldosterone System (RAAS). The use of BioRica allowed us to build an hierarchical model for this system by means of directly mapping modules to BioRica nodes. The results of each node were validated by comparison with published results.

  8. Vesicoureteral Reflux, a Scarred kidney, and Minimal Proteinuria: An Unusual Cause of Adult Secondary Hypertension

    OpenAIRE

    Apurv Khanna; Shaifali Sandal

    2011-01-01

    Hypertension affects about 65 million individuals in the United States. In adult patients, primary aldosteronism and renovascular causes are described as most prevalent. Vesicoureteral reflux as a cause of hypertension, while commonly described in pediatric populations, is less prevalent in the adult population especially in the absence of proteinuria. We present the case of a 31-year-old female presenting with early onset hypertension. Workup for renovascular hypertension was unrevealing. Sh...

  9. Nephroprotection by Hypoglycemic Agents: Do We Have Supporting Data?

    OpenAIRE

    Jose Luis Górriz; Javier Nieto; Navarro-González, Juan F; Pablo Molina; Alberto Martínez-Castelao; Pallardó, Luis M.

    2015-01-01

    Current therapy directed at delaying the progression of diabetic nephropathy includes intensive glycemic and optimal blood pressure control, renin angiotensin-aldosterone system blockade and multifactorial intervention. However, the renal protection provided by these therapeutic modalities is incomplete. There is a scarcity of studies analysing the nephroprotective effect of antihyperglycaemic drugs beyond their glucose lowering effect and improved glycaemic control on the prevention and prog...

  10. Efficacy of adrenal venous sampling is increased by point of care cortisol analysis

    OpenAIRE

    Viste, Kristin; Grytaas, Marianne A; Jørstad, Melissa D; Jøssang, Dag E; Høyden, Eivind N; Fotland, Solveig S; Jensen, Dag K; Løvås, Kristian; Thordarson, Hrafnkell; Almås, Bjørg; Mellgren, Gunnar

    2013-01-01

    Primary aldosteronism (PA) is a common cause of secondary hypertension and is caused by unilateral or bilateral adrenal disease. Treatment options depend on whether the disease is lateralized or not, which is preferably evaluated with selective adrenal venous sampling (AVS). This procedure is technically challenging, and obtaining representative samples from the adrenal veins can prove difficult. Unsuccessful AVS procedures often require reexamination. Analysis of cortisol during the procedur...

  11. Relative value of computed tomography scanning and venous sampling in establishing the cause of primary hyperaldosteronism

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the relative merits of the postural simulation test, adrenal computed tomography (CT) and venous sampling in the differential diagnosis of patients presenting with primary hyperaldosteronism. The records of 20 patients presenting with primary hyperaldosteronism were reviewed retrospectively. There were 15 patients with a unilateral aldosterone-producing adenoma (APA), 4 patients with idiopathic hyperaldosteronism (IHA) and 1 patient with primary adrenal hyperplasia (PAH). Bilateral venous sampling of adrenal veins was attempted in all patients and blood collected for aldosterone and cortisol assay. Plasma aldosterone concentration increased after 4 h of standing in all cases of hyperplasia, but was also demonstrated in 10/15 patients with a surgically-proven APA. CT scanning correctly identified all 15 cases of APA and also classified correctly the remaining 5 cases of hyperplasia. CT scanning may be used alone to confirm the cause of hyperaldosteronism where postural studies suggest an adrenal adenoma, and such patients may be considered for early surgery. 21 refs

  12. Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms.

    Science.gov (United States)

    Hall, John E; do Carmo, Jussara M; da Silva, Alexandre A; Wang, Zhen; Hall, Michael E

    2015-03-13

    Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65% to 75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include (1) physical compression of the kidneys by fat in and around the kidneys, (2) activation of the renin-angiotensin-aldosterone system, and (3) increased sympathetic nervous system activity. Activation of the renin-angiotensin-aldosterone system is likely due, in part, to renal compression, as well as sympathetic nervous system activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for sympathetic nervous system activation in obesity have not been fully elucidated but may require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes mellitus, and inflammation. Unless effective antiobesity drugs are developed, the effect of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase. PMID:25767285

  13. 131I-iodocholesterol (NP-59) scintigraphy in adrenocortical diseases

    International Nuclear Information System (INIS)

    The diagnostic usefulness of adrenal imaging with 131I-iodocholesterol (NP-59) is now well established. In order to correlate histopathology with the adrenal scan the authors examine and report their experience in 37 patients with surgically proven adrenal lesions or pituitary adenomas. This series included 24 patients with Cushing's syndrome: 14 caused by benign adrenal adenoma and 10 due to bilateral pituitary-ACTH-dependent adrenocortical hyperplasia. Ten patients with primary aldosteronism were submitted to surgery which confirmed the presence of aldosterone-producing adrenal adenomas. Two women with hyperandrogenism (due to virilizing ovarian tumors) had normal adrenals but the ovarian stromal luteoma markedly concentrated the iodocholesterol while the arrhenoblastoma did not. A patient with adrenal hematoma is also included in this report. The overall histopathological correlation with the radiocholesterol scintiscan yields an accuracy in our series of 97 percent (36/37). The false-negative adrenal scan (also missed by other non-invasive techniques) occurred in a patient with an aldosterone-producing adrenal adenoma measuring 1.0 x 1.5 cm

  14. /sup 131/I-iodocholesterol (NP-59) scintigraphy in adrenocortical diseases

    Energy Technology Data Exchange (ETDEWEB)

    Taillefer, R.; Soucy, J.P.; Eybalin, M.C.; Levasseur, A. (Hopital Maisonneuve-Rosemont, Montreal, Quebec (Canada))

    1983-06-01

    The diagnostic usefulness of adrenal imaging with /sup 131/I-iodocholesterol (NP-59) is now well established. In order to correlate histopathology with the adrenal scan the authors examine and report their experience in 37 patients with surgically proven adrenal lesions or pituitary adenomas. This series included 24 patients with Cushing's syndrome: 14 caused by benign adrenal adenoma and 10 due to bilateral pituitary-ACTH-dependent adrenocortical hyperplasia. Ten patients with primary aldosteronism were submitted to surgery which confirmed the presence of aldosterone-producing adrenal adenomas. Two women with hyperandrogenism (due to virilizing ovarian tumors) had normal adrenals but the ovarian stromal luteoma markedly concentrated the iodocholesterol while the arrhenoblastoma did not. A patient with adrenal hematoma is also included in this report. The overall histopathological correlation with the radiocholesterol scintiscan yields an accuracy in our series of 97 percent (36/37). The false-negative adrenal scan (also missed by other non-invasive techniques) occurred in a patient with an aldosterone-producing adrenal adenoma measuring 1.0 x 1.5 cm.

  15. The spironolactone renaissance.

    Science.gov (United States)

    Doggrell, S A; Brown, L

    2001-05-01

    Until recently, spironolactone was considered only as an antagonist at the aldosterone receptors of the epithelial cells of the kidney and was used clinically in the treatment of hyperaldosteronism and, occasionally, as a K(+)-sparing diuretic. The spironolactone renaissance started with the experimental finding that spironolactone reversed aldosterone-induced cardiac fibrosis by a cardiac action. Experimentally, spironolactone also has direct effects on blood vessels. Spironolactone reduces vascular fibrosis and injury, inhibits angiogenesis, reduces vascular tone and reduces portal hypertension. The rationale for the Randomized Aldactone Evaluation Study (RALES) of spironolactone in heart failure was that 'aldosterone escape' occurred through non-angiotensin II mechanisms. The RALES clinical trial was stopped early when it was shown that there was a 30% reduction in risk of death among the spironolactone patients. In RALES, spironolactone also reduced hospitalisation for worsening heart failure and improved the symptoms of heart failure. Other recent clinical trials have shown that spironolactone reduces cardiac and vascular collagen turnover, improves heart variability, reduces ventricular arrhythmias, improves endothelial dysfunction and dilates blood vessels in human heart failure and these effects probably all contribute to the increased survival in heart failure. Spironolactone may also be useful in the treatment of left ventricular hypertrophy, portal hypertension and cirrhosis. There have also been some recent small clinical trials of spironolactone as an anti-androgen showing potential in acne, hirsutism and precocious puberty. PMID:11322868

  16. Pseudohypoaldosteronism: Case Report

    Directory of Open Access Journals (Sweden)

    Kazım Küçüktaşçı

    2009-12-01

    Full Text Available Introduction: Pseudohypoaldosteronism is a disease which occurs as a result of peripheral resistance to aldosterone and is characterised by salt wasting. Case Report: Hyponatremia, hyperkalemia, metabolic acidosis, high renin and aldosterone levels were determined in the patient admitted with decrease in sucking and getting sleepy during breast-feeding. The case was diagnosed as systemic form of pseudohypoaldosteronism. His treatment was continued with oral salt. Conclusion: Pseudohypoaldosteronism has three types as primary, secondary and Gordon syndrome. Primary form is due to epithelial sodium channel and mineralocorticoid receptor gene mutation, whilst secondary form is frequently caused by urinary malformation and urinary tract infections. In Gordon syndrome, plasma aldosterone level is usuallly normal, and plasma renin activity is depressed, there is an adequate response to mineralocorticoids. Probability of secondary pseudohypoaldosteronism was investigated at the same time because of the urinary infection present in our subject. The patient was accepted as systemic form of primary pseudohypoaldosteronism because of positive sweat test result and prolonged salt necessity. (Journal of Current Pediatrics 2009; 7: 151-3

  17. Familial hyperaldosteronism.

    Science.gov (United States)

    Stowasser, M; Gordon, R D

    2001-09-01

    Primary aldosteronism (PAL) may be as much as ten times more common than has been traditionally thought, with most patients normokalemic. The study of familial varieties has facilitated a fuller appreciation of the nature and diversity of its clinical, biochemical, morphological and molecular aspects. In familial hyperaldosteronism type I (FH-I), glucocorticoid-remediable PAL is caused by inheritance of an ACTH-regulated, hybrid CYP11B1/CYP11B2 gene. Genetic testing has greatly facilitated diagnosis. Hypertension severity varies widely, demonstrating relationships with gender, affected parent's gender, urinary kallikrein level, degree of biochemical disturbance and hybrid gene crossover point position. Analyses of aldosterone/PRA/cortisol 'day-curves' have revealed that (1) the hybrid gene dominates over wild type CYP11B2 in terms of aldosterone regulation and (2) correction of hypertension in FH-I requires only partial suppression of ACTH, and much smaller glucocorticoid doses than those previously recommended. Familial hyperaldosteronism type II is not glucocorticoid-remediable, and is clinically, biochemically and morphologically indistinguishable from apparently sporadic PAL. In one informative family available for linkage analysis, FH-II does not segregate with either the CYP11B2, AT1 or MEN1 genes, but a genome-wide search has revealed linkage with a locus in chromosome 7. As has already occurred in FH-I, elucidation of causative mutations is likely to facilitate earlier detection of PAL and other curable or specifically treatable forms of hypertension. PMID:11595502

  18. Identification of the mineralocorticoid receptor in human spermatozoa.

    Science.gov (United States)

    Fiore, Cristina; Sticchi, Daniele; Pellati, Donatella; Forzan, Sante; Bonanni, Guglielmo; Bertoldo, Alessandro; Massironi, Michele; Calò, Lorenzo; Fassina, Ambrogio; Rossi, Gian Paolo; Armanini, Decio

    2006-10-01

    Aldosterone seems to play a role in the regulation of the electrolyte content of sperm and in the motility of spermatozoa. The aim of the study was to evaluate the presence of the mineralocorticoid receptor (MR) in human ejaculated spermatozoa. We have assayed MR on spermatozoa of freshly ejaculated sperm from healthy donors. The identification of MR was made by using immunohistochemistry and immunofluorescence analyses, while MR mRNA expression was evaluated by real-time PCR assay. The immunohistochemical and immunofluorescence analyses showed positive staining both in the midpiece and in the tail of the spermatozoa. Relative quantification of MR by using real-time PCR shows that the mRNA expression of MR in spermatozoa is lower than in mononuclear leukocytes (positive controls). Sequencing showed complete identity between the sequence obtained from spermatozoa and the human MR cDNA sequence. Further studies should be performed in order to elucidate a possible physiological role of aldosterone in regulating electrolyte concentration, and the pro-oxidant effect of excess aldosterone in this new target tissue. PMID:16964418

  19. Transient Pseudohypoaldosteronism due to Urinary Tract Infection in Infancy: A Report of 4 Cases

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    Kaplowitz Paul

    2009-05-01

    Full Text Available Hyponatremia with hyperkalemia in infancy is an uncommon but life-threatening occurrence. In the first weeks of life, this scenario is often associated with aldosterone deficiency due to salt-wasting congenital adrenal hyperplasia. However, alternative diagnoses involving inadequate mineralocorticoid secretion or action must be considered, particularly for infants one month of age or older. We report four infants who presented with profound hyponatremia accompanied by urinary tract infection, ultimately leading to the diagnosis of transient pseudohypoaldosteronism. Our cases provide support for the idea that the renal tubular resistance to aldosterone is due to urinary tract infection itself rather than to underlying urinary tract anomalies typically found in these infants. Awareness of this condition is important so that serum aldosterone, urine sodium, and urine cultures may be obtained immediately in any infant presenting with hyponatremia and hyperkalemia in whom a diagnosis of congenital adrenal hyperplasia was not found. Adequate replacement with intravenous saline and antibiotic therapy is sufficient to correct sodium levels over 24–48 hours.

  20. Hyperaldosteronism: Screening and Diagnostic Tests.

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    Sabbadin, Chiara; Fallo, Francesco

    2016-06-01

    Primary aldosteronism (PA) is the most common secondary cause of hypertension, accounting for 10 % of hypertensives and 20 % of those with drug-resistant hypertension. Aldosterone excess is associated with the development of adverse cardiovascular, renal and metabolic effects that are partly independent of its effect on blood pressure. Guidelines recommended wider screening for PA in an effort to maximize detection of patients who may benefit from optimal, specific management. All patient groups with increased prevalence of PA, including hypertensive patients with type 2 diabetes mellitus and those with obstructive sleep apnea, should be carefully screened for PA. Screening with aldosterone-to-renin ratio (ARR) is the most practical and informative initial test. Subsequent confirmatory tests are: (1) oral salt loading; (2) saline infusion; (3) captopril challenge and (4) fludrocortisone suppression test. Confirmation of PA can avoid that patients with a false positive ARR would inappropriately undergo costly and harmful lateralization procedures. If confirmatory testing is positive, further investigations are directed toward determining the subtype of PA, as the treatment differs for each subtype. PMID:26971505

  1. A reappraisal of loop diuretic choice in heart failure patients

    Science.gov (United States)

    Buggey, Jonathan; Mentz, Robert J.; Pitt, Bertram; Eisenstein, Eric L.; Anstrom, Kevin J.; Velazquez, Eric J.; O’Connor, Christopher M.

    2015-01-01

    The health and economic burden of heart failure is significant, and continues to grow each year. Loop diuretics are an integral part of symptom management in heart failure. Furosemide is used disproportionately compared to other loop diuretics and there is currently no guidance for physicians regarding which agent to choose. However, there exist pharmacologic differences as well as other mechanistic differences that appear to favor torsemide use over furosemide. Compared to furosemide, torsemide improves surrogate markers of heart failure severity such as left ventricular function, plasma brain natriuretic peptide levels, and New York Heart Association functional class and may also reduce hospitalizations, readmissions, and mortality. Data suggest these benefits could be mediated through torsemide’s ability to positively affect the renin-angiotensin-aldosterone system. Specifically, torsemide has been shown to inhibit aldosterone secretion, synthesis, and receptor binding in vitro, as well as decrease transcardiac extraction of aldosterone, myocardial collagen production and cardiac fibrosis in patients with heart failure. We identified pertinent literature using keyword MEDLINE searches and cross-referencing prior bibliographies. We summarize the available data suggesting potential benefits with torsemide over furosemide, and call attention to the need for a reappraisal of diuretic use in heart failure patients and also for a well powered, randomized control trial assessing torsemide versus furosemide use. PMID:25728721

  2. A novel method for analysing key corticosteroids in polar bear (Ursus maritimus) hair using liquid chromatography tandem mass spectrometry.

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    Weisser, Johan J; Hansen, Martin; Björklund, Erland; Sonne, Christian; Dietz, Rune; Styrishave, Bjarne

    2016-04-01

    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 as a useful tool for long-term and retrospective information. We developed a combined pressurized liquid extraction (PLE)-solid phase extraction (SPE) procedure for corticosteroid extraction and clean-up followed by high pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) analysis. 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 sample pooled from four East Greenland polar bears. Herein cortisol and corticosterone were successfully determined in levels of 0.32±0.02ng/g hair and 0.13±0.02ng/g hair, respectively. Aldosterone was below limit of detection (LODpolar bears was consistent with cortisol levels previously determined in the Southern Hudson Bay and James Bay in Canada using ELISA kits. PMID:26945133

  3. Saturation analysis studies of corticosteroid levels in normal Greek subjects and in subjects with haemolytic diseases

    International Nuclear Information System (INIS)

    Between 1970 and 1974 a saturation analysis for cortisol in plasma and free cortisol in urine, and a radioimmunoassay method for aldosterone in plasma and urine were developed. In order to permit a comparative evaluation it was necessary to study corticosteroids, diurnal rhythm and the probable effect of a siesta on this rhythm both in normal subjects and in patients suffering from hemic diseases, in particular from sickle-cell anemia. Saturation assay for cortisol, using serum from pregnant women as source of transcortin, and radioimmunoassay for aldosterone were the basic methods used. Serum cortisol was estimated twice a day (8-9 a.m. and 5-6 p.m.). Cortisol and aldosterone were also estimated in serum and in urine before and after adrenalin stimulation with ACTH. No significant influence of a siesta on the diurnal rhythm of cortisol was observed, nor did the levels of serum cortisol or the diurnal rhythm appear affected in congenital hemolytic anemias, following adrenalin stimulation. The report lists experimental results briefly and refers to a paper in which these are published in more detail

  4. Effects of general anaesthesia on endocrine system of body in paediatric patients during surgical intervention

    International Nuclear Information System (INIS)

    A total of 50 children (mean age 7, range 2-12 years), undergoing minor to major surgical operations were evaluated for hormonal changes induced by anaesthesia 15 hormones i.e. GH, ACTH, OH, FISH, TSH, PTH, FT4, T3, prolactin, insulin estradiol, testosterone, aldosterone, progesterone, and cortisol were studies results obtained showed significant increase in the levels of GH, cortisol, aldosterone, prolactin, progesterone, and PTH at the time of induction of anaesthesia. Of these GH, prolactin and aldosterone levels showed further increase during surgery (maintenance of anaesthesia). Values of TSH, LH, FSH, FT4 and testosterone levels remained essentially unaffected at induction of anaesthesia, but showed significant rise during surgery (maintenance of anaesthesia). Serum levels of ACTH, insulin, estradiol, and T3 were basically unaffected by anaesthesia and surgery. Furthermore, increase in cortisol and PTH levels was more prominent in patients anaesthetized with halothane alone. In this group ACTH level recorded a decrease while in thiopentone, halothane+nitrous oxide anaesthesia group ACTH showed a significantly rise. Growth hormone and insulin response was significantly more prominent in patients undergoing major surgery as compared to others. These findings under score the importance of stress response resulting from general anaesthesia and surgical trauma in children, and brings into focus the need of careful pre and post operative monitoring of patients in this age group. (author)

  5. Role of 11β-hydroxysteroid dehydrogenase 2 renal activity in potassium homeostasis in rats with chronic renal failure

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    N.L. Yeyati

    2010-01-01

    Full Text Available Aldosterone concentrations vary in advanced chronic renal failure (CRF. The isozyme 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2, which confers aldosterone specificity for mineralocorticoid receptors in distal tubules and collecting ducts, has been reported to be decreased or normal in patients with renal diseases. Our objective was to determine the role of aldosterone and 11β-HSD2 renal microsome activity, normalized for glomerular filtration rate (GFR, in maintaining K+ homeostasis in 5/6 nephrectomized rats. Male Wistar rats weighing 180-220 g at the beginning of the study were used. Rats with experimental CRF obtained by 5/6 nephrectomy (N = 9 and sham rats (N = 10 were maintained for 4 months. Systolic blood pressure and plasma creatinine (Pcr concentration were measured at the end of the experiment. Sodium and potassium excretion and GFR were evaluated before and after spironolactone administration (10 mg·kg-1·day-1 for 7 days and 11β-HSD2 activity on renal microsomes was determined. Systolic blood pressure (means ± SEM; Sham = 105 ± 8 and CRF = 149 ± 10 mmHg and Pcr (Sham = 0.42 ± 0.03 and CRF = 2.53 ± 0.26 mg/dL were higher (P < 0.05 while GFR (Sham = 1.46 ± 0.26 and CRF = 0.61 ± 0.06 mL/min was lower (P < 0.05 in CRF, and plasma aldosterone (Pald was the same in the two groups. Urinary sodium and potassium excretion was similar in the two groups under basal conditions but, after spironolactone treatment, only potassium excretion was decreased in CRF rats (sham = 0.95 ± 0.090 (before vs 0.89 ± 0.09 µEq/min (after and CRF = 1.05 ± 0.05 (before vs 0.37 ± 0.07 µEq/min (after; P < 0.05. 11β-HSD2 activity on renal microsomes was lower in CRF rats (sham = 0.807 ± 0.09 and CRF = 0.217 ± 0.07 nmol·min-1·mg protein-1; P < 0.05, although when normalized for mL GFR it was similar in both groups. We conclude that K+ homeostasis is maintained during CRF development despite normal Pald levels. This adaptation may be mediated by

  6. Hyponatremia and brain injury: absence of alterations of serum brain natriuretic peptide and vasopressin Hiponatremia e traumatismo cranioencefálico: ausência de alteração sanguínea do peptídeo natriurético cerebral e hormônio antidiurético

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    Karina Nascimento Costa

    2009-12-01

    Full Text Available OBJECTIVE: To study any possible relation between hyponatremia following brain injury and the presence of cerebral salt-wasting syndrome (CSWS or the syndrome of inappropriate secretion of antidiuretic hormone (SIADH, and if vasopressin, brain natriuretic peptide (BNP and aldosterone have a role in its mechanism. METHOD: Patients with brain injury admitted to the intensive care unit were included and had their BNP, aldosterone and vasopressin levels dosed on day 7. RESULTS: Twenty six adult patients were included in the study. Nine (34.6% had hyponatremia and presented with a negative water balance and higher values of urinary sodium, serum potassium and diuresis than patients with normonatremia. The serum levels of BNP, aldosterone, and vasopressin were normal and no relation was observed between plasma sodium and BNP, aldosterone or vasopressin. CONCLUSION: The most likely cause of hyponatremia was CSWS and there was no correlation between BNP, aldosterone and vasopressin with serum sodium level.OBJETIVO: Estudar a possível relação entre a hiponatremia seguindo traumatismo cranioencefálico e a presença da síndrome cerebral perdedora de sal (SCPS ou a síndrome da secreção inapropriada do hormônio antidiurético (SSIHAD, e se a vasopressina, peptídeo natriurético cerebral (BNP e aldosterona têm um papel nesse mecanismo. MÉTODO: Foram incluídos pacientes com traumatismo cranioencefálico admitidos na unidade de terapia intensiva e foram dosados no sétimo dia seguindo o trauma, BNP, aldosterona e vasopressina. RESULTADOS: Vinte e seis pacientes foram incluídos no estudo. Nove (34,6% tiveram hiponatremia e apresentaram um balanço hídrico mais negativo e altos valores de sódio urinário, potássio sérico e diurese quando comparados com o grupo que apresentou normonatremia. Os níveis séricos de BNP, aldosterona e vasopressina foram normais e não foi observada relação entre o sódio sérico e BNP, aldosterona e vasopressina

  7. [Cardiovascular risk in polycystic kidney disease].

    Science.gov (United States)

    Di Lorenzo, Adelaide; Stallone, Giovanni; Infante, Barbara; Grandaliano, Giuseppe; Schena, Francesco Paolo

    2015-09-01

    Hypertension is common and occurs in the majority of autosomal dominant polycystic kidney disease (ADPKD) patients prior to loss of kidney function. Hypertension relates to progressive kidney enlargement, and is a significant independent risk factor for progression to end-stage renal disease. The pathogenesis of hypertension in ADPKD is complex and depends on many factors that influence each other. High expression of PKD1 and PKD2 genes is present in the cilia of tubular epithelial cells, in endothelial cells and in vascular smooth muscle cells. Decreased or absent polycystin-1 or -2 expression is associated with abnormal vascular structure and function. PKD1/PKD2 deficiency results in reduced nitric oxide levels, altered endothelial response to shear stress with attenuation in vascular relaxation. Activation of the renin-angiotensin-aldosterone system occurs in ADPKD due to decreased nitric oxide production as well as bilateral cyst expansion and intra-renal ischemia. With increasing cyst size, further activation of the renin-angiotensin-aldosterone system occurs, blood pressure increases and a vicious cycle ensues with enhanced cyst growth and hypertension ultimately leading to end-stage renal disease. Inhibition of the angiotensin-aldosterone system is possible with angiotensin-converting enzyme inhibitors and seems to be the first-line treatment for hypertension in these subjects. As suggested by the HALT-PKD study, an aggressive blood pressure control is safe and recommended and is associated with preservation of kidney function and a reduction in total kidney volume over time. A collaborative multidisciplinary approach between nephrologists and cardiologists is necessary for the monitoring of kidney and heart complications. PMID:26418387

  8. Adrenal scintigraphy using 131I-Adosterol

    International Nuclear Information System (INIS)

    131I-Adosterol (6β-iodomethyl-19-norcholest-5(10)-3β-ol) was administered to evaluate adrenal grand in 20 patients including 9 patients with primary aldosteronism, 5 with Cushing's syndrome, one with pheochromocytoma, one with retroperitoneal tumor, 3 with essential hypertension and one with obesity. Standard scintigraphies were performed at 3rd day and again 6th day after administration of 131I-adosterol (1-1.5 mCi). Suppression scintigraphies were obtained while the patients were taking dexamethasone 2 to 3 mg daily from 3 days prior to injection of the tracer until adrenal imaging. In the cases with essential hypertension and obesity, both adrenal glands were delineated equally by standard scintigraphy, and in one patient, undergone suppression scintigraphy, the uptake of 131I-adosterol by both glands were completely inhibited by dexamethasone administration. In primary aldosteronism, six of the 9 patients demonstrated the increased radioactivity in one side, and were diagnosed as aldosteronoma. In 3 cases, failed to show the lesions on standard scintigraphy, the lesions could be detected by suppression scintigraphy, and aldosteronomas measuring 1 x 1 x 0.7, 2 x 2 x 1 and 1.7 x 1.5 x 0.8 cm were confirmed by operation. In Cushing's syndrome, standard scintigraphy could easily distinguish between adenoma (one case) and bilateral hyperplasia (4 cases). Adrenal scintigraphy was also a useful method in order to assess the effect of pituitary irradiation therapy in the case of hyperplasia. In pheochromocytoma and retroperitoneal tumor, the side of the lesion was identified by the absence of a functioning gland. Suppression scintigraphy was particularly useful in detecting the localization of the small tumor in primary aldosteronism. (auth.)

  9. Diagnostic evaluation of the adrenal scanning using 131I-adosterol

    International Nuclear Information System (INIS)

    We have performed adrenal scanning in the 30 patients with suspected adrenal disorders eight days after the intravenous administration of about 500 μCi of 131I-adosterol (NCL-6-131I), using 5 inch crystal rectilinear scintiscanner. Successful image of the adrenals was obtained in all the patients. In the 30 patients, 27 were proved to have adrenal disorders by surgical and hormonal findings. In 13 patients with primary aldosteronism, the side of adrenal adenoma was diagnosed correctly in all the cases by adrenal scanning. We could detected a small aldosterone-producing adenoma which measured 11 x 8 x 6 mm in size. In two patients with idiopathic hyperaldosteronism, asymmetrical radio-uptake between the two adrenals was seen on the standard scanning, and it was difficult to differentiate between tumor or hyperplasia. Dexamethazone-modified suppression scanning was very effective in lateralizing adenomas in the patients with primary aldosteronism. Two patients with Cushing's syndrome due to adrenal hyperplasia showed prominent and almost equal radioactivity of both the adrenal glands. Adrenal adenomas in 8 patients with Cushing's syndrome were definitely visualized on adrenal scanning, with no uptake in the contralateral sides. In one patient with Cushing's syndrome due to an adrenal carcinoma, adrenal scanning showed significant activity in the area of the carcinoma, and no uptake on the opposite side. In one patient with adrenogenital syndrome due to a virilizing adenoma with focal malignancy, adrenal scanning showed high radioactivity in the region of the tumor, and moderate activity on the opposite side. Also in the case of adrenal carcinoma, we appreciated diagnostic value of the adrenal scanning utilizing 131I-adosterol. (author)

  10. Impacts of ABCB1 (G1199A) polymorphism on resistance, uptake, and efflux to steroid drugs.

    Science.gov (United States)

    Peng, Rui; Zhang, Hong; Zhang, Ying; Wei, Dan-Yun

    2016-10-01

    1. P-glycoprotein (P-gp) substrates, including steroid drugs, involve in the inter-individual differences in resistant phenotype. This study was performed to evaluate whether G1199A polymorphism in ABCB1 gene can alter the sensitivity, accumulation, and transepithelial efflux to steroids in LLC-PK1 cells. 2. The stable recombinant LLC-PK1 cell lines transfected with ABCB1 1199G and ABCB1 1199A were used to assess the sensitivity, accumulation, and transepithelial permeability to steroids. 3. The cells transfected with 1199A allele displayed stronger resistance to aldosterone, dexamethasone, and cortisol (2.5-, 2.0-, and 1.6-fold, respectively) than cells overexpressing 1199G allele, while the two types of recombinant cells showed a similar resistance to corticosterone. The accumulation of aldosterone, dexamethasone, and cortisol in recombinant 1199A cells were significantly decreased when compared to 1199G cells (2.9-, 4.4-, and 3.9-fold, respectively). The net efflux ratios of P-gp-mediated aldosterone, dexamethasone, and cortisol in cells expressing 1199A allele were apparently greater than cells transfected with 1199G allele (3.3-, 3.5-, and 4.0-fold, respectively). 4. The impacts of ABCB1 (G1199A) single nucleotide polymorphism on the efflux of P-gp substrates presented as drug-specific. Overall, the transport ability of P-gp-dependent steroid drugs in recombinant model overexpressing variant 1199A allele is stronger in comparison to cells overexpressing wild-type 1199G allele. Therefore, the ABCB1 (G1199A) polymorphism may affect effective steroids concentration in target cells by regulating the drug transport and distribution. PMID:26822676

  11. Transient pseudohypoaldosteronism

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    Stajić Nataša

    2011-01-01

    Full Text Available Introduction. Infants with urinary tract malformations (UTM presenting with urinary tract infection (UTI are prone to develop transient type 1 pseudohypoaldosteronism (THPA1. Objective. Report on patient series with characteristics of THPA1, UTM and/or UTI and suggestions for the diagnosis and therapy. Methods. Patients underwent blood and urine electrolyte and acid-base analysis, serum aldosterosterone levels and plasma rennin activity measuring; urinalysis, urinoculture and renal ultrasound were done and medical and/or surgical therapy was instituted. Results. Hyponatraemia (120.9±5.8 mmol/L, hyperkalaemia (6.9±0.9 mmol/L, metabolic acidosis (plasma bicarbonate, 11±1.4 mmol/L, and a rise in serum creatinine levels (145±101 μmol/L were associated with inappropriately high urinary sodium (51.3±17.5 mmol/L and low potassium (14.1±5.9 mmol/L excretion. Elevated plasma aldosterone concentrations (170.4±100.5 ng/dL and the very high levels of the plasma aldosterone to potassium ratio (25.2±15.6 together with diminished urinary K/Na values (0.31±0.19 indicated tubular resistance to aldosterone. After institution of appropriate medical and/or surgical therapy, serum electrolytes, creatinine, and acid-base balance were normalized. Imaging studies showed ureteropyelic or ureterovesical junction obstruction in 3 and 2 patients, respectively, posterior urethral valves in 3, and normal UT in 1 patient. According to our knowledge, this is the first report on THPA1 in the Serbian literature. Conclusion. Male infants with hyponatraemia, hyperkalaemia and metabolic acidosis have to have their urine examined and the renal ultrasound has to be done in order to avoid both, the underdiagnosis of THPA1 and the inappropriate medication.

  12. Possible Association of ACE Gene I/D Polymorphism With Blood Pressure——Lowering Response to Hydrochlorothiazide

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To explore the association between polymorphism in the ACE I/D gene and blood pressure-lowering response to hydrochlorothiazide (HCTZ) in 829 patients. Methods HCTZ 12.5 mg was taken once a day for six weeks. The blood pressure reduction and ratio reaching target blood pressure were compared in different ACE genotype groups. Results The reduction in SBP of patients carrying DD was greater than that in other groups carrying Ⅱ or ID (12.2 mmHg versus 5.4 mmHg,12.2 mmHg versus 4.4 mmHg, respectively, P<0.05). The reduction in MAP of patients carrying DD was also greater than that in other groups carrying Ⅱ or ID (6.9 mmHg versus 3.9 mmHg, 6.9 mmHg versus 3.6 mmHg, respectively, P<0.05). The ratio reaching target blood pressure in DD groups was significantly higher than that in Ⅱ or ID groups (P<0.05). The pre-treatment SBP, DD genotype, aldosterone levels entered the multi-linear regression model significantly and might affect the reduction of SBP. The pre-treatment DBP, aldosterone levels, DD genotype entered the multi-linear regression model significantly and might affect the reduction of DBP. The pre-treatment MAP, DD genotype, aldosterone levels entered the multi-linear regression model significantly and might affect the reduction of MAP. Conclusion ACE genotyping is associated with blood pressure-lowering response to HCTZ. Specific genotypes might be associated with the response to specific antihypertensive treatment.

  13. Management of patients with resistant hypertension: current treatment options

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    Kumar N

    2013-10-01

    Full Text Available Nilay Kumar,1 David A Calhoun,2 Tanja Dudenbostel21Department of Medicine, 2Division of Cardiovascular Disease, Hypertension and Vascular Biology Program, University of Alabama at Birmingham, Birmingham, AL, USAAbstract: Resistant hypertension (RHTN is an increasingly common clinical problem that is often heterogeneous in etiology, risk factors, and comorbidities. It is defined as uncontrolled blood pressure on optimal doses of three antihypertensive agents, ideally one being a diuretic. The definition also includes controlled hypertension with use of four or more antihypertensive agents. Recent observational studies have advanced the characterization of patients with RHTN. Patients with RHTN have higher rates of cardiovascular events and mortality compared with patients with more easily controlled hypertension. Secondary causes of hypertension, including obstructive sleep apnea, primary aldosteronism, renovascular disease, are common in patients with RHTN and often coexist in the same patient. In addition, RHTN is often complicated by metabolic abnormalities. Patients with RHTN require a thorough evaluation to confirm the diagnosis and optimize treatment, which typically includes a combination of lifestyle adjustments, and pharmacologic and interventional treatment. Combination therapy including a diuretic, a long-acting calcium channel blocker, an angiotensin-converting enzyme inhibitor, a beta blocker, and a mineralocorticoid receptor antagonist where warranted is the classic regimen for patients with treatment-resistant hypertension. Mineralocorticoid receptor antagonists like spironolactone or eplerenone have been shown to be efficacious in patients with RHTN, heart failure, chronic kidney disease, and primary aldosteronism. Novel interventional therapies, including baroreflex activation and renal denervation, have shown that both of these methods may be used to lower blood pressure safely, thereby providing exciting and promising new

  14. Angiotensin and mineralocorticoid receptor antagonism attenuates cardiac oxidative stress in angiotensin II-infused rats.

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    Minas, Jacqueline N; Thorwald, Max A; Conte, Debra; Vázquez-Medina, Jose-Pablo; Nishiyama, Akira; Ortiz, Rudy M

    2015-11-01

    Angiotensin II (Ang II) and aldosterone contribute to hypertension, oxidative stress and cardiovascular damage, but the contributions of aldosterone during Ang II-dependent hypertension are not well defined because of the difficulty to assess each independently. To test the hypothesis that during Ang II infusion, oxidative and nitrosative damage is mediated through both the mineralocorticoid receptor (MR) and angiotensin type 1 receptor (AT1), five groups of Sprague-Dawley rats were studied: (i) control; (ii) Ang II infused (80 ng/min × 28 days); (iii) Ang II + AT1 receptor blocker (ARB; 10 mg losartan/kg per day × 21 days); (iv) Ang II + mineralocorticoid receptor (MR) antagonist (Epl; 100 mg eplerenone/day × 21 days); and (v) Ang II + ARB + Epl (Combo; × 21 days). Both ARB and combination treatments completely alleviated the Ang II-induced hypertension, whereas eplerenone treatment only prolonged the onset of the hypertension. Eplerenone treatment exacerbated the Ang II-mediated increase in plasma and heart aldosterone 2.3- and 1.8-fold, respectively, while ARB treatment reduced both. Chronic MR blockade was sufficient to ameliorate the AT1-mediated increase in oxidative damage. All treatments normalized protein oxidation (nitrotyrosine) levels; however, only ARB and Combo treatments completely reduced lipid peroxidation (4-hydroxynonenal) to control levels. Collectively, these data suggest that receptor signalling, and not the elevated arterial blood pressure, is the principal culprit in the oxidative stress-associated cardiovascular damage in Ang II-dependent hypertension. PMID:26234762

  15. Effects of mildly increasing dialysis sodium removal on renin and sympathetic system in hemodialysis patients

    Institute of Scientific and Technical Information of China (English)

    Shen Yang; Sun Fang; Liu Jing; Ma Lijie; Huang Jing; Zhou Yilun; Liu Wenhu

    2014-01-01

    Background It has been argued that the benefits of reducing sodium loading may be offset by increased activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system.This study aimed to investigate the long-term effects of an increase in dialysis sodium removal on circulating RAAS and sympathetic system in hypertensive hemodialysis (HD) patients with "normal" post-HD volume status.Methods Thirty hypertensive HD patients were enrolled in this pilot trial.After one month period of dialysis with standard dialysate sodium of 138 mmol/L,the patients were followed up for a four months period with dialysate sodium set at 136 mmol/L,without changes in instructions regarding dietary sodium control.During the period of study,the dry weight was adjusted monthly under the guidance of bioimpedance spectroscopy to maintain post-HD volume status in a steady state; 44-hour ambulatory blood pressure,plasma renin,angiotensin Ⅱ (Ang Ⅱ),aldosterone,and norepinephrine (NE) were measured.Results After four months of HD with low dialysate sodium of 136 mmol/L,44-hour systolic and diastolic blood pressures (BPs) were significantly lower (-10 and-6 mmHg),in the absence of changes in antihypertensive medications.No significant changes were observed in plasma renin,Ang Ⅱ,aldosterone,and NE concentrations.The post-HD volume parameters were kept constant.Conclusion Mildly increasing dialysis sodium removal over 4 months can significantly improve BP control and does not activate circulating RAAS and sympathetic nervous system in hypertensive HD patients.

  16. Reduction of complex ventricular arrhythmias after enalapril treatment in patients with advanced stable heart failure.

    Science.gov (United States)

    Pomini, G; Gribaldo, R; Rugna, A; Lupia, M; Molfese, G; Carenza, P

    1991-01-01

    We studied, by 48-hour Holter monitoring, 33 patients with chronic stable heart failure (radionuclide ejection fraction less than 35%), complex ventricular arrhythmias and no electrolyte abnormalities, after a period during which they were treated with digoxin and diuretics. Before Holter monitoring blood samples were analyzed for serum concentration of sodium, potassium, magnesium, urea, creatinine, digoxin, aldosterone and for plasmatic renin activity in addition to urinary aldosterone and catecholamines determination. After these investigations in 23 patients, 5-20 mg of enalapril were progressively added to the conventional therapy, while 10 patients continued the previous therapy. After 8 weeks 30 patients were subjected to a second 48-hour Holter monitoring and to the same biochemical and hormonal tests. One patient died and 2 were lost to follow up. Only the enalapril group showed a significant decrease in the number of premature ventricular complexes (PVC) (p less than 0.01), and the frequency of couplets and episodes of ventricular tachycardia (VT) declined significantly (P less than 0.01). In the two groups there were no significant changes in digoxin, sodium, or magnesium, while potassium concentration increased in both groups (p less than 0.01). In the enalapril group heart rate and systolic and diastolic pressure declined significantly (p less than 0.01), and New York Heart Association class (NYHA) improved (p less than 0.001). In the other group there were no significant changes in these parameters. Enalapril caused a significant increase in the plasmatic renin activity (p less than 0.01) and a significant fall of plasma and urinary aldosterone (p less than 0.01; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2055378

  17. Physiological and Molecular Response of Ostrich to the Seasonal and Diurnal Variations in Egyptian conditions

    International Nuclear Information System (INIS)

    Twelve immature ostrich›s birds, 7 months old were used to evaluate the effect of ambient temperature variation and diurnal effect on response changes of some physiological and chemical parameters. All birds were reared out doors and exposed to daily ambient temperatures fluctuations during summer and winter. Blood samples were taken twice, one in the morning at 7 Am and once in the afternoon at 3 Pm during a representative 7 hot days of June (summer) (40±2ºC) and the 7 cold days of January (winter) (18±2ºC). Serum calcium, inorganic phosphorus, sodium, potassium, uric acid concentrations and aldosterone level were determined. The amount of total body water (TBW) and serum heat shock proteins (HSP) were estimated. Serum calcium, phosphorus, sodium and potassium concentrations in ostrich were significantly decreased, while uric acid concentration and aldosterone hormone level were significantly increased in summer as compared in winter during both at morning and at afternoon periods. Concerning the diurnal variation, serum calcium, phosphorus, sodium and potassium concentrations and aldosterone hormone level in ostrich were significantly increased, while uric acid concentration was significantly decreased at morning as compared at afternoon during both summer and winter seasons. TBW was significantly higher in summer season by 15.04% than winter season. It is concluded from the present study that heat or cold stress has a negative effect on most of the parameters studied and we recommend must be supplement diet with some nutrients like vitamins C, and E, sodium bicarbonate or yeast to overcome the negative effect and to better perform under such conditions

  18. Intestinal Na+ Loss and Volume Depletion in JAK3-Deficient Mice

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    Anja T. Umbach

    2013-11-01

    Full Text Available Background/Aims: The Janus kinase 3 JAK3 participates in the signaling of immune cells. Lack of JAK3 triggers inflammatory bowel disease, which in turn has been shown to affect intestinal activity of the epithelial Na+ channel ENaC and thus colonic sodium absorption. At least in theory, inflammatory bowel disease in JAK3-deficient mice could lead to intestinal salt loss compromizing extracellular volume maintenance and blood pressure regulation. The present study thus explored whether JAK3 deficiency impacts on colonic ENaC activity, fecal Na+ exretion, blood pressure and extracellular fluid volume regulation. Methods: Experiments were performed in gene-targeted mice lacking functional JAK3 (jak3-/- and in wild type mice (jak3+/+. Colonic ENaC activity was estimated from amiloride-sensitive current in Ussing chamber experiments, fecal, serum and urinary Na+ concentration by flame photometry, blood pressure by the tail cuff method and serum aldosterone levels by immunoassay. Results: The amiloride (50 µM-induced deflection of the transepithelial potential difference was significantly lower and fecal Na+ excretion significantly higher in jak3-/- mice than in jak3+/+ mice. Moreover, systolic arterial blood pressure was significantly lower and serum aldosterone concentration significantly higher in jak3-/- mice than in jak3+/+ mice. Both, absolute and fractional renal Na+ excretion were significantly lower in jak3-/- mice than in jak3+/+ mice. Conclusions: JAK3 deficiency leads to impairment of colonic ENaC activity with intestinal Na+ loss, decrease of blood pressure, increased aldosterone release and subsequent stimulation of renal tubular Na+ reabsorption.

  19. The Early Endocrine Stress Response in Experimental Subarachnoid Hemorrhage.

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    Christoffer Nyberg

    Full Text Available In patients with severe illness, such as aneurysmal subarachnoid hemorrhage (SAH, a physiologic stress response is triggered. This includes activation of the hypothalamic-pituitary-adrenal (HPA axis and the sympathetic nervous system. The aim of this study was to investigate the very early responses of these systems.A porcine animal model of aneurysmal SAH was used. In this model, blood is injected slowly to the basal cisterns above the anterior skull base until the cerebral perfusion pressure is 0 mm Hg. Sampling was done from blood and urine at -10, +15, +75 and +135 minutes from time of induction of SAH. Analyses of adrenocorticotropic hormone (ACTH, cortisol, aldosterone, catecholamines and chromogranin-A were performed.Plasma ACTH, serum cortisol and plasma aldosterone increased in the samples following induction of SAH, and started to decline after 75 minutes. Urine cortisol also increased after SAH. Urine catecholamines and their metabolites were found to increase after SAH. Many samples were however below detection level, not allowing for statistical analysis. Plasma chromogranin-A peaked at 15 minutes after SAH, and thereafter decreased.The endocrine stress response after aneurysmal SAH was found to start within 15 minutes in the HPA axis with early peak values of ACTH, cortisol and aldosterone. The fact that the concentrations of the HPA axis hormones decreased 135 minutes after SAH may suggest that a similar pattern exists in SAH patients, thus making it difficult to catch these early peak values. There were also indications of early activation of the sympathetic nervous system, but the small number of valid samples made interpretation difficult.

  20. Challenges posed to the maternal circulation by pregnancy

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    Valdés G

    2011-08-01

    Full Text Available Gloria Valdés, Jenny CorthornCentro de Investigaciones Médicas y Departamento Nefrología, Escuela Medicina, Pontificia Universidad Católica, Santiago, ChileAbstract: In primates, adequate growth of the fetus depends on the development of the uteroplacental unit. On the fetal side, this is achieved by the creation of the vascular network of the placenta. On the maternal side, the transformation of the spiral arteries into saccular nonreactive vessels by the trophoblast provides high blood flow to the intervillous space. Apart from the changes in the uterine arteries, the mother expands her plasma volume – at the expense of stimulating the renin-angiotensin-aldosterone system – and her cardiac output. In the maintaining of normotension in the face of an increased cardiac output and plasma volume, the renin-angiotensin-aldosterone system requires an enhanced vasodilator synthesis. Finally, in the late stages of pregnancy, a normal endothelial function is required to provide an ample margin to the activation provoked by deportation of syncytiotrophoblast fragments/factors to the maternal circulation. These four adaptative processes require various interrelated vasodilator systems. Deficient adaptations cause isolated or proteinuric arterial hypertension, intrauterine growth restriction, preterm delivery, and stillbirths, among others. Moreover, a normal or a defective adaptation to pregnancy influences maternal cardiovascular health in later life, as evidenced by various studies, most of them epidemiological; thus, pregnancy is now considered a stress test to the maternal cardiovascular system. Because of this, women planning to become pregnant should be screened for clinical and biochemical cardiovascular risks. Inversely, women presenting with hypertension in pregnancy should be thoroughly studied to detect and correct cardiovascular risks. The incorporation of the predictive value of a hypertensive pregnancy should help reduce