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Sample records for aldosterone antagonist therapy

  1. 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

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

    Directory of Open Access Journals (Sweden)

    Nappi J

    2011-06-01

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

  3. Suppression of Aldosterone Synthesis and Secretion by Channel Antagonists

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda

    2012-01-01

    Full Text Available Aldosterone, a specific mineralocorticoid receptor (MR agonist and a key player in the development of hypertension, is synthesized as a final product of renin-angiotensin-aldosterone system. Hypertension can be generally treated by negating the effects of angiotensin II through the use of angiotensin-converting enzyme inhibitors (ACE-Is or angiotensin II type 1 receptor antagonists (ARBs. However, the efficacy of angiotensin II blockade by such drugs is sometimes diminished by the so-called “aldosterone breakthrough” effect, by which ACE-Is or ARBs (renin-angiotensin system (RAS inhibitors gradually lose their effectiveness against hypertension due to the overproduction of aldosterone, known as primary aldosteronism. Although MR antagonists are used to antagonize the effects of aldosterone, these drugs may, however, give rise to life-threatening adverse actions, such as hyperkalemia, particularly when used in conjunction with RAS inhibitors. Recently, several groups have reported that some dihydropyridine Ca2+ channel blockers (CCBs have inhibitory actions on aldosterone production in in vitro and in the clinical setting. Therefore, the use of such dihydropyridine CCBs to treat aldosterone-related hypertension may prove beneficial to circumvent such therapeutic problems. In this paper, we discuss the mechanism of action of CCBs on aldosterone production and clinical perspectives for CCB use to inhibit MR activity in hypertensive patients.

  4. Long-term use of aldosterone-receptor antagonists in uncontrolled hypertension: A retrospective analysis

    NARCIS (Netherlands)

    P.M. Jansen (Pieter); K. Verdonk (Koen); B.P. Imholz (Ben); A.H.J. Danser (Jan); A.H. van den Meiracker (Anton)

    2011-01-01

    textabstractBackground. The long-term efficacy of aldosterone-receptor antagonists (ARAs) as add-on treatment in uncontrolled hypertension has not yet been reported. Methods. Data from 123 patients (21 with primary aldosteronism, 102 with essential hypertension) with difficult-to-treat hypertension

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

    DEFF Research Database (Denmark)

    Winkler, Christine; Hobolth, Lise; Krag, Aleksander;

    2011-01-01

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

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

  7. Application of aldosterone antagonists in the treatment of heart failure%醛固酮拮抗剂在心力衰竭治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    高修仁; 黄至斌

    2013-01-01

    人们对醛固酮致病作用的认识已有50多年的历史,但相关指南推荐使用醛固酮拮抗剂治疗纽约心脏协会心功能分级Ⅲ~Ⅳ级、左心室射血分数≤35%的重度心力衰竭患者却仅有10年的时间。2012年,欧洲心脏病学学会发表的更新指南又将醛固酮拮抗剂治疗心力衰竭的适用人群扩展到纽约心脏协会心功能分级Ⅱ级患者。本文概要介绍醛固酮拮抗剂的作用机制、循证医学证据和注意事项等。%More than 50 years ago, scientist first observed the relationship between heart failure and aldosterone. However aldosterone antagonists were not guideline-recommended as a therapy for patients with moderate to severe heart failure till 10 years ago. In 2012 ESC guideline for aldosterone antagonists in the treatment of systolic heart failure extended to patients with mild heart failure. This review introduces the main mechanism, evidence-based medicine, clinical therapy and announcements for aldosterone antagonists in the treatment of systolic heart failure.

  8. 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

    HeFT and CHARM-ADDED have shown that combined RAAS inhibition with an ACE inhibitor and ARB significantly reduced the morbidity endpoint in certain patient subgroups compared with standard therapy. However, in clinical practice, dual RAAS blockade is rarely employed, as seen, for instance, in the CORONA trial. The RALES and EPHESUS trials, investigating the effects of aldosterone blockade on cardiovascular outcomes in CHF patients, revealed that the addition of an aldosterone antagonist to standard heart failure therapy conferred powerful relative risk reductions for both morbidity and mortality. Future studies will elucidate whether this also holds true for patients who are asymptomatic or who have heart failure with preserved ejection fraction. In selected patients with renal disease, several studies have suggested that combined RAAS blockade brings about additional renoprotective antiproteinuric effects independent of blood pressure reduction, and large trials with robust endpoints are underway. In summary, combined therapy with several RAAS inhibitors is not recommended for all patients along the cardiorenovascular continuum. Patients with CHF with incomplete neuroendocrine blockade, as indicated, for example, by repetitive cardiac decompensation or refractory symptoms, might benefit from dual therapy as long as safety issues are well controlled. Finally, novel pharmacological agents such as the direct renin inhibitor aliskiren may provide additional therapeutic tools, but their role has yet to be established. PMID:20568830

  9. Antagonistic effects of aldosterone on corticosterone-mediated changes in exploratory behavior of adrenalectomized rats

    NARCIS (Netherlands)

    Veldhuis, H D; De Kloet, E R

    1983-01-01

    The effect of aldosterone administration on exploratory activity of chronic adrenalectomized (10 days) male rats was investigated. Aldosterone (30 micrograms/100 g body wt sc) administered 1 hr or 30 min prior to the behavioral test failed to normalize disturbed exploratory activity of adrenalectomi

  10. 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.

  11. 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.

  12. Interleukin-2 receptor antagonists as induction therapy after heart transplantation

    DEFF Research Database (Denmark)

    Møller, Christian H; Gustafsson, Finn; Gluud, Christian;

    2008-01-01

    About half of the transplantation centers use induction therapy after heart transplantation. Interleukin-2 receptor antagonists (IL-2Ras) are used increasingly for induction therapy. We conducted a systematic review of randomized trials assessing IL-2Ras....

  13. 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.

  14. Renin-angiotensin-aldosterone system inhibition: overview of the therapeutic use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and direct renin inhibitors.

    Science.gov (United States)

    Mercier, Kelly; Smith, Holly; Biederman, Jason

    2014-12-01

    Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy in hypertensive diabetic patients with macroalbuminuria, microalbuminuria, or normoalbuminuria has been repeatedly shown to improve cardiovascular mortality and reduce the decline in glomerular filtration rate. Renin-angiotensin-aldosterone system (RAAS) blockade in normotensive diabetic patients with normoalbuminuria or microalbuminuria cannot be advocated at present. Dual RAAS inhibition with ACE inhibitors plus ARBs or ACE inhibitors plus direct renin inhibitors has failed to improve cardiovascular or renal outcomes but has predisposed patients to serious adverse events. PMID:25439533

  15. 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

  16. 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.

  17. 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

  18. First Irish birth following IVF therapy using antagonist protocol.

    LENUS (Irish Health Repository)

    Mocanu, E V

    2012-02-01

    BACKGROUND: During in vitro fertilization (IVF), the prevention of a premature LH surge was traditionally achieved using a gonadotrophin releasing hormone agonist (GnRH-a), and more recently, a GnRH antagonist. AIMS: We report a case of a 37 year old treated using the GnRH antagonist in a second completed cycle of IVF. METHODS: IVF was performed for primary infertility of 5-year duration due to frozen pelvis secondary to endometriosis. RESULTS: Following controlled ovarian hyperstimulation, oocyte recovery and fertilization, cleavage and transfer of two zygotes, a pregnancy established. A twin gestation was diagnosed at 7-weeks scan and pregnancy ended with the delivery of twin girls by emergency caesarean section. CONCLUSION: This is a first report of a delivery following IVF using the antagonist protocol in Ireland. Such therapy is patient friendly and its use should be introduced on a larger scale in clinical practice.

  19. 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

  20. Implications of hedgehog signaling antagonists for cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Jingwu Xie

    2008-01-01

    The hedgehog(Hh)pathway,initially discovered inDrosophila by two Nobel laureates,Dr.Eric Wieschaus and Dr.Christiane Nusslein-Volhard,is a major regulator for cell differentiation,tissue polarity and cell proliferation.Studies from many laboratories,including ours,reveal activation of this pathway in most basal cell carcinomas and in approximately 30% of extracutaneous human cancers,including medulloblastomas,gastrointestinal,lung,breast and prostate cancers.Thus,it is believed that targeted inhibition of Hh signaling may be effective in treating and preventing many types of human cancers.Even more exciting is the discovery and synthesis of specific signaling antagonists for the Hh pathway,which have significant clinical implications in novel cancer therapeutics.This review discusses the major advances in the current understanding of Hh signaling activation in different types of human cancers,the molecular basis of Hh signaling activation,the major antagonists for Hh signaling inhibition and their potential clinical application in human cancer therapy.

  1. Safety of Aldosterone Receptor Antagonists in Heart Failure%醛固酮受体拮抗剂在心力衰竭患者中应用的安全性

    Institute of Scientific and Technical Information of China (English)

    戴士鹏(综述); 徐泽升(审校)

    2015-01-01

    Although the benefits of aldosterone receptor antagonists have been confirmed with multiple randomized,controlled studies and recommended by heart failure guideline,only a fraction of the patients with heart failure who are eligible for the indications receive this medication .This maybe, in part, concerns of adverse events-hyperkalemia and deteriorated renal function known to occur with using of these drugs.Here is to make a review of the safety of aldosterone receptor antagonists in heart failure , in order to improve the knowledge of this kind of drugs.%尽管应用醛固酮受体拮抗剂治疗心力衰竭的益处被多个大型临床随机对照试验所证实,并被临床治疗指南所推荐,但仅有一小部分适合应用醛固酮受体拮抗剂治疗的心力衰竭患者应用了这一药物,其部分原因是临床医师对醛固酮受体拮抗剂的主要不良反应———高钾血症和肾功能恶化的担心。该文对醛固酮受体拮抗剂在心力衰竭患者中应用的安全性做一综述,以提高人们对于这类药物的认识。

  2. 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

  3. Long-term treatment with an aldosterone synthase inhibitor improves cardiac function and myocardial structure in rats with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    VirginieMELLIN; PaulMULDER; BenoitDiMEGLIO; JeanPaulHENRY; ChristianTHUILLEZ

    2004-01-01

    AIM: Aldosterone receptor antagonists reduce total and cardiovascular mortality in patients with chronic heart failure (CHF) under active angiotensin converting enzyme inhibition treatment,illustrating the deleterious involvement of aldosterone in the progression of CHF. The reduction of aldosterone synthesis through inhibition of aldosterone synthase is an alternative way to prevent the effects of aldosterone. However, whether chronic aldosterone synthase inhibition exerts beneficial effects in CHF

  4. 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

  5. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement

    DEFF Research Database (Denmark)

    Solovic, I; Sester, M; Gomez-Reino, J J;

    2010-01-01

    Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased...... risk of reactivating latent infections, especially tuberculosis (TB). Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-¿ release assays or, as an alternative in individuals without a history...

  6. 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

  7. Dual-function CXCR4 Antagonist Polyplexes to Deliver Gene Therapy and Inhibit Cancer Cell Invasion**

    OpenAIRE

    Li, Jing; Zhu, Yu; Hazeldine, Stuart T.; Li, Chunying; Oupický, David

    2012-01-01

    A bicyclam-based biodegradable polycation with CXCR4 antagonistic activity was developed with potential for combined drug/gene cancer therapies. The dual-function polycation prevents cancer cell invasion by inhibiting CXCL12 stimulated CXCR4 activation, while at the same time efficiently and safely delivers plasmid DNA into cancer cells.

  8. 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;

    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 myocardi...

  9. 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.

  10. 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.

  11. 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 ...

  12. Effects and Safety of Linagliptin as an Add-on Therapy in Advanced-Stage Diabetic Nephropathy Patients Taking Renin–Angiotensin–Aldosterone System Blockers

    Science.gov (United States)

    Ueda, Yuichiro; Ishii, Hiroki; Kitano, Taisuke; Shindo, Mitsutoshi; Miyazawa, Haruhisa; Ito, Kiyonori; Hirai, Keiji; Kaku, Yoshio; Mori, Honami; Hoshino, Taro; Ookawara, Susumu; Kakei, Masafumi; Tabei, Kaoru; Morishita, Yoshiyuki

    2016-01-01

    BACKGROUND We investigated the effects and safety of linagliptin as an add-on therapy in patients with advanced-stage diabetic nephropathy (DMN) taking renin–angiotensin–aldosterone system (RAAS) blockers. METHOD Twenty advanced-stage DMN patients (estimated glomerular filtration rate (eGFR): 24.5 ± 13.4 mL/min/1.73 m2) taking RAAS blockers were administered 5 mg/day linagliptin for 52 weeks. Changes in glucose and lipid metabolism and renal function were evaluated. RESULTS Linagliptin decreased glycosylated hemoglobin levels (from 7.32 ± 0.77% to 6.85 ± 0.87%, P < 0.05) without changing fasting blood glucose levels, and significantly decreased total cholesterol levels (from 189.6 ± 49.0 to 170.2 ± 39.2 mg/dL, P < 0.05) and low-density lipoprotein cholesterol levels (from 107.1 ± 32.4 to 90.2 ± 31.0 mg/dL, P < 0.05) without changing high-density lipoprotein cholesterol and triglyceride levels. Urine protein/creatinine ratio and annual change in eGFR remained unchanged. No adverse effects were observed. CONCLUSION Linagliptin as an add-on therapy had beneficial effects on glucose and lipid metabolism without impairment of renal function, and did not have any adverse effects in this population of patients with advanced-stage DMN taking RAAS blockers. PMID:27660406

  13. 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. ...

  14. Comprehensive evaluation of a somatostatin-based radiolabelled antagonist for diagnostic imaging and radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xuejuan; Fani, Melpomeni [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Schulz, Stefan [Jena University Hospital - Friedrich Schiller University Jena, Department of Pharmacology and Toxicology, Jena (Germany); Rivier, Jean [The Salk Institute for Biological Studies, The Clayton Foundation Laboratories for Peptide Biology, La Jolla, CA (United States); Reubi, Jean Claude [University of Bern, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, Bern (Switzerland); Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-12-15

    Targeting of tumours positive for somatostatin receptors (sst) with radiolabelled peptides is of interest for tumour localization, staging, therapy follow-up and targeted radionuclide therapy. The peptides used clinically are exclusively agonists, but recently we have shown that the radiolabelled somatostatin-based antagonist {sup 111}In-DOTA-sst2-ANT may be preferable to agonists. However, a comprehensive study of this radiolabelled antagonist to determine its significance was lacking. The present report describes the evaluation of this novel antagonist labelled with {sup 111}In and {sup 177}Lu in three different tumour models. Radiopeptide binding, internalization and dissociation studies were performed using cells expressing HEK293-rsst{sub 2}. Biodistribution studies were performed in HEK293-rsst{sub 2}, HEK293-hsst{sub 2} and HEK293-rsst{sub 3} xenografted mice. Saturation binding analysis confirmed earlier IC{sub 50} data for {sup 111/nat}In-DOTA-sst2-ANT and showed similar affinity of {sup 177/nat}Lu-DOTA-sst2-ANT for the sst{sub 2}. Only low internalization was found in cell culture (6.68 {+-} 0.06 % at 4 h), which was not unexpected for an antagonist, and this could be further reduced by the addition of sucrose. No internalization was observed in HEK293 cells not expressing sst. Both results indicate that the internalization was specific. {sup 111}In-DOTA-sst2-ANT and {sup 177}Lu-DOTA-sst2-ANT were shown to target tumour xenografts expressing the rat and the human sst{sub 2} receptor with no differences in their uptake or pharmacokinetics. The uptake in rsst{sub 2} and hsst{sub 2} was high (about 30 %IA/g 4 h after injection) and surprisingly long-lasting (about 20-23 %IA/g 24 h after injection). Kidney uptake was blocked by approximately 50 % by lysine or Gelofusine. These results indicate that radiolabelled somatostatin-based antagonists may be superior to corresponding agonists. The long tumour retention time of {sup 177}Lu-DOTA-sst2-ANT indicates that

  15. 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;

    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...... arteries of wild type and COX-2(-/-) mice but it was significantly diminished in preparations from eNOS(-/-) mice. Aldosterone pretreatment inhibited recovery from wild type and COX-2(-/-) mice. The NO-donor sodium nitroprusside (SNP) restored recovery in arteries from eNOS(-/-) mice and this was inhibited...... 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...

  16. Clinical observation and analysis of aldosterone escape in patients with non-diabetic nephropathy by RASI-therapy%非糖尿病慢性肾病患者RASI治疗后醛固酮逃逸现象

    Institute of Scientific and Technical Information of China (English)

    杨庆春; 罗慧洁; 柏琳; 施海涛; 张志任

    2016-01-01

    Objective To investigate the incidence and influencing factors of aldosterone escape in patients with non-diabetic nephropathy by RASI-therapy. Methods A total of 104 patients with non-diabetic nephropathy were treated with ARB or combination therapy of ACEI and ARB in a mean follow-up period of 12 months. Aldosterone escape was determined according to the change of plasma aldosterone concentration before and after treatment during 6-month and 12-month ACEI/ARB treatment, while the influencing factors of aldosterone escape in patients with non-diabetic nephropathy was also analyzed after therapy with RASI . Results In 12 months, the incidence of aldosterone escape was significantly higher than that in 6 months (26.92% vs. 14.42%, P = 0.007). After 12-month treatment, the difference was statistically significant in incidence of aldosterone escape among different stages of CKD (P = 0.027). Compared with 6-month incidence of aldosterone escape in the losartan group, 12-month incidence increased evidently (P = 0.020). The Ald level was positively correlated with urinary protein excretion and the Scr level (r = 0.431, P = 0.003 and r = 0.336, P = 0.009, respectively), and negetively correlated with levels of the eGFR (r = -0.275, P = 0.006). Univariate Logistic regression demonstrated that risk factors of aldosterone escape included pre-treatment values of the urinary protein excretion (OR = 3.671, P = 0.028) and the eGFR (OR = 0.972, P = 0.019). Multivariate Logistic model revealed pre-treatment values of the eGFR was positively associated with aldosterone escape (OR = 0.970, P = 0.012). Conclusion The incidence of the aldosterone escape increases along with the time of treatment. Renal function has correlated with aldosterone escape and pre-treatment value of the eGFR is an independent risk factor of aldosterone escape.%目的:研究非糖尿病慢性肾病(CKD)患者醛固酮(Ald)逃逸的发生率及影响因素分析。方

  17. 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...... the short-term antiproteinuric effect and safety of the selective aldosterone antagonist eplerenone in non-diabetic CKD....

  18. Performance of ultrasound to monitor Achilles enthesitis in patients with ankylosing spondylitis during TNF-a antagonist therapy.

    Science.gov (United States)

    Wang, Cong-hua; Feng, Yuan; Ren, Zhen; Yang, Xichao; Jia, Jun-feng; Rong, Meng-yao; Li, Xue-yi; Wu, Zhen-biao

    2015-06-01

    Enthesitis is considered as the primary anatomical lesion in ankylosing spondylitis (AS). We aimed to investigate the potential of ultrasound to detect early changes after TNF-a antagonist therapy of Achilles enthesitis of AS patients. One hundred AS patients with active disease, requiring TNF-a antagonist therapy, were included (etanercept n = 25, infliximab n = 25, adalimumab n = 25, non-biologic disease-modifying antirheumatic drugs (DMARDs) n = 25). Physical examination was performed to evaluate disease activity and detect Achilles enthesitis and/or retrocalcaneal bursitis. Ultrasound of the Achilles enthesitis was performed bilaterally. Follow-up examinations were performed 3 months after the initiation of therapy. Gray scale (GS) scores, Power Doppler (PD) scores, and total additive scores (TS) decreased significantly during TNF-a antagonist therapy but not in traditional non-biologic traditional DMARDs group. The bath ankylosing spondylitis disease activity index (BASDAI), bath ankylosing spondylitis metrology index (BASMI), bath ankylosing spondylitis functional index (BASFI), and Maastricht ankylosing spondylitis enthesitis score (MASES) all showed significant improvements. When three different TNF-a antagonists were analyzed separately, no significant difference was observed in GS, PD, and total scores. Subclinical Achilles enthesitis, detected only with GS ultrasound, is present in a subset of AS patients and a significant improvement can be demonstrated after 3 months of TNF-a antagonist therapy. Doppler ultrasound provides a reliable estimation to monitor the therapeutic response to TNF antagonists in AS patients with Achilles enthesitis. TNF-a antagonists have been shown to be effective in decreasing ultrasound signs of enthesitis after 3 months of therapy in AS patients.

  19. Aldosterone and Its Blockade: A Cardiovascular and Renal Perspective

    Directory of Open Access Journals (Sweden)

    V. Lahera

    2006-01-01

    Full Text Available Aldosterone not only contributes to salt and water homeostasis, but also exerts direct cardiovascular and renal effects. Numerous experimental and clinical studies indicate that aldosterone participate in cardiac alterations associated with hypertension, heart failure, diabetes and other pathological entities. It is important to mention that dietary salt is a key factor in aldosterone-mediated cardiovascular damage, since damage was moreevident in animals on a high-salt diet than animals on a low salt diet. A pathophysiological action of aldosterone involves development of extracellular matrix and fibrosis, inflammation, stimulation of reactive oxygen species production, endothelial dysfunction, cell growth and proliferation. Many studies showed local extra-adrenal production of aldosterone in brain blood vessel, and the heart, which contribute in an important manner to the pathological actions of this mineralocorticoid.Several studies such as RALES, EPHESUS, 4E and others, recently showed that mineralocorticoid-receptor (MR antagonists, alone or in combination with ACE inhibitors or ARBs, reduced the risk of progressive target organ damage and hospitalization in patients with hypertension and heart failure. These clinical benefits support the therapeutic usefulness of MR antagonists.

  20. 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

  1. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies.

    Science.gov (United States)

    Graudins, Andis; Lee, Hwee Min; Druda, Dino

    2016-03-01

    Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This can also be the case for some BBs. Peak toxicity can be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation might mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings, to improve myocardial contractility, and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in the treatment of vasodilatory shock. Optimizing serum calcium concentration can confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock. PMID:26344579

  2. Intracerebral Hematoma Occurring During Warfarin Versus Non-Vitamin K Antagonist Oral Anticoagulant Therapy.

    Science.gov (United States)

    Takahashi, Haruhiko; Jimbo, Yasushi; Takano, Hiroki; Abe, Hiroshi; Sato, Masahito; Fujii, Yukihiko; Aizawa, Yoshifusa

    2016-07-15

    The neuroradiological findings and its outcomes of intracerebral hemorrhage (ICH) were compared between the non-vitamin K antagonist oral anticoagulant (NOAC) therapy and warfarin therapy. In the latest 3 years, 13 cases of nonvalvular atrial fibrillation on NOAC therapy were admitted for ICH. For comparison, 65 age- and gender-comparable patients with ICH on warfarin therapy were recruited. Three NOACs had been prescribed: dabigatran (n = 4), rivaroxaban (n = 2), and apixaban (n = 7). The average ages were 76 ± 9 and 78 ± 8 years in the warfarin (n = 65) and NOAC groups (n = 13), respectively. There was no difference in the clinical features, including the CHADS2 score or HAS-BLED score: 2.62 ± 1.31 versus 2.62 ± 1.33, or 1.09 ± 0.43 versus 1.00 ± 0.41, for the warfarin and NOAC groups, respectively. The volume of ICH warfarin (p = 0.0106). The expansion of hematoma was limited to 7 patients (10.8%) of the warfarin group. A lower hospital mortality and better modified Rankin Scale were observed in the NOAC group than in the warfarin group: 1 (7.7%) versus 27 (41.5%; p = 0.0105) and 3.2 ± 1.4 versus 4.5 ± 1.6 (p = 0.0057), respectively. In conclusion, ICH on NOAC therapy had smaller volume of hematoma with reduced rate of expansion and decreased mortality compared with its occurrence on warfarin. PMID:27289294

  3. Characteristics of Symptomatic Intracranial Hemorrhage in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulant Therapy.

    Directory of Open Access Journals (Sweden)

    Hisanao Akiyama

    Full Text Available The first non-vitamin K antagonist oral anticoagulant (NOAC introduced to the market in Japan was dabigatran in March 2011, and three more NOACs, rivaroxaban, apixaban, and edoxaban, have since become available. Randomized controlled trials of NOACs have revealed that intracranial hemorrhage (ICH occurs less frequently with NOACs compared with warfarin. However, the absolute incidence of ICH associated with NOACs has increased with greater use of these anticoagulants, and we wanted to explore the incidence, clinical characteristics, and treatment course of patients with NOACs-associated ICH.We retrospectively analyzed the characteristics of symptomatic ICH patients receiving NOACs between March 2011 and September 2014.ICH occurred in 6 patients (5 men, 1 woman; mean ± SD age, 72.8 ± 3.2 years. Mean time to onset was 146.2 ± 111.5 days after starting NOACs. Five patients received rivaroxaban and 1 patient received apixaban. None received dabigatran or edoxaban. Notably, no hematoma expansion was observed within 24 h of onset in the absence of infusion of fresh frozen plasma, activated prothrombin complex concentrate, recombinant activated factor VIIa or hemodialysis. When NOAC therapy was initiated, mean HAS-BLED and PANWARDS scores were 1.5 ± 0.5 and 39.5 ± 7.7, respectively. Mean systolic blood pressure was 137.8 ± 15.9 mmHg within 1 month before spontaneous ICH onset.Six symptomatic ICHs occurred early in NOAC therapy but hematoma volume was small and did not expand in the absence of infusion of reversal agents or hemodialysis. The occurrence of ICH during NOAC therapy is possible even when there is acceptable mean systolic blood pressure control (137.8 ± 15.9 mmHg and HAS-BLED score ≤ 2. Even stricter blood pressure lowering and control within the acceptable range may be advisable to prevent ICH during NOAC therapy.

  4. 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

  5. Aldosterone aggravates glucose intolerance induced by high fructose.

    Science.gov (United States)

    Sherajee, Shamshad J; Rafiq, Kazi; Nakano, Daisuke; Mori, Hirohito; Kobara, Hideki; Hitomi, Hirofumi; Fujisawa, Yoshihide; Kobori, Hiroyuki; Masaki, Tsutomu; Nishiyama, Akira

    2013-11-15

    We previously reported that aldosterone impaired vascular insulin signaling in vivo and in vitro. Fructose-enriched diet induces metabolic syndrome including hypertension, insulin resistance, hyperlipidemia and diabetes in animal. In the current study, we hypothesized that aldosterone aggravated fructose feeding-induced glucose intolerance in vivo. Rats were divided into five groups for six-week treatment; uninephrectomy (Unx, n=8), Unx+aldosterone (aldo, 0.75 µg/h, s.c., n=8), Unx+fructose (fruc, 10% in drinking water, n=8), Unx+aldo+fruc, (aldo+fruc, n=8), and Unx+aldo+fruc+spironolactone, a mineralocorticoid receptor antagonist (aldo+fruc+spiro, 20mg/kg/day, p.o., n=8). Aldo+fruc rats manifested the hypertension, and induced glucose intolerance compared to fruc intake rats assessed by oral glucose tolerance test, homeostasis model assessment of insulin resistance and hyperinsulinemic-euglycemic clamp study. Spironolactone, significantly improved the aldosterone-accelerated glucose intolerance. Along with improvement in insulin resistance, spironolactone suppressed upregulated mineralocorticoid receptor (MR) target gene, serum and glucocorticoid-regulated kinases-1 mRNA expression in skeletal muscle in aldo+fruc rats. In conclusion, these data suggested that aldosterone aggravates fructose feeding-induced glucose intolerance through MR activation.

  6. The History of Antithrombotic Therapy: The Discovery of Heparin, the Vitamin K Antagonists, and the Utility of Aspirin.

    Science.gov (United States)

    Handin, Robert I

    2016-10-01

    The administration of intravenous heparin to postoperative patients by Barritt and Jordan reduced the incidence of fatal and nonfatal pulmonary embolism and established heparin as the standard for parenteral anticoagulation. The coumarin family of vitamin K antagonists quickly became the standard for long-term oral anticoagulation. Aspirin became a widely used antithrombotic agent after the discovery that chronic oral administration reduced the incidence of secondary strokes and myocardial infarction. This article gives a brief history of antithrombotic therapy, including the discovery of heparin, the vitamin k antagonists, and the utility of aspirin. PMID:27637302

  7. Global- and renal-specific sympathoinhibition in aldosterone hypertension.

    Science.gov (United States)

    Lohmeier, Thomas E; Liu, Boshen; Hildebrandt, Drew A; Cates, Adam W; Georgakopoulos, Dimitrios; Irwin, Eric D

    2015-06-01

    Recent technology for chronic electric activation of the carotid baroreflex and renal nerve ablation provide global and renal-specific suppression of sympathetic activity, respectively, but the conditions for favorable antihypertensive responses in resistant hypertension are unclear. Because inappropriately high plasma levels of aldosterone are prevalent in these patients, we investigated the effects of baroreflex activation and surgical renal denervation in dogs with hypertension induced by chronic infusion of aldosterone (12 μg/kg per day). Under control conditions, basal values for mean arterial pressure and plasma norepinephrine concentration were 100±3 mm Hg and 134±26 pg/mL, respectively. By day 7 of baroreflex activation, plasma norepinephrine was reduced by ≈40% and arterial pressure by 16±2 mm Hg. All values returned to control levels during the recovery period. Arterial pressure increased to 122±5 mm Hg concomitant with a rise in plasma aldosterone concentration from 4.3±0.4 to 70.0±6.4 ng/dL after 14 days of aldosterone infusion, with no significant effect on plasma norepinephrine. After 7 days of baroreflex activation at control stimulation parameters, the reduction in plasma norepinephrine was similar but the fall in arterial pressure (7±1 mm Hg) was diminished (≈55%) during aldosterone hypertension when compared with control conditions. Despite sustained suppression of sympathetic activity, baroreflex activation did not have central actions to inhibit either the stimulation of vasopressin secretion or drinking induced by increased plasma osmolality during chronic aldosterone infusion. Finally, renal denervation did not attenuate aldosterone hypertension. These findings suggest that aldosterone excess may portend diminished blood pressure lowering to global and especially renal-specific sympathoinhibition during device-based therapy.

  8. 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

  9. "Ejaculatory disorders and α1-adrenoceptor antagonists therapy: clinical and experimental researches"

    Directory of Open Access Journals (Sweden)

    Lania Caterina

    2006-07-01

    Full Text Available Abstract Background It is well known that the use of the α-adrenergic receptor antagonists in the BPH therapy may induce ejaculatory disorder. A review of clinical literature shows a greater incidence of ejaculatory disorder during the use of tamsulosin compared with alfuzosin. Anejaculation has been until now referred to retrograde ejaculation due to relaxation of prostatic and bladder neck smooth muscle tone. In a recent researches was evaluated the effect of tamsulosin and alfuzosin on rat vas deferent "in vitro", concluding that tamsulosin may "cause ejaculatory dysfunction by altering the progression and emission of sperm". An abnormal increase of contraction would be the cause of ejaculatory disorder. The aim of our paper is to compare human and rat vas deferens contractile activity and to evaluate with a clinical study if tamsulosin causes retrograde ejaculation disorder. Methods We have revaluated the human and rat vas deferens contractile activity in vitro according to our experience and literature. We have also performed a clinical study on 10 patients (48–72 y affected by anejaculation. Post-coital urine was examined to search spermatozoa. Results Human and rat vas deferens activity is not comparable. Contractile activity induced by norepinephrin after tamsulosin incubation in rat prostatic vas deferens strips is similar to the contractile activity evoked by norepinephrin in human strips. Spermatozoa were found in post coital urine of 6 patients. Conclusion In our opinion the treatment with tamsulosin may induce retrograde ejaculation but not other ejaculatory disorder due to abnormal sperm progression.

  10. CXCR4-antagonist Peptide R-liposomes for combined therapy against lung metastasis.

    Science.gov (United States)

    Ieranò, Caterina; Portella, Luigi; Lusa, Sara; Salzano, Giuseppina; D'Alterio, Crescenzo; Napolitano, Maria; Buoncervello, Maria; Macchia, Daniele; Spada, Massimo; Barbieri, Antonio; Luciano, Antonio; Barone, Maria Vittoria; Gabriele, Lucia; Caraglia, Michele; Arra, Claudio; De Rosa, Giuseppe; Scala, Stefania

    2016-03-31

    The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide R were developed (PL-Peptide R). In vitro PL-Peptide R efficiently inhibited CXCR4-dependent migration and in vivo it significantly reduced lung metastases and increased overall survival in B16-CXCR4 injected C57BL/6 mice. To evaluate if PL-Peptide R could also be a drug delivery system for CXCR4 expressing tumors, the PL-Peptide R was loaded with doxorubicin (DOX) (PL-Peptide R-DOX). PL-Peptide R-DOX efficiently delivered DOX to CXCR4 expressing cell lines with a consequent decrease in the DOX IC50 efficient dose. In vivo, B16-CXCR4 injected C57BL/6 mice treated with PL-Peptide R-DOX developed fewer lung metastases compared to PL-DOX treated mice. This work provides the proof-of-concept to prevent metastasis by using combined nanomedicine. PMID:26983756

  11. 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

  12. 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.

  13. Survivin mRNA antagonists using locked nucleic acid, potential for molecular cancer therapy

    DEFF Research Database (Denmark)

    Fisker, Niels; Westergaard, Majken; Hansen, Henrik Frydenlund;

    2007-01-01

    synergistic effect when combining the mRNA antagonists against Survivin with the chemotherapeutic Taxol. This effect was demonstrated at concentrations of antagonists far lower than any previously demonstrated, indicating the high potential of locked nucleic acid for therapeutic use. Further characterisations...

  14. Opioid substitution and antagonist therapy trials exclude the common addiction patient: a systematic review and analysis of eligibility criteria

    OpenAIRE

    Brittany B. Dennis; Roshanov, Pavel S.; Naji, Leen; Bawor, Monica; Paul, James; Plater, Carolyn; Pare, Guillaume; Worster, Andrew; Varenbut, Michael; Daiter, Jeff; David C. Marsh; Desai, Dipika; Samaan, Zainab; Thabane, Lehana

    2015-01-01

    Background Eligibility criteria that result in the exclusion of a substantial number of patients from randomized trials jeopardize the generalizability of treatment effect to much of the clinical population. This is important when evaluating opioid substitution and antagonist therapies (OSATs), especially given the challenges associated with treating the opioid-dependent population. We aimed to identify OSAT trials' eligibility criteria, quantify the percentage of the clinical population excl...

  15. 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...

  16. CXCR4-antagonist Peptide R-liposomes for combined therapy against lung metastasis

    Science.gov (United States)

    Ieranò, Caterina; Portella, Luigi; Lusa, Sara; Salzano, Giuseppina; D'Alterio, Crescenzo; Napolitano, Maria; Buoncervello, Maria; Macchia, Daniele; Spada, Massimo; Barbieri, Antonio; Luciano, Antonio; Barone, Maria Vittoria; Gabriele, Lucia; Caraglia, Michele; Arra, Claudio; De Rosa, Giuseppe; Scala, Stefania

    2016-03-01

    The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide R were developed (PL-Peptide R). In vitro PL-Peptide R efficiently inhibited CXCR4-dependent migration and in vivo it significantly reduced lung metastases and increased overall survival in B16-CXCR4 injected C57BL/6 mice. To evaluate if PL-Peptide R could also be a drug delivery system for CXCR4 expressing tumors, the PL-Peptide R was loaded with doxorubicin (DOX) (PL-Peptide R-DOX). PL-Peptide R-DOX efficiently delivered DOX to CXCR4 expressing cell lines with a consequent decrease in the DOX IC50 efficient dose. In vivo, B16-CXCR4 injected C57BL/6 mice treated with PL-Peptide R-DOX developed fewer lung metastases compared to PL-DOX treated mice. This work provides the proof-of-concept to prevent metastasis by using combined nanomedicine.The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide

  17. 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.

  18. 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

  19. 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

  20. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement

    DEFF Research Database (Denmark)

    Solovic, I.; Sester, M.; Gomez-Reino, J.J.;

    2010-01-01

    Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased...

  1. A systematic review of prothrombin complex concentrate dosing strategies to reverse vitamin K antagonist therapy

    NARCIS (Netherlands)

    Khorsand, Nakisa; Kooistra, Hilde A. M.; van Hest, Reinier M.; Veeger, Nic J. G. M.; Meijer, Karina

    2015-01-01

    Management of patients with a major bleed while on vitamin K antagonist (VKA) is a common clinical challenge. Prothrombin Complex Concentrates (PCC) provide a rapid reversal of VKA induced coagulopathy. However, a well-defined PCC dosing strategy, especially in emergency setting, is still lacking. W

  2. The risk of tuberculosis related to tumour necrosis factor antagonist therapies : a TBNET consensus statement

    NARCIS (Netherlands)

    Solovic, I.; Sester, M.; Gomez-Reino, J. J.; Rieder, H. L.; Ehlers, S.; Milburn, H. J.; Kampmann, B.; Hellmich, B.; Groves, R.; Schreiber, S.; Wallis, R. S.; Sotgiu, G.; Scholvinck, E. H.; Goletti, D.; Zellweger, J. P.; Diel, R.; Carmona, L.; Bartalesi, F.; Ravn, P.; Duarte, R.; Erkens, C.; Clark, J.; Migliori, G. B.; Lange, C.

    2010-01-01

    Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased ris

  3. 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

  4. Why are mineralocorticoid receptor antagonists cardioprotective?

    NARCIS (Netherlands)

    W. Chai (Wenxia); A.H.J. Danser (Jan)

    2006-01-01

    textabstractTwo clinical trials, the Randomized ALdosterone Evaluation Study (RALES) and the EPlerenone HEart failure and SUrvival Study (EPHESUS), have recently shown that mineralocorticoid receptor (MR) antagonists reduce mortality in patients with heart failure on top of ACE inhibition. This effe

  5. Does route of administration affect the outcome of TNF antagonist therapy?

    OpenAIRE

    Schwartzman, Sergio; Morgan, G James

    2004-01-01

    The tumor necrosis factor (TNF) antagonists are parenterally administered biologic response modifiers indicated for the management of rheumatoid arthritis. Although infliximab, etanercept, and adalimumab are all members of this class, they differ in route of administration and dosing regimen. In the USA and in Europe, infliximab, in combination with oral methotrexate, is administered intravenously, initially at a dose of 3 mg/kg at weeks 0, 2, and 6, then every 8 weeks thereafter. The US Food...

  6. 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

  7. 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

  8. 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

  9. Incidence and influencing factors of aldosterone breakthrough in patients with non-diabetic nephro-pathy after therapy with RAAS inhibitor%RAAS抑制剂治疗后非糖尿病性慢性肾脏病患者醛固酮逃逸的发生率及影响因素

    Institute of Scientific and Technical Information of China (English)

    王敏; 张倩

    2016-01-01

    目的:研究非糖尿病性慢性肾脏病(CKD)患者醛固酮逃逸的发生率及影响因素。方法选取本院2013年9月至2014年3月收治的非糖尿病性CKD 152例患者为研究对象,并给予血管紧张素Ⅱ受体拮抗剂(ARB)或ARB联合血管紧张素转化酶抑制剂(ACEI)治疗12个月,根据治疗前后醛固酮水平的变化,确定是否发生醛固酮逃逸。结果肾素-血管紧张素-醛固酮系统(RAAS)抑制剂治疗12个月时醛固酮逃逸的发生率显著高于治疗6个月时醛固酮逃逸的发生率(26.97%︰14.47%,P=0.007)。24小时尿蛋白基线值、估算肾小球滤过率(eGFR)基线值与RAAS抑制剂治疗12个月醛固酮逃逸的发生相关(分别为:OR=3.671,P=0.028;OR=0.972,P=0.019),eGFR基线值是醛固酮逃逸的独立预测因素(OR=0.970,P=0.012)。结论部分非糖尿病性CKD患者在RAAS抑制剂治疗后出现醛固酮逃逸,醛固酮逃逸的发生率随RAAS抑制剂治疗时间延长呈升高趋势。eGFR基线值是醛固酮逃逸发生的独立预测因素。%ObjectiveTo investigate the incidence and influencing factors of aldosterone breakthrough in patients with non-diabetic nephropathy after therapy with RAAS inhibitor.MethodFrom September 2013 to March 2014, a total of 152 patients with non-diabetic nephropathy were treated with ARB or combination therapy of ACEI and ARB for a mean follow-up period of 12 months. Aldosterone breakthrough was determined according to the change of plasma aldosterone concentration before and after treatment during 6-month and 12-month ACEI/ARB treatment.ResultIn 12 months, the incidence of aldosterone breakthrough was signiifcantly higher than that in 6 months (26.97%︰14.47%,P=0.007). Univariate Logistic regression demonstrated that risk factors of aldosterone breakthrough included pre-treatment values of the urinary protein excretion (OR=3.671,P=0.028) and eGFR (OR=0.972,P=0

  10. 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.

  11. Targeting the aldosterone pathway in cardiovascular disease

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Azizi, Michel; Bauersachs, Johann;

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    1980-01-01

    Regional venous plasma aldosterone concentrations were determined and assessed against concurrent arterial levels in 16 patients with primary aldosteronism. The results obtained by sampling from the left adrenal vein or the left renal vein allowed correct side prediction of the presupposed adenoma...... in each patient. The problems caused by intermittent secretion of aldosterone by the tumour and the importance of correct positioning of the catheter are emphasized. Repeated sampling and continuing reference to systemic, arterial aldosterone levels proved valuable....

  13. Relationship between aldosterone and the metabolic syndrome in patients with obstructive sleep apnea hypopnea syndrome: effect of continuous positive airway pressure treatment.

    Directory of Open Access Journals (Sweden)

    Antonia Barceló

    Full Text Available BACKGROUND: Metabolic syndrome (MS occurs frequently in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS. We hypothesized that aldosterone levels are elevated in OSAHS and associated with the presence of MS. METHODS: We studied 66 patients with OSAHS (33 with MS and 33 without MS and 35 controls. The occurrence of the MS was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III clinical criteria. Measurements of plasma renin activity (PRA, aldosterone, aldosterone:PRA ratio, creatinine, glucose, triglycerides, cholesterol and HDL cholesterol were obtained at baseline and after CPAP treatment. RESULTS: Aldosterone levels were associated with the severity of OSAHS and higher than controls (p = 0.046. Significant differences in aldosterone levels were detected between OSAHS patients with and without MS (p = 0.041. A significant reduction was observed in the aldosterone levels in patients under CPAP treatment (p = 0.012. CONCLUSION: This study shows that aldosterone levels are elevated in OSAHS in comparison to controls, and that CPAP therapy reduces aldosterone levels. It also shows that aldosterone levels are associated with the presence of metabolic syndrome, suggesting that aldosterone excess might predispose or aggravate the metabolic and cardiovascular complications of OSAHS. TRIAL REGISTRATION: The study is not a randomized controlled trial and was not registered.

  14. Novel migraine therapy with calcitonin gene-regulated peptide receptor antagonists

    DEFF Research Database (Denmark)

    Edvinsson, Lars

    2007-01-01

    Primary headaches, for example, migraine and cluster headaches represent the most prevalent neurological disorders, affecting up to 15-20% of the adult population. There is a clear association between head pain and the release of calcitonin gene-related peptide (CGRP). In this review the role...... and that they are not vasoconstrictive, providing a new dimension in therapy....

  15. Therapy for acute pancreatitis with platelet-activating factor receptor antagonists

    Institute of Scientific and Technical Information of China (English)

    Chong Chen; Shi-Hai Xia; Hong Chen; Xiao-Hong Li

    2008-01-01

    Acute pancreatitis (AP) causes release of plateletactivating factor (PAF),which induces systemic effects that contribute to circulatory disturbances and multiple organ failure.PAF is a cell surface secretion of bioactive lipid,which could produce physiological and pathological effects by binding to its cell surface receptor called platelet-activating factor receptor (PAF-R).Studies showed that PAF participates in the occurrence and development of AP and administration of platelet-activating factor receptor antagonists (PAF-RAs) could significantly reduce local and systemic events after AP.PAF has also been implicated as a key mediator in the progression of severe AP,which can lead to complications and unacceptably high mortality rates.Several classes of PAF-RA show PAFRAs significant local and systemic effects on reducing inflammatory changes.As a preventive treatment,PAF-RA could block a series of PAF-mediatedinflammatory injury and thus improve the prognosis of AR This review introduces the important role of PAF-RA in the treatment of AP.

  16. [Therapy education for patients receiving oral anti-coagulants vitamin K antagonists].

    Science.gov (United States)

    Satger, Bernadette; Blaise, Sophie; Fontaine, Michèle; Yver, Jacqueline; Allenet, Benoît; Baudrant, Magali; Pernod, Gilles; Bosson, Jean-Luc

    2009-12-01

    The vitamin K antagonists (VKA) remain to this day the only oral form of therapeutic anticoagulation. Approximately 1% of the French population, mainly elderly, is treated with these anticoagulants. Oral anticoagulants have significant risks of iatrogenic complications; indeed they are the leading cause of such drug-induced complications, predominantly hemorrhages. AFSSAPS (French Drug and Medical Products Agency) clinical practice recommendations, repeatedly disseminated, emphasize the education of patients receiving VKAs. Managing oral anticoagulant treatment is challenging, with a significant risk of under- or overdosing and consequently, thrombosis or hemorrhage. The therapeutic window is narrow, multiple drug-interactions are possible, and the specific dose required for a particular individual to achieve appropriate International Normalized Ratio (INR) levels is unpredictable. The literature contains few randomized controlled trials about the efficacy of education for patients treated with oral anticoagulants. These education programs are not standardized and are therefore varied and difficult to compare. Nevertheless, studies demonstrate the importance of patient education programs in reducing the risk of hemorrhage and achieving better treatment stability. The Grenoble region hospital-community network for vascular diseases (GRANTED) has developed an education program for these patients, consisting of individual sessions for the patient and/or a friend or family member (either at a health care facility or at the patient's home), telephone support and group sessions, and using educational tools and supports. There is also a link with the general practitioner who receives a report. This approach makes it possible to adapt the educational message to individual patients and their daily lives, as well as directly involving them in the management of their treatment. PMID:19815369

  17. 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

  18. Aldosterone stimulates nuclear factor-kappa B activity and transcription of intercellular adhesion molecule-1 and connective tissue growth factor in rat mesangial cells via serum- and glucocorticoid-inducible protein kinase-1.

    Science.gov (United States)

    Terada, Yoshio; Ueda, Satoko; Hamada, Kazu; Shimamura, Yoshiko; Ogata, Koji; Inoue, Kosuke; Taniguchi, Yoshinori; Kagawa, Toru; Horino, Taro; Takao, Toshihiro

    2012-02-01

    Several clinical and experimental data support the hypothesis that aldosterone contributes to the progression of renal injury. To determine the signaling pathway of aldosterone in relation to fibrosis and inflammation in mesangial cells, we investigated the effects of aldosterone on expression and activation of serum- and glucocorticoid-inducible protein kinase-1 (SGK1), the activation of nuclear factor-kappa B (NF-κB activation, and the expressions of intercellular adhesion molecule-1 (ICAM-1) and connective tissue growth factor (CTGF). Aldosterone stimulated SGK1 expression, phosphorylation (Ser-256), and kinase activity. The increments of phosphorylation and expression of SGK1 induced by aldosterone were inhibited by mineralocorticoid receptor (MR) inhibitor (eplerenone). Aldosterone stimulated NF-κB activity measured by NF-κB responsive elements, luciferase assay, and the levels of inhibitor of kappa B (IκB) phosphorylation. This aldosterone-induced activation of NF-κB was inhibited by the transfection of dominant-negative SGK1. Furthermore, aldosterone augmented the promoter activities and protein expressions of ICAM-1 and CTGF. The effects of aldosterone on ICAM-1 and CTGF promoter activities and protein expressions were inhibited by the transfection of dominant-negative SGK1 and dominant-negative IκBα. We also found that the MR antagonist significantly ameliorated the glomerular injury and enhancements in SGK1, ICAM-1, and CTGF expressions induced by 1% sodium chloride and aldosterone in vivo. In conclusion, our findings suggest that aldosterone stimulates ICAM-1 and CTGF transcription via activation of SGK1 and NF-κB, which may be involved in the progression of aldosterone-induced mesangial fibrosis and inflammation. MR antagonists may serve as useful therapeutic targets for the treatment of glomerular inflammatory disease.

  19. 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

  20. 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.

  1. H_2-receptor Antagonist Therapy : With Special Reference to Ranitidine(Current Medical Therapy for Upper Gastrointestinal Ulcer Disease)

    OpenAIRE

    渡辺,裕; 村山, 久夫; Watanabe, Yutaka; Murayama, Hisao

    1988-01-01

    The cure rate for endoscopic therapy was determined in 61 patients with a gastroduodenal ulcer who received Ranitidine at a dose of 150 mg twice daily, in the morning and evening. The ulcer patients were classified into initial-, recurrent-and intractable-ulcer groups, and the cumulative cure rate was compared among the three types of ulcers. The cure rate was 93% for the initial ulcer, 78% for recurrent and 50% for intractable. Uncured ulcers accounted for about 10% of the patients, and the ...

  2. 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

  3. Intra-articular therapy with tumor necrosis factor-α antagonists: an update

    Directory of Open Access Journals (Sweden)

    S. Bello

    2014-03-01

    Full Text Available The aim of the study was to review from the present literature the intra-articular (IA use of the TNF-blocking drugs. A total of 28 papers about this topic were found through a search in PubMed; the first publication’s date was July 2003. These studies include a total of 214 patients affected by 12 different joint diseases that reported a total of 1046 intra-articular therapies carried out in 10 different joint sites. Infliximab and etanercept were the most widely used medications. The safety of this treatment clearly emerges from our analysis, while more difficult was the evaluation of its efficacy. Nevertheless we deduced an ideal patient profile that may better respond to the IA anti-TNF treatment.

  4. 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 ...

  5. Is self-monitoring an effective option for people receiving long-term vitamin K antagonist therapy? A systematic review and economic evaluation

    OpenAIRE

    Sharma, Pawana; Scotland, Graham; Cruickshank, Moira; Tassie, Emma; Fraser, Cynthia; Burton, Christopher; Croal, Bernard; Ramsay, Craig R.; Brazzelli, Miriam

    2015-01-01

    Objectives To investigate the clinical and cost-effectiveness of self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy compared with standard clinic care. Design Systematic review of current evidence and economic modelling. Data sources Major electronic databases were searched up to May 2013. The economic model parameters were derived from the clinical effectiveness review, routine sources of cost data and advice from clinical experts. Study eligibil...

  6. Antarlides: A New Type of Androgen Receptor (AR) Antagonist that Overcomes Resistance to AR-Targeted Therapy.

    Science.gov (United States)

    Saito, Shun; Fujimaki, Takahiro; Panbangred, Watanalai; Igarashi, Yasuhiro; Imoto, Masaya

    2016-02-18

    Prostate cancer is treated with androgen receptor (AR) antagonists but most patients experience disease progression after long-term treatment with these compounds. Therefore, new AR antagonists are required for patient follow-up treatment. In the course of screening for a new AR antagonist, we isolated the novel compounds antarlides A-E (1-5) from Streptomyces sp. BB47. Antarlides are mutually isomeric with respect to the double bond and have a 22-membered-ring macrocyclic structure. The full stereostructure of 1 was established by chemical modifications, including methanolysis, the Trost method, acetonide formation, and the PGME method. 1-5 inhibited the binding of androgen to ARs in vitro. In addition, 2 inhibited the transcriptional activity of not only wild-type AR but also mutant ARs, which are seen in patients with acquired resistance to clinically used AR antagonists. Therefore, antarlides are a potent new generation of AR antagonists that overcome resistance.

  7. 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

  8. Diagnostic evaluation of plasma aldosterone concentration to plasma renin activity ratio in primary aldosteronism

    Institute of Scientific and Technical Information of China (English)

    Huilan ZHANG; Daowen WANG

    2008-01-01

    Using the plasma aldosterone concentration to plasma renin activity ratio (PAC/PRA ratio) as the screening test of choice for primary aldosteronism in hypertensive patients, we studied the clinical character-istics and the diagnostic value of PAC/PRA ratio in primary aldosteronism. The plasma aldosterone concen-tration (PAC) and plasma renin activity (PRA) levels were measured by radioimmunoassay in 902 hypertensive patients from out-patient clinics or hospitals. One hundred and twenty-six suspected primary aldosteronism patients whose PAC/PRA ratio was > 25 ng/dL/ng/mL/ hr had a lamellar computed tomography (CT) scan in the adrenal gland and follow-up visits. The proportion of primary aldosteronism in hypertensive patients was 14% (126/902). There were 54 patients with unilateral or bilateral hyperplasia and 25 patients with adenoma according to the CT scan. 39% (49/126) of the patients with primary aldosteronism had hypokalemia. Twenty-five patients received surgical treatment. The efficacy and cure rates were 100% (25/25) and 48% (12/25), respect-ively. The effective rate of aldactone and the single-drug cure rate were 89% (48/54) and 24% (13/54), respectively. Primary aldosteronism affects over 10% of hypertensive patients in China. The PAC/PRA ratio can be considered as a routine screening test in hypertensives, especially resistant hypertensive patients and a high PAC/PRA ratio is an invaluable index in primary aldosteronism diagnosis.

  9. Aldosterone response to angiotensin II during hypoxemia

    Energy Technology Data Exchange (ETDEWEB)

    Colice, G.L.; Ramirez, G.

    1986-07-01

    Exercise stimulates the renin-angiotensin-aldosterone system (RAAS). However, increases in plasma aldosterone concentrations (PAC) are suppressed when exercise is performed at high altitude or under hypoxemic conditions. As the angiotensin-II response to high-altitude exercise is normal, it is speculated that an inhibitor, discharged during hypoxemia, acted to suppress angiotensin-II-mediated aldosterone release. A study was conducted to test this hypothesis, taking into account the measurement of the aldosterone response to exogenous angiotensin II during normoxemia and hypoxemia. It was found that the dose-response curve of PAC to angiotensin II was not significantly inhibited by the considered model of hypoxemia. The hypoxemia-mediated release of an angiotensin II inhibitor does, therefore, not explain the previous observations of PAC suppression during hypoxemic exercise. 28 references.

  10. Aldosterone assessment in patients with Meniere's disease

    NARCIS (Netherlands)

    Mateijsen, DJM; Kingma, CM; De Jong, PE; Wit, HP; Albers, FWJ

    2001-01-01

    Since 1938 endolymphatic hydrops has generally been accepted as the basic histopathological substrate of Meniere's disease. In animal studies it has been found that exogenous administration of aldosterone resulted in endolymphatic hydrops. Manifestations of Meniere's disease are frequently observed

  11. Increased aldosterone: mechanism of hypertension in obesity.

    Science.gov (United States)

    Flynn, Colleen

    2014-05-01

    The prevalence of both obesity and hypertension are increasing worldwide. Hypertension is a common consequence of obesity. Increased central adiposity is associated with increased aldosterone levels and blood pressure in human beings. A number of small studies have shown an association between obesity-mediated hypertension and mechanisms directly linked to increased levels of aldosterone. These studies have shown a trend toward relatively greater blood pressure reduction using aldosterone-receptor blockers compared with other classes of antihypertensive agents. Other than treatment for weight loss, treatment of hypertension with specific antihypertensive medications that block or reduce aldosterone action are appropriate in obese patients. Further research is needed to understand the exact role of the adipocyte in obesity-mediated hypertension.

  12. 醛固酮与代谢综合征%Aldosterone and metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    李平; 陈名道

    2010-01-01

    Aldosterone and metabolic syndrome are known cardiovascular risk factors associated with increased morbidity and mortality. This review focuses on the recent advances and clinical significance of the relationship between aldosterone and each single component of metabolic syndrome. The possible role of aldosterone receptor antagonist or aldosterone synthetase inhibitor in the treatment of metabolic syndrome is discussed.%醛固酮与代谢综合征均为心血管疾病危险因子.探讨醛固酮与代谢综合征之间的关系及机制有重要意义.本文综述了醛固酮与代谢综合征各组分之间相关性的最新进展和临床意义,探讨醛固酮受体拮抗剂或醛固酮合成酶抑制剂在代谢综合征治疗中的可能作用.

  13. 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

  14. Primary Aldosteronism and ARMC5 Variants

    Science.gov (United States)

    Zilbermint, Mihail; Xekouki, Paraskevi; Faucz, Fabio R.; Berthon, Annabel; Gkourogianni, Alexandra; Schernthaner-Reiter, Marie Helene; Batsis, Maria; Sinaii, Ninet; Quezado, Martha M.; Merino, Maria; Hodes, Aaron; Abraham, Smita B.; Libé, Rossella; Assié, Guillaume; Espiard, Stéphanie; Drougat, Ludivine; Ragazzon, Bruno; Davis, Adam; Gebreab, Samson Y.; Neff, Ryan; Kebebew, Electron; Bertherat, Jérôme; Lodish, Maya B.

    2015-01-01

    Context: Primary aldosteronism is one of the leading causes of secondary hypertension, causing significant morbidity and mortality. A number of genetic defects have recently been identified in primary aldosteronism, whereas we identified mutations in ARMC5, a tumor-suppressor gene, in cortisol-producing primary macronodular adrenal hyperplasia. Objective: We investigated a cohort of 56 patients who were referred to the National Institutes of Health for evaluation of primary aldosteronism for ARMC5 defects. Methods: Patients underwent step-wise diagnosis, with measurement of serum aldosterone and plasma renin activity followed by imaging, saline suppression and/or oral salt loading tests, plus adrenal venous sampling. Cortisol secretion was also evaluated; unilateral or bilateral adrenalectomy was performed, if indicated. DNA, protein, and transfection studies in H295R cells were conducted by standard methods. Results: We identified 12 germline ARMC5 genetic alterations in 20 unrelated and two related individuals in our cohort (39.3%). ARMC5 sequence changes in 6 patients (10.7%) were predicted to be damaging by in silico analysis. All affected patients carrying a variant predicted to be damaging were African Americans (P = .0023). Conclusions: Germline ARMC5 variants may be associated with primary aldosteronism. Additional cohorts of patients with primary aldosteronism and metabolic syndrome, particularly African Americans, should be screened for ARMC5 sequence variants because these may underlie part of the known increased predisposition of African Americans to low renin hypertension. PMID:25822102

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

    Energy Technology Data Exchange (ETDEWEB)

    Slavnov, V.N.; Yakovlev, A.A.; Gandzha, T.I.; Yugrinov, O.G. (AN Ukrainskoj SSR, Kiev)

    1985-01-01

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

  16. 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

  17. Role of ACTH and Other Hormones in the Regulation of Aldosterone Production in Primary Aldosteronism.

    Science.gov (United States)

    El Ghorayeb, Nada; Bourdeau, Isabelle; Lacroix, André

    2016-01-01

    The major physiological regulators of aldosterone production from the adrenal zona glomerulosa are potassium and angiotensin II; other acute regulators include adrenocorticotropic hormone (ACTH) and serotonin. Their interactions with G-protein coupled hormone receptors activate cAMP/PKA pathway thereby regulating intracellular calcium flux and CYP11B2 transcription, which is the specific steroidogenic enzyme of aldosterone synthesis. In primary aldosteronism (PA), the increased production of aldosterone and resultant relative hypervolemia inhibits the renin and angiotensin system; aldosterone secretion is mostly independent from the suppressed renin-angiotensin system, but is not autonomous, as it is regulated by a diversity of other ligands of various eutopic or ectopic receptors, in addition to activation of calcium flux resulting from mutations of various ion channels. Among the abnormalities in various hormone receptors, an overexpression of the melanocortin type 2 receptor (MC2R) could be responsible for aldosterone hypersecretion in aldosteronomas. An exaggerated increase in plasma aldosterone concentration (PAC) is found in patients with PA secondary either to unilateral aldosteronomas or bilateral adrenal hyperplasia (BAH) following acute ACTH administration compared to normal individuals. A diurnal increase in PAC in early morning and its suppression by dexamethasone confirms the increased role of endogenous ACTH as an important aldosterone secretagogue in PA. Screening using a combination of dexamethasone and fludrocortisone test reveals a higher prevalence of PA in hypertensive populations compared to the aldosterone to renin ratio. The variable level of MC2R overexpression in each aldosteronomas or in the adjacent zona glomerulosa hyperplasia may explain the inconsistent results of adrenal vein sampling between basal levels and post ACTH administration in the determination of source of aldosterone excess. In the rare cases of glucocorticoid remediable

  18. Aldosterone blockade in post-acute myocardial infarction heart failure

    NARCIS (Netherlands)

    Pitt, Bertram; Ferrari, Roberto; Gheorghiade, Mihai; van Veldhuisen, Dirk J.; Krum, Henry; McMurray, John; Lopez-Sendon, Jose

    2006-01-01

    Development of heart failure (HF) or left ventricular systolic dysfunction (LVSD) significantly increases mortality post acute myocardial infarction (AMI). Aldosterone contributes to the development and progression of HF post AMI, and major guidelines now recommend aldosterone blockade in this setti

  19. Hypokalemic rhabdomyolysis: a rare manifestation of primary aldosteronism.

    Science.gov (United States)

    Zavatto, A; Concistrè, A; Marinelli, C; Zingaretti, V; Umbro, I; Fiacco, F; Tinti, F; Petramala, L; Mitterhofer, A P; Letizia, C

    2015-10-01

    Rhabdomyolysis is a rare presentation of hypokalemia, although muscle weakness is a well-known manifestation of hypokalemia. Primary aldosteronism is characterized by hypertension, suppressed plasma renin activity, increased aldosterone excretion and hypokalemia with metabolic alkalosis. Rhabdomyolysis is not common in primary aldosteronism. We present here a 40-year-old woman presenting with rhabdomyolysis accompanied by severe hypokalemia as heralding symptom of primary aldosteronism.

  20. 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...... level of aldosterone is found in patients with AF, decreasing in patients with restored SR....

  1. 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

  2. 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...

  3. 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

  4. [Four cases of aldosterone synthase deficiency in childhood].

    Science.gov (United States)

    Collinet, E; Pelissier, P; Richard, O; Gay, C; Pugeat, M; Morel, Y; Stephan, J-L

    2012-11-01

    Neonatal salt-wasting syndromes are rare but potentially serious conditions. Isolated hypoaldosteronism is an autosomal recessive inherited disorder of terminal aldosterone synthesis, leading to selective aldosterone deficiency. Two different biochemical forms of this disease have been described, called aldosterone synthase deficiency or corticosterone methyl oxydase, types I and II. In type I, there is no aldosterone synthase activity and the 18 hydroxycorticosterone (18 OHB) level is low, whereas in type II, a residual activity of aldosterone synthase persists and 18 OHB is overproduced. We report on four patients with isolated hypoaldosteronism. In 2 of them, who were recently diagnosed with aldosterone synthase deficit, we discuss the symptoms and treatment. The 2 other patients are now adults. We discuss the long-term outcome, the quality of adult life, aldosterone synthase deficits, as well as the pathophysiology and molecular analysis.

  5. Aldosterone regulated sodium transport in the kidney

    NARCIS (Netherlands)

    Dijkink, Elizabeth Jacomina Wilhelmina

    2001-01-01

    The main factors influencing blood pressure are cardiac output, peripheral resistance, and Na+ balance. The blood Na+ concentration is tightly controlled by the amount of Na+ reabsorption in the distal nephron of the kidney. The Na+ reabsorption at these sites is under hormonal control of aldosteron

  6. Reviving the use of aldosterone inhibitors in treating hypertension in obesity.

    Science.gov (United States)

    Huby, Anne-Cecile; Belin De Chantemèle, Eric J

    2015-11-01

    Obesity is a multifactorial disease associated with hypertension. In the obese population, the incidence of hypertension is high and resistant hypertension is commonly observed. Mechanisms to explain the resistance to current antihypertensive treatments are still poorly understood. Emerging knowledge of the role of aldosterone in controlling blood pressure in obesity may have therapeutic benefit. Mineralocorticoid receptor (MR) inhibitors are currently used as the fourth line of treatment. Clinical studies summarized in this short review suggest that MR antagonists have a strong efficacy in decreasing blood pressure in the hypertensive obese population and could be used as a primary antihypertensive in obesity.

  7. Combination Therapy of Nifedipine and Sulphonylureas Exhibits a Mutual Antagonistic Effect on the Endothelial Cell Dysfunction Induced by Hyperglycemia Linked to Vascular Disease

    Directory of Open Access Journals (Sweden)

    Li-Ping Wang

    2016-05-01

    Full Text Available Background/Aims: By inducing severe endothelial impairment, hypertension and diabetes are two leading causes of morbidity and mortality. Hypertensive patients with concomitant diabetes must take both antihypertensive and hypoglycaemic medications, for which there is a lack of experimental and clinical guidelines. This study aimed to examine the interaction between these two types of medication on the endothelial cell function. Methods: The effect of antihypertensive (nifedipine and irbesartan and anti-diabetic (metformin and glibenclamide/glimepiride drugs on human umbilical vein cells (HUVECs function was examined using a modified Boyden chamber assay. The intracellular NO and O2- levels of HUVECs were detected through flow cytometry. Results: Our findings showed that nifedipine/sulphonylurea monotherapy significantly attenuated high glucose-induced (33 mM HUVECs migration incapacity, while combination therapy of nifedipine and glibenclamide/glimepiride showed no protective effect. Both nifedipine/metformin monotherapy and combined therapy significantly mitigated the migration incapacity induced by high glucose in HUVECs. Combined with either metformin or sulphonylureas, irbesartan therapy was able to attenuate the high glucose-induced migration incapacity of HUVECs. Nifedipine monotherapy decreased the O2- levels and increased the NO levels in in vitro-cultured HUVECs treated with high glucose. However, the combination therapy of nifedipine and glibenclamide increased the O2- levels and decreased the NO levels compared to the nifedipine monotherapeutic group. Conclusion: The nifedipine and glibenclamide/glimepiride combination exerted a mutual antagonistic effect on the protection from high glucose-induced impairment in endothelial cells, which might be partially attributed to the increased O2- level and decreased NO level. These results imply that calcium channel blockers + sulphonylurea combination therapy warrants further attention in

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Lumayi Ruth

    2008-04-01

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

  10. 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.

  11. Aldosterone and the heart: still an unresolved issue?

    Directory of Open Access Journals (Sweden)

    Cristiana eCatena

    2014-10-01

    Full Text Available Receptors for mineralocorticoid hormones are expressed in myocardial cells and evidence obtained in animal studies suggests that activation of these receptors causes cardiac damage independent from blood pressure levels. In the last years, many of the issues related to the effects of aldosterone on the heart have received convincing answers and clinical investigation has focused on a variety of conditions including systolic and diastolic heart failure, arrhythmia, primary hypertension, and primary aldosteronism. Some issues, however, await clarification in order to obtain better understanding of what could be the role of aldosterone blockade in prevention and treatment of cardiovascular diseases. In this article, we overview the most recent findings of animal studies that have examined the contribution of aldosterone to cardiac function and clinical studies that have investigated the influence of aldosterone on left ventricular structure and function in the setting of primary hypertension and primary aldosteronism.

  12. 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.

  13. 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...

  14. A critical review of the evidence supporting aldosterone in the etiology and its blockade in the treatment of obesity-associated hypertension.

    Science.gov (United States)

    Byrd, J B; Brook, R D

    2014-01-01

    Obesity is epidemic and is associated with increased blood pressure, which often manifests as treatment-resistant hypertension. Mineralocorticoids have been hypothesized to have a pathogenic role in human obesity-associated hypertension. In this review, we critically appraise the existing data regarding aldosterone in the pathophysiology and treatment of obesity-associated hypertension. We begin by reviewing the mechanisms by which obesity may increase mineralocorticoid activity. We then discuss human studies of plasma and urine aldosterone in obesity and with weight loss. From these studies, we conclude that aldosterone is often, but not always, mildly increased in obesity. Further study is needed to define circumstances in which aldosterone is increased in obesity. We discuss clinical studies in which measures of body size or weight were evaluated as potential predictors of response to mineralocorticoid receptor antagonists. In addition, we review three randomized, controlled clinical trials that exemplify a rigorous approach to determining the role of mineralocorticoid activity in a human disease. We propose that a similar clinical trial is warranted in order to definitively clarify the role of inappropriate mineralocorticoid activity in the etiology of human obesity-associated hypertension. Finally, we conclude that additional research is needed into the possible role of non-aldosterone mineralocorticoids in human obesity-associated hypertension.

  15. 醛固酮对靶器官心脏的损伤作用%Cardiac Injury Caused by Aldosterone

    Institute of Scientific and Technical Information of China (English)

    张美娟

    2011-01-01

    醛固酮可由心脏及血管生成并在心血管系统的调节及多种心血管疾病的致病过程中起重要的作用,且独立于通过调节盐水平衡而介导的血压升高.醛固酮受体拮抗剂如螺内酯及依普利酮可以显著降低心力衰竭患者的发病率及病死率.醛固酮与盐皮质激素受体结合并通过多种机制造成靶器官心脏的损伤.心脏组织醛固酮与盐皮质激素受体结合有赖于11β-羟基类固醇脱氢酶2型的表达,且其心脏损伤与食盐摄入水平有关,新近研究显示醛固酮在心脏电重构中起重要作用.%Aldosterone, which can be generated by the heart and blood vessels,also plays an important role in pathogenesis of several cardiovascular diseases, and the effect is independent from the elevation of blood pressure which is mediated by water and sodium regulation. Clinical studies show that aldosterone receptor antagonists such as spironolactone and eplerenone reduced the incidence of morbidity and mortality of patients with heart failure significantly. The combination of aldosterone and mineralocorticoid receptor( MR ), which is dependent on the expression of 11 (3-hydroxysteroid dehydrogenase type 2, injures the heart through a variety of mechanisms, and the heart injury of aldosterone is correlated with salt intake. Recent study showed that aldosterone play an important role in cardiac electrical remodeling.

  16. PTEN deficiency promotes macrophage infiltration and hypersensitivity of prostate cancer to IAP antagonist/radiation combination therapy.

    Science.gov (United States)

    Armstrong, Chris W D; Maxwell, Pamela J; Ong, Chee Wee; Redmond, Kelly M; McCann, Christopher; Neisen, Jessica; Ward, George A; Chessari, Gianni; Johnson, Christopher; Crawford, Nyree T; LaBonte, Melissa J; Prise, Kevin M; Robson, Tracy; Salto-Tellez, Manuel; Longley, Daniel B; Waugh, David J J

    2016-02-16

    PTEN loss is prognostic for patient relapse post-radiotherapy in prostate cancer (CaP). Infiltration of tumor-associated macrophages (TAMs) is associated with reduced disease-free survival following radical prostatectomy. However, the association between PTEN loss, TAM infiltration and radiotherapy response of CaP cells remains to be evaluated. Immunohistochemical and molecular analysis of surgically-resected Gleason 7 tumors confirmed that PTEN loss correlated with increased CXCL8 expression and macrophage infiltration. However PTEN status had no discernable correlation with expression of other inflammatory markers by CaP cells, including TNF-α. In vitro, exposure to conditioned media harvested from irradiated PTEN null CaP cells induced chemotaxis of macrophage-like THP-1 cells, a response partially attenuated by CXCL8 inhibition. Co-culture with THP-1 cells resulted in a modest reduction in the radio-sensitivity of DU145 cells. Cytokine profiling revealed constitutive secretion of TNF-α from CaP cells irrespective of PTEN status and IR-induced TNF-α secretion from THP-1 cells. THP-1-derived TNF-α increased NFκB pro-survival activity and elevated expression of anti-apoptotic proteins including cellular inhibitor of apoptosis protein-1 (cIAP-1) in CaP cells, which could be attenuated by pre-treatment with a TNF-α neutralizing antibody. Treatment with a novel IAP antagonist, AT-IAP, decreased basal and TNF-α-induced cIAP-1 expression in CaP cells, switched TNF-α signaling from pro-survival to pro-apoptotic and increased radiation sensitivity of CaP cells in co-culture with THP-1 cells. We conclude that targeting cIAP-1 can overcome apoptosis resistance of CaP cells and is an ideal approach to exploit high TNF-α signals within the TAM-rich microenvironment of PTEN-deficient CaP cells to enhance response to radiotherapy. PMID:26799286

  17. 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...

  18. 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.

  19. Early autophagy activation inhibits podocytes from apoptosis induced by aldosterone

    Institute of Scientific and Technical Information of China (English)

    王文琰

    2013-01-01

    Objective To explore the protection of early autoph-agy activation on podocyte injury induced by aldosterone.Methods In vitro cultured mouse podocyte clones(MPC5) were treated with aldosterone for 6,12,24,48 hrespectively. Apoptosis of podocytes was detected by

  20. Prevalence of Malignancies in Patients With Primary Aldosteronism.

    Science.gov (United States)

    Lang, K; Weber, K; Quinkler, M; Dietz, A S; Wallaschofski, H; Hannemann, A; Friedrichs, N; Rump, L C; Heinze, B; Fuss, C T; Quack, I; Willenberg, H S; Reincke, M; Allolio, B; Hahner, S

    2016-04-01

    In the multicenter MEPHISTO study, the prevalence of benign and malignant tumors has been investigated in 335 patients with confirmed primary aldosteronism and compared to matched controls. Compared to hypertensive controls, the prevalence of malignancies was positively correlated with aldosterone levels, tended to be higher in PA patients, but did not differ significantly.

  1. Adrenal vein sampling in the diagnosis of aldosteronism

    Directory of Open Access Journals (Sweden)

    Deipolyi AR

    2015-06-01

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

  2. Effect of platelet-activating factor receptor antagonist, etizolam, on resolution of chronic subdural hematoma. A prospective study to investigate use as conservative therapy

    International Nuclear Information System (INIS)

    Inflammatory reaction is very important for formation of the neomembrane of chronic subdural hematoma (CSDH). The present study evaluated medical treatment with the platelet-activating factor receptor antagonist, etizolam, for the resolution of CSDH, and the factors indicating surgery or conservative therapy. Alternate patients were assigned to the etizolam group or control group without medical treatment. Patients in the etizolam group received 3.0 mg etizolam per day for 14 days. A total of 53 patients were followed up for at least 6 months. Univariate analysis of differences in demographic characteristics, clinical findings, and initial computed tomography (CT) findings, and multiple logistic regression analysis of the relationship between etizolam treatment and requirement for surgery using age, sex, low density of hematoma on CT, and paresis as confounders were performed. Etizolam treatment (adjusted odds ratio [OR] 0.156, 95% confidence interval [CI] 0.024-0.999, p=0.049) was negatively correlated with requirement for surgery. Low density of hematoma (adjusted OR 0.125, 95% CI 0.019-0.846, p=0.033) was found to be an independent negative predictor, and paresis as an initial symptom (adjusted OR 6.35, 95% CI 1.04-38.7, p=0.045) was an independent positive predictor of requirement for surgery. Etizolam administration can promote the resolution of CSDH, especially at the stage of hygroma appearing as low density on CT. Surgery is recommended if the patient presents with paresis. (author)

  3. Effect of platelet-activating factor receptor antagonist, etizolam, on resolution of chronic subdural hematoma--a prospective study to investigate use as conservative therapy.

    Science.gov (United States)

    Hirashima, Yutaka; Kurimoto, Masanori; Nagai, Shoichi; Hori, Emiko; Origasa, Hideki; Endo, Shunro

    2005-12-01

    Inflammatory reaction is very important for formation of the neomembrane of chronic subdural hematoma (CSDH). The present study evaluated medical treatment with the platelet-activating factor receptor antagonist, etizolam, for the resolution of CSDH, and the factors indicating surgery or conservative therapy. Alternate patients were assigned to the etizolam group or control group without medical treatment. Patients in the etizolam group received 3.0 mg etizolam per day for 14 days. A total of 53 patients were followed up for at least 6 months. Univariate analysis of differences in demographic characteristics, clinical findings, and initial computed tomography (CT) findings, and multiple logistic regression analysis of the relationship between etizolam treatment and requirement for surgery using age, sex, low density of hematoma on CT, and paresis as confounders were performed. Etizolam treatment (adjusted odds ratio [OR] 0.156, 95% confidence interval [CI] 0.024-0.999, p = 0.049) was negatively correlated with requirement for surgery. Low density of hematoma (adjusted OR 0.125, 95% CI 0.019-0.846, p = 0.033) was found to be an independent negative predictor, and paresis as an initial symptom (adjusted OR 6.35, 95% CI 1.04-38.7, p = 0.045) was an independent positive predictor of requirement for surgery. Etizolam administration can promote the resolution of CSDH, especially at the stage of hygroma appearing as low density on CT. Surgery is recommended if the patient presents with paresis. PMID:16377949

  4. Tumor necrosis factor-alpha and interleukin-1 antagonists alleviate inflammatory skin changes associated with epidermal growth factor receptor antibody therapy in mice.

    Science.gov (United States)

    Surguladze, David; Deevi, Dhanvanthri; Claros, Nidia; Corcoran, Erik; Wang, Su; Plym, Mary Jane; Wu, Yan; Doody, Jacqueline; Mauro, David J; Witte, Larry; Busam, Klaus J; Pytowski, Bronek; Rodeck, Ulrich; Tonra, James R

    2009-07-15

    Cancer patients receiving epidermal growth factor receptor (EGFR) antibody therapy often experience an acneiform rash of uncertain etiology in skin regions rich in pilosebaceous units. Currently, this condition is treated symptomatically with very limited, often anecdotal success. Here, we show that a monoclonal antibody targeting murine EGFR, ME1, caused a neutrophil-rich hair follicle inflammation in mice, similar to that reported in patients. This effect was preceded by the appearance of lipid-filled hair follicle distensions adjacent to enlarged sebaceous glands. The cytokine tumor necrosis factor-alpha (TNFalpha), localized immunohistochemically to this affected region of the pilosebaceous unit, was specifically up-regulated by ME1 in skin but not in other tissues examined. Moreover, skin inflammation was reduced by cotreatment with the TNFalpha signaling inhibitor, etanercept, indicating the involvement of TNFalpha in this inflammatory process. Interleukin-1, a cytokine that frequently acts in concert with TNFalpha, is also involved in this process given the efficacy of the interleukin-1 antagonist Kineret. Our results provide a mechanistic framework to develop evidence-based trials for EGFR antibody-induced skin rash in patients with cancer. PMID:19584274

  5. 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

  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. GABAB antagonists

    DEFF Research Database (Denmark)

    Frydenvang, Karla Andrea; Hansen, J J; Krogsgaard-Larsen, P;

    1994-01-01

    Phaclofen, which is the phosphonic acid analogue of the GABAB agonist (RS)-3-(4-chlorophenyl)-4-aminobutyric acid (baclofen), is a GABAB antagonist. As part of our studies on the structural requirements for activation and blockade of GABAB receptors, we have resolved phaclofen using chiral...... chromatographic techniques. The absolute stereochemistry of (-)-(R)-phaclofen was established by X-ray crystallographic analysis. (-)-(R)-Phaclofen was shown to inhibit the binding of [3H]-(R)-baclofen to GABAB receptor sites on rat cerebellar membranes (IC50 = 76 +/- 13 microM), whereas (+)-(S)-phaclofen was...... inactive in this binding assay (IC50 > 1000 microM). (-)-(R)-Phaclofen (200 microM) was equipotent with (RS)-phaclofen (400 microM) in antagonizing the action of baclofen in rat cerebral cortical slices, while (+)-(S)-phaclofen (200 microM) was inactive. The structural similarity of the agonist (R)-baclofen...

  8. 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.

  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. Raised plasma aldosterone and natriuretic peptides in atrial fibrillation

    DEFF Research Database (Denmark)

    Dixen, U; Ravn, L; Soeby-Rasmussen, C;

    2007-01-01

    During atrial fibrillation (AF), the renin-angiotensin-aldosterone system (RAAS) may be activated. In this study, our aim was to evaluate at a long-term follow-up visit the levels of plasma aldosterone and natriuretic peptides as markers of neurohormonal remodeling in patients with earlier......, documented AF in relation to present heart rhythm, clinical data, and the left ventricular ejection fraction (LVEF). We hypothesized that increased levels of aldosterone and natriuretic peptides were significantly associated with present AF as markers of RAAS activation during the arrhythmia....

  12. The risk of bleeding of triple therapy with vitamin K-antagonists, aspirin and clopidogrel after coronary stent implantation: Facts and questions

    Institute of Scientific and Technical Information of China (English)

    Andrea Rubboli

    2011-01-01

    Background Triple therapy (TT) with vitamin K-antagonists (VKA),aspirin and clopidogrel is the recommended antithrombotic treatment following percutaneous coronary intervention with stent implantation (PCI-S) in patients with an indication for oral anticoagulation.TT is associated with an increased risk of bleeding,but available evidence is flawed by important limitations,including the limited size and the retrospective design of most of the studies,as well as the rare reporting of the incidence of in-hospital bleeding and the treatment which was actually ongoing at the time of bleeding.Since the perceived high bleeding risk of TT may deny patients effective strategies,the determination of the true safety profile of TT is of paramount importance.Methods All the 27 published studies where the incidence of bleeding at various time points during follow-up has been reported separately for patients on TT were reviewed,and the weakness of the data was analyzed.Results The absolute incidence of major bleeding upon discharge at in-hospital,< 1 month,6 months,12 months and ≥ 12months was: 3.3% ± 1.9%,5.1% ± 6.7%,8.0% ± 5.2%,9.0% ± 8.0,and 6.2% ± 7.8%,respectively,and not substantially different from that observed in previous studies with prolonged dual antiplatelet treatment with aspirin and clopidogrel.Conclusions While waiting for the ongoing,large-scale,registries and clinical trials to clarify the few facts and to answer the many questions regarding the risk of bleeding of TT,this treatment should not be denied to patients with an indication for VKA undergoing PCI-S provided that the proper measures and cautions are implemented.

  13. Non-Vitamin K Antagonist Oral Anticoagulants and Antiplatelet Therapy for Stroke Prevention in Patients With Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Kumar, Shashi; Danik, Stephan B; Altman, Robert K; Barrett, Conor D; Lip, Gregory Y H; Chatterjee, Saurav; Roubin, Gary S; Natale, Andrea; Danik, Jacqueline S

    2016-01-01

    Non-vitamin K antagonist oral anticoagulants (NOACs) are frequently used to prevent stroke in patients with atrial fibrillation. These patients are often also on aspirin or other antiplatelet agents. It is possible that treatment with both NOACs and aspirin or other antiplatelet drug may be effective in decreasing stroke, but data are sparse regarding the efficacy and safety of using both agents for stroke prevention. To address these issues, data were pooled from the 4 recent randomized, controlled trials of NOACs: apixaban, rivaroxaban, dabigatran, and edoxaban, which included 42,411 patients; 14,148 (33.4%) were also on aspirin or other antiplatelet drug. The number of thromboembolic events among participants on NOAC and aspirin/antiplatelet was compared with the number of events in patients on NOAC alone. Bleeding rates were also compared between those on NOAC + aspirin/antiplatelet and on NOAC alone. These results were compared with thromboembolic and bleeding events in the warfarin + aspirin/antiplatelet versus warfarin alone. No greater risk for thromboembolism was seen in patients on NOACs compared with patients on both NOACs and aspirin/antiplatelet drug. In this nonrandomized comparison, there was initially a signal toward higher thromboembolic rates among NOAC users also on aspirin/antiplatelet drugs (relative risk, 1.16; 95% confidence intervals, 1.05, 1.29) when compared with NOAC alone. This likely reflected the higher CHADS2 scores of those on aspirin/antiplatelet drugs. When the analysis was limited to studies that included aspirin rather than other antiplatelet drugs, no difference was seen for thromboembolic rates comparing dual therapy to NOAC alone (relative risk, 1.02; 95% confidence intervals, 0.90, 1.15). Higher rates of bleeding were seen with aspirin/antiplatelet drug in conjunction with NOAC. In this meta-analysis and nonrandomized comparison of aspirin/antiplatelet users and nonusers also on anticoagulation, there was no additional

  14. 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

  15. 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.

  16. ACTH Antagonists

    Science.gov (United States)

    Clark, Adrian John; Forfar, Rachel; Hussain, Mashal; Jerman, Jeff; McIver, Ed; Taylor, Debra; Chan, Li

    2016-01-01

    Adrenocorticotropin (ACTH) acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R), is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP) for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1) Cushing’s disease and ectopic ACTH syndrome – especially while preparing for definitive treatment of a causative tumor, or in refractory cases, or (2) congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article, we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role. PMID:27547198

  17. ACTH antagonists

    Directory of Open Access Journals (Sweden)

    Adrian John Clark

    2016-08-01

    Full Text Available ACTH acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1 Cushing’s disease and ectopic ACTH syndrome – especially whilst preparing for definitive treatment of a causative tumour, or in refractory cases, or (2 congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role.

  18. ACTH Antagonists.

    Science.gov (United States)

    Clark, Adrian John; Forfar, Rachel; Hussain, Mashal; Jerman, Jeff; McIver, Ed; Taylor, Debra; Chan, Li

    2016-01-01

    Adrenocorticotropin (ACTH) acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R), is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP) for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1) Cushing's disease and ectopic ACTH syndrome - especially while preparing for definitive treatment of a causative tumor, or in refractory cases, or (2) congenital adrenal hyperplasia - as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article, we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role. PMID:27547198

  19. 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)

  20. Raised Plasma Aldosterone and Natriuretic Peptides in Atrial Fibrillation

    DEFF Research Database (Denmark)

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

    2006-01-01

    BACKGROUND AND AIMS: During atrial fibrillation (AF), the renin-angiotensin-aldosterone system (RAAS) may be activated. In this study, our aim was to evaluate at a long-term follow-up visit the levels of plasma aldosterone and natriuretic peptides as markers of neurohormonal remodeling in patients...... with earlier, documented AF in relation to present heart rhythm, clinical data, and the left ventricular ejection fraction (LVEF). We hypothesized that increased levels of aldosterone and natriuretic peptides were significantly associated with present AF as markers of RAAS activation during the arrhythmia....... METHODS: We studied 158 patients with earlier ECG-documented AF followed by restored sinus rhythm (SR) attending a follow-up visit 2.6 years (mean) after primary inclusion. RESULTS: At follow-up, 93 patients had SR. Heart rhythm at follow-up visit (SR/AF), plasma aldosterone, plasma N-terminal pro Brain...

  1. 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

  2. 醛固酮诱导大鼠肾脏衰老机制研究%Mechanism of aldosterone induced rat kdney senescence

    Institute of Scientific and Technical Information of China (English)

    范愈燕; 孙永新; 支楠; 张善东; 黄雯; 张梅; 西山成

    2013-01-01

    目的 观察醛固酮是否诱导肾脏衰老.方法 将大鼠右肾切除后随机分为4组:对照组(n=10)、模型组(n=8)、依普利酮组(100 mg·kg-1·d-1;n=8)及肼苯哒嗪组(80 mg· L-1,饮用;n=10);除对照组外,其余各组分别泵入醛固酮(0.75 μg·h-1),观察5周后肾脏衰老改变.结果 醛固酮可诱导5周龄的大鼠肾组织衰老标记物β-ga1、p53和p21表达升高,SIRT1基因表达下降,伴高血压及蛋白尿、N-乙酰基-β-D氨基葡萄糖苷酶(NAG)的排泄率增加,这些变化可以被依普利酮阻断,但是肼苯哒嗪影响不大.结论 醛固酮诱导肾小管上皮细胞损伤和衰老是通过醛固酮受体和p21依赖的途径.%Objective To investigate whether aldosterone induces cell senescence in the kidney. Methods Rats were randomly separated to vehicle (n = 10) ; aldosterone (0. 75 μg · h-1 ; n=8) ; aldosterone + eplerenone (100mg · kg-1 · d-1 ; n = 8 ) ; aldosterone + hydralazine (80 mg · L-1 in drinking water; n - 10). Results Aldosterone induced rats for 5 weeks exhibited by increased expression of senescence - associated β - galactosidase , p53 and cyclin - dependent kinase inhibitor ( p21) , and decreased expression of SIRT1. While, rats also showed hypertension and increased urinary excretion rates of proteins and N - acetyl - β - D - glucosaminidase by aldosterone infusion. These changes were abolished by eplerenone, a mineralocorticoid receptor (MR) antagonist, but unaffected by hydralazine (80 mg/liter in drinking water). Conclusion These findings indicate that aldosterone induces renal senescence in proximal tubular cells via the MR and p21 - dependent pathway, which may be involved in aldosterone - induced renal injury.

  3. 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

  4. Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion.

    Science.gov (United States)

    Qi, Ying; Wang, Xiaojing; Rose, Kristie L; MacDonald, W Hayes; Zhang, Bing; Schey, Kevin L; Luther, James M

    2016-02-01

    Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry-based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112-122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112-122] concentration may provide a useful biomarker of ENaC activation in future clinical studies.

  5. 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

  6. Long-acting muscarinic antagonist use in adults with asthma: real-life prescribing and outcomes of add-on therapy with tiotropium bromide

    Directory of Open Access Journals (Sweden)

    Price D

    2015-01-01

    Full Text Available David Price,1,2 Alan Kaplan,3 Rupert Jones,4 Daryl Freeman,5 Anne Burden,2 Shuna Gould,2 Julie von Ziegenweidt,2 Muzammil Ali,2 Christine King,2 Mike Thomas6 1Academic Centre of Primary Care, University of Aberdeen, Aberdeen, 2Research in Real-Life, Cambridge, UK; 3Family Physician Airways Group of Canada, Richmond Hill, ON, Canada; 4Centre for Clinical Trials and Health Research, Plymouth University, Plymouth, 5Norfolk Community Health and Care NHS Trust, Norwich, 6Primary Care Research, University of Southhampton, Southhampton, UK Background: Randomized controlled trials indicate that addition of a long-acting muscarinic antagonist (LAMA such as tiotropium may improve asthma control and reduce exacerbation risk in patients with poorly controlled asthma, but broader clinical studies are needed to investigate the effectiveness of LAMA in real-life asthma care. Methods: Medical records of adults with asthma (aged ≥18 years prescribed tiotropium were obtained from the UK Optimum Patient Care Research Database for the period 2001–2013. Patients diagnosed with chronic obstructive pulmonary disease were excluded, but no other clinical exclusions were applied. Two primary outcomes were compared in the year before (baseline and the year after (outcome addition of tiotropium: exacerbations (asthma-related hospital emergency department attendance or inpatient admission, or acute oral corticosteroid course and acute respiratory events (exacerbation or antibiotic prescription with lower respiratory consultation. Secondary outcomes included lung function test results and short-acting β2 agonist usage. The Wilcoxon signed-rank test was used for variables measured on the interval scale, the marginal homogeneity test for categorized variables, and the paired t-test for lung function indices. Results: Of the 2,042 study patients, 83% were prescribed an inhaled corticosteroid and 68% a long-acting ß2 agonist during the baseline year; 67% were prescribed

  7. The mineralocorticoid receptor-p38MAPK-NFκB or ERK-Sp1 signal pathways mediate aldosterone-stimulated inflammatory and profibrotic responses in rat vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Chuan-jiang ZHU; Qing-qing WANG; Jun-lan ZHOU; Han-zhi LIU; Fang HUA; Hong-zheng YANG; Zhuo-wei HU

    2012-01-01

    Aim:To explore the signalling pathways involved in aldosterone-induced inflammation and fibrosis in rat vascular smooth muscle cells (VSMCs).Methods:Using Western blotting and real-time RT-PCR,we investigated the effects of aldosterone on the expression of cyclooxygenase-2 (Cox-2) and IL-6,two important proinflammatory factors,and TGFβ1,a critical profibrotic factor,in VSMCs.Results:Aldosterone treatment significantly increased the expression of Cox-2 and IL-6 and activation of p38MAPK and NF-κB.The expression of both Cox-2 and IL-6 could be blocked by the mineralocorticoid receptor (MR) antagonist spironolactone and the p38MAPK inhibitor SB203580.Also,the rapid phosphorylation of p38MAPK could be suppressed by SB203580 but not by spironolactone,implicating in nongenomic effects of aldosterone.Similar to SB203580 and spironolactone,the NF-κB inhibitor α-p-tosyl-L-lysine chloromethyl ketone (TLCK) markedly attenuated expression of Cox-2,indicating that MR,p38MAPK and NF-KB are associated with aldosterone-induced inflammatory responses.Furthermore,aldosterone enhanced expression of TGFβ1 in rat VSMCs.This result may be related to activation of the MR/ERK-Sp1 signalling pathway because PD98059,an ERK1/2 inhibitor,significantly blocked the rapid phosphorylation of ERK1/2 and function of Sp1 and led to reduced expression of TGFβ1.Spironolactone was also shown to significantly inhibit TGFβ1 and Sp1 expression but not ERK1/2 phosphorylation.Conclusion:These results suggest that aldosterone-induced inflammatory responses and fibrotic responses may be mediated by the MR/p38MAPK-NF-κB pathways and the MR/ERK-Sp1 pathways in VSMCs,respectively.

  8. 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.

  9. 醛固酮促进心室成纤维细胞增殖作用%THE EFFECT OF ALDOSTERONE OF PROMOTION ON PROLIFERATION OF VENTRICULAR FIBROBLASTS

    Institute of Scientific and Technical Information of China (English)

    龚素珍; 刘培庆; 鲁伟; 谈智; 符史干; 潘敬运

    2001-01-01

    To study the effect of promoting aldosterone on proliferation of ventricular fibroblasts. Methods: Assay of [3H]-TdR incorporat ion rate and RT-PCR were used.Results: Aldosterone could promote [ 3H]-TdR incoporation of ventricular fibrolasts,the effective dose of aldost erone was among (1×10-9~1×10-6)mol/L,and had dose-dependent mann er,the c-fos gene was expressed after stimulated by aldosterone for 15 min,and studied the highest in 1 h,then reduced later.Spironolactone,aldosterone recepto r antagonist could block the effect of aldosterone.Conclusion: Aldos terone promotes the proliferation of ventricular fibroblasts,mediated by aldoste rone receptor.%目的:探讨醛固酮促进心室成纤维细胞增殖作用。方法:采用[3H ]-TdR掺 入率测定和RT-PCR。结果:醛固酮(1×10-9~1×10-6)mol/L能明 显促进心室 成纤维细胞的[3H]-TdR掺入率,且呈剂量依赖方式;醛固酮孵育15 min,可见c-fos mRNA的表达,至1 h表达达高峰,以后逐渐降低,醛固酮受体拮抗剂螺旋内酯能阻断醛固酮的作 用。结论:醛固酮能促进心室成纤维细胞增殖,是通过其特异性受体介导的 。

  10. Early, but not late therapy with a vasopressin V-1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy

    NARCIS (Netherlands)

    Windt, Willemijn A. K. M.; Tahara, Atsua; Kluppel, Alex C. A.; de Zeeuw, Dick; Henning, Robert H.; van Dokkum, Richard P. E.

    2006-01-01

    Introduction. Vasopressin, mainly through the VIA-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V-1a-receptor-selective antagonist,

  11. Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy

    NARCIS (Netherlands)

    Windt, Willemijn A K M; Tahara, Atsua; Kluppel, Alex C A; de Zeeuw, Dick; Henning, Robert H; van Dokkum, Richard P E

    2006-01-01

    INTRODUCTION: Vasopressin, mainly through the V1a-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V1a-receptor-selective antagonist,

  12. 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

  13. Clinical analysis of spironolactone in treatment of primary aldosteronism%螺内酯治疗原发性醛固酮增多症临床分析

    Institute of Scientific and Technical Information of China (English)

    宁泽; 刘会峰; 解南

    2015-01-01

    Objective To investigate the clinical effect of spironolactone on primary aldosteronism.Methods The clinical data of 62 patients with primary aldosteronism disease were retrospectively analyzed.All patients received clinically conventional drug therapy combined with spironolactone.The urinary aldosterone, plasma aldosterone changes and incidence of adverse reactions before and after the treatment were recorded, and concluded by statistical analysis.Results After sixty-two patients with primary aldosteronism used spironolactone based on the conventional therapy, the urinary aldosterone and plasma aldosterone levels decreased compared with before treatment, the differences were significant (P < 0.05).Conclusions The clinical efficacy of spironolactone combined with conventional treatment on patients with primary aldosteronism is satisfactory, and can effectively guarantee their quality of life and life safety.%目的 探讨螺内酯治疗原发性醛固酮增多症的临床应用效果.方法 对62例原发性醛固酮增多症患者临床资料进行回顾性分析,所有患者均经临床常规药物联合螺内酯治疗.记录其治疗前后尿醛固酮、血浆醛固酮变化情况及不良反应发生率,给予统计学分析后得出结论.结果 62例原发性醛固酮增多症患者经常规治疗基础上加用螺内酯联合给药后,其尿醛固酮及血浆醛固酮检验水平均较治疗前有所下降,差异有统计学意义(P<0.05).结论 原发性醛固酮增多症患者经常规治疗基础上加入螺内酯联合给药可获得满意临床疗效,有效保障其生活质量及生命安全.

  14. 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)...

  15. Aldosterone-induced apoptosis of MIN6 cells and its mechanism%醛固酮诱导MIN6细胞凋亡及作用机制研究

    Institute of Scientific and Technical Information of China (English)

    潘瑜; 刘晓莉; 束金莲; 张霞; 金惠敏

    2012-01-01

    Objective To investigate the effects of aldosterone on apoptosis of tnurine pancreatic islets B cell line MIN6, and explore its possible mechanism. Methods Murine pancreatic islets B cell line MIN6 cultured in vitro was divided into control group (treated with serum-free DMEM culture medium), aldosterone group (treated with 10, 100 or 1 000 nmol/L aldosterone) and aldosterone + aldosterone antagonist group ( treated with 100 nmol/L aldosterone and 100 nmol/L aldactone). Cell viability was determined by MTT assay, glucose-stimulated insulin secretion ( GSIS) was measured by radioimmunoassay, cell apoptosis was detected by flow cytometry in combination with FITC-Annexin V/PI fluorescein staining, Caspase-3 activity in supernatant of culture fluid was determined by ELISA, and the expression of apoptosis-related proteins of cytochrome C(Cyt-C), Bcl-2, Bax and phosphorylated protein kinase C ( p-Akt) was detected by Western blotting. Results The viability of MIN6 cells decreased with the increase of concentrations of aldosterone, with a concentration-dependent manner. Under physical glucose concentration (5.6 mmol/L) and high glucose concentration (28 mmol/L) environment, GSIS of aldosterone group was significantly lower than that of control group ( P <0. 01), and GSIS of aldosterone + aldosterone antagonist group was significantly higher than that of aldosterone group ( P < 0. 01). The cell apoptosis ratio of aldosterone group was significantly higher than that of control group ( P <0.01), and the cell apoptosis ratio of aldosterone + aldosterone antagonist group was significantly lower than that of aldosterone group (P < 0. 01). Compared with control group, the Caspase-3 activity and expression of Cyt-C were significantly higher, and Bcl-2/ Bax and the expression of p-Akt were significantly lower ( P < 0. 01 for all), while aldosterone antagonist significantly inhibited aldosterone-mediated Caspase-3 activity increase and abnormal expression of related proteins

  16. 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...

  17. 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

  18. 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 §...

  19. 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.

  20. 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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    ). In addition to increased PTH levels, low vitamin D levels may also directly increase risk of CVD, as vitamin D, itself, has been shown to inhibit the RAAS. Angiotensin II, aldosterone and cortisol all negatively impact bone health. Hyperaldosteronism is associated with a reversible secondary...

  2. Type I receptors in parotid, colon, and pituitary are aldosterone selective in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Sheppard, K.; Funder, J.W. (Prince Henry' s Hospital, Melbourne (Australia))

    1987-10-01

    Previous in vivo studies have demonstrated that type I receptors in the rat kidney are aldosterone selective, whereas those in the hippocampus do not appear to discriminate between aldosterone and corticosterone. The authors have injected mature rats with ({sup 3}H)aldosterone or ({sup 3}H)corticosterone plus 100-fold excess of RU 28362, with or without unlabeled aldosterone or corticosterone, and compared type I receptor occupancy in two classic mineralocorticoid target tissues (parotid and colon) and in the pituitary. Mature rats were killed 10-180 min after tracer administration; ({sup 3}H)aldosterone was well taken up and retained in all tissues, whereas ({sup 3}H)corticosterone was significantly retained only in the pituitary 10 min after tracer administration. To assess a possible role for corticosterone-binding globulin (CBG) in conferring aldosterone specificity on type I receptors, 10-day-old rats (with very low levels of CBG) were similarly injected. In the colon and parotid, ({sup 3}H)aldosterone binding was at least an order of magnitude higher than that of corticosterone; in the pituitary aldosterone binding was approximately three times that of corticosterone. They interpret these data as evidence that in the parotid and colon type I receptors are aldosterone selective by a non-CBG-requiring mechanism, whereas in the pituitary there appear to be both aldosterone-selective and nonselective type I sites.

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

    Science.gov (United States)

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

    2015-03-30

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

  4. Association of restriction fragment length polymorphism at the atrial natriuretic peptide gene locus with aldosterone responsiveness to angiotensin in aldosterone-producing adenoma.

    Science.gov (United States)

    Tunny, T J; Jonsson, J R; Klemm, S A; Ballantine, D M; Stowasser, M; Gordon, R D

    1994-11-15

    Primary aldosteronism is an important, potentially curable, form of hypertension. We examined the possible association between restriction fragment length polymorphisms in the atrial natriuretic peptide (ANP) gene and responsiveness of aldosterone to angiotensin II in 59 patients with primary aldosteronism due to aldosterone-producing adenoma (APA). Significant differences in the allelic frequencies of the BglI, TaqI and XhoI polymorphic sites at the ANP gene locus (chromosome 1; 1p36) between angiotensin II-unresponsive and angiotensin II-responsive tumors were observed. Variation in the ANP gene between the two groups may result in altered expression of ANP within the adrenal gland, and may contribute to the biochemical regulation of aldosterone production of these two subgroups of patients with APA.

  5. DEFICIENCY OF INTERLEUKIN-1 RECEPTOR ANTAGONIST RESPONSIVE TO ANAKINRA

    OpenAIRE

    SCHNELLBACHER, CHARLOTTE; CIOCCA, GIOVANNA; MENENDEZ, ROXANNA; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela; DUARTE, ANAM.; RIVAS-CHACON, RAFAEL

    2012-01-01

    We describe a 3-month-old infant who presented to our institution with interleukin (IL)-1 receptor antagonist deficiency (DIRA), which consists of neutrophilic pustular dermatosis, periostitis, aseptic multifocal osteomyelitis, and persistently high acutephase reactants. Skin findings promptly improved upon initiation of treatment with anakinra (recombinant human IL-1 receptor antagonist), and the bony lesions and systemic inflammation resolved with continued therapy.

  6. 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

    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 (MR) 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, temporal and spatial aspects are relevant. The acute response includes vasodilation through endothelial nitric oxide...

  7. 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.

  8. 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

  9. 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

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

    Directory of Open Access Journals (Sweden)

    Yumei Zhang

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

  11. 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...

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. Higher serum aldosterone correlates with lower hearing thresholds: a possible protective hormone against presbycusis.

    Science.gov (United States)

    Tadros, Sherif F; Frisina, Susan T; Mapes, Frances; Frisina, D Robert; Frisina, Robert D

    2005-11-01

    Aldosterone hormone is a mineralocorticoid secreted by adrenal gland cortex and controls serum sodium (Na(+)) and potassium (K(+)) levels. Aldosterone has a stimulatory effect on expression of sodium-potassium ATPase (Na, K-ATPase) and sodium-potassium-chloride cotransporter (NKCC) in cell membranes. In the present investigation, the relation between serum aldosterone levels and age-related hearing loss (presbycusis) and the correlation between these levels versus the degree of presbycusis in humans were examined. Serum aldosterone concentrations were compared between normal hearing and presbycusic groups. Pure-tone audiometry, transient evoked otoacoustic emissions (TEOAE), hearing in noise test (HINT) and gap detection were tested for each subject and compared to the serum aldosterone levels. A highly significant difference between groups in serum aldosterone concentrations was found (p = 0.0003, t = 3.95, df = 45). Highly significant correlations between pure-tone thresholds in both right and left ears, and HINT scores versus serum aldosterone levels were also discovered. On the contrary, no significant correlations were seen in the case of TEOAEs and gap detection. We conclude that aldosterone hormone may have a protective effect on hearing in old age. This effect is more peripheral than central, appearing to affect inner hair cells more than outer hair cells.

  17. Current concepts in combination therapy for the treatment of hypertension: combined calcium channel blockers and RAAS inhibitors

    Directory of Open Access Journals (Sweden)

    Alberto F Rubio-Guerra

    2009-11-01

    Full Text Available Alberto F Rubio-Guerra1, David Castro-Serna2, Cesar I Elizalde Barrera2, Luz M Ramos-Brizuela21Metabolic and Research Clinic, 2Internal Medicine Department, Hospital General de Ticomán SS DF, MéxicoAbstract: Recent guidelines for the management of hypertension recommend target blood pressures <140/90 mmHg in hypertensive patients, or <130/80 mmHg in subjects with diabetes, chronic kidney disease, or coronary artery disease. Despite the availability and efficacy of antihypertensive drugs, most hypertensive patients do not reach the recommended treatment targets with monotherapy, making combination therapy necessary to achieve the therapeutic goal. Combination therapy with 2 or more agents is the most effective method for achieving strict blood pressure goals. Fixed-dose combination simplifies treatment, reduces costs, and improves adherence. There are many drug choices for combination therapy, but few data are available about the efficacy and safety of some specific combinations. Combination therapy of calcium antagonists and inhibitors of the renin-angiotensin-aldosterone system (RAAS are efficacious and safe, and have been considered rational by both the JNC 7 and the 2007 European Society of Hypertension – European Society of Cardiology guidelines for the management of arterial hypertension. The aim of this review is to discuss some relevant issues about the use of combinations with calcium channel blockers and RAAS inhibitors in the treatment of hypertension.Keywords: hypertension, calcium channel blockers, renin-angiotensin-aldosterone system inhibitors, fixed-dose combination, adherence

  18. 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...

  19. 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...... oxygen species. The effect of aldosterone on vascular function, however, is far from clear. By rapid non-genomic mechanisms aldosterone may cause calcium mobilization and vasoconstriction, or may stimulate nitric oxide formation through the PI-3 kinase/Akt pathway and thereby counteract vasoconstriction....... Vasoconstrictor, vasodilator or no effects of aldosterone have been reported from studies on human forearm blood flow. Inhibition of MR with spironolactone improves endothelial function in patients with heart failure but worsens endothelial function in type 2 diabetic patients. The aim of the present review...

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. Case Report: A case report of acromegaly associated with primary aldosteronism [v2; ref status: indexed, http://f1000r.es/3ke

    Directory of Open Access Journals (Sweden)

    Joanna Matrozova

    2014-06-01

    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.

  6. 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.

  7. Diagnostic value of plasma aldosterone/potassium ratio in hypoaldosteronism.

    Science.gov (United States)

    Shiah, C J; Wu, K D; Tsai, D M; Liao, S T; Siauw, C P; Lee, L S

    1995-05-01

    The diagnosis of hypoaldosteronism usually depends upon a combination of abnormal clinical and laboratory findings. The most common abnormality in hypoaldosteronism is hyperkalemia, which may be combined with sodium depletion. In the present study, 5 of 16 patients diagnosed with isolated hypoaldosteronism (IHA) had sodium depletion due to renal salt wasting, and four patients had normokalemia. Of these 16 IHA patients, 70% had subnormal baseline and stimulated plasma renin activity (PRA). Six patients diagnosed with type I pseudohypoaldosteronism (PHA) had normal or high PRA and plasma aldosterone concentrations (PAC). In 11 control subjects, supine PAC correlated positively with serum potassium (SK), and PAC stimulated by furosemide and ambulation correlated with the 24-hour urinary potassium excretion (UK). However, these correlations were not found in IHA and PHA patients. The ratio of UK/UNa+K and UNa/UK correlated with the stimulated PAC when the IHA and control subjects were taken as a whole. However, these electrolyte excretion parameters bore no relationship to the supine PAC. The stimulated PAC/SK ratio was used to discriminate the three groups; all IHA patients had a ratio below 3. The results indicate that stimulated PAC reflects the bioactivity of aldosterone on the collecting tubule, and the stimulated PAC/SK ratio is useful for the diagnosis of hypoaldosteronism and pseudohypoaldosteronism.

  8. Pharmacology of heart failure: From basic science to novel therapies.

    Science.gov (United States)

    Lother, Achim; Hein, Lutz

    2016-10-01

    Chronic heart failure is one of the leading causes for hospitalization in the United States and Europe, and is accompanied by high mortality. Current pharmacological therapy of chronic heart failure with reduced ejection fraction is largely based on compounds that inhibit the detrimental action of the adrenergic and the renin-angiotensin-aldosterone systems on the heart. More than one decade after spironolactone, two novel therapeutic principles have been added to the very recently released guidelines on heart failure therapy: the HCN-channel inhibitor ivabradine and the combined angiotensin and neprilysin inhibitor valsartan/sacubitril. New compounds that are in phase II or III clinical evaluation include novel non-steroidal mineralocorticoid receptor antagonists, guanylate cyclase activators or myosine activators. A variety of novel candidate targets have been identified and the availability of gene transfer has just begun to accelerate translation from basic science to clinical application. This review provides an overview of current pharmacology and pharmacotherapy in chronic heart failure at three stages: the updated clinical guidelines of the American Heart Association and the European Society of Cardiology, new drugs which are in clinical development, and finally innovative drug targets and their mechanisms in heart failure which are emerging from preclinical studies will be discussed.

  9. 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.

  10. 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.)

  11. 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

  12. 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

  13. 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.

  14. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ceremuzynski, L.K.; Klos, J.; Barcikowski, B.; Herbaczynska-Cedro, K. (Department of Cardiology, Postgraduate Medical School, Warsaw (Poland))

    1991-06-01

    A considerable amount of data suggest the involvement of calcium-mediated processes in the activation of the renin-angiotensin-aldosterone (RAA) cascade. To investigate the effect of calcium-channel inhibition on the RAA system, the authors studied 21 conscious pigs. Blood renin and aldosterone levels increased by subjecting animals to 24 hours of immobilization stress. Renin and aldosterone levels were repeatedly measured by radioimmunoassay in blood samples taken periodically over 24 hours from a chronically implanted arterial cannula. Pretreatment of the animals (N = 11) with nisoldipine, 2 {times} 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Slavnov, V.N.; Yakovlev, A.A.; Yugrinov, O.G.; Gandzha, T.I. (Kievskij Nauchno-Issledovatel' skij Inst. Ehndokrinologii i Obmena Veshchestv (Ukrainian SSR))

    1983-02-01

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

  17. Cardiac Hypertrophy and Fibrosis in the Metabolic Syndrome: A Role for Aldosterone and the Mineralocorticoid Receptor

    Directory of Open Access Journals (Sweden)

    Eric E. Essick

    2011-01-01

    Full Text Available Obesity and hypertension, major risk factors for the metabolic syndrome, render individuals susceptible to an increased risk of cardiovascular complications, such as adverse cardiac remodeling and heart failure. There has been much investigation into the role that an increase in the renin-angiotensin-aldosterone system (RAAS plays in the pathogenesis of metabolic syndrome and in particular, how aldosterone mediates left ventricular hypertrophy and increased cardiac fibrosis via its interaction with the mineralocorticoid receptor (MR. Here, we review the pertinent findings that link obesity with elevated aldosterone and the development of cardiac hypertrophy and fibrosis associated with the metabolic syndrome. These studies illustrate a complex cross-talk between adipose tissue, the heart, and the adrenal cortex. Furthermore, we discuss findings from our laboratory that suggest that cardiac hypertrophy and fibrosis in the metabolic syndrome may involve cross-talk between aldosterone and adipokines (such as adiponectin.

  18. 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...

  19. 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...

  20. 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

  1. 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

  2. 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

  3. Addition of the Neurokinin-1-Receptor Antagonist (RA) Aprepitant to a 5-Hydroxytryptamine-RA and Dexamethasone in the Prophylaxis of Nausea and Vomiting Due to Radiation Therapy With Concomitant Cisplatin

    International Nuclear Information System (INIS)

    Purpose: To assess, in a prospective, observational study, the safety and efficacy of the addition of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant to concomitant radiochemotherapy, for the prophylaxis of radiation therapy–induced nausea and vomiting. Patients and Methods: This prospective observational study compared the antiemetic efficacy of an NK1-RA (aprepitant), a 5-hydroxytryptamine-RA, and dexamethasone (aprepitant regimen) versus a 5-hydroxytryptamine-RA and dexamethasone (control regimen) in patients receiving concomitant radiochemotherapy with cisplatin at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. The primary endpoint was complete response in the overall phase, defined as no vomiting and no use of rescue therapy in this period. Results: Fifty-nine patients treated with concomitant radiochemotherapy with cisplatin were included in this study. Thirty-one patients received the aprepitant regimen and 29 the control regimen. The overall complete response rates for cycles 1 and 2 were 75.9% and 64.5% for the aprepitant group and 60.7% and 54.2% for the control group, respectively. Although a 15.2% absolute difference was reached in cycle 1, a statistical significance was not detected (P=.22). Furthermore maximum nausea was 1.58 ± 1.91 in the control group and 0.73 ± 1.79 in the aprepitant group (P=.084); for the head-and-neck subset, 2.23 ± 2.13 in the control group and 0.64 ± 1.77 in the aprepitant group, respectively (P=.03). Conclusion: This is the first study of an NK1-RA–containing antiemetic prophylaxis regimen in patients receiving concomitant radiochemotherapy. Although the primary endpoint was not obtained, the absolute difference of 10% in efficacy was reached, which is defined as clinically meaningful for patients by international guidelines groups. Randomized phase 3 studies are necessary to further define the potential role of an NK1-RA in this setting

  4. Addition of the Neurokinin-1-Receptor Antagonist (RA) Aprepitant to a 5-Hydroxytryptamine-RA and Dexamethasone in the Prophylaxis of Nausea and Vomiting Due to Radiation Therapy With Concomitant Cisplatin

    Energy Technology Data Exchange (ETDEWEB)

    Jahn, Franziska, E-mail: franziska.jahn@uk-halle.de [Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Riesner, Anica [Department of Gastroenterology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Jahn, Patrick [Nursing Research Unit, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Sieker, Frank; Vordermark, Dirk [Department of Radiation Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Jordan, Karin [Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany)

    2015-08-01

    Purpose: To assess, in a prospective, observational study, the safety and efficacy of the addition of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant to concomitant radiochemotherapy, for the prophylaxis of radiation therapy–induced nausea and vomiting. Patients and Methods: This prospective observational study compared the antiemetic efficacy of an NK1-RA (aprepitant), a 5-hydroxytryptamine-RA, and dexamethasone (aprepitant regimen) versus a 5-hydroxytryptamine-RA and dexamethasone (control regimen) in patients receiving concomitant radiochemotherapy with cisplatin at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. The primary endpoint was complete response in the overall phase, defined as no vomiting and no use of rescue therapy in this period. Results: Fifty-nine patients treated with concomitant radiochemotherapy with cisplatin were included in this study. Thirty-one patients received the aprepitant regimen and 29 the control regimen. The overall complete response rates for cycles 1 and 2 were 75.9% and 64.5% for the aprepitant group and 60.7% and 54.2% for the control group, respectively. Although a 15.2% absolute difference was reached in cycle 1, a statistical significance was not detected (P=.22). Furthermore maximum nausea was 1.58 ± 1.91 in the control group and 0.73 ± 1.79 in the aprepitant group (P=.084); for the head-and-neck subset, 2.23 ± 2.13 in the control group and 0.64 ± 1.77 in the aprepitant group, respectively (P=.03). Conclusion: This is the first study of an NK1-RA–containing antiemetic prophylaxis regimen in patients receiving concomitant radiochemotherapy. Although the primary endpoint was not obtained, the absolute difference of 10% in efficacy was reached, which is defined as clinically meaningful for patients by international guidelines groups. Randomized phase 3 studies are necessary to further define the potential role of an NK1-RA in this setting.

  5. 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 <...

  6. [Rational diuretic therapy in patients with liver cirrhosis].

    Science.gov (United States)

    Vogt, B; Reichen, J

    2000-06-01

    When ascites develops in a patient with liver cirrhosis his probability to survive the following two years amounts to 50%. It is determined essentially by the residual functional capacity of the liver. In 80 to 90% of patients ascites due to portal hypertension can be managed by salt restriction and diuretics. A daily reduction of body weight of 0.5 to 0.75 kg should not be exceeded because prerenal failure may become a threat. Aldosterone-antagonists are more efficient and have fewer side-effects than loop diuretics. The urinary ratio of Na/K may be used to adjust the therapy. They may lower portal hypertension by an additional direct effect on the vasculature. If diuretics are insufficient or when a rapid therapeutic success is needed, paracentesis of 4-6 l is a safe option if intravascular volume is substituted simultaneously with albumin. Only in the few patients whose ascites is intractable by the forementioned measures, alternatives such as peritoneo-, venous or porto-systemic shunts (nowadays mostly by interventional techniques via a transjugular catheter) should be evaluated. The only treatment which not only attacks ascites symptomatically but also corrects the underlying disease is liver transplantation. PMID:10894019

  7. 醛固酮通过调节ACE2-Ang(1-7)-Mas受体轴诱导内皮细胞凋亡的研究%Aldosterone induced endothelial cell apoptosis via modulation of ACE2-Ang (1-7)-Mas receptor axis

    Institute of Scientific and Technical Information of China (English)

    张霞; 潘瑜; 金惠敏

    2013-01-01

    目的 探讨醛固酮对内皮细胞ACE2-Ang(1-7)-Mas受体轴的影响及其与凋亡的关系.方法 将体外培养的人脐静脉内皮细胞(HUVEC)分为对照组(DMEM/F12培养基)、醛固酮组(10、100、1 000 nmol/L醛固酮干预)和醛固酮拮抗组(100 nmol/L醛固酮+1μmol/L醛固酮受体拮抗剂共同干预).采用免疫荧光细胞化学染色法观察细胞ACE2蛋白的表达;Western blotting检测细胞中ACE2和Mas受体的表达;酶联免疫吸附实验(ELISA)检测细胞培养上清中AngⅡ和Ang(1-7)蛋白的含量以及凋亡相关蛋白caspase-3的活性;流式细胞术结合FITC-Annexin V/PI荧光染色检测细胞凋亡.结果 与对照组比较,醛固酮组细胞ACE2和Mas受体的表达明显下调(P<0.01),并呈浓度依赖性.在100 nmol/L醛固酮组,随着干预时间的延长,细胞ACE2和Mas受体的表达明显下调(P<0.01),呈时间依赖性;而醛固酮拮抗组细胞ACE2和Mas受体的表达显著高于100 nmol/L醛固酮组(P<0.01).ELISA检测结果显示,随着干预时间的延长,醛固酮组细胞培养上清中AngⅡ浓度和caspase-3活性均显著升高,而Ang(1-7)浓度降低.流式细胞术检测结果显示:醛固酮组细胞凋亡率显著高于对照组,醛固酮拮抗组细胞凋亡率显著低于醛固酮组(P<0.05).结论 醛固酮具有调节ACE2-Ang(1-7)-Mas受体轴的作用,并可能通过此轴诱导内皮细胞凋亡.%Objective To investigate the effect of aldosterone on ACE2 - Ang ( 1 -7) - Mas receptor axis of endothelial cells, and explore its association with apoptosis. Methods Human umbilical vein endothelial cells ( HUVEC) cultured in vitro were divided into control group ( DMEM/F12 culture medium), aldosterone group (treatment with 10, 100, 1 000 nmol/L aldosterone) and aldosterone antagonist group ( 100 nmol/L aldosterone + 1 μmol/L aldosterone antagonist) . The expression of ACE2 protein in cells was observed with immunofluorescence cytochemical staining, the expression of

  8. 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.

  9. 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

  10. 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...... that the aldosterone- mineralocorticoid receptor (MR) pathway maintains prostasin abundance in human kidney. Design and method: Urine and plasma prostasin was measured by ELISA in urine and plasma from a cohort of type-2 diabetes patients (n = 112) with treatment resistant hypertension before and after intervention......-i/ANGII receptor blocker compared to patients given no medication; in kidney membranes from adrenalectomized rats compared to control and in kidney and colon membranes from aldosterone synthase-/- mice compared to wild type littermates. Conclusions: Kidney tissue prostasin is not regulated by aldosterone whereas...

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

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, R.; Savastano, S.; Tommaselli, A.P. [Univ. of Naples (Italy)] [and others

    1995-03-01

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

  12. Adipogenesis and aldosterone: a study in lean tryptophan-depleted rats.

    Science.gov (United States)

    Pokusa, Michal; Hlavacova, Natasa; Csanova, Agnesa; Franklin, Michael; Zorad, Stefan; Jezova, Daniela

    2016-07-01

    Next to epithelial tissues, mineralocorticoid receptors are also expressed in adipose tissue and are involved in the process of adipogenesis. Mineralocorticoid receptors in adipose tissue are likely to be activated mainly by glucocorticoids. The aim of the present study was to test the hypothesis that the processes related to adipogenesis are modified under the conditions associated with high circulating aldosterone. We have made advantage of a model of depression based on tryptophan depletion in which we have previously demonstrated that the elevation of serum aldosterone precedes that of corticosterone. Sixty adult female Sprague-Dawley rats were fed either a low tryptophan diet or control diet for 4 (elevation of aldosterone only), 7 and 14 days (broader neuroendocrine activation) respectively. Gene expression of several adipogenic factors, CD31, interleukin-6, adiponectin, resistin and leptin were evaluated. Levels of mRNAs coding for adipogenic, angiogenic and inflammatory factors in adipose tissue were elevated at 4 and 7 days of tryptophan depletion. Additionally, gene expression of aldosterone sensing 11-β-hydroxysteroid dehydrogenase 2 and mineralocorticoid receptors were elevated. All changes disappeared at 14 days of tryptophan depletion. Synchronously an increase of adipose tissue mass was observed. Although direct evidence is not provided, observed changes in gene expression may be related to the action of aldosterone on mineralocorticoid receptors. Our findings represent the first data on any changes in gene expression in adipose tissue in animal models of depression. PMID:27253873

  13. 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.

  14. 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.

  15. Venous Thromboembolism Anticoagulation Therapy

    Institute of Scientific and Technical Information of China (English)

    刘泽霖

    2009-01-01

    @@ VTE of the main treatment for anticoagulant thera-py, anticoagulant therapy drug of choice for low molecu-lar weight heparin (LMWH) for the overwhelming major-ity of clinicians agree that long-term oral anticoagulant therapy is still Vit. K antagonist (mainly warfarin).

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  17. 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.

  18. 拮抗针法结合改良强制性运动疗法对脑梗死后上肢痉挛状态的影响%Effect of Modified Constraint Induced Movement Combined with Antagonistic Acupuncture Therapy on Upper Limb Spastic Hemiplegia after Cerebral Infarction

    Institute of Scientific and Technical Information of China (English)

    杨加顺; 孙茹; 王绚; 王虹; 张居婵; 高潇

    2016-01-01

    Objective:To study the effect of modified constraint induced movement combined with antagonistic acupuncture therapy on upper limb spastic hemiplegia after cerebral infarction .Methods:100 patients with cer-ebral infarction were divided randomly into two groups ,a control group (50 cases) with baclofen therapy and a treatment group ( 50 cases ) with modified constraint induced movement combined with antagonistic acupunc-ture therapy .The modified Ashworth Score and Fugl Meyer Assessment were used to evaluate the efficacy be-fore and after treatment .Results:In the treatment group the scores of Ashworth Score and FMA of upper limbs increased more significantly than those in the control group (P﹤0.01,P﹤0.05).Conclusion:Modified con-straint induced movement combined with antagonistic acupuncture therapy is better than baclofen therapy .%目的::研究拮抗针法结合改良强制性运动疗法对脑梗死患者上肢痉挛状态的影响。方法:将符合纳入标准100例脑梗死上肢痉挛状态患者随机分为拮抗针法结合改良强制性运动疗组(治疗组)和巴氯芬组(对照组),各50例。采用改良Ashworth分级评定法和Fugl Meyer 运动功能(FMA)评分法评价临床疗效。结果:治疗组治疗后Ashworth及FMA评分优于对照组(P﹤0.01,P﹤0.05)。结论:拮抗针法结合改良强制性运动疗法能显著改善脑梗死后的上肢痉挛状态,综合临床疗效优于巴氯芬。

  19. 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

  20. 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.

  1. A typical Realization of the process with linear recovery of Aldosterone

    Directory of Open Access Journals (Sweden)

    Geetha. T

    2014-11-01

    Full Text Available Hypercortisolism as a sign of hypothamamus-pituitary-adrenocortical (HPA axis overactivity and sleep EEG changes are frequently observed in depression. Closely related to the HPA axis is the renin-angiotensin-aldosterone system (RAAS as 1. adrenocorticotropic hormone (ACTH is a common stimulus for cortisol and aldosterone, 2. cortisol release is suppressed by mineralocorticoid receptor (MR agonists 3. angiotensin II (ATII releases CRH and vasopressin from the hypothalamus. The first passage time and the bounds of the survival functions for the application are also obtained

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

    DEFF Research Database (Denmark)

    Cheema, Muhammad Umar; Poulsen, Ebbe Toftgaard; Enghild, Jan J;

    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...... contained various rat keratins known to be expressed in renal tubules as assessed by protein mass spectrometry. Aldosterone administration increased the abundance of the proximal tubular aggresomal protein keratin 5, the ribosomal protein RPL27, ataxin-3, and the chaperone heat shock protein 70...

  3. 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...

  4. Studies on antagonistic marine streptomycetes

    Digital Repository Service at National Institute of Oceanography (India)

    Chandramohan, D.; Nair, S.

    Sixty nine strains of Streptomyces sp. isolated from the sediments of Andaman and Nicobar islands (Bay of Bengal) were screened for their antagonistic property against a number of test cultures (Vibrio sp., Klebsiella sp., Escherichia coli, Shigella...

  5. 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

  6. 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

  7. 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

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

    Directory of Open Access Journals (Sweden)

    Xiaojing Geng

    2016-01-01

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

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

    DEFF Research Database (Denmark)

    de Seigneux, Sophie; Nielsen, Jakob; Olesen, Emma T B;

    2007-01-01

    The purpose of the present studies was to determine the effects of high-dose aldosterone and dDAVP treatment on renal aquaporin-2 (AQP2) regulation and urinary concentration. Rats were treated for 6 days with either vehicle (CON; n = 8), dDAVP (0.5 ng/h, dDAVP, n = 10), aldosterone (Aldo, 150...... microg/day, n = 10) or combined dDAVP and aldosterone treatment (dDAVP+Aldo, n = 10) and had free access to water with a fixed food intake. Aldosterone treatment induced hypokalemia, decreased urine osmolality, and increased the urine volume and water intake in ALDO compared with CON and d...... of hypokalemia in aldosterone-treated rats, we studied dietary-induced hypokalemia in rats, which also reduced apical AQP2 expression in the CCD but did not induce any increase in basolateral AQP2 expression in the CCD as observed with aldosterone treatment. The aldosterone-induced basolateral AQP2 expression...

  10. 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

  11. Application and evaluation of postural stimulation test and captopril challenge test in diagnosis of primary aldosteronism

    Institute of Scientific and Technical Information of China (English)

    郝岩

    2014-01-01

    Methods One hundred and twenty-eight patients with essential hypertension and 71 patients with primary aldosteronism were included in this study.The efficacy of different diagnostic indices of postural stimulation test(PST)with captopril challenge test(CCT)were compared by constructing receiver operating characteristic curve.The

  12. 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.

  13. 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

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

    NARCIS (Netherlands)

    Chai, WX; Garrelds, IM; Arulmani, U; Schoemaker, RG; Lamers, JMJ; Danser, AHJ

    2005-01-01

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

  15. 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.

  16. 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

  17. 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

  18. Congenital hyperreninemic hypoaldosteronism unlinked to the aldosterone synthase (CYP11B2) gene.

    Science.gov (United States)

    Kayes-Wandover, K M; Tannin, G M; Shulman, D; Peled, D; Jones, K L; Karaviti, L; White, P C

    2001-11-01

    Isolated hyperreninemic hypoaldosteronism presenting in infancy is usually caused by mutations in the CYP11B2 gene encoding aldosterone synthase. We studied five patients in four unrelated kindreds with hyperreninemic hypoaldosteronism, in whom we were unable to find such mutations. All presented in infancy with failure to thrive, hyponatremia, hyperkalemia, markedly elevated plasma renin activity, and low or inappropriately normal aldosterone levels. All had normal cortisol levels and no signs or symptoms of congenital adrenal hyperplasia. All responded to fludrocortisone treatment. There were no mutations detected in exons or splice junctions of CYP11B2. Linkage of the disorder to CYP11B2 was studied in two unrelated consanguineous patients and in an affected sib pair. The consanguineous patients were each heterozygous for at least one of three polymorphic microsatellite markers near CYP11B2, excluding linkage to CYP11B2. However, linkage of the disease to CYP11B2 could not be excluded in the affected sib pair. Genes involved in the regulation of aldosterone biosynthesis, including those encoding angiotensinogen, angiotensin-converting enzyme, and the AT1 angiotensin II receptor were similarly excluded from linkage. These results demonstrate the existence of an inherited form of hyperreninemic hypoaldosteronism distinct from aldosterone synthase deficiency. The affected gene(s) remain to be determined.

  19. 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...

  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. Different effects of calcium antagonist and beta-blocker therapy on left-ventricular diastolic function in ischemic heart disease. A direct comparison of the impact of mibefradil and atenolol

    DEFF Research Database (Denmark)

    Hassager, C; Thygesen, K; Grande, P;

    2001-01-01

    OBJECTIVE: To compare the effect of a calcium antagonist and a beta-blocker on left-ventricular diastolic function in patients with ischemic heart disease. METHODS: 138 patients with chronic stable angina pectoris were randomized in a multicenter, double-blind trial to treatment with either...... mibefradil or atenolol for 6 weeks (50 mg once daily for 2 weeks followed by 100 mg once daily for 4 weeks). The ratio between early (E) and late (A) diastolic mitral flow velocities (E/A), the E wave deceleration time (DT) and the left ventricular isovolumetric relaxation time (IRT) were measured by Doppler...... echocardiography as parameters of left-ventricular diastolic function initially, after 4 and after 6 weeks of treatment. RESULTS: Mibefradil did not change the E/A ratio significantly (+4%, NS), while atenolol treatment resulted in a significant increase in the E/A ratio (+20%, p treatment...

  2. Determinants and Changes Associated with Aldosterone Breakthrough after Angiotensin II Receptor Blockade in Patients with Type 2 Diabetes with Overt Nephropathy

    Science.gov (United States)

    Moranne, Olivier; Bakris, George; Fafin, Coraline; Favre, Guillaume; Pradier, Christian

    2013-01-01

    Summary Background and objectives Inhibition of the renin-angiotensin-aldosterone system decreases proteinuria and slows estimated GFR decline in patients with type 2 diabetes mellitus with overt nephropathy. Serum aldosterone levels may increase during renin-angiotensin-aldosterone system blockade. The determinants and consequences of this aldosterone breakthrough remain unknown. Design, setting, participants, & measurements This study examined the incidence, determinants, and changes associated with aldosterone breakthrough in a posthoc analysis of a randomized study that compared the effect of two angiotensin II receptor blockers in patients with type 2 diabetes mellitus with overt nephropathy. Results Of 567 of 860 participants included in this posthoc analysis, 28% of participants developed aldosterone breakthrough, which was defined by an increase greater than 10% over baseline values of serum aldosterone levels after 1 year of angiotensin II receptor blocker treatment. Factors independently associated with aldosterone breakthrough at 1 year were lower serum aldosterone and potassium levels at baseline, higher decreases in sodium intake, systolic BP, and estimated GFR from baseline to 1 year, and use of losartan versus telmisartan. Aldosterone breakthrough at 6 months was not sustained at 1 year in 69% of cases, and it did not predict estimated GFR decrease and proteinuria increase between 6 months and 1 year. Conclusions Aldosterone breakthrough is a frequent event 1 year after initiating renin-angiotensin-aldosterone system blockade, particularly in participants exposed to intensive lowering of BP with sodium depletion and short-acting angiotensin II receptor blockers. Short-term serum aldosterone level increases at 6 months are not associated with negative kidney outcomes between 6 months and 1 year. PMID:23929924

  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. 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

  5. Misdiagnosis of two cases of primary aldosteronism owing to failure of computed tomography to detect adrenal microadenoma.

    Science.gov (United States)

    Fujiwara, Mako; Murao, Koji; Imachi, Hitomi; Yoshida, Kazuya; Muraoka, Tomie; Ohyama, Tomoyo; Kushida, Yoshio; Haba, Reiji; Kakehi, Yoshiyuki; Ishida, Toshihiko

    2010-10-01

    Recent studies have suggested that primary aldosteronism (PA) is a common form of hypertension. However, some cases of PA are overlooked because microadenoma is difficult to detect by imaging. The author report 2 cases in which aldosterone-producing microadenoma was diagnosed by selective adrenal venous sampling (AVS) and furosemide plus upright test. These adenomas were resected by laparoscopic adrenalectomy. Both cases presented with hypertension and hypokalemia. Experimental data, including those obtained from furosemide plus upright test, suggested PA. In both cases, computed tomography imaging revealed a normal adrenal gland without any tumor. However, selective AVS indicated unilateral hypersecretion of aldosterone. Laparoscopic adrenalectomy was performed, and clinical symptoms of the patients improved. The histopathologic findings revealed aldosterone-producing microadenomas with diameters of 6 and 3 mm, respectively, in cases 1 and 2. In conclusion, AVS should be performed to confirm the diagnosis of PA when computed tomography imaging does not provide definite results.

  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. High-sodium intake aggravates myocardial injuriesinduced by aldosterone via oxidative stress inSprague-Dawley rats

    Institute of Scientific and Technical Information of China (English)

    Jing-yi LI; Shao-ling ZHANG; Meng REN; Yan-ling WEN; Li YAN; Hua CHENG

    2012-01-01

    To evaluate the effects of aldosterone with or without high sodium intake on blood pressure,myocardial structure and left ventricular function in rats,and to investigate the mechanisms underlying the effects.Methods:Eight-week-old male Sprague-Dawley rats were randomly divided into 3 groups:(1) control (CON) group fed a normal sodium diet,(2) aldosterone (ALD) group receiving aldosterone infusion and a normal sodium diet,and (3) high sodium plus aldosterone (HS-ALD) group receiving 1% NaCl diet in conjunction with aldosterone infusion.Aldosterone was administered through continuously subcutaneous infusion with osmotic minipump at the rate of 0.75 μg/h for 8 weeks.The myocardium structure was observed using transt-horacic echocardiography and transmission electron microscopy.The collagen deposition in left ventricle was evaluated with Masson'strichrome staining.The expression of IL-18,p22phox,and p47phox proteins was examined using Western blot analysis.Results:The systolic blood pressure in the ALD and HS-ALD groups was significantly higher than that in the CON group after 2-week treatment.But the blood pressure showed no significant difference between the HS-ALD and ALD groups.The left ventricular hyper-trophy,myocardial collagen deposition and oxidative stress were predominantly found in the HS-ALD and ALD group.Furthermore,the breakdown of myocardial structure and oxidative stress were more apparent in the HS-ALD group as compared with those in the ALDgroup.Conclusion:Long-term infusion of aldosterone results in hypertension and profibrotic cardiovascular responses in rats fed a normal sodium diet,which were mediated by oxidative stress.High-sodium intake could aggravate myocardial injuries induced by aldosterone.

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

    Science.gov (United States)

    Geng, Xiaojing; Yan, Li; Dong, Jun; Liang, Ying; Deng, Yajuan; Li, Ting; Luo, Tongfeng; Lin, Hailun; Zhang, Shaoling

    2016-01-01

    Adrenal aldosterone-producing adenoma (APA), producing the salt-retaining hormone aldosterone, commonly causes secondary hypertension, which often persists after unilateral adrenalectomy. Although persistent hypertension was correlated with residual hormone aldosterone, the in vivo mechanism remains unclear. NADPH oxidase is the critical cause of aldosterone synthesis in vitro. Nox2 and p22phox comprise the NADPH oxidase catalytic core, serving to initiate a reactive oxygen species (ROS) cascade that may participate in the pathology. mRNAs of seven NADPH oxidase isoforms in APA were evaluated by RT-PCR and Q-PCR and their proteins by immunohistochemistry and Western blotting. NADPH oxidase activity was also detected. Nox2 and p22phox were especially abundant in APA. Particularly higher Nox2 and p22phox gene and protein levels were seen in APA than controls. Significant correlations between Nox2 mRNA and aldosterone synthase (CYP11B2) mRNA (R = 0.66, P PAC) (R = 0.503, P PAC. Importantly, we found that Nox2 localized specifically in hyperplastic zona glomerulosa cells. In conclusion, our results highlight that Nox2 and p22phox may be directly involved in pathological aldosterone production and zona glomerulosa cell proliferation after APA resection. PMID:27057164

  10. Investigation of the role of aldosterone in hypertension associated with spontaneous pituitary-dependent hyperadrenocorticism in dogs.

    Science.gov (United States)

    Goy-Thollot, I; Péchereau, D; Kéroack, S; Dezempte, J C; Bonnet, J M

    2002-11-01

    The aim of this study was to evaluate the role of aldosterone as an initiating and/or perpetuating factor in hypertension associated with pituitary-dependent hyperadrenocorticism (PDH) in dogs. Thirteen dogs with PDH and 11 healthy control dogs were used. In all dogs, arterial blood pressure and plasma sodium, potassium, basal aldosterone, post-ACTH aldosterone, basal cortisol and post-ACTH cortisol concentrations were measured. The tests were repeated 10 days and three months after the beginning of o,p'-DDD treatment in PDH dogs. In untreated PDH dogs, plasma aldosterone was significantly decreased, whereas cortisol, sodium and arterial blood pressure were significantly increased compared to healthy dogs. Hypertension remained in most treated PDH dogs despite normalisation of cortisol and persistently low aldosterone levels. These results did not demonstrate that aldosterone is involved in the development and perpetuation of hypertension in PDH. However, glucocorticoids seemed to play a major role as an initiating and perpetuating factor in PDH in dogs.

  11. 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

  12. Antagonistic Interfa(e)ces

    DEFF Research Database (Denmark)

    Cox, Geoff; Jackson, Robert

    2011-01-01

    "lingering stink" so that it became purer and closer to authority. The paper will further link the purification of code to the structure of ideology inherent in Zizek’s psychoanalytical model between Symbolic reality, the antagonistic Real and ideological concealment. The purification is technical in so far...

  13. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B;

    1997-01-01

    We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation......)-phenylethylamine salt of N-BOC-(R)-ATAA. Like ATAA, neither (R)- nor (S)-ATAA significantly affected (IC50 > 100 microM) the receptor binding of tritiated AMPA, kainic acid, or (RS)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the latter being a competitive NMDA antagonist. Electrophysiological experiments......, using the rat cortical wedge preparation, showed the NMDA antagonist effect as well as the AMPA antagonist effect of ATAA to reside exclusively in the (R)-enantiomer (Ki = 75 +/- 5 microM and 57 +/- 1 microM, respectively). Neither (R)- nor (S)-ATAA significantly reduced kainic acid-induced excitation...

  14. Synthesis of potential mescaline antagonists.

    Science.gov (United States)

    DeSantis, F; Nieforth, K A

    1976-10-01

    1-[2-(3,4,5-Trimethoxyphenyl)ethyl]-3-pyrroline, 2-(3,4,5-trimethoxybenzyl)-1,2,3,6-tetrahydropyridine, N-n-propylmescaline, N-cyclopropylmethylmescaline, and N-allylmescaline were synthesized as potential mescaline antagonists. The ability of these compounds to antagonize mescaline-induced disruption of swim behavior is also given.

  15. 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

  16. 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.

  17. PL 03-3 THE FUTURE DEVELOPMENT OF DRUG THERAPY FOR HYPERTENSION.

    Science.gov (United States)

    Kjeldsen, Sverre

    2016-09-01

    There is a whole armament of good drugs for treatment of hypertension including diuretics, calcium antagonist, angiotensin receptor antagonists and angiotensin converting enzyme inhibitors. Secondary drugs mostly used for special indications include beta-blockers, alpha-blockers, mineralocorticoid receptor antagonists (aldosterone antagonists), renin-inhibitors, centrally acting drugs, direct vasodilators and others.A variety of new drugs targeting different pressor mechanism exist and have partly been studies experimentally but will unlikely make it to clinical use in human hypertension. The reason for this is mainly the fact that all existing drugs are generic and inexpensive. The clinical development of new drugs has thus halted because industry does not get paid back for their investments. A recent example is the angiotensin receptor neprilysin inhibitor which has success in the treatment of heart failure at least partly because of powerful blood pressure lowering properties. However, one may also wonder whether potential harmful effects from long term treatment such as deposition of beta-amyloid in the brain may influence the risk of Alzheimer and prohibit development for use in hypertension.Against the solid documentation of today's first line drugs on preventing the cardiovascular complications of hypertension potential new drugs on the market would need to be tested in mega-trials before likely to be successful. Even if proven effective the cost issue would remain as a major barrier.Thus, the future development of drug therapy for hypertension would be improving the clinical aspects including overcoming clinical inertia and adherence to the drugs. In other words education of physicians and patients to make the right choices and follow-up on treatment that has been initiated. Targets are always the same - patients with well controlled blood pressure and without side effects. Adherence may be facilitated with drug monitoring in blood and urine, and

  18. 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

  19. 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...

  20. 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.

  1. 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...

  2. 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

  3. 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; Phypertension and endothelial dysfunction via aldosterone-dependent mechanisms in female mice and suggest that obesity leads to cardiovascular disease via sex-specific mechanisms.

  4. The Effect of Moderate Hypothermia on Renin-Angiotensin – Aldosterone System in Male Rats

    Directory of Open Access Journals (Sweden)

    M. Kourosh Arami

    2004-04-01

    Full Text Available Hypothermia in nature occurs in hibernating animals. It has applications in medicine in open heart surgery,organ and connective tissue preserving, altitude medicine and geriatrics. Despite the vastness of studies on hypothermia many of its biologic and physiologic effects including endocrine system alterations are still poorly recognized. In this study the effect of hypothermia on renin- angiotensin-aldosterone axis was explored. Ten male wistar albino rats (mean age 5 months were anesthetized by intraperitoneal injection of chloralhydrat (0.5 m1/100gr body weight. Then animals were placed in hypothermia apparatus . Their body temperature were reduced to 250 C. AngiotensinI(ANGI and aldosterone (ALD levels of serum were measured by radioimmunoassay before and after hypothermia induction and once every 24 hours for three days. Plasma renin activity (PRA was also measured by using the standard formula of angiotensin determinates at two temperatures of 40C and 370C . The results showed that PRA,ANGI and ALD increased significantly immedietly after hypothermia (p<0.03. Later changes were followed as these factors decreased to basal level, except in the case of aldosterone which maintained its increased level significantly for 24 hours (p<0.05. It seems that moderate hypothermia have stimulatory effect on PRA,ANGI and ALD that results of this study confirm it.

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

    Science.gov (United States)

    Yorke, Ekua; Stafford, Sara; Holmes, Daniel; Sheth, Sachiv; Melck, Adrienne

    2015-01-01

    Introduction Approximately 35% of cases of Conn’s syndrome (primary aldosteronism) result from a solitary functioning adrenal adenoma, and these patients are best managed by adrenalectomy. Postoperative hypoaldosteronism after unilateral adrenalectomy is uncommon. Case presentation We present a case and literature review of hypoaldosteronism after unilateral adrenalectomy for Conn’s syndrome, which demonstrates the insidious and sometimes delayed presentation. Discussion In this clinical case we summarize the previously published cases of post-adrenalectomy hypoaldosteronism based on a PUBMED and EBSCOhost search of all peer-reviewed publications (original articles and reviews) on this topic. A few cases of aldosterone insufficiency post-adrenalectomy for Conn’s syndrome were identified. The etiological factors for prolonged selective suppression of aldosterone secretion after unilateral adrenalectomy remain unclear. Conclusion It is important to be aware of the risk of postoperative hypoaldosteronism in this patient population. Close postoperative follow-up is necessary and strongly recommended, especially in patients with certain risk factors. Patients may need mineralocorticoid supplementation during this period. PMID:25604311

  6. 不同体位血浆肾素和醛固酮及其比值诊断原发性醛固酮增多症的价值%Value of plasma renin, aldosterone and aldosterone to renin ratio in different positions to diagnosing primary aldosteronism

    Institute of Scientific and Technical Information of China (English)

    张玉杰; 李南方; 张菊红; 姚晓光; 李变

    2013-01-01

    Objective To discuss the values of plasma renin activity,plasma aldosterone concentration and aldosterone to renin ratio (ARR) in three positions (upright,sitting and supine positions) to diagnosing primary aldosteronism.Methods A total of 108 patients were detected plasma renin activity and plasma aldosterone concentration in three positions by using radioimmunity assay,and received intravenous saline load test.The ROC curves of plasma renin activity,plasma aldosterone concentration and ARR were drawn respectively on the basis of the intravenous saline load test results as diagnostic standard for primary aldosteronism.Results The AUC values of plasma aldosterone concentration and ARR in supine position were the biggest,indicating a high diagnostic accuracy for primary aldosteronism.The optimum cut-off points of ARR and plasma aldosterone concentration in supine position were 118.3 hours and 53 ng/L,with the coincidences of 57.1 % and 41.1% with intravenous saline load test to diagnose primary aldosteronism.The sensitivity,specificity and Youden index of the combination of ARR ≥ 118.3 hours with plasma aldosterone concentration ≥53 ng/L in supine position were 47.6%,94.1% and 0.471,with the coincident rate of 85.7 %.Conclusion In the patients unable to undergo intravenous saline load test,ARR (≥118.3 hours) combined with plasma aldosterone concentration (≥ 53 ng/L in supine position could improve the diagnosis rate of primary aldosteronism.%目的 探讨立、坐、卧位血浆肾素、醛固酮及醛固酮/肾素比值(aldosterone to renin ratio,ARR)对原发性醛固酮增多症(primary aldosteronism,PA)的诊断价值.方法 采用放射免疫法检测108例高血压患者立、坐、卧位血浆肾素活性及醛固酮水平,并行静脉盐水负荷试验;以静脉盐水负荷试验为PA的诊断标准,分别绘制肾素、醛固酮及ARR的ROC曲线.结果 卧位醛固酮的AUC最大,卧位ARR的AUC最大,诊断PA的准确性较高;

  7. 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.

  8. Ingestion of sodium citrate suppresses aldosterone level in blood at rest and during exercise.

    Science.gov (United States)

    Oöpik, Vahur; Timpmann, Saima; Hackney, Anthony C; Kadak, Kadri; Medijainen, Luule; Karelson, Kalle

    2010-06-01

    The purpose of this study was to determine if the ingestion of sodium citrate (CIT) alters blood levels of fluid and electrolyte regulatory hormones at rest and during exercise. Using a randomized, double-blinded, crossover design, 13 young, male well-trained runners performed continuous incremental running tests to volitional exhaustion on a treadmill 2 h after ingestion of 0.5 g.kg-1 body mass of CIT or placebo (PLC) in 1000 mL of solution. These trials were separated by 2 weeks. Baseline (before ingestion) aldosterone concentration did not differ between the 2 trials; however, it was 36.5% (p = 0.003) lower in the CIT trial compared with the PLC trial before the running test (i.e., after ingestion). The extent of the running-induced increase in aldosterone was 33% (p = 0.009) smaller in the CIT trial. There were no between-trial differences in the levels of adrenocorticotropic hormone, N-terminal pro-B-type natriuretic peptide, or renin activity at any stage of the study. However, a greater relative increase in plasma volume (mean +/- SD, 6.41% +/- 3.78% vs. 4.08% +/- 3.33%; p = 0.042) was observed after administering the CIT compared with the PLC drink. Serum Na+ concentration increased (by 3.1 +/- 1.2 mmol.L-1; p < 0.0001) after ingestion of the CIT but not the PLC drink. A higher Na+ level was observed in the CIT trial than in the PLC trial (142.4 +/- 1.6 vs. 139.3 +/- 1.4 mmol.L-1, p = 0.00001) after completion of the run. In conclusion, pre-exercise ingestion of CIT induces a decrease in serum aldosterone concentration in the resting condition and a blunting of the aldosterone response during incremental running exercise to volitional exhaustion. The observed effect of CIT on the serum aldosterone level may be mediated by an acute increase in plasma volume and serum Na+ concentration alterations.

  9. Effective use of TNF antagonists

    OpenAIRE

    Yocum, David

    2004-01-01

    Tumor necrosis factor (TNF) antagonists are biologic response modifiers that have significantly improved functional outcomes in patients with rheumatoid arthritis (RA). RA is a progressive disease in which structural joint damage can continue to develop even in the face of symptomatic relief. Before the introduction of biologic agents, the management of RA involved the use of disease-modifying antirheumatic drugs (DMARDs) early in the course of disease. This focus on early treatment, combined...

  10. In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron.

    Science.gov (United States)

    Nesterov, Viatcheslav; Krueger, Bettina; Bertog, Marko; Dahlmann, Anke; Palmisano, Ralf; Korbmacher, Christoph

    2016-06-01

    The epithelial sodium channel (ENaC) is rate limiting for Na(+) absorption in the aldosterone-sensitive distal nephron comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT), and the entire collecting duct. Liddle syndrome (pseudohyperaldosteronism), a severe form of salt-sensitive hypertension, is caused by gain-of-function mutations of ENaC, but the precise tubular site of increased ENaC function is unknown. In the cortical collecting duct (CCD), ENaC is known to be regulated by aldosterone. In contrast, we recently reported aldosterone-independent ENaC regulation in the early part of the aldosterone-sensitive distal nephron. Here, we investigated ENaC function in the transition zone of DCT2/CNT or CNT/CCD microdissected from mice homozygous for Liddle syndrome mutation or from wild-type control mice. Whole-cell patch-clamp recordings were used to measure amiloride-sensitive ENaC currents in nephron fragments from mice maintained on different sodium diets to vary plasma aldosterone levels. Our data indicate that in mice with Liddle syndrome, the primary site of increased Na(+) reabsorption is the DCT2/CNT. In addition, increased aldosterone responsiveness of ENaC in CNT/CCD may contribute to salt-sensitive hypertension in Liddle syndrome. Single channel properties of ENaC were similar in Liddle syndrome mutation and wild-type mice, but ENaC expression at the apical membrane was increased in Liddle syndrome mutation when compared with wild-type mice, in particular, in animals maintained on a high salt diet. Our findings highlight the importance of ENaC function and regulation in the early part of the aldosterone-sensitive distal nephron for the maintenance of sodium balance and blood pressure control.

  11. The clinical significance of aldosterone synthase deficiency: report of a novel mutation in the CYP11B2 gene

    Science.gov (United States)

    2014-01-01

    Background Aldosterone synthase (CYP11B2) deficiency is a rare autosomal recessive disorder, usually presenting with severe salt-wasting in infancy or stress-induced hyperkalaemia and postural hypotension in adulthood. Neonatal screening for congenital adrenal hyperplasia, another cause of salt wasting, using 17-hydroxyprogesterone measurement would fail to detect aldosterone synthase deficiency, a diagnosis which may be missed until the patient presents with salt-wasting crisis. Due to this potential life-threatening risk, comprehensive hormonal investigation followed by genetic confirmation for suspected patients would facilitate clinical management of the patient and assessment of the genetic implication in their offspring. Case presentation We describe a 33-year old Chinese man who presented in infancy with life-threatening hyponatraemia and failure to thrive, but remained asymptomatic on fludrocortisone since. Chromosomal analysis confirmed a normal male karyotype of 46, XY. Plasma steroid profile showed high plasma renin activity, low aldosterone level, and elevated 18-hydroxycorticosterone, compatible with type 2 aldosterone synthase deficiency. The patient was heterozygous for a novel CYP11B2 mutation: c.977C > A (p.Thr326Lys) in exon 3. He also carried a heterozygous mutation c.523_525delAAG (p.Lys175del) in exon 6, a known pathogenic mutation causing aldosterone synthase deficiency. Sequencing of CYP11B2 in his parents demonstrated that the mother was heterozygous for c.977C > A, and the father was heterozygous for c.523_525delAAG. Conclusion Although a rare cause of hyperreninaemic hypoaldosteronism, aldosterone synthase deficiency should be suspected and the diagnosis sought in patients who present with life-threatening salt-wasting in infancy, as it has a good long-term prognosis when adequate fludrocortisone replacement is instituted. To our knowledge, this is the first Chinese patient in which the molecular basis of aldosterone synthase

  12. IAP antagonists sensitize murine osteosarcoma cells to killing by TNFα

    Science.gov (United States)

    Shekhar, Tanmay M.; Miles, Mark A.; Gupte, Ankita; Taylor, Scott; Tascone, Brianna; Walkley, Carl R.; Hawkins, Christine J.

    2016-01-01

    Outcomes for patients diagnosed with the bone cancer osteosarcoma have not improved significantly in the last four decades. Only around 60% of patients and about a quarter of those with metastatic disease survive for more than five years. Although DNA-damaging chemotherapy drugs can be effective, they can provoke serious or fatal adverse effects including cardiotoxicity and therapy-related cancers. Better and safer treatments are therefore needed. We investigated the anti-osteosarcoma activity of IAP antagonists (also known as Smac mimetics) using cells from primary and metastatic osteosarcomas that arose spontaneously in mice engineered to lack p53 and Rb expression in osteoblast-derived cells. The IAP antagonists SM-164, GDC-0152 and LCL161, which efficiently target XIAP and cIAPs, sensitized cells from most osteosarcomas to killing by low levels of TNFα but not TRAIL. RIPK1 expression levels and activity correlated with sensitivity. RIPK3 levels varied considerably between tumors and RIPK3 was not required for IAP antagonism to sensitize osteosarcoma cells to TNFα. IAP antagonists, including SM-164, lacked mutagenic activity. These data suggest that drugs targeting XIAP and cIAP1/2 may be effective for osteosarcoma patients whose tumors express abundant RIPK1 and contain high levels of TNFα, and would be unlikely to provoke therapy-induced cancers in osteosarcoma survivors. PMID:27129149

  13. Effect of weight support exercise therapy on the cardiac function in patients with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    Dong-Dong Jiao; Wen-Yu Zhang; Jing Xu; Guang-Jian Zhu; Jia Chen

    2016-01-01

    Objective:To explore the effect of weight support exercise therapy on the cardiac function and living quality in patients with chronic heart failure.Methods: A total of 75 patients with CHF were included in the study and randomized into the observation group (n=38) and the control group (n=37). the patients in the control group were given routine drug therapy. on the above basis, the patients in the observation group were given weight support exercise therapy for rehabilitation. six-month treatment was regarded as one course. the plasma BNP and aldosterone levels before and after treatment in the two groups were detected. the related cardiac function indicators in the two groups were compared. 6mwt and MHL were used to evaluate the exercise tolerance and living quality, respectively.Results:The comparison of plasma BNP and aldosterone levels, various cardiac function indicators, 6 min walking distance, and MHL score before treatment between the two groups was not statistically significant. BNP and aldosterone levels after treatment in the two groups were significantly reduced, and the reduced degree in the observation group was significantly greater than that in the control group. after treatment, HR, LVEDD, and MHL score were significantly reduced, LVEF, FS, and 6 min walking distance were significantly increased, and the comparison between the two groups was statistically significant.Conclusions:Weight support exercise therapy can significantly reduce the plasma BNP and aldosterone levels in CHF patients, improve the cardiac function, and enhance the exercise tolerance and living quality.

  14. The metabolism and binding properties of 3H-aldosterone in plasma and its sex dependence in adrenalectomized rats.

    Science.gov (United States)

    Morris, D J; Graham, W C; Davis, R P

    1975-01-01

    The rates of clearance of plasma 3-H radioactivitivity following intravenous injection of 3-H aldosterone was demonstrated to be sex-dependent in adrenalectomized rats. The perchantage plasma radioactivity which is CH-2CL-2extractable is greater in female than in male rats from 5 min to 90 min postinjection; however the quantities of CH2-CL2-extractable label are not significantly different until 60 min postinjection. The quantities of nonextractable, water-soluble metabolites of adosterone (NEPD), which are markedly greater in the plasma of males, reach peak levels 30 min after injections of aldosterone, during the latent period of the hormone.N females, these polar metabolites (NEPD)are rapidly cleared from the blood. The quantities of 3-H-radioactivity associated with the plasma binding proteins are similar in both males and females. The unbound levels of aldosterone and its metabolities are significantly greater in the plasma of males. These findings indicate that the sex hormones may influence not only the metabolism of aldosterone in rats, but also the plasma levels of unmetabolized aldosterone and its metabolites. PMID:1109901

  15. Two novel mutations of the CYP11B2 gene in a Japanese patient with aldosterone deficiency type 1.

    Science.gov (United States)

    Kondo, Eisuke; Nakamura, Akie; Homma, Keiko; Hasegawa, Tomonobu; Yamaguchi, Takeshi; Narugami, Masahiko; Hattori, Tetsuo; Aoyagi, Hayato; Ishizu, Katsura; Tajima, Toshihiro

    2013-01-01

    Isolated hypoaldosteronism is a rare and occasionally life-threatening cause of salt wasting in infancy. A 2-month-old Japanese boy of unrelated parents was examined for failure to thrive and poor weight gain. Laboratory findings were hyponatremia, hyperkalemia, high plasma renin and low aldosterone levels. Spot urine analysis by gas chromatography-mass spectrometry (GC-MS) showed that urinary excretion of corticosterone metabolites was elevated. Whereas excretion of 18-hydroxycortricosterone metabolites was within the normal range, excretion of aldosterone metabolites was undetectable. The patient was therefore suspected to have aldosterone synthase deficiency type 1. Sequence analysis of CYP11B2, the gene encoding aldosterone synthase (CYP11B2), showed that the patient was a compound heterozygote for c.168G>A, p.W56X in exon 1 and c.1149C>T, p.R384X in exon 7. p.W56X was inherited from his mother and p.R384X was from his father. Since both alleles contain nonsense mutations, a lack of CYP11B2 activity was speculated to cause his condition. To our knowledge, this is the first Japanese patient in which the molecular basis of aldosterone synthase deficiency type 1 has been clarified. This case also indicates that spot urinary steroid analysis is useful for diagnosis.

  16. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J

    2012-02-03

    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  17. Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data

    DEFF Research Database (Denmark)

    Sørensen, Rikke; Hansen, Morten L; Abildstrøm, Steen;

    2009-01-01

    BACKGROUND: Combinations of aspirin, clopidogrel, and vitamin K antagonists are widely used in patients after myocardial infarction. However, data for the safety of combinations are sparse. We examined the risk of hospital admission for bleeding associated with different antithrombotic regimens...... according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Risk of hospital admission for bleeding...... was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. With aspirin as reference, adjusted hazard ratios...

  18. Oral mineralocorticoid antagonists for recalcitrant central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Chin EK

    2015-08-01

    Full Text Available Eric K Chin, David RP Almeida, C Nathaniel Roybal, Philip I Niles, Karen M Gehrs, Elliott H Sohn, H Culver Boldt, Stephen R Russell, James C FolkDepartment of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USAPurpose: To evaluate the effect and tolerance of oral mineralocorticoid antagonists, eplerenone and/or spironolactone, in recalcitrant central serous chorioretinopathy.Methods: Retrospective consecutive observational case series. Primary outcome measures included central macular thickness (CMT, µm, macular volume (MV, mm3, Snellen visual acuity, and prior treatment failures. Secondary outcomes included duration of treatment, treatment dosage, and systemic side effects.Results: A total of 120 patients with central serous chorioretinopathy were reviewed, of which 29 patients were treated with one or more mineralocorticoid antagonists. The average age of patients was 58.4 years. Sixteen patients (69.6% were recalcitrant to other interventions prior to treatment with oral mineralocorticoid antagonists, with an average washout period of 15.3 months. The average duration of mineralocorticoid antagonist treatment was 3.9±2.3 months. Twelve patients (52.2% showed decreased CMT and MV, six patients (26.1% had increase in both, and five patients (21.7% had negligible changes. The mean decrease in CMT of all patients was 42.4 µm (range, -136 to 255 µm: 100.7 µm among treatment-naïve patients, and 16.9 µm among recalcitrant patients. The mean decrease in MV of all patients was 0.20 mm3 (range, -2.33 to 2.90 mm3: 0.6 mm3 among treatment-naïve patients, and 0.0 mm3 among recalcitrant patients. Median visual acuity at the start of therapy was 20/30 (range, 20/20–20/250, and at final follow-up it was 20/40 (range, 20/20–20/125. Nine patients (39.1% experienced systemic side effects, of which three patients (13.0% were unable to continue therapy.Conclusion: Mineralocorticoid antagonist treatment had a positive treatment

  19. Mizoribine ameliorates renal injury and hypertension along with the attenuation of renal caspase-1 expression in aldosterone-salt-treated rats.

    Directory of Open Access Journals (Sweden)

    Toshiki Doi

    Full Text Available Aldosterone-salt treatment induces not only hypertension but also extensive inflammation that contributes to fibrosis in the rat kidney. However, the mechanism underlying aldosterone-salt-induced renal inflammation remains unclear. Pyroptosis has recently been identified as a new type of cell death that is accompanied by the activation of inflammatory cytokines. We hypothesized that aldosterone-salt treatment could induce inflammation through pyroptosis and that mizoribine, an effective immunosuppressant, would ameliorate the renal inflammation that would otherwise cause renal fibrosis. Ten days after recovery from left uninephrectomy, rats were given drinking water with 1% sodium chloride. The animals were divided into three groups (n = 7 per group: (1 vehicle infusion group, (2 aldosterone infusion group, or (3 aldosterone infusion plus oral mizoribine group. Aldosterone-salt treatment increased the expression of the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 and caspase-1, and also increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. However, the oral administration of mizoribine attenuated these alterations. Furthermore, mizoribine inhibited hypertension and renal fibrosis, and also attenuated the aldosterone-induced expression of serum/glucocorticoid-regulated kinase and α epithelial sodium channel. These results suggest that caspase-1 activation plays an important role in the development of inflammation induced by aldosterone-salt treatment and that it functions as an anti-inflammatory strategy that protects against renal injury and hypertension.

  20. Effect of renin-angiotensin-aldosterone system gene polymorphisms on blood pressure response to antihypertensive treatment

    Institute of Scientific and Technical Information of China (English)

    JIANG Xiao; SHENG Hai-hui; LIN Gang; LI Jian; LU Xin-zheng; CHENG Yun-lin; HUANG Jun; XIAO Hua-sheng; ZHAN Yi-yang

    2007-01-01

    Background The renin-angiotensin-aldosterone system (RAAS) is important for the development of essential hypertension, and many antihypertensive drugs target it. This study was undertaken to determine whether polymorphisms in the renin-angiotensin-aldosterone system are related to the blood pressure (BP) response to diuretic treatment in a Chinese Han ethnic population.Methods Fifty-four patients with essential hypertension received hydrochlorothiazide (12.5 mg, once daily) as monotherapy for four weeks. Seven polymorphisms in RAAS genes were genotyped by gene chip technology. The relationship between these polymorphisms and the change in blood pressure was observed after the 4-week treatment.Results The patients with angiotensinogen (AGT) -6G allele showed a greater reduction in diastolic BP (P= 0.025) and mean BP (P=0.039) than those carrying AA genotype. Patients carrying aldosterone synthase (CYP11B2) CC genotype exhibited a greater BP reduction than those carrying CT and TT genotypes (systolic BP: P= 0.030; diastolic BP: P= 0.026; mean BP: P=0.003). In addition, patients with a combination of CYP11B2 CC genotype and angiotensin converting enzyme (ACE) D allele might have a more pronounced reduction of systolic BP than those with any other genotypic combinations of the two genes (P= 0.007).Conclusions AGT-6G allele, CYP11B2 -344CC genotype and its combination with ACE D allele are associated with BP response to hydrochlorothiazide treatment. Larger studies are warranted to validate this finding.

  1. Intracellular Molecular Differences in Aldosterone- Compared to Cortisol-Secreting Adrenal Cortical Adenomas.

    Science.gov (United States)

    Seidel, Eric; Scholl, Ute I

    2016-01-01

    The adrenal cortex is a major site of steroid hormone production. Two hormones are of particular importance: aldosterone, which is produced in the zona glomerulosa in response to volume depletion and hyperkalemia, and cortisol, which is produced in the zona fasciculata in response to stress. In both cases, acute stimulation leads to increased hormone production, and chronic stimulation causes hyperplasia of the respective zone. Aldosterone- and cortisol-producing adenomas (APAs and CPAs) are benign tumors of the adrenal cortex that cause excess hormone production, leading to primary aldosteronism and Cushing's syndrome, respectively. About 40% of the APAs carry somatic heterozygous gain-of-function mutations in the K(+) channel KCNJ5. These mutations lead to sodium permeability, depolarization, activation of voltage-gated Ca(2+) channels, and Ca(2+) influx. Mutations in the Na(+)/K(+)-ATPase subunit ATP1A1 and the plasma membrane Ca(2+)-ATPase ATP2B3 similarly cause Na(+) or H(+) permeability and depolarization, whereas mutations in the Ca(2+) channel CACNA1D directly lead to increased calcium influx. One in three CPAs carries a recurrent gain-of-function mutation (L206R) in the PRKACA gene, encoding the catalytic subunit of PKA. This mutation causes constitutive PKA activity by abolishing the binding of the inhibitory regulatory subunit to the catalytic subunit. These mutations activate pathways that are relatively specific to the respective cell type (glomerulosa versus fasciculata), and there is little overlap in mutation spectrum between APAs and CPAs, but co-secretion of both hormones can occur. Mutations in CTNNB1 (beta-catenin) and GNAS (Gsα) are exceptions, as they can cause both APAs and CPAs through pathways that are incompletely understood. PMID:27445978

  2. Analysis of renin-angiotensin-aldosterone system gene polymorphisms in resistant hypertension

    Directory of Open Access Journals (Sweden)

    S.R.S. Freitas

    2007-03-01

    Full Text Available Essential hypertension is a disease multifactorially triggered by genetic and environmental factors. The contribution of genetic polymorphisms of the renin-angiotensin-aldosterone system and clinical risk factors to the development of resistant hypertension was evaluated in 90 hypertensive patients and in 115 normotensive controls living in Southwestern Brazil. Genotyping for insertion/deletion of angiotensin-converting enzyme, angiotensinogen M235T, angiotensin II type 1 receptor A1166C, aldosterone synthase C344T, and mineralocorticoid receptor A4582C polymorphisms was performed by PCR, with further restriction analysis when required. The influence of genetic polymorphisms on blood pressure variation was assessed by analysis of the odds ratio, while clinical risk factors were evaluated by logistic regression. Our analysis indicated that individuals who carry alleles 235-T, 1166-A, 344-T, or 4582-C had a significant risk of developing resistant hypertension (P < 0.05. Surprisingly, when we tested individuals who carried the presumed risk genotypes A1166C, C344T, and A4582C we found that these genotypes were not associated with resistant hypertension. However, a gradual increase in the risk to develop resistant hypertension was detected when the 235-MT and TT genotypes were combined with one, two or three of the supposedly more vulnerable genotypes - A1166C (AC/AA, C344T (TC/TT and A4582C (AC/CC. Analysis of clinical parameters indicated that age, body mass index and gender contribute to blood pressure increase (P < 0.05. These results suggest that unfavorable genetic renin-angiotensin-aldosterone system patterns and clinical risk variables may contribute to increasing the risk for the development of resistant hypertension in a sample of the Brazilian population.

  3. 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

  4. 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.

  5. Selective hypoaldosteronism due to combined defects of the conversion from inactive renin to active renin and the aldosterone biosynthesis from corticosterone.

    Science.gov (United States)

    Muto, S; Akai, Y; Ono, S; Kusano, E; Asano, Y

    2001-07-01

    A 24-year-old Japanese woman with IgA nephropathy exhibited a decreased serum aldosterone level with normal plasma renin activity after toxemia of pregnancy. Our studies revealed selective hypoaldosteronism with normal adrenoglucocorticoid functions. Levels of serum corticosterone and deoxycorticosterone were normal. Resting plasma renin activity was normal, and plasma levels of total and inactive renin were increased. Rapid ACTH administration failed to stimulate any secretion of aldosterone, whereas it adequately increased serum cortisol, deoxycorticosterone, and corticosterone concentrations. Responses of both plasma renin activity and serum aldosterone level to the furosemide-posture challenge were blunted. Angiotensin II also failed to stimulate any secretion of aldosterone despite a progressive rise in blood pressure and an appropriate increase in serum corticosterone. These results suggest that combined defects of the conversion from inactive renin to active renin and aldosterone biosynthesis are the causes of selective hypoaldosteronism in our patient.

  6. Correlation of renin angiotensin and aldosterone system activity with subcutaneous and visceral adiposity: the framingham heart study

    Directory of Open Access Journals (Sweden)

    O'Seaghdha Conall M

    2012-04-01

    Full Text Available Abstract Background Animal studies suggest that local adipocyte-mediated activity of the renin-angiotensin-aldosterone system (RAAS contributes to circulating levels, and may promote the development of obesity-related hypertension in rodents. Methods We examined relations of systemic RAAS activity, as assessed by circulating plasma renin activity (PRA, serum aldosterone level, and aldosterone:renin ratio (ARR, with specific regional adiposity measures in a large, community-based sample. Third Generation Framingham Heart Study participants underwent multidetector computed tomography assessment of SAT and VAT volumes during Exam 1 (2002 and 2005. PRA and serum aldosterone were measured after approximately 10 minutes of supine rest; results were log-transformed for analysis. Correlation coefficients between log-transformed RAAS measures and adiposity measurements were calculated, adjusted for age and sex. Partial correlations between log-transformed RAAS measures and adiposity measurements were also calculated, adjusted for standard CVD risk factors. Results Overall, 992 women and 897 men were analyzed (mean age 40 years; 7% hypertension; 3% diabetes. No associations were observed with SAT (renin r = 0.04, p = 0.1; aldosterone r = -0.01, p = 0.6 or VAT (renin r = 0.03, p = 0.2; aldosterone r = -0.03, p = 0.2. Similar results were observed for ARR, in sex-stratified analyses, and for BMI and waist circumference. Non-significant partial correlations were also observed in models adjusted for standard cardiovascular risk factors. Conclusions Regional adiposity measures were not associated with circulating measures of RAAS activity in this large population-based study. Further studies are required to determine whether adipocyte-derived RAAS components contribute to systemic RAAS activity in humans.

  7. Aldosterone increases oxidant stress to impair guanylyl cyclase activity by cysteinyl thiol oxidation in vascular smooth muscle cells.

    Science.gov (United States)

    Maron, Bradley A; Zhang, Ying-Yi; Handy, Diane E; Beuve, Annie; Tang, Shiow-Shih; Loscalzo, Joseph; Leopold, Jane A

    2009-03-20

    Hyperaldosteronism is associated with impaired endothelium-dependent vascular reactivity owing to increased reactive oxygen species and decreased bioavailable nitric oxide (NO(.)); however, the effects of aldosterone on vasodilatory signaling pathways in vascular smooth muscle cells (VSMC) remain unknown. Soluble guanylyl cyclase (GC) is a heterodimer that is activated by NO(.) to convert cytosolic GTP to cGMP, a second messenger required for normal VSMC relaxation. Here, we show that aldosterone (10(-9)-10(-7) mol/liter) diminishes GC activity by activating NADPH oxidase in bovine aortic VSMC to increase reactive oxygen species levels and induce oxidative posttranslational modification(s) of Cys-122, a beta(1)-subunit cysteinyl residue demonstrated previously to modulate NO(.) sensing by GC. In VSMC treated with aldosterone, Western immunoblotting detected evidence of GC beta(1)-subunit disulfide bonding, whereas mass spectrometry analysis of a homologous peptide containing the Cys-122-bearing sequence exposed to conditions of increased oxidant stress confirmed cysteinyl sulfinic acid (m/z 435), sulfonic acid (m/z 443), and disulfide (m/z 836) bond formation. The functional effect of these modifications was examined by transfecting COS-7 cells with wild-type GC or mutant GC containing an alanine substitution at Cys-122 (C122A). Exposure to aldosterone or hydrogen peroxide (H(2)O(2)) significantly decreased cGMP levels in cells expressing wild-type GC. In contrast, aldosterone or H(2)O(2) did not influence cGMP levels in cells expressing the mutant C122A GC, confirming that oxidative modification of Cys-122 specifically impairs GC activity. These findings demonstrate that pathophysiologically relevant concentrations of aldosterone increase oxidant stress to convert GC to an NO(.)-insensitive state, resulting in disruption of normal vasodilatory signaling pathways in VSMC.

  8. 局部醛固酮系统与糖尿病肾病%Local aldosterone system and diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    杨珊; 杜超; 周波

    2012-01-01

    肾上腺以外组织局部醛固酮合酶(CYP11B2)及盐皮质激素受体(MR)的表达提示了局部醛固酮系统的形成,研究证实肾脏内存在局部醛固酮系统,在肾脏足细胞、系膜细胞和肾小管上皮细胞内存在局部醛固酮系统的全部组分.高血糖可激活肾脏局部醛固酮系统,进而通过炎性反应、氧化应激、细胞外基质积聚、细胞凋亡和肾小管间质转分化等方式加速糖尿病肾病的发生与发展.MR拮抗剂和CYP11 B2抑制剂均可阻断局部醛固酮系统,这将是糖尿病肾病治疗的一个新方向.%The expression of aldosterone synthase(CYP11B2) and mineralocorticoid receptor(MR) in extraadrenal tissues suggests the formation of local aldosterone system.Studies have confirmed the presence of local aldosterone systems in kidney.All the essential components of an aldosterone system could be found in renal podocytes,mesangial cells and renal tubular epithelial cells.Hyperglycemia could activate these renal aldosterone systems,which may accelerate the development and progression of diabetic nephropathy (DN) via inflammatory response,oxidative stress,extracellular matrix accumulation,cell apoptosis and renal tubular mesenchymal transdifferentiation.Both MR antagonsits and CYP11B2 inhibitors could block local aldosterone system,this may be a new direction in the treatment of DN.

  9. Effect of atrial natriuretic peptide on potassium-stimulated aldosterone secretion: potential relevance to hypoaldosteronism in man.

    Science.gov (United States)

    Clark, B A; Brown, R S; Epstein, F H

    1992-08-01

    Atrial natriuretic peptide (ANP) has been shown to suppress aldosterone secretion under certain circumstances, although the physiological significance of this is uncertain. We wondered if ANP would suppress potassium-stimulated aldosterone secretion in man and, if so, whether we might find high circulating levels of ANP in patients with the syndrome of acquired hypoaldosteronism. We studied seven healthy young subjects under two conditions: 1) infusion of KCl (0.5 mmol/kg) over 45 min, and 2) KCl infused with ANP (0.01 microgram/kg.min) for 60 min. We also evaluated ANP levels in eight elderly subjects with the syndrome of acquired hypoaldosteronism, as defined by hyperkalemia (mean serum K+, 5.3 +/- 0.1 mmol/L) associated with inappropriately low aldosterone levels (216 +/- 50 pmol/L). In the normal subjects, ANP almost completely suppressed the aldosterone response to KCl infusion (P less than 0.001, by analysis of variance) despite a similar rise in the serum potassium level with KCl alone (0.70 +/- 0.07 mmol/L) and KCl plus ANP (0.75 +/- 0.09 mmol/L). PRA fell slightly during KCl plus ANP treatment, but did not change during the infusion of KCl alone. ANP levels were approximately 800 pmol/L during the ANP infusion studies. Endogenous ANP levels in the hyperkalemic patients with hypoaldosteronism were markedly elevated at 1186 +/- 340 pmol/L (compared to 93 +/- 10 pmol/L in healthy elderly controls), a level that would be capable of suppressing the potassium-mediated aldosterone response. Exogenous infusion of ANP suppressed the aldosterone response to hyperkalemia, and ANP levels were found to be markedly elevated in a group of patients with hyperkalemia and hypoaldosteronism. We suggest that ANP may contribute to clinically significant hypoaldosteronism and hyperkalemia in the syndrome of acquired hypoaldosteronism.

  10. 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.

  11. 详释醛固酮逃逸%Interpretation of Aldosterone Escape

    Institute of Scientific and Technical Information of China (English)

    梁昊; 周小青

    2012-01-01

    从“醛固酮逃逸”的概念入手,结合国内外多篇文献,全面解读其含义,并提出了相应的修改意见,以便能够规范应用。%Although the term "aldosterone escape" has been used for years, its concept is not explicit. Hence, it's misused by people, which misled basic research and clinical practice. We interpret the meaning in detail based on related literatures, and put forward some modification suggestions for standardized use.

  12. Mineralocorticoid receptor in the NTS stimulates saline intake during fourth ventricular infusions of aldosterone.

    Science.gov (United States)

    Koneru, Bhuvaneswari; Bathina, Chandra Sekhar; Cherry, Brandon H; Mifflin, Steve W

    2014-01-01

    The purpose of this study was to determine whether neurons within the nucleus tractus solitarius (NTS) that express the mineralocorticoid receptor (MR) play a role in aldosterone stimulation of salt intake. Adult Wistar-Kyoto (WKY) rats received microinjections into the NTS of a short-hairpin RNA (shRNA) for the MR, to site specifically reduce levels of the MR by RNA interference (shRNA; n = 9) or scrambled RNA as a control (scRNA; n = 8). After injection of the viral construct, aldosterone-filled osmotic minipumps were implanted subcutaneously and connected to a cannula extending into the fourth ventricle to infuse aldosterone at a rate of 25 ng/h. Before and after surgeries, rats had ad libitum access to normal sodium (0.26%) rat chow and two graduated drinking bottles filled with either distilled water or 0.3 M NaCl. Before the surgeries, basal saline intake was 1.6 ± 0.6 ml in the scRNA group and 1.56 ± 0.6 ml in the shRNA group. Twenty-four days postsurgery, saline intake was elevated to a greater extent in the scRNA group (5.9 ± 1.07 ml) than in the shRNA group (2.41 ± 0.6 ml). Post mortem immunohistochemistry revealed a significant reduction in the number of NTS neurons exhibiting immunoreactivity for MR in shRNA-injected rats (23 ± 1 cells/section) versus scRNA-injected rats (33 ± 2 cells/section; P = 0.008). shRNA did not alter the level of 11-β-hydroxysteroid dehydrogenase type II (HSD2) protein in the NTS as judged by the number of HSD2 immunoreactive neurons. These results suggest that fourth ventricular infusions of aldosterone stimulate saline intake, and that this stimulation is at least in part mediated by hindbrain NTS neurons that express MR.

  13. GABAA receptor partial agonists and antagonists

    DEFF Research Database (Denmark)

    Krall, Jacob; Balle, Thomas; Krogsgaard-Larsen, Niels;

    2015-01-01

    antagonists and describes the development of potent antagonists from partial agonists originally derived from the potent GABAAR agonist muscimol. In this process, several heterocyclic aromatic systems have been used in combination with structural models in order to map the orthosteric binding site...... and to reveal structural details to be used for obtaining potency and subtype selectivity. The challenges connected to functional characterization of orthosteric GABAAR partial agonists and antagonists, especially with regard to GABAAR stoichiometry and alternative binding sites are discussed. GABAAR...

  14. Pathophysiology of the cysteinyl leukotrienes and effects of leukotriene receptor antagonists in asthma.

    Science.gov (United States)

    Bisgaard, H

    2001-01-01

    Cysteinyl leukotrienes, synthesized de novo from cell membrane phospholipids, are proinflammatory mediators that play an important role in the pathophysiology of asthma. These mediators are among the most potent of bronchoconstrictors and cause vasodilation, increased microvascular permeability, exudation of macromolecules and edema. The cysteinyl leukotrienes also have potent chemoattractant properties for eosinophils, causing an influx of eosinophils into the airway mucosa, which further fuels the inflammatory process. In addition, the cysteinyl leukotrienes are potent secretagogues and reduce ciliary motility, which may hinder mucociliary clearance. Asthmatic patients demonstrate increased production of cysteinyl leukotrienes during naturally occurring asthma and acute asthma attacks as well as after allergen and exercise challenge. The leukotriene receptor antagonists montelukast, zafirlukast and pranlukast inhibit bronchoconstriction in asthmatic patients undergoing allergen, exercise, cold air or aspirin challenge. They attenuate the hallmarks of asthmatic inflammation, including eosinophilia in the airway mucosa and peripheral blood. Moreover, exhaled nitric oxide concentrations, another correlate of airway inflammation, are decreased during montelukast treatment in children. Cysteinyl leukotriene synthesis is not blocked by corticosteroid therapy. This important observation suggests that the leukotriene receptor antagonists represent a novel therapeutic approach, one that may provide benefits that are additive with corticosteroid therapy. This supposition is supported by clinical observations that treatment with leukotriene receptor antagonists significantly improve asthma control when added to inhaled corticosteroid therapy. Moreover, the bronchodilator properties of the leukotriene receptor antagonists are additive with those of beta agonists. These data provide strong support for the use of leukotriene receptor antagonists for treating asthma. PMID

  15. ARMC5 mutation analysis in patients with primary aldosteronism and bilateral adrenal lesions.

    Science.gov (United States)

    Mulatero, P; Schiavi, F; Williams, T A; Monticone, S; Barbon, G; Opocher, G; Fallo, F

    2016-06-01

    Idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia is the most common subtype of primary aldosteronism (PA). The pathogenesis of IHA is still unknown, but the bilateral disease suggests a potential predisposing genetic alteration. Heterozygous germline mutations of armadillo repeat containing 5 (ARMC5) have been shown to be associated with hypercortisolism due to sporadic primary bilateral macronodular adrenal hyperplasia and are also observed in African-American PA patients. We investigated the presence of germline ARMC5 mutations in a group of PA patients who had bilateral computed tomography-detectable adrenal alterations. We sequenced the entire coding region of ARMC5 and all intron/exon boundaries in 39 patients (37 Caucasians and 2 black Africans) with confirmed PA (8 unilateral, 27 bilateral and 4 undetermined subtype) and bilateral adrenal lesions. We identified 11 common variants, 5 rare variants with a minor allele frequency <1% and 2 new variants not previously reported in public databases. We did not detect by in silico analysis any ARMC5 sequence variations that were predicted to alter protein function. In conclusion, ARMC5 mutations are not present in a fairly large series of Caucasian patients with PA associated to bilateral adrenal disease. Further studies are required to definitively clarify the role of ARMC5 in the pathogenesis of adrenal nodules and aldosterone excess in patients with PA. PMID:26446392

  16. 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.

  17. 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

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

    Science.gov (United States)

    Molina-Ayala, Mario; Ramírez-Rentería, Claudia; Manguilar-León, Analleli; Paúl-Gaytán, Pedro; Ferreira-Hermosillo, Aldo

    2015-01-01

    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. PMID:26161274

  19. 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.

  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. 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

  2. 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

  3. New antagonist agents of neuropeptide y receptors

    Directory of Open Access Journals (Sweden)

    Ignacio Aldana

    2000-12-01

    Full Text Available In the CNS, NPY has been implicated in obesity and feeding, endocrine function and metabolism. Potent and selective rNPY antagonists will be able to probe the merits of this approach for the treatment of obesity. We report the synthesis and preliminary evaluation of some hydrazide derivatives as antagonists of rNPY.

  4. Client Perceptions of Two Antagonist Programs.

    Science.gov (United States)

    Capone, Thomas A.; And Others

    1980-01-01

    Reports results of a questionnaire administered to participants in an antagonist drug outpatient clinic and an antagonist drug work-release program to obtain awareness of acceptance of the program participants. Naltrexone patients recommended an alternative method of administering the drug and changing the money system to award deserving inmates…

  5. Analysis of the Clinical Features of Adrenal Aldosterone Tumor and Idiopathic Aldosterone in Patients with Primary Aldosterone%浅析原发性醛固酮增多症中肾上腺醛固酮瘤和特发性醛固酮增多症的临床特点

    Institute of Scientific and Technical Information of China (English)

    赵伟军

    2016-01-01

    Objective To study the clinical characteristics of adrenal aldosterone tumor and idiopathic aldosterone in patients with primary aldosterone. Methods 16 cases with aldosterone-producing adenoma from July to December 2015 were selected as observation group, and 12 cases with idiopathic aldosterone gain were selected as control group. Clinical characteristics of two groups were compared. Results Lack the main results of the study data: patients in the observation group and the patients in the control group, serum potassium, potassium in the urine and urinary aldosterone and plasma aldosterone levels respectively: (2.44±0.37)mmol/L, (51.25±28.93) mmol/L, (55.45±28.93)nmol/L, (1240.94±783.37) pmol/L and (2.96±0.42) mmol/L, (59.83±29.01)mmol/L, (40.24±2.107) nmol/L, (709.21±546.62) pmol/L. Adrenal aldosterone producing adenoma and idiopathic hyperaldosteronism increased compared. The serum aldosterone levels and urinary aldosterone levels were significantly higher, and serum potassium level is relatively lower, and the difference was statistically significant (P<0.05). Conclusion The biochemical abnormalities of adrenal aldosterone tumor is relatively speaking, its characteristics are more obvious, which can be widely used in clinical practice.%目的:研究分析原发性醛固酮增多症中肾上腺醛固酮瘤和特发性醛固酮增多症的临床特点。方法选取2015年7~12月我院内分泌科所收治的肾上腺醛固酮瘤患者16例作为本研究观察组研究对象,12例特发性醛固酮增多症患者作为对照组,对比分析两组患者的临床特点。结果观察组患者与对照组患者血钾、尿钾、尿醛固酮以及血醛固酮水平分别为:(2.44±0.37)mmol/L、(51.25±28.93)mmol/L、(55.45±28.93)nmol/L、(1240.94±783.37)pmol/L 与(2.96±0.42) mmol/L、(59.83±29.01)mmol/L、(40.24±21.07)nmol/L、(709.21±546.62)pmol/L。肾上腺醛固酮瘤与特发性醛固酮增多症相比

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

    Directory of Open Access Journals (Sweden)

    Ting-Ting Xiao

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

  7. Temporal trends in the prescription of vitamin K antagonists in patients with atrial fibrillation

    DEFF Research Database (Denmark)

    Friberg, J; Gislason, G H; Gadsbøll, N;

    2006-01-01

    OBJECTIVES: Anticoagulation therapy is recommended in patients with atrial fibrillation (AF) and risk factors for stroke. We studied the temporal trends in the prescription of vitamin K antagonists (VKA) in patients with a first hospital diagnosis of AF in Denmark, 1995-2002. DESIGN: The Danish...

  8. TGF-.beta. antagonists as mitigators of radiation-induced tissue damage

    Science.gov (United States)

    Barcellos-Hoff, Mary H.

    1997-01-01

    A method for treating tissue damage caused by radiation is described by use of a TGF-.beta. antagonist, such as an anti-TGF-.beta. antibody or a TGF-.beta. latency associated protein. It is administered not more than a week after exposure, and is particularly useful in mitigating the side effects of breast cancer therapy.

  9. TGF-{beta} antagonists as mitigators of radiation-induced tissue damage

    Science.gov (United States)

    Barcellos-Hoff, M.H.

    1997-04-01

    A method for treating tissue damage caused by radiation is described by use of a TGF-{beta} antagonist, such as an anti-TGF-{beta} antibody or a TGF-{beta} latency associated protein. It is administered not more than a week after exposure, and is particularly useful in mitigating the side effects of breast cancer therapy.

  10. Acute changes in plasma renin activity, plasma aldosterone concentration and plasma electrolyte concentrations following furosemide administration in patients with congestive heart failure--interrelationships and diuretic response.

    Science.gov (United States)

    Mulder, H; Schopman, W; van der Lely, A J; Schopman, W

    1987-02-01

    We studied the effects of furosemide on plasma renin and plasma aldosterone in 8 patients with mild to moderate congestive heart failure. In particular, we tried to correlate these effects with changes in plasma electrolyte concentrations and with the diuretic response on furosemide. We concluded that the diuretic response in patients with congestive heart failure is not dependent on the initial serum renin nor on the initial serum aldosterone concentration. The diuretic response did not correlate either with the changes in serum renin and/or serum aldosterone concentration. Serum renin and serum aldosterone correlated mutually before and after intravenous furosemide. We confirmed the inverse correlation between serum sodium and serum renin. SeNa and SeK correlated at all times with serum aldosterone; SeCl correlated with serum aldosterone only before intravenous furosemide administration. Indirect evidence could be provided that in patients with congestive heart failure a decreased renal blood flow is present, using the urinary beta 2-microglobulin concentration. Aldosterone has again, indirectly, proved to be integrated in the renal magnesium handling. PMID:3549504

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-08-01

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

  12. 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

  13. 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

    OBJECTIVE: Several studies have shown activation of the renin-angiotensin-aldosterone system (RAAS) in cirrhosis. Although the activated RAAS may have several determinants, the system is often considered a surrogate marker of effective hypovolaemia. In this study we investigated the activity...

  14. Gene-load score of the renin-angiotensin-aldosterone system is associated with coronary heart disease in familial hypercholesterolaemia

    NARCIS (Netherlands)

    J.B. van der Net (Jeroen); J. van Etten (Jeroen); M. Yazdanpanah (Mojgan); G.M. Dallinga-Thie (Geesje); J.J.P. Kastelein (John); J.C. Defesche (Joep); R.P. Koopmans (Richard); E.W. Steyerberg (Ewout); E.J.G. Sijbrands (Eric)

    2008-01-01

    textabstractAims: Familial hypercholesterolaemia (FH) is characterized by premature coronary heart disease (CHD). However, the incidence of CHD varies considerably among FH patients. Genetic variation in the renin-angiotensin-aldosterone system (RAAS) and the adrenalin/noradrenalin system may be of

  15. Rapid screening test for primary hyperaldosteronism: ratio of plasma aldosterone to renin concentration determined by fully automated chemiluminescence immunoassays.

    NARCIS (Netherlands)

    Perschel, F.H.; Schemer, R.; Seiler, L.; Reincke, M.; Deinum, J.; Maser-Gluth, C.; Mechelhoff, D.; Tauber, R.; Diederich, S.

    2004-01-01

    BACKGROUND: The ratio of plasma aldosterone concentration to plasma renin activity (PAC/PRA) is the most common screening test for primary hyperaldosteronism (PHA), but it is not standardized among laboratories. We evaluated new automated assays for the simultaneous measurement of PAC and plasma ren

  16. 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.

  17. Plasma 18-hydroxycorticosterone and aldosterone responses to angiotensin II and corticotropin in diabetic patients with hyporeninemic and normoreninemic hypoaldosteronism.

    Science.gov (United States)

    Iwasaki, R; Kigoshi, T; Uchida, K; Morimoto, S

    1989-07-01

    To examine the nature of adrenal abnormalities in diabetic patients with hyporeninemic and normoreninemic hypoaldosteronism, responses of plasma 18-hydroxycorticosterone and plasma aldosterone to angiotension II infusions and ACTH injection were investigated in 8 diabetic patients with hyporeninemic hypoaldosteronism and 9 diabetic patients with normoreninemic hypoaldosteronism compared to 11 control subjects. In both the patients with hyporeninemic and normoreninemic hypoaldosteronism, plasma 18-hydroxycorticosterone and plasma aldosterone were low, whereas plasma cortisol and plasma corticosterone were within normal ranges. Percent increments of plasma 18-hydroxycorticosterone and plasma aldosterone above their baseline levels after angiotensin II infusions were low or somewhat low in the patients with hyporeninemic hypoaldosteronism and low in the patients with normoreninemic hypoaldosteronism. Percent increments of plasma 18-hydroxycorticosterone and plasma aldosterone above their baseline levels after ACTH injection were similar in three groups. These results suggest that in diabetic patients with isolated hypoaldosteronism, the adrenal abnormality, regardless of whether it is primary or secondary, is mainly due to impaired adrenal responsiveness to angiotension II and atrophy and the zona glomerulosa.

  18. Interleukin-1 antagonists for diabetes

    DEFF Research Database (Denmark)

    Mandrup-Poulsen, Thomas

    2013-01-01

    INTRODUCTION: Diabetes is a currently incurable, epidemically growing global health concern. Contemporary symptomatic treatment targets acute and chronic metabolic consequences of relative or absolute insulin deficiency. Intensive multifactorial therapy is required to attenuate morbidity and mort......INTRODUCTION: Diabetes is a currently incurable, epidemically growing global health concern. Contemporary symptomatic treatment targets acute and chronic metabolic consequences of relative or absolute insulin deficiency. Intensive multifactorial therapy is required to attenuate morbidity...... and mortality from late micro- and macrovascular complications, and despite current best clinical practice diabetes is still associated with shortened lifespan. There is an unmet need for interventions targeting pathogenetic mechanisms in diabetes, and the market for such therapies is huge. AREAS COVERED......: Diabetes occurs when insulin secretion fails to meet tissue needs as a consequence of reduced functional beta-cell mass or reduced insulin sensitivity. Chronic inflammation contributes to beta-cell failure and insulin resistance. Molecular details are accumulating on the underlying cellular and molecular...

  19. New combination therapies for asthma.

    Science.gov (United States)

    Donohue, J F; Ohar, J A

    2001-03-01

    Combination products often have useful clinical benefits in asthma. The scientific rationale for combination therapy includes the fact that different agents have complimentary modes of action. Long-acting beta(2)-agonists have effects on airway smooth muscle, and inhaled corticosteroids have potent topical antiinflammatory effect. This combination has been shown to effectively reduce exacerbations and improve symptoms. Substantial clinical trial data provide a rationale for dual-control therapy supported by basic scientific data. Another combined therapy is inhaled steroids plus leukotriene-receptor antagonists, which provides the patient with two effective therapies. Leukotriene-receptor antagonist can also be combined with antihistamines for improved asthma control. Older therapies including theophylline and controlled release albuterol have been effectively added to inhaled corticosteroids, enabling a reduction in the dose of the inhaled steroids. Many other combination therapies are presently being tested. PMID:11224725

  20. Molecular Gymnastics: Mechanisms of HIV-1 Resistance to CCR5 Antagonists and Impact on Virus Phenotypes.

    Science.gov (United States)

    Roche, Michael; Borm, Katharina; Flynn, Jacqueline K; Lewin, Sharon R; Churchill, Melissa J; Gorry, Paul R

    2016-01-01

    Human immunodeficiency virus type 1 (HIV-1) enters host cells through the binding of its envelope glycoproteins (Env) to the host cell receptor CD4 and then subsequent binding to a chemokine coreceptor, either CCR5 or CXCR4. CCR5 antagonists are a relatively recent class addition to the armamentarium of anti-HIV-1 drugs. These compounds act by binding to a hydrophobic pocket formed by the transmembrane helices of CCR5 and altering the conformation of the extracellular domains, such that they are no longer recognized by Env. Maraviroc is the first drug within this class to be licenced for use in HIV-1 therapy regimens. HIV resistance to CCR5 antagonists occurs either through outgrowth of pre-existing CXCR4-using viruses, or through acquisition of the ability of CCR5-using HIV-1 to use the antagonist bound form of CCR5. In the latter scenario, the mechanism underlying resistance is through complex alterations in the way that resistant Envs engage CCR5. These significant changes are unlikely to occur without consequence to the viral entry phenotype and may also open up new avenues to target CCR5 antagonist resistant viruses. This review discusses the mechanism of action of CCR5 antagonists, how HIV resistance to CCR5 antagonists occurs, and the subsequent effects on Env function. PMID:26324043

  1. Molecular Gymnastics: Mechanisms of HIV-1 Resistance to CCR5 Antagonists and Impact on Virus Phenotypes.

    Science.gov (United States)

    Roche, Michael; Borm, Katharina; Flynn, Jacqueline K; Lewin, Sharon R; Churchill, Melissa J; Gorry, Paul R

    2016-01-01

    Human immunodeficiency virus type 1 (HIV-1) enters host cells through the binding of its envelope glycoproteins (Env) to the host cell receptor CD4 and then subsequent binding to a chemokine coreceptor, either CCR5 or CXCR4. CCR5 antagonists are a relatively recent class addition to the armamentarium of anti-HIV-1 drugs. These compounds act by binding to a hydrophobic pocket formed by the transmembrane helices of CCR5 and altering the conformation of the extracellular domains, such that they are no longer recognized by Env. Maraviroc is the first drug within this class to be licenced for use in HIV-1 therapy regimens. HIV resistance to CCR5 antagonists occurs either through outgrowth of pre-existing CXCR4-using viruses, or through acquisition of the ability of CCR5-using HIV-1 to use the antagonist bound form of CCR5. In the latter scenario, the mechanism underlying resistance is through complex alterations in the way that resistant Envs engage CCR5. These significant changes are unlikely to occur without consequence to the viral entry phenotype and may also open up new avenues to target CCR5 antagonist resistant viruses. This review discusses the mechanism of action of CCR5 antagonists, how HIV resistance to CCR5 antagonists occurs, and the subsequent effects on Env function.

  2. SIRT1 IS REQUIRED FOR ANTAGONIST-INDUCED TRANSCRIPTIONAL REPRESSION OF ANDROGEN-RESPONSIVE GENES BY THE ANDROGEN RECEPTOR

    OpenAIRE

    Dai, Yan; Ngo, Duyen; Forman, Lora W.; Qin, David C.; Jacob, Johanna; Faller, Douglas V

    2007-01-01

    Androgen antagonists or androgen deprivation is a primary therapeutic modality for the treatment of prostate cancer. Invariably, however, the disease becomes progressive and unresponsive to androgen ablation therapy (hormone refractory). The molecular mechanisms by which the androgen antagonists inhibit prostate cancer proliferation are not fully defined. In this report, we demonstrate that SIRT1, a nicotinamide adenosine dinucleotide-dependent histone deacetylase linked to the regulation of ...

  3. 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

  4. 原发性醛固酮增多症的发病机制%Pathogenesis of primary aldosteronism

    Institute of Scientific and Technical Information of China (English)

    徐媛媛; 王卫庆

    2011-01-01

    Primary aldosteronism is one of the most common causes of secondary hypertension. Compared with essential hypertension patients who have same risk factors, impared cardiovascular, cerebrovascular and kidney damage are more prevalent in patients with primary aldosteronism. In recent years,with the further research of primary aldosteronism, it was shown that the pathogenesis of primary aldosteronism related to CYP11β2 gene polymorphisms, production of hybird gene, expression of ectopic adrenal receptors, 7p21-22gene and so on. Researches of pathogenesis of primary aldosteronism may provide a novel therapeutic strategy.%原发性醛固酮增多症是继发性高血压最常见的原因之一,与具有相同危险程度的原发性高血压患者比较,原发性醛固酮增多症患者心、脑血管及肾脏等靶器官的损伤更为多见.近年来,随着对原发性醛固酮增多症的深入研究,发现其发病机制涉及融合基因的产生、醛固酮合成酶(CYP11β2)基因多态性的改变、肾上腺异位受体的表达及7p21-22基因的改变等.对原发性醛固酮增多症发病机制的研究可能为此病的治疗开辟新的方向.

  5. Suvorexant: The first orexin receptor antagonist to treat insomnia

    Directory of Open Access Journals (Sweden)

    Ashok K Dubey

    2015-01-01

    Full Text Available Primary insomnia is mainly treated with drugs acting on benzodiazepine receptors and a few other classes of drugs used for different co-morbidities. A novel approach to treat insomnia has been introduced recently, with the approval of suvorexant, the first in a new class of orexin receptor antagonists. Orexin receptors in the brain have been found to play an important role in the regulation of various aspects of arousal and motivation. The drugs commonly used for insomnia therapy to date, have often been associated with adverse effects, such as, day-time somnolence, amnesia, confusion, and gait disturbance, apart from the risk of dependence on chronic use. Suvorexant has not shown these adverse effects because of its unique mechanism of action. It also appears to be suitable as a chronic therapy for insomnia, because of minimal physical dependence. The availability of this new drug as an effective and safe alternative is an important and welcome development in insomnia management.

  6. Suvorexant: The first orexin receptor antagonist to treat insomnia.

    Science.gov (United States)

    Dubey, Ashok K; Handu, Shailendra S; Mediratta, Pramod K

    2015-01-01

    Primary insomnia is mainly treated with drugs acting on benzodiazepine receptors and a few other classes of drugs used for different co-morbidities. A novel approach to treat insomnia has been introduced recently, with the approval of suvorexant, the first in a new class of orexin receptor antagonists. Orexin receptors in the brain have been found to play an important role in the regulation of various aspects of arousal and motivation. The drugs commonly used for insomnia therapy to date, have often been associated with adverse effects, such as, day-time somnolence, amnesia, confusion, and gait disturbance, apart from the risk of dependence on chronic use. Suvorexant has not shown these adverse effects because of its unique mechanism of action. It also appears to be suitable as a chronic therapy for insomnia, because of minimal physical dependence. The availability of this new drug as an effective and safe alternative is an important and welcome development in insomnia management. PMID:25969666

  7. Genetic determinants of response and adverse effects following vitamin K antagonist oral anticoagulants

    Directory of Open Access Journals (Sweden)

    Parameshwar S.

    2016-06-01

    Full Text Available Background: Vitamin K antagonist anticoagulants (warfarin/acenocoumarol are commonly used anticoagulants that require careful clinical management to balance the risks of over anticoagulation and bleeding with those of under anticoagulation and clotting. Genetic variants of the enzyme that metabolizes vitamin K antagonist anticoagulant, cytochrome P-450 2C9 (CYP2C9, and of a key pharmacologic target of vitamin K antagonists anticoagulant, vitamin K epoxide reductase (VKORC1, contribute to differences in patients responses to various anticoagulant doses. Methods: In thirty patients on oral vitamin K antagonist anticoagulant therapy, presented with either clotting manifestations (valve thrombosis, pulmonary embolism and DVT or prolonged INR/bleeding manifestations, we assessed CYP2C9 genotypes, VKORC1 haplotypes, clinical characteristics, response to therapy (as determined by the international normalized ratio [INR], and bleeding events. Results: Of the thirty patients, thirteen patients INR was high and four patients presented with major bleeding and four with minor bleeding manifestations. Out of thirteen patients with high INR, ten patients showed CYP2C9 polymorphism ( 1/ 3 and 2/ 3 of poor metabolizer genotype. Most of the high INR patients were recently started on oral vitamin K antagonist anticoagulant. Most patients presented with clotting manifestations with below therapeutic INR are noncompliant with anticoagulants. Conclusions: The results of this study suggest that the CYP2C9 polymorphisms are associated with an increased risk of over anticoagulation and of bleeding events among patients on vitamin K antagonists' anticoagulant setting. Screening for CYP2C9 variants may allow clinicians to develop dosing protocols and surveillance techniques to reduce the risk of adverse drug reactions in patients receiving vitamin K antagonist anticoagulants. However the cost-effectiveness of genotyping of patients must be considered. [Int J Res Med Sci

  8. 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

  9. 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 ...

  10. The influence of certain molecular descriptors of fecal elimination of angiotensin II receptor antagonists

    Directory of Open Access Journals (Sweden)

    Trbojević-Stanković Jasna B.

    2015-01-01

    Full Text Available Angiotensin II receptor antagonists (ARBs modulate the function of the renin-angiotensin-aldosterone system and are commonly prescribed antihypertensive drugs, especially in patients with renal failure. In this study, the relationship between several molecular properties of seven ARBs (candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan and their fecal elimination data obtained from the literature were investigated. The ARB molecular descriptors were calculated using three software packages. Simple linear regression analysis showed the best 2 correlation between fecal elimination data and lipophilicity descriptor, ClogP values (R2 = 0.725. Multiple linear regression was applied to examine the correlation of ARBs’ fecal elimination data with their lipophilicity and one additional, calculated descriptor. The best correlation (R2 = 0.909 with an acceptable probability value, P <0.05 was established between the ARB fecal elimination data and their lipophilicity and aqueous solubility data. Applying computed molecular descriptors for evaluating drug elimination is of great importance in drug research.

  11. Antagonistic formation motion of cooperative agents

    Institute of Scientific and Technical Information of China (English)

    卢婉婷; 代明香; 薛方正

    2015-01-01

    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonis-tic interactions. A distributed formation control algorithm is proposed for each agent to realize the antagonistic formation motion. A sufficient condition is derived to ensure that all agents make an antagonistic formation motion in a distributed manner. It is shown that all agents can be spontaneously divided into several groups, and agents in the same group collab-orate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results.

  12. Role of extracellular signal-regulated kinases in aldosterone-induced rat mesangial cells proliferation%细胞外信号调节蛋白激酶介导醛固酮诱导的肾小球系膜细胞增殖

    Institute of Scientific and Technical Information of China (English)

    姚丽; 孙立; 魏敏; 葛丹梅; 王力宁

    2011-01-01

    ERK1/2 activation induced by aldosterone was at a concentration of 100 nmol/L. Aldosterone (100 nmol/L)-induced activation of ERK1/2 peaked at 10 minutes (P<0.05).Pretreatment with a selective MR antagonist eplerenone (1 μmol/L) significantly attenuated aldosterone-induced ERK1/2 phosphorylation. Aldosterone (100 nmol/L) treatment for 30 hours increased [3H]-thymidine incorporation of RMCs (135% ±8% of controls, P <0.05). Cellular proliferation induced by aldosterone could be prevented by pretreatment with eplerenone or an ERK (MEK) inhibitor PD988059. Conclusion Aldosterone induces RMCs proliferation through MR and ERK1/2 activation, which may contribute to the pathogenesis of glomerular mesangial injury.

  13. CURRENT TARGET OF ANTIHYPERTENSIVE THERAPY. DATA FROM CLINICAL TRIALS. PART 2

    Directory of Open Access Journals (Sweden)

    V. V. Popov

    2012-01-01

    Full Text Available Arterial hypertension (HT takes leading position in the structure of morbidity and mortality among the cardiovascular diseases in the economically developed and developing countries of the world. Despite progress in treatment of this disease, a number of people with uncontrolled or resistant HT increases. There is a problem of inefficiency of therapy or lack of patients' adherence to treatment. Therefore, search for new approaches to treatment of HT continues. Current most effective agents for blood pressure control, and possible future antihypertensive agents, are related to groups of agents, which inhibit renin–angiotensin–aldosterone system (RAAS. Novel targets for antihypertensive therapy could include the angiotensin II type 2 and type 1 receptor , neutral endopeptidase, aldosterone synthase, renalase, endothelin receptors, (prorenin receptors, vaccine against RAAS components. Development of novel agents and approaches to HT therapy is discussed.

  14. CURRENT TARGET OF ANTIHYPERTENSIVE THERAPY. DATA FROM CLINICAL TRIALS. PART 1

    Directory of Open Access Journals (Sweden)

    V. V. Popov

    2012-01-01

    Full Text Available Arterial hypertension (HT takes leading position in the structure of morbidity and mortality among the cardiovascular diseases in the economically developed and developing countries of the world. Despite progress in treatment of this disease, a number of people with uncontrolled or resistant HT increases. There is a problem of inefficiency of therapy or lack of patients' adherence to treatment. Therefore, search for new approaches to treatment of HT continues. Current most effective agents for blood pressure control, and possible future antihypertensive agents, are related to groups of agents, which inhibit renin–angiotensin–aldosterone system (RAAS. Novel targets for antihypertensive therapy could include the angiotensin II type 2 and type 1 receptor , neutral endopeptidase, aldosterone synthase, renalase, endothelin receptors, (prorenin receptors, vaccine against RAAS components. Development of novel agents and approaches to HT therapy is discussed.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wood, C.E.; Silbiger, J.

    1987-03-01

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

  16. Gene Expression Profile of Persistent Postoperative Hypertension Patients with Aldosterone-producing Adenomas

    Institute of Scientific and Technical Information of China (English)

    Li-Fang Xie; Jin-Zhi Ouyang; An-Ping Wang; Wen-Bo Wang; Xin-Tao Li; Bao-Jun Wang; Yi-Ming Mu

    2015-01-01

    Background:Hypertension often persists after adrenalectomy for primary aldosteronism (PA).Many studies have analyzed the outcomes of adrenalectomy for aldosterone-producing adenomas (APA) to identify predictive factors for persistent hypertension.However,differentially expressed genes in persistent postoperative hypertension remain unknown.Our aim was to describe gene expression profile of persistent postoperative hypertension patients with APA.Methods:In this study,we described and compared gene expression profiles in persistent postoperative hypertension and postoperative normotension in Chinese patients with APA using microarray analysis.Confirmation was performed with quantitative real time-polymerase chain reaction analysis.Bioinformatic analysis (gene ontology analysis,pathway analysis and network analysis) was used for further research.Results:Microarray analysis identified a total of 99 differentially expressed genes,including 18 up-regulated and 81 down-regulated genes.Among the dysregulated genes were fat atypical cadherin 1 as well as fatty acid binding protein 4 and other genes that have not been previously studied in persistent postoperative hypertension with APA.Bioinformatics analysis indicated that differentially expressed genes were associated with lipid metabolic process,metal ion binding,and cell differentiation.Pathway analysis determined that five pathways corresponded to the dysregulated transcripts.The mRNAs-ncRNAs co-expression network was composed of 49 network nodes and 72 connections between 18 coding genes and 31 noncoding genes.Conclusions:This study revealed differentially expressed genes in persistent postoperative hypertension with APA and provided a resource of candidate genes for exploration of possible drug targets and prognostic markers.

  17. 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.

  18. Medical Therapy of Acromegaly

    Directory of Open Access Journals (Sweden)

    U. Plöckinger

    2012-01-01

    Full Text Available This paper outlines the present status of medical therapy of acromegaly. Indications for permanent postoperative treatment, postirradiation treamtent to bridge the interval until remission as well as primary medical therapy are elaborated. Therapeutic efficacy of the different available drugs—somatostatin receptor ligands (SRLs, dopamine agonists, and the GH antagonist Pegvisomant—is discussed, as are the indications for and efficacy of their respective combinations. Information on their mechanism of action, and some pharmakokinetic data are included. Special emphasis is given to the difficulties to define remission criteria of acromegaly due to technical assay problems. An algorithm for medical therapy in acromegaly is provided.

  19. Vascular endothelial growth factor antagonist therapy for retinopathy of prematurity.

    Science.gov (United States)

    Hartnett, M Elizabeth

    2014-12-01

    In this article, the growing problem of retinopathy of prematurity (ROP) worldwide, treatments for severe ROP including standard-of-care laser treatment, and the need for new treatments are discussed. Also discussed are the reasons to consider inhibiting the vascular endothelial growth factor (VEGF) signaling pathway in severe ROP and the concerns about broad VEGF inhibition. Finally, the potential role of VEGF in ROP based on studies in animal models of oxygen-induced retinopathy, the effects of anti-VEGF based on basic research data, and the clinical relevance of these data are covered. PMID:25459781

  20. 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

  1. Benzodiazepine receptor antagonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy....

  2. 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

  3. 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

  4. 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, ...

  5. 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

  6. 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...

  7. 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

  8. Effect of heat stress and drinking water salt supplements on plasma electrolytes and aldosterone concentration in broiler chickens

    Science.gov (United States)

    Deyhim, F.; Teeter, R. G.

    1995-12-01

    An experiment was conducted to evaluate the effects of supplementing drinking water with isomolar (0.067 mol/l) KCl or NaCl on mass gain, food and water consumption, rectal temperature, and plasma concentrations of aldosterone, Na+, and K+ in broiler chickens reared in thermoneutral and cycling heat stressing environments. Heat stress decreased ( P≤0.05) mass gain, food consumption, and plasma concentrations of Na+ and K+, while increases ( P≤0.05) in plasma concentrations of aldosterone, rectal temperature, and water consumption were observed. Drinking water supplemented with either KCl or NaCl increased ( P≤0.05) broiler mass gain and water consumption, but had no effect ( P>0.1) on the other variables evaluated. The results of this study indicate that broiler chickens in a heat stress environment are under osmotic stress and supplementing drinking water with 0.067 mol/1 KCl or NaCl does not lessen this stress.

  9. 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...

  10. The Renin-Angiotensin-Aldosterone system in patients with depression compared to controls – a sleep endocrine study

    Directory of Open Access Journals (Sweden)

    Künzel Heike

    2003-10-01

    Full Text Available Abstract Background Hypercortisolism as a sign of hypothamamus-pituitary-adrenocortical (HPA axis overactivity and sleep EEG changes are frequently observed in depression. Closely related to the HPA axis is the renin-angiotensin-aldosterone system (RAAS as 1. adrenocorticotropic hormone (ACTH is a common stimulus for cortisol and aldosterone, 2. cortisol release is suppressed by mineralocorticoid receptor (MR agonists 3. angiotensin II (ATII releases CRH and vasopressin from the hypothalamus. Furthermore renin and aldosterone secretion are synchronized to the rapid eyed movement (REM-nonREM cycle. Methods Here we focus on the difference of sleep related activity of the RAAS between depressed patients and healthy controls. We studied the nocturnal plasma concentration of ACTH, cortisol, renin and aldosterone, and sleep EEG in 7 medication free patients with depression (1 male, 6 females, age: (mean +/-SD 53.3 ± 14.4 yr. and 7 age matched controls (2 males, 5 females, age: 54.7 ± 19.5 yr.. After one night of accommodation a polysomnography was performed between 23.00 h and 7.00 h. During examination nights blood samples were taken every 20 min between 23.00 h and 7.00 h. Area under the curve (AUC for the hormones separated for the halves of the night (23.00 h to 3.00 h and 3.00 h to 7.00 h were used for statistical analysis, with analysis of co variance being performed with age as a covariate. Results No differences in ACTH and renin concentrations were found. For cortisol, a trend to an increase was found in the first half of the night in patients compared to controls (p Conclusion Hyperaldosteronism could be a sensitive marker for depression. Further our findings point to an altered renal mineralocorticoid sensitivity in patients with depression.

  11. Oxidative damages in tubular epithelial cells in IgA nephropathy: role of crosstalk between angiotensin II and aldosterone

    Directory of Open Access Journals (Sweden)

    Lim Ai-Ing

    2011-10-01

    Full Text Available Abstract Background Inhibition of the renin-angiotensin-aldosterone system (RAAS slows down the progression of chronic renal diseases (CKD including IgA nephropathy (IgAN. Herein, we studied the pathogenetic roles of aldosterone (Aldo in IgAN. Methods Human mesangial cells (HMC was activated with polymeric IgA (pIgA from IgAN patients and the effects on the expression of RAAS components and TGF-β synthesis examined. To study the roles of RAAS in the glomerulotubular communication, proximal tubular epithelial cells (PTEC was cultured with conditioned medium from pIgA-activated HMC with eplerenone or PD123319, the associated apoptotic event was measured by the generation of nicotinamide adenine dinucleotide phosphate (NADPH oxidase and reactive oxygen species (ROS. Results Polymeric IgA up-regulated the Aldo synthesis and aldosterone synthase expression by HMC. The release of TGF-β by HMC was up-regulated synergistically by AngII and Aldo and this was inhibited by incubation of HMC with losartan plus eplerenone. Cultured PTEC express the mineralocorticoid receptor, but not synthesizing aldosterone. Apoptosis, demonstrated by cleaved PARP expression and caspase 3 activity, was induced in PTEC activated by conditioned medium prepared from HMC cultured with pIgA from IgAN patients. This apoptotic event was associated with increased generation of NADPH oxidase and ROS. Pre-incubation of PTEC with PD123319 and eplerenone achieved complete inhibition of PTEC apoptosis. Conclusions Our data suggest that AngII and Aldo, released by pIgA activated HMC, served as mediators for inducing apoptosis of PTEC in glomerulo-tubular communications. Crosstalk between AngII and Aldo could participate in determining the tubular pathology of IgAN.

  12. Catheterization during adrenal vein sampling for primary aldosteronism: failure to use (1-24) ACTH may increase apparent failure rate.

    Science.gov (United States)

    Kline, Gregory A; So, Benny; Dias, Valerian C; Harvey, Adrian; Pasieka, Janice L

    2013-07-01

    "Successful" adrenal vein catheterization in primary aldosteronism (PA) is often defined by a ratio of >3:1 of cortisol in the adrenal vein vs the inferior vena cava. Non-use of corticotropin (ACTH) during sampling may increase the apparent failure rate of adrenal vein catheterization due to lower cortisol levels. A retrospective study was performed on all patients with confirmed unilateral PA between June 2005 and August 2011. Adrenal vein sampling (AVS) included simultaneous bilateral baseline samples with repeat sampling 15 minutes after intravenous infusion of 250 μg of Cortrosyn (ACTH-S). Successful catheter placement was judged as adrenal cortisol:IVC cortisol of >3:1, applied to both baseline and ACTH-S samples and lateralization of aldosteronism was judged as normalized aldosterone/cortisol (A/C) ratio >3 times the contralateral A/C ratio. In ACTH-S samples, 94% of right-sided catheterizations were biochemically successful with 100% success on the left. Among baseline samples, only 47% of right- and 44% of left-sided samples met the 3:1 cortisol criteria. However, 95% of apparent "failed" baseline cortisol sets still showed lateralization of A/C ratios that matched the ultimate pathology. Non-ACTH-stimulated samples may be incorrectly judged as failed catheter placement when a 3:1 ratio is used. ACTH-stimulated sampling is the preferred means to confirm catheterization during AVS.

  13. Medical therapy in acromegaly.

    LENUS (Irish Health Repository)

    Sherlock, Mark

    2011-05-01

    Acromegaly is a rare disease characterized by excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) concentrations. The disease is associated with increased morbidity and premature mortality, but these effects can be reduced if GH levels are decreased to <2.5 μg\\/l and IGF-1 levels are normalized. Therapy for acromegaly is targeted at decreasing GH and IGF-1 levels, ameliorating patients\\' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, radiotherapy and medical therapies, such as dopamine agonists, somatostatin receptor ligands and the GH receptor antagonist pegvisomant. Medical therapy is currently most widely used as secondary treatment for persistent or recurrent acromegaly following noncurative surgery, although it is increasingly used as primary therapy. This Review provides an overview of current and future pharmacological therapies for patients with acromegaly.

  14. 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

  15. Auxin-Oxylipin Crosstalk: Relationship of Antagonists

    Institute of Scientific and Technical Information of China (English)

    Maik Hoffmann; Mathias Hentrich; Stephan Pollmann

    2011-01-01

    Phytohormones regulate a wide array of developmental processes throughout the life cycle of plants. Herein, the various plant hormones may interact additively, synergistically, or antagonistically. By their cooperation they create a delicate regulatory network whose net output largely depends on the action of specific phytohormone combinations rather than on the independent activities of separate hormones. While most classical studies of plant hormonal control have focused mainly on the action of single hormones or on the synergistic interaction of hormones in regulating various developmental processes, recent work is beginning to shed light on the crosstalk of nominally antagonistic plant hormones, such as gibberellins and auxins with oxylipins or abscisic acid. In this review, we summarize our current understanding of how two of the first sight antagonistic plant hormones, i.e. auxins and oxylipins,interact in controlling plant responses and development.

  16. Antagonistic formation motion of cooperative agents

    Science.gov (United States)

    Lu, Wan-Ting; Dai, Ming-Xiang; Xue, Fang-Zheng

    2015-02-01

    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonistic interactions. A distributed formation control algorithm is proposed for each agent to realize the antagonistic formation motion. A sufficient condition is derived to ensure that all of the agents make an antagonistic formation motion in a distributed manner. It is shown that all of the agents can be spontaneously divided into several groups and that agents in the same group collaborate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results. Project supported by the National Natural Science Foundation of China (Grant Nos. 61203080 and 61473051) and the Natural Science Foundation of Chongqing City (Grant No. CSTC 2011BB0081).

  17. Research progress of antagonistic interactions among root canal irrigations disease

    Directory of Open Access Journals (Sweden)

    Chen QU

    2013-07-01

    Full Text Available Root canal therapy is the most effective way to treat various pulposis and periapical disease. Simple mechanical apparatus can not clean root canal thoroughly, but may affect tight filling instead. It can achieve a satisfactory cleansing effect only when it is combined with a chemical solution. Irrigation fluid for root canal should possess the properties of tissue dissolution, antimicrobial, lubrication, and removal of smear layer. So far, no solution is able to fulfill all these functions. Therefore, a combined use of multiple irrigation solutions is suggested. It can not only achieve good effect in cleaning and disinfection, also it can lower the concentration of different solutions, thus reducing the side effects. Nevertheless, some experiments proved that antagonism existed among the chemicals used for irrigations. The purpose of present article is to review the antagonistic effect among the chemicals used for irrigation when they are used together for root canal treatment.

  18. Orexin receptor antagonists as therapeutic agents for insomnia

    Directory of Open Access Journals (Sweden)

    Ana Clementina Equihua

    2013-12-01

    Full Text Available Insomnia is a common clinical condition characterized by difficulty initiating or maintaining sleep, or non-restorative sleep with impairment of daytime functioning.Currently, treatment for insomnia involves a combination of cognitive behavioral therapy and pharmacological therapy. Among pharmacological interventions, the most evidence exists for benzodiazepine receptor agonist drugs (GABAA receptor, although concerns persist regarding their safety and their limited efficacy. The use of these hypnotic medications must be carefully monitored for adverse effects.Orexin (hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep by promoting cholinergic/monoaminergic neural pathways. This has led to the development of a new class of pharmacological agents that antagonize the physiological effects of orexin. The development of these agents may lead to novel therapies for insomnia without the side effect profile of hypnotics (e.g. impaired cognition, disturbed arousal, and motor balance difficulties. However, antagonizing a system that regulates the sleep-wake cycle may create an entirely different side effect profile. In this review, we discuss the role of orexin and its receptors on the sleep-wake cycle and that of orexin antagonists in the treatment of insomnia.

  19. Direct control of Na(+)-K(+)-2Cl(-)-cotransport protein (NKCC1) expression with aldosterone.

    Science.gov (United States)

    Ding, Bo; Frisina, Robert D; Zhu, Xiaoxia; Sakai, Yoshihisa; Sokolowski, Bernd; Walton, Joseph P

    2014-01-01

    Sodium/potassium/chloride cotransporter (NKCC1) proteins play important roles in Na(+) and K(+) concentrations in key physiological systems, including cardiac, vascular, renal, nervous, and sensory systems. NKCC1 levels and functionality are altered in certain disease states, and tend to decline with age. A sensitive, effective way of regulating NKCC1 protein expression has significant biotherapeutic possibilities. The purpose of the present investigation was to determine if the naturally occurring hormone aldosterone (ALD) could regulate NKCC1 protein expression. Application of ALD to a human cell line (HT-29) revealed that ALD can regulate NKCC1 protein expression, quite sensitively and rapidly, independent of mRNA expression changes. Utilization of a specific inhibitor of mineralocorticoid receptors, eplerenone, implicated these receptors as part of the ALD mechanism of action. Further experiments with cycloheximide (protein synthesis inhibitor) and MG132 (proteasome inhibitor) revealed that ALD can upregulate NKCC1 by increasing protein stability, i.e., reducing ubiquitination of NKCC1. Having a procedure for controlling NKCC1 protein expression opens the doors for therapeutic interventions for diseases involving the mis-regulation or depletion of NKCC1 proteins, for example during aging.

  20. Development of Time Resolved Fluorescence Resonance Energy Transfer-based Assay for FXR Antagonist Discovery

    OpenAIRE

    Yu, Donna D.; Lin, Wenwei; Chen, Taosheng; Forman, Barry M.

    2013-01-01

    FXR (farnesoid X receptor, NRIH4), a nuclear receptor, plays a major role in the control of cholesterol metabolism. FXR ligands have been investigated in preclinical studies for targeted therapy against metabolic diseases, but have shown limitations. Therefore, there is a need for new agonist or antagonist ligands of FXR, both for potential clinical applications, as well as to further elucidate its biological functions. Here we describe the use of the X-ray crystal structure of FXR complexed ...

  1. Pharmacologic Therapies in Anticoagulation.

    Science.gov (United States)

    Ferreira, Joana Lima; Wipf, Joyce E

    2016-07-01

    Anticoagulants are beneficial for prevention and treatment of venous thromboembolism and stroke prevention in atrial fibrillation. The development of target-specific oral anticoagulants is changing the landscape of anticoagulation therapy and created growing interest on this subject. Understanding the pharmacology of different anticoagulants is the first step to adequately treat patients with best available therapy while avoiding serious bleeding complications. This article reviews the pharmacology of the main anticoagulant classes (vitamin K antagonists, direct oral anticoagulants, and heparins) and their clinical indications based on evidence-based data currently available in the literature. PMID:27235611

  2. Genetic factors influencing pyrimidine-antagonist chemotherapy

    NARCIS (Netherlands)

    Maring, JG; Groen, HJM; Wachters, FM; Uges, DRA; de Vries, EGE

    2005-01-01

    Pyrimidine antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of

  3. Oxazolidinones as novel human CCR8 antagonists.

    Science.gov (United States)

    Jin, Jian; Wang, Yonghui; Wang, Feng; Kerns, Jeffery K; Vinader, Victoria M; Hancock, Ashley P; Lindon, Matthew J; Stevenson, Graeme I; Morrow, Dwight M; Rao, Parvathi; Nguyen, Cuc; Barrett, Victoria J; Browning, Chris; Hartmann, Guido; Andrew, David P; Sarau, Henry M; Foley, James J; Jurewicz, Anthony J; Fornwald, James A; Harker, Andy J; Moore, Michael L; Rivero, Ralph A; Belmonte, Kristen E; Connor, Helen E

    2007-03-15

    High-throughput screening of the corporate compound collection led to the discovery of a novel series of N-substituted-5-aryl-oxazolidinones as potent human CCR8 antagonists. The synthesis, structure-activity relationships, and optimization of the series that led to the identification of SB-649701 (1a), are described. PMID:17267215

  4. Azines as histamine H4 receptor antagonists.

    Science.gov (United States)

    Lazewska, Dorota; Kiec-Kononowicz, Katarzyna

    2012-01-01

    Since 2000, when the histamine H4 receptor (H4R) was cloned, it has constituted an interesting target for drug development. Pharmacological studies suggest the potential utility of histamine H4R antagonists/inverse agonists in the treatment of inflammatory diseases, e.g. allergic rhinitis, asthma, atopic dermatitis, colitis, or pruritus. The first H4R ligands were non-selective compounds, but intensive chemical and pharmacological work has led to the discovery of highly potent and selective H4R antagonists (e.g. JNJ7777120, CZC-13788, PF-2988403, A-940894, A-987306). The first compound (UR-63325) has finally entered into clinical studies for the treatment of allergic respiratory diseases (completing the phase I ascending dose trial) and has been found to be safe and well tolerated. The number of scientific publications and patent applications in the H4 field is increasing annually. Among the diverse chemical structures of the H4R antagonists described a 2-aminopyrimidine scaffold is repeatedly found. This review looked at recent advances in the search for H4R antagonists as reflected in patent applications/patents and peer-reviewed publications over the last two years. The work concerns azines (mono-, di-, triazines) and their fused analogues. The chemistry and pharmacology has been described. PMID:22202103

  5. Diagnosis and treatment of primary aldosteronism%原发性醛固酮增多症的诊断与治疗

    Institute of Scientific and Technical Information of China (English)

    龚伟

    2012-01-01

    Primary aldosteronism is the most common cause of secondary hypertension. In the past, screening for primary aldosteronism was offered only in patients with hypertension associated with hypokalemia. Recent studies showed that hypokalemia was examined in only 25% of the patients with primary aldosteronism, which has increased the prevalence of primary aldosteronism to 10 15% of all cases with new onset hypertension. The article reviews the diagnosis and treatment of primary aldosteronism.%原发性醛固酮增多症(原醛症)是继发性高血压最常见的病因之一,以往通常只对低血钾的高血压患者进行原醛相关筛查.近期研究表明原醛症患者中仅25%可见低血钾表现,目前新发高血压患者中原醛症患者的发生率可达10% ~ 15%.本文就原醛症的诊断与治疗做一综述.

  6. Endocrine functional diagnosis in primary aldosteronism%原发性醛固酮增多症的内分泌功能诊断

    Institute of Scientific and Technical Information of China (English)

    张妮娅; 郑仁东; 刘超

    2012-01-01

    原发性醛固酮增多症(原醛症)是继发性高血压最常见的原因之一,以低肾素和高醛固酮血症为特征,血浆醛固酮/肾素比值(ARR)是筛查原醛症的可靠指标.而口服高钠负荷试验、生理盐水试验、氟氯可的松抑制试验或卡托普利试验中的任何一项均可作为ARR阳性患者的确诊试验;肾上腺静脉插管采血(AVS)是原醛症分型诊断的金标准.%Primary aldosteronism is one of the most common causes of secondary hypertension,which is characterized by low plasma renin and high aldosterone,and a major reliable tool for screening primary aldosteronism is the plasma aldosterone/renin activity ratio (ARR).Any of the four confirmatory tests such as oral sodium loading,intravenous saline infusion,captopril challenge and fludrocortisone administration plus sodium loading may carry out in patients who have positive ARR.And adrenal vein sampling (AVS) is recommended as the golden standard to diagnose primary aldosteronism.

  7. EFFECT OF ANGIOTENSIN II RECEPTOR ANTAGONIST AND ENDOTHELIN RECEPTOR ANTAGONIST ON NITROGLYCERIN TOLERANCE IN RATS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty-four rats were divided into 4 groups (n=6,each): Control group, Nitroglycerin (Nit) group, Nit+ bosentan group and Nit+ losartan group. Nitroglycerin tolerance was induced by 2-day treatment of nitroglycerin patch (0.05 mg/h). AngiotensinⅡ receptor antagonist losartan ( 10 mg· kg- 1· d- 1 ) and endothelin receptor antagonist bosentan ( 100 mg· kg- 1· d- 1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group . The effective percentages of hypotensive response to SNP were increased in both Nit+ losartan group and Nit+ bosentan group compared with Nit group [(31.95± 4.45 ) % vs (21.00± 3.69 ) % , P Conclusion. Endothelin receptor antagonist and angiotensin Ⅱ receptor antagonist could prevent against the Nit tolerance .

  8. High affinity retinoic acid receptor antagonists: analogs of AGN 193109.

    Science.gov (United States)

    Johnson, A T; Wang, L; Gillett, S J; Chandraratna, R A

    1999-02-22

    A series of high affinity retinoic acid receptor (RAR) antagonists were prepared based upon the known antagonist AGN 193109 (2). Introduction of various phenyl groups revealed a preference for substitution at the para-position relative to the meta-site. Antagonists with the highest affinities for the RARs possessed hydrophobic groups, however, the presence of polar functionality was also well tolerated.

  9. 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...

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. Montelukast: More than a Cysteinyl Leukotriene Receptor Antagonist?

    Directory of Open Access Journals (Sweden)

    Gregory R. Tintinger

    2010-01-01

    Full Text Available The prototype cysteinyl leukotriene receptor antagonist, montelukast, is generally considered to have a niche application in the therapy of exercise- and aspirin-induced asthma. It is also used as add-on therapy in patients whose asthma is poorly controlled with inhaled corticosteroid monotherapy, or with the combination of a long-acting β(2-agonist and an inhaled corticosteroid. Recently, however, montelukast has been reported to possess secondary anti-inflammatory properties, apparently unrelated to conventional antagonism of cysteinyl leukotriene receptors. These novel activities enable montelukast to target eosinophils, monocytes, and, in particular, the corticosteroid-insensitive neutrophil, suggesting that this agent may have a broader spectrum of anti-inflammatory activities than originally thought. If so, montelukast is potentially useful in the chemotherapy of intermittent asthma, chronic obstructive pulmonary disease, cystic fibrosis, and viral bronchiolitis, which, to a large extent, involve airway epithelial cell/neutrophil interactions. The primary objective of this mini-review is to present evidence for the cysteinyl leukotrien–independent mechanisms of action of montelukast and their potential clinical relevance.

  17. Expression of Angiotensin Ⅱ Receptors in Aldosterone-producing Adenoma of the Adrenal Gland and Their Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    吴准; 倪栋; 闫永吉; 李俊; 王保军; 欧阳金枝; 张国玺; 马鑫; 李宏召; 张旭

    2010-01-01

    The expression of angiotensin Ⅱ type 1 receptor (AT1R) and angiotensin Ⅱ type 2 receptor (AT2R) in aldosterone-producing adenoma (APA) of the adrenal gland was detected, and their relationship with clinical indexes of APA was analyzed. The mRNA expression of AT1R and AT2R in 50 cases of APA and tissues adjacent to tumors and 12 cases of normal adrenal tissues was detected by using reverse transcriptase polymerase chain reaction (RT-PCR). The expression of AT1R and AT2R proteins in paraffin-embedded slices o...

  18. [Cutaneous adverse effects of TNFalpha antagonists].

    Science.gov (United States)

    Failla, V; Sabatiello, M; Lebas, E; de Schaetzen, V; Dezfoulian, B; Nikkels, A F

    2012-01-01

    The TNFalpha antagonists, including adalimumab, etanercept and infliximab, represent a class of anti-inflammatory and immunosuppressive drugs. Although cutaneous adverse effects are uncommon, they are varied. There is no particular risk profile to develop cutaneous adverse effects. The principal acute side effects are injection site reactions and pruritus. The major long term cutaneous side effects are infectious and inflammatory conditions. Neoplastic skin diseases are exceptional. The association with other immunosuppressive agents can increase the risk of developing cutaneous adverse effects. Some adverse effects, such as lupus erythematosus, require immediate withdrawal of the biological treatment, while in other cases temporary withdrawal is sufficient. The majority of the other cutaneous adverse effects can be dealt without interrupting biologic treatment. Preclinical and clinical investigations revealed that the new biologics, aiming IL12/23, IL23 and IL17, present a similar profile of cutaneous adverse effects, although inflammatory skin reactions may be less often encountered compared to TNFalpha antagonists.

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

    DEFF Research Database (Denmark)

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

    1987-01-01

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

  20. Antagonistic parent-offspring co-adaptation.

    Directory of Open Access Journals (Sweden)

    Mathias Kölliker

    Full Text Available BACKGROUND: In species across taxa, offspring have means to influence parental investment (PI. PI thus evolves as an interacting phenotype and indirect genetic effects may strongly affect the co-evolutionary dynamics of offspring and parental behaviors. Evolutionary theory focused on explaining how exaggerated offspring solicitation can be understood as resolution of parent-offspring conflict, but the evolutionary origin and diversification of different forms of family interactions remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In contrast to previous theory that largely uses a static approach to predict how "offspring individuals" and "parental individuals" should interact given conflict over PI, we present a dynamic theoretical framework of antagonistic selection on the PI individuals obtain/take as offspring and the PI they provide as parents to maximize individual lifetime reproductive success; we analyze a deterministic and a stochastic version of this dynamic framework. We show that a zone for equivalent co-adaptation outcomes exists in which stable levels of PI can evolve and be maintained despite fast strategy transitions and ongoing co-evolutionary dynamics. Under antagonistic co-adaptation, cost-free solicitation can evolve as an adaptation to emerging preferences in parents. CONCLUSIONS/SIGNIFICANCE: We show that antagonistic selection across the offspring and parental life-stage of individuals favors co-adapted offspring and parental behavior within a zone of equivalent outcomes. This antagonistic parent-offspring co-adaptation does not require solicitation to be costly, allows for rapid divergence and evolutionary novelty and potentially explains the origin and diversification of the observed provisioning forms in family life.

  1. Aminopyrimidine derivatives as adenosine antagonists / Janke Kleynhans

    OpenAIRE

    Kleynhans, Janke

    2013-01-01

    Aims of this project - The aim of this study was to design and synthesise novel 2-aminopyrimidine derivatives as potential adenosine A1 and A2A receptor antagonists. Background and rationale - Parkinson’s disease is the second most common neurodegenerative disorder (after Alzheimer’s disease) and is characterised by the selective death of the dopaminergic neurons of the nigro-striatal pathway. Distinctive motor symptoms include bradykinesia, muscle rigidity and tremor, while non-m...

  2. Medicinal chemistry of competitive kainate receptor antagonists.

    Science.gov (United States)

    Larsen, Ann M; Bunch, Lennart

    2011-02-16

    Kainic acid (KA) receptors belong to the group of ionotropic glutamate receptors and are expressed throughout in the central nervous system (CNS). The KA receptors have been shown to be involved in neurophysiological functions such as mossy fiber long-term potentiation (LTP) and synaptic plasticity and are thus potential therapeutic targets in CNS diseases such as schizophrenia, major depression, neuropathic pain and epilepsy. Extensive effort has been made to develop subtype-selective KA receptor antagonists in order to elucidate the physiological function of each of the five subunits known (GluK1-5). However, to date only selective antagonists for the GluK1 subunit have been discovered, which underlines the strong need for continued research in this area. The present review describes the structure-activity relationship and pharmacological profile for 10 chemically distinct classes of KA receptor antagonists comprising, in all, 45 compounds. To the medicinal chemist this information will serve as reference guidance as well as an inspiration for future effort in this field. PMID:22778857

  3. 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

  4. The discovery of novel human androgen receptor antagonist chemotypes using a combined pharmacophore screening procedure.

    Science.gov (United States)

    Voet, Arnout; Helsen, Christine; Zhang, Kam Y J; Claessens, Frank

    2013-04-01

    Unraveling the mechanisms involved in castration- and therapy-resistant prostate cancer has led to a renewed interest in androgen receptor (AR)-targeted therapeutics. Anti-androgens that block the activity of the AR therefore remain a valid therapeutic option. However, they must be more effective than, or display a distinct mechanism of action or binding mode from those of bicalutamide and hydroxyflutamide, which are currently in clinical use. For that reason, the second-generation anti-androgen MDV3100 was developed. MDV3100, however, shares its 4-cyano-3-(trifluoromethyl)phenyl group with bicalutamide and hydroxyflutamide required for binding to the AR. In this work, we used a combined strategy to find new antagonist structures distinct from the 4-cyano-3-(trifluoromethyl)phenyl group to avoid cross-resistance for these compounds and to find structures without agonist activity on mutant ARs (AR W741C and AR T877A). We found two novel chemotypes with AR-antagonistic activity (IC(50): 3-6 μM) by virtual screening and confirmed their biological activity in an androgen-responsive reporter assay. The design of our computational approach was validated by the observation of strongly decreased or absence of agonistic activity on the two mutant ARs. Further structural derivatization to optimize the potency of these compounds can render these chemotypes into very promising, alternative AR antagonists for prostate cancer therapy.

  5. Personalized medicine: theranostics (therapeutics diagnostics) essential for rational use of tumor necrosis factor-alpha antagonists.

    Science.gov (United States)

    Bendtzen, Klaus

    2013-04-01

    With the discovery of the central pathogenic role of tumor necrosis factor (TNF)-alpha in many immunoinflammatory diseases, specific inhibition of this pleiotropic cytokine has revolutionized the treatment of patients with several non-infectious inflammatory disorders. As a result, genetically engineered anti-TNF-alpha antibody constructs now constitute one of the heaviest medicinal expenditures in many countries. All currently used TNF antagonists may dramatically lower disease activity and, in some patients, induce remission. Unfortunately, however, not all patients respond favorably, and safety can be severely impaired by immunogenicity, i.e., the ability of a drug to induce anti-drug antibodies (ADA). Assessment of ADA is therefore an important component of the evaluation of drug safety in both pre-clinical and clinical studies and in the process of developing less immunogenic and safer biopharmaceuticals. Therapeutics diagnostics, also called theranostics, i.e., monitoring functional drug levels and neutralizing ADA in the circulation, is central to more effective use of biopharmaceuticals. Hence, testing-based strategies rather than empirical dose-escalation may provide more cost-effective use of TNF antagonists as this allows therapies tailored according to individual requirements rather than the current universal approach to diagnosis. The objective of the present review is to discuss the reasons for recommending theranostics to implement an individualized use of TNF antagonists and to highlight some of the methodological obstacles that have obscured cost-effective ways of using these therapies.

  6. A case of primary selective hypoaldosteronism carrying three mutations in the aldosterone synthase (Cyp11b2) gene.

    Science.gov (United States)

    Taranta, Anna; Bizzarri, Carla; Masotti, Andrea; Sciré, Giuseppe; Pampanini, Valentina; Cappa, Marco

    2012-05-25

    An infant with a clinical phenotype of early onset hypoaldosteronism has been screened for mutation analysis of the Cyp11b2 gene encoding aldosterone synthase enzyme. We have described a novel nonsense mutation in exon 3 (c.508C>T) that gave rise to a shorter protein (Q170X) and two known concurrent missense mutations (c.594A>C in exon 3 and c.1157T>C in exon 7) that led to substitution of glutamic acid for aspartic acid at amino acid position 198 (E198D) and of valine for alanine at amino acid position 386 (V386A). The father, who carried E198D plus V386A mutations, showed a fractional sodium excretion of 1.25% that was unmodified by dietary salt restriction, suggesting a mild haploinsufficiency. We examined by in silico analysis the effect of the mutations on the secondary and tertiary structures of aldosterone synthase to explain the inefficient enzymatic activity. The Q170X mutation produced a truncated protein, which was consequently associated with a loss of catalytic activity. As predicted by JPred web system and Dock 6.3 software, the concurrent expression of E198D and V386A mutations induced a significant secondary structure rearrangement and a shift of the heme group and the 18-hydroxycorticosterone substrate from their optimal placement.

  7. Unmasked renal impairment and prolonged hyperkalemia after unilateral adrenalectomy for primary aldosteronism coexisting with primary hyperparathyroidism: report of a case.

    Science.gov (United States)

    Hibi, Yatsuka; Hayakawa, Nobuki; Hasegawa, Midori; Ogawa, Kimio; Shimizu, Yoshimi; Shibata, Masahiro; Kagawa, Chikara; Mizuno, Yutaka; Yuzawa, Yukio; Itoh, Mitsuyasu; Iwase, Katsumi

    2015-02-01

    We herein report the case of a patient with critical hyperkalemia after unilateral adrenalectomy (ADX) for aldosterone-producing adenomas, which were coexisting with primary hyperparathyroidism. A right adrenal tumor oversecreting mineral corticoid was identified in a 62-year-old female whose kidney function had been impaired due to primary hyperaldosteronism and hyperparathyroidism. The ADX improved her hypertension with normalization of the plasma aldosterone concentration, but without adequately increasing her plasma renin activity. Her eGFR further decreased postoperatively, hyperkalemia appeared and the serum potassium level rose to 6.3 mEq/L at 3 months after ADX. Then, treatment with calcium polystyrene sulfonate jelly was started. Eight months after ADX, a left lower parathyroidectomy was performed, and the serum calcium and intact parathyroid hormone levels decreased to the normal range. The hyperkalemia was difficult to control within 20 months postoperatively without treatment with calcium polystyrene sulfonate jelly or hydrocortisone. This suggests that unmasking the renal impairment and relative hypoaldosteronism after ADX might induce critical hyperkalemia.

  8. EFFECT OF ANGIOTENSIN II RECEPTOR ANTAGONIST AND ENDOTHELIN RECEPTOR ANTAGONIST ON NITROGLYCERIN TOLERANCE IN RATS

    Institute of Scientific and Technical Information of China (English)

    张建梅; 陈永红; 王晓红; 唐朝枢

    2001-01-01

    Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty-four rats were divided into 4 groups (n =6, each): Control group, Nitroglycerin (Nit) group, Nit + bosentan group and Nit + losartan group. Nitroglycerin tolerance was induced by 2-day treatment ofnitroglycerin patch (0. 05mg/h). Angiotensin I1 receptor antagonist losartan (10mg ·kg-1·d-1) and endothe-lin receptor antagonist bosentan ( 100 mg·kg-1· d-1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group. The effec-tive percentages of hypotensive response to SNP were increased in both Nit + losartan group and Nit + bosentangroup compared with Nit group [(31.95±4.45) % vs (21.00±3.69) %, P <0.01and (33. 18±6. 16)% vs (21.00±3.69 ) %, P < 0. 01 , respectivelyl. The maximal vessel relaxation induced by SNP was thesame in 4 different groups but the highest EC50 (concentration which produces 50% of the maximal response toSNP) was found in tolerant group[ (34 ±10) nmol/L, P < 0. 01 ]. The ET-1 amounts in plasma and vasculartissue were markedly increased by 54% and 60% in Nit group compared with those in control group( P<0. 01). The ET-1 amounts in plasma and vascular tissue were decreased by 30% and 37% in Nit + losartangroup compared with those in Nit group ( P < 0.01 ). Conclusion. Endothelin receptor antagonist and angiotensin Ⅱ receptor antagonist could prevent against the Nit tolerance.

  9. Insights into cardio-oncology:Polypharmacology of quinazoline-based α1-adrenoceptor antagonists

    Institute of Scientific and Technical Information of China (English)

    Salvatore; Patanè

    2015-01-01

    New uses of cardiovascular drugs with proven experience are emerging,including for treating cancer.Quinazoline is a compound made up of two fused six member simple aromatic rings,benzene and pyrimidine rings,with several biological effects.Cardiologists first used quinazoline-based α1-adrenoceptor antagonists prazosin,doxazosin,and terazosin; currently available data support their use as safe,well tolerated,and effective add-on therapy in uncontrolled hypertension with additional favourable metabolic effects.Recent findings highlight the anticancer effects of quinazoline-based α1-adrenoceptor antagonists,indicating that they may have a significant role in uncontrolled hypertensive cancer patients without signs of ischemia.

  10. P2Y12 Receptor Antagonists and Morphine: A Dangerous Liaison?

    Science.gov (United States)

    Giannopoulos, Georgios; Deftereos, Spyridon; Kolokathis, Fotios; Xanthopoulou, Ioanna; Lekakis, John; Alexopoulos, Dimitrios

    2016-09-01

    P2Y12 receptor antagonists, concurrently administered with aspirin in what has come to be commonly called dual antiplatelet therapy, are a mainstay of treatment for patients with acute coronary syndromes. Morphine, on the contrary, is a commonly used drug in the acute phase of acute coronary syndromes to relieve pain-with the added potential benefit of attenuating acutely raised sympathetic tone. In current guidelines, though, morphine is recommended with decreasing strength of recommendation. One reason is that it raises concern regarding the potentially significant interaction with antiplatelet agents, leading to impaired inhibition of platelet activation. In any case, it is still considered a mandatory part of the inventory of available medications in prehospital acute myocardial infarction management. The goal of the present review is to present published evidence on morphine and its potential interactions with P2Y12 receptor antagonists, as well as on the central issue of whether such interactions may underlie clinically significant effects on patient outcomes.

  11. The safety of interleukin-1 receptor antagonist (anakinra in the treatment of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    L. Riente

    2011-09-01

    Full Text Available The safety profile of interleukin-1 receptor antagonist (anakinra has been studied with randomised, placebo-controlled trials involving 2932 patients affected by rheumatoid arthritis. The most frequently reported adverse events were represented by injection site reactions (71% and headache (13.6%. No statistically significant difference in the incidence of infections was observed among the patients treated with the interleukin-1 receptor antagonist and the patients receiving placebo. In particular, the incidence of serious infections was 1,8% in rheumatoid arthritis patients on anakinra therapy and 0,7% in patients on placebo. The reported serious infections consisted of pneumonia, cellulitis, bone and joint infections, bursitis. No case of opportunistic infections or tubercolosis was observed. The results of clinical studies suggest that anakinra is a new well-tolerated drug for the treatment of patients affected by rheumatoid arthritis.

  12. Couple Control Model Implementation on Antagonistic Mono- and Bi-Articular Actuators

    CERN Document Server

    Prattico, Flavio; Yamamoto, Shin-ichiroh

    2014-01-01

    Recently, robot assisted therapy devices are increasingly used for spinal cord injury (SCI) rehabilitation in assisting handicapped patients to regain their impaired movements. Assistive robotic systems may not be able to cure or fully compensate impairments, but it should be able to assist certain impaired functions and ease movements. In this study, a couple control model for lower-limb orthosis of a body weight support gait training system is proposed. The developed leg orthosis implements the use of pneumatic artificial muscle as an actuation system. The pneumatic muscle was arranged antagonistically to form two pair of mono-articular muscles (i.e., hip and knee joints), and a pair of bi-articular actuators (i.e., rectus femoris and hamstring). The results of the proposed couple control model showed that, it was able to simultaneously control the antagonistic mono- and bi-articular actuators and sufficiently performed walking motion of the leg orthosis.

  13. Prothrombin complex concentrate for reversal of vitamin K antagonist treatment in bleeding and non-bleeding patients

    DEFF Research Database (Denmark)

    Johansen, Mathias; Wikkelsø, Anne; Lunde, Jens;

    2015-01-01

    BACKGROUND: Treatment with vitamin K antagonists is associated with increased morbidity and mortality. Reversal therapy with prothrombin complex concentrate (PCC) is used increasingly and is recommended in the treatment of patients with bleeding complications undertaking surgical interventions......, as well as patients at high risk of bleeding. Evidence is lacking regarding indication, dosing, efficacy and safety. OBJECTIVES: We assessed the benefits and harms of PCC compared with fresh frozen plasma in the acute medical and surgical setting involving vitamin K antagonist-treated bleeding and non...... finding a beneficial effect of PCC in reducing the volume of fresh frozen plasma (FFP) transfused to reverse the effect of vitamin K antagonist treatment. The number of new occurrences of transfusion of red blood cells (RBCs) did not seem to be associated with the use of PCC (RR 1.08, 95% CI 0.82 to 1...

  14. 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

  15. 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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  17. Effects of trilostane treatment on the pituitary-adrenocortical and renin-aldosterone axis in dogs with pituitary-dependent hypercortisolism

    NARCIS (Netherlands)

    Galac, S.; Buijtels, J.J.C.W.M.; Mol, J.A.; Kooistra, H.S.

    2010-01-01

    Vet J. 2010 Jan;183(1):75-80. Epub 2008 Nov 29. Effects of trilostane on the pituitary-adrenocortical and renin-aldosterone axis in dogs with pituitary-dependent hypercortisolism. Galac S, Buijtels JJ, Mol JA, Kooistra HS. Department of Clinical Sciences of Companion Animals, Faculty of Veterinary M

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

    DEFF Research Database (Denmark)

    Pöschke, Antje; Kern, Niklas; Maruyama, Takayuki;

    2012-01-01

    renal PGE(2) synthesis, which stimulates the renin-angiotensin-aldosterone system by activation of EP4 receptor. Most likely, defects at the step of EP4 receptor block negative feedback mechanisms on the renal COX system, leading to persistently high PGE(2) levels, diuresis, and K(+) loss....

  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

    normoalbuminuric diabetic patients who later progressed to overt kidney disease, and may hold the potential for selection of high-risk patients for early intervention. Combining the ability of CKD273 to identify patients at highest risk of progression with prescription of preventive aldosterone blockade only...

  20. 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.

  1. 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....

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

    Science.gov (United States)

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

    2000-01-01

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

  3. Evaluation of H2 receptor antagonists in chronic idiopathic urticaria

    Directory of Open Access Journals (Sweden)

    Minocha Y

    1995-01-01

    Full Text Available H1-antagonist (hydroxyzine hydrochloride in dosage of 10 mg-25 mg thrice a day failed to elicit satisfactory response in 60 out of 170 patients of chronic idiopathic urticaria. Additional administration of H2-antagonist (cimetidine in dosage of 200 mg four times a day, in patients not responding earlier to H1-antagonist alones exhibited moderate to good improvement of various parameters of urticaria in approximately 85% patients

  4. 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

  5. Sexually antagonistic selection in human male homosexuality.

    Science.gov (United States)

    Camperio Ciani, Andrea; Cermelli, Paolo; Zanzotto, Giovanni

    2008-01-01

    Several lines of evidence indicate the existence of genetic factors influencing male homosexuality and bisexuality. In spite of its relatively low frequency, the stable permanence in all human populations of this apparently detrimental trait constitutes a puzzling 'Darwinian paradox'. Furthermore, several studies have pointed out relevant asymmetries in the distribution of both male homosexuality and of female fecundity in the parental lines of homosexual vs. heterosexual males. A number of hypotheses have attempted to give an evolutionary explanation for the long-standing persistence of this trait, and for its asymmetric distribution in family lines; however a satisfactory understanding of the population genetics of male homosexuality is lacking at present. We perform a systematic mathematical analysis of the propagation and equilibrium of the putative genetic factors for male homosexuality in the population, based on the selection equation for one or two diallelic loci and Bayesian statistics for pedigree investigation. We show that only the two-locus genetic model with at least one locus on the X chromosome, and in which gene expression is sexually antagonistic (increasing female fitness but decreasing male fitness), accounts for all known empirical data. Our results help clarify the basic evolutionary dynamics of male homosexuality, establishing this as a clearly ascertained sexually antagonistic human trait. PMID:18560521

  6. Sexually antagonistic selection in human male homosexuality.

    Directory of Open Access Journals (Sweden)

    Andrea Camperio Ciani

    Full Text Available Several lines of evidence indicate the existence of genetic factors influencing male homosexuality and bisexuality. In spite of its relatively low frequency, the stable permanence in all human populations of this apparently detrimental trait constitutes a puzzling 'Darwinian paradox'. Furthermore, several studies have pointed out relevant asymmetries in the distribution of both male homosexuality and of female fecundity in the parental lines of homosexual vs. heterosexual males. A number of hypotheses have attempted to give an evolutionary explanation for the long-standing persistence of this trait, and for its asymmetric distribution in family lines; however a satisfactory understanding of the population genetics of male homosexuality is lacking at present. We perform a systematic mathematical analysis of the propagation and equilibrium of the putative genetic factors for male homosexuality in the population, based on the selection equation for one or two diallelic loci and Bayesian statistics for pedigree investigation. We show that only the two-locus genetic model with at least one locus on the X chromosome, and in which gene expression is sexually antagonistic (increasing female fitness but decreasing male fitness, accounts for all known empirical data. Our results help clarify the basic evolutionary dynamics of male homosexuality, establishing this as a clearly ascertained sexually antagonistic human trait.

  7. Activins and activin antagonists in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Alev Deli; Emanuel Kreidl; Stefan Santifaller; Barbara Trotter; Katja Seir; Walter Berger; Rolf Schulte-Hermann; Chantal Rodgarkia-Dara; Michael Grusch

    2008-01-01

    In many parts of the world hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood. There is increasing evidence that activins, which are members of the transforming growth factor β (TGFβ) superfamily of growth and differentiation factors, could play important roles in liver carcinogenesis. Activins are disulphide-linked homo-or heterodimers formed from four different β subunits termed βA, βB, βC, and βE, respectively. Activin A, the dimer of two βA subunits, is critically involved in the regulation of cell growth, apoptosis, and tissue architecture in the liver, while the hepatic function of other activins is largely unexplored so far. Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG, and at the cell membrane antagonistic co-receptors like Cripto or BAMBI. Additionally, in the intracellular space inhibitory Smads can modulate and control activin activity. Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation, fibrosis and development of cancer. The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis.

  8. Smoking, calcium, calcium antagonists, and aging.

    Science.gov (United States)

    Nicita-Mauro, V

    1990-01-01

    Aging is characterized, besides other changes, by a progressive increase in calcium content in the arterial wall, which is enhanced by diabetes mellitus, osteoporosis, arterial hypertension, and tabagism. As to tabagism, experiments in animals have shown that nicotine can increase calcium content of the arterial wall, and clinical studies have demonstrated that cigarette smoking induces peripheral vasoconstriction, with consequent increase in blood pressure levels. In order to study the role of calcium ions in the pathogenesis of the vasoconstrictive lesions caused by "acute" smoking, the author has studied the peripheral vascular effects of the calcium-channel antagonist nifedipine, a dihydropyridine derivative, and calcitonin, a hypocalcemizing hormone which possess vasoactive actions on 12 elderly regular smokers (mean age 65.8 years). The results demonstrated that both nifedipine (10 mg sublingually 20 min before smoking) and salmon calcitonin (100 MRC U/daily intramuscularly for three days) are able to prevent peripheral vasoconstriction evaluated by Doppler velocimetry, as well as the increase of blood pressure induced by smoking. On the basis of our results, the author proposes that cigarette smoking-induced vasoconstriction is a calcium-mediated process, which can be hindered by drugs with calcium antagonist action. PMID:2226675

  9. 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

  10. Update on leukotriene receptor antagonists in preschool children wheezing disorders

    Directory of Open Access Journals (Sweden)

    Montella Silvia

    2012-06-01

    Full Text Available Abstract Asthma is the most common chronic disease in young children. About 40% of all preschool children regularly wheeze during common cold infections. The heterogeneity of wheezing phenotypes early in life and various anatomical and emotional factors unique to young children present significant challenges in the clinical management of this problem. Anti-inflammatory therapy, mainly consisting of inhaled corticosteroids (ICS, is the cornerstone of asthma management. Since Leukotrienes (LTs are chemical mediators of airway inflammation in asthma, the leukotriene receptor antagonists (LTRAs are traditionally used as potent anti-inflammatory drugs in the long-term treatment of asthma in adults, adolescents, and school-age children. In particular, montelukast decreases airway inflammation, and has also a bronchoprotective effect. The main guidelines on asthma management have confirmed the clinical utility of LTRAs in children older than five years. In the present review we describe the most recent advances on the use of LTRAs in the treatment of preschool wheezing disorders. LTRAs are effective in young children with virus-induced wheeze and with multiple-trigger disease. Conflicting data do not allow to reach definitive conclusions on LTRAs efficacy in bronchiolitis or post-bronchiolitis wheeze, and in acute asthma. The excellent safety profile of montelukast and the possibility of oral administration, that entails better compliance from young children, represent the main strengths of its use in preschool children. Montelukast is a valid alternative to ICS especially in poorly compliant preschool children, or in subjects who show adverse effects related to long-term steroid therapy.

  11. The role of leukotriene receptor antagonists in the treatment of chronic asthma in childhood.

    Science.gov (United States)

    Warner, J O

    2001-01-01

    A considerable increase in the prevalence of childhood asthma over the last few decades has been mirrored by a dramatic increase in usage of anti-asthma drugs; however, there has been no reduction in the numbers of patients dying of asthma. Concern has been expressed about the development of tolerance with continuous use of inhaled beta-agonist bronchodilators and about the potential adverse systemic effects of high-dose inhaled corticosteroids in children. Moreover, patient compliance with inhaled therapy tends to be poor. The leukotriene receptor antagonists, including montelukast, pranlukast and zafirlukast, are orally administered agents with proven benefits in asthma. In a large, placebo-controlled pediatric trial, montelukast significantly (P exercise-induced bronchospasm in both adults and children, and this protection was maintained during the trough period at the end of the once-daily administration interval (namely, 20-24 h post-dose). Several studies have demonstrated that the formation of cysteinyl leukotrienes in the airways of asthmatic patients is not suppressed by corticosteroids; thus, it is not surprising that montelukast demonstrates complementary effects when given with inhaled corticosteroids. Currently, the most compelling evidence from published trials suggests that leukotriene receptor antagonists can be used as add-on therapy to inhaled corticosteroids to allow tapering of corticosteroid dose and reduction in beta-agonist use. Recent clinical trial results suggest there may also be a role for these agents as first-line therapy in children with mild asthma. PMID:11421938

  12. 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

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

    Directory of Open Access Journals (Sweden)

    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

  14. New drugs for the treatment of hyperkalemia in patients treated with renin-angiotensin-aldosterone system inhibitors -- hype or hope?

    Science.gov (United States)

    Tamargo, Juan; Caballero, Ricardo; Delpón, Eva

    2014-11-01

    Hyperkalemia (serum potassium >5.5 mmol/L) may result from increased potassium intake, impaired distribution between the intracellular and extracellular spaces, and/or reduced renal excretion. Renin-angiotensin-aldosterone system inhibitors (RAASIs) represent an important therapeutic strategy in patients with hypertension, heart failure, chronic kidney disease, and diabetes, but hyperkalemia is a key limitation to fully titrate RAASIs in these patients who are most likely to benefit from treatment. Thus, we need new drugs to control hyperkalemia in these patients while maintaining the use of RAASIs. We review two new polymer-based, non-systemic agents under clinical development, patiromer calcium and zirconium silicate, designed to increase potassium loss via the gastrointestinal tract for the management of hyperkalemia.

  15. 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

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Annayya R Aroor

    2013-10-01

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

  18. Corticospinal control of antagonistic muscles in the cat.

    Science.gov (United States)

    Ethier, Christian; Brizzi, Laurent; Giguère, Dominic; Capaday, Charles

    2007-09-01

    We recently suggested that movement-related inter-joint muscle synergies are recruited by selected excitation and selected release from inhibition of cortical points. Here we asked whether a similar cortical mechanism operates in the functional linking of antagonistic muscles. To this end experiments were done on ketamine-anesthetized cats. Intracortical microstimulation (ICMS) and intramuscular electromyographic recordings were used to find and characterize wrist, elbow and shoulder antagonistic motor cortical points. Simultaneous ICMS applied at two cortical points, each evoking activity in one of a pair of antagonistic muscles, produced co-contraction of antagonistic muscle pairs. However, we found an obvious asymmetry in the strength of reciprocal inhibition; it was always significantly stronger on physiological extensors than flexors. Following intravenous injection of a single bolus of strychnine, a cortical point at which only a physiological flexor was previously activated also elicited simultaneous activation of its antagonist. This demonstrates that antagonistic corticospinal neurons are closely grouped, or intermingled. To test whether releasing a cortical point from inhibition allows it to be functionally linked with an antagonistic cortical point, one of three GABA(A) receptor antagonists, bicuculline, gabazine or picrotoxin, was injected iontophoretically at one cortical point while stimulation was applied to an antagonistic cortical point. This coupling always resulted in co-contraction of the represented antagonistic muscles. Thus, antagonistic motor cortical points are linked by excitatory intracortical connections held in check by local GABAergic inhibition, with reciprocal inhibition occurring at the spinal level. Importantly, the asymmetry of cortically mediated reciprocal inhibition would appear significantly to bias muscle maps obtained by ICMS in favor of physiological flexors. PMID:17880397

  19. Churg-Strauss syndrome and leukotriene antagonist use: a respiratory perspective.

    LENUS (Irish Health Repository)

    Nathani, N

    2008-10-01

    Churg-Strauss syndrome (CSS) is a rare granulomatous small vessel vasculitis that occurs against a background of longstanding asthma. Leukotriene antagonists (LTAs) are used in the management of asthma and may facilitate a reduction in steroid dosage. Reports of the development of CSS in patients with asthma following the initiation of LTA therapy suggest either a causal association or an unmasking of latent CSS as steroid doses fall. We have undertaken a systematic review to establish whether evidence of a drug induced syndrome exists.

  20. Effects of cysteinyl leukotrienes and leukotriene receptor antagonists on markers of inflammation

    DEFF Research Database (Denmark)

    Sampson, Anthony P; Pizzichini, Emilio; Bisgaard, Hans

    2003-01-01

    treatment and management, and investigation of the relation between CysLTs and airway inflammation in asthma. Nitric oxide is also a surrogate marker of asthma and reflects airway inflammation. The anti-inflammatory effects of the leukotriene receptor antagonists and the markers of their activity continue......The understanding that asthma pathophysiology includes an inflammatory component has spurred the more aggressive use of anti-inflammatory therapies and created a need for effective tools to measure inflammation. Biomarkers of airway inflammation proposed are obtained by methods that are direct...

  1. Comparative efficacy and safety of the non-vitamin K antagonist oral anticoagulants for patients with nonvalvular atrial fibrillation.

    Science.gov (United States)

    Senoo, Keitaro; Lip, Gregory Y H

    2015-03-01

    The non-vitamin K antagonist oral anticoagulants (NOACs), such as the thrombin inhibitor (dabigatran) and the direct factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), have been shown to be at least as efficacious and safe as conventional oral anticoagulants, such as the vitamin K antagonists (VKAs) (e.g., warfarin), for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). Each NOAC has various advantages and specific features, and therefore decisions regarding appropriate stroke prevention require individual assessment of stroke and bleeding risk on anticoagulation with VKA therapy and NOACs when starting on any of these drugs. This review briefly describes the results of the four NOACs clinical randomized trials and discusses how they might impact clinical practice and choice of anticoagulants in atrial fibrillation patients. Moreover, this review discusses the differences of the proposed management of antithrombotic therapy in several international guidelines and pragmatic issues of NOACs for stroke prophylaxis. PMID:25682085

  2. Mutually-antagonistic interactions in baseball networks

    Science.gov (United States)

    Saavedra, Serguei; Powers, Scott; McCotter, Trent; Porter, Mason A.; Mucha, Peter J.

    2010-03-01

    We formulate the head-to-head matchups between Major League Baseball pitchers and batters from 1954 to 2008 as a bipartite network of mutually-antagonistic interactions. We consider both the full network and single-season networks, which exhibit structural changes over time. We find interesting structure in the networks and examine their sensitivity to baseball’s rule changes. We then study a biased random walk on the matchup networks as a simple and transparent way to (1) compare the performance of players who competed under different conditions and (2) include information about which particular players a given player has faced. We find that a player’s position in the network does not correlate with his placement in the random walker ranking. However, network position does have a substantial effect on the robustness of ranking placement to changes in head-to-head matchups.

  3. Mutually-Antagonistic Interactions in Baseball Networks

    CERN Document Server

    Saavedra, Serguei; McCotter, Trent; Porter, Mason A; Mucha, Peter J

    2009-01-01

    We formulate the head-to-head matchups between Major League Baseball pitchers and batters from 1954 to 2008 as a bipartite network of mutually-antagonistic interactions. We consider both the full network and single-season networks, which exhibit interesting structural changes over time. We also find that these networks exhibit a significant network structure that is sensitive to baseball's rule changes. We then study a biased random walk on the matchup networks as a simple and transparent way to compare the performance of players who competed under different conditions. We find that a player's position in the network does not correlate with his success in the random walker ranking but instead has a substantial effect on its sensitivity to changes in his own aggregate performance.

  4. The Attractiveness of Opposites: Agonists and Antagonists.

    LENUS (Irish Health Repository)

    O'Brien, Tony

    2015-02-02

    ABSTRACT Opioid-induced bowel dysfunction, of which constipation is the most common aspect, is a major limiting factor in the use of opioids for pain management. The availability of an oral, long-acting formulation of oxycodone and naloxone represents a highly significant development in pain management. The combination of an opioid analgesic with an opioid antagonist offers reliable pain control with a significant reduction in the burden of opioid-induced constipation. This report is adapted from paineurope 2014; Issue 3, ©Haymarket Medical Publications Ltd, and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, LTD and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the website: http:\\/\\/www.paineurope.com at which European health professionals can register online to receive copies of the quarterly publication.

  5. ETA-receptor antagonists or allosteric modulators?

    DEFF Research Database (Denmark)

    De Mey, Jo G R; Compeer, Matthijs G; Lemkens, Pieter;

    2011-01-01

    The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects. In resista......The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects......(A) and that ERAs and the physiological antagonist allosterically reduce ET(A) functions. Combining the two-state model and the two-domain model of GPCR function and considering receptor activation beyond agonist binding might lead to better anti-endothelinergic drugs. Future studies could lead to compounds...

  6. Antagonistic activity of marine sponges associated Actinobacteria

    Institute of Scientific and Technical Information of China (English)

    Selvakumar Dharmaraj; Dhevendaran Kandasamy

    2016-01-01

    Objective: To focus on the isolation and preliminary characterization of marine sponges associated Actinobacteria particularly Streptomyces species and also their antagonistic activities against bacterial and fungal pathogens. Methods: The sponges were collected from Kovalam and Vizhinjam port of south-west coast of Kerala, India. Isolation of strains was carried out from sponge extracts using international Streptomyces project media. For preliminary identification of the strains, morphological (mycelial colouration, soluble pigments, melanoid pigmentation, spore morphology), nutritional uptake (carbon utilisation, amonoacids influence, sodium chloride tolerance), physiological (pH, temperature) and chemotaxonomical characterization were done. Antimicrobial studies were also carried out for the selected strains. Results: With the help of the spicule structures, the collected marine sponges were identified as Callyspongia diffusa, Mycale mytilorum, Tedania anhelans and Dysidea fragilis. Nearly 94 strains were primarily isolated from these sponges and further they were sub-cultured using international Streptomyces project media. The strains exhibited different mycelial colouration (aerial and substrate), soluble and melanoid pigmentations. The strains possessed three types of sporophore morphology namely rectus flexibilis, spiral and retinaculiaperti. Among the 94 isolates, seven exhibited antibacterial and antifungal activities with maximal zone of inhibition of 30 mm. The nutritional, physiological and chemotaxonomical characteristic study helped in the conventional identification of the seven strains and they all suggest that the strains to be grouped under the genus Streptomyces. Conclusions: The present study clearly helps in the preliminary identification of the isolates associated with marine sponges. Antagonistic activities prove the production of antimicrobial metabolites against the pathogens. Marine sponges associated Streptomyces are universally well

  7. 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

  8. 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.

  9. Optimisation of GnRH antagonist use in ART

    NARCIS (Netherlands)

    Hamdine, O.

    2014-01-01

    This thesis focuses on the optimisation of controlled ovarian stimulation for IVF using exogenous FSH and GnRH antagonist co-treatment, by studying the timing of the initiation of GnRH antagonist co-medication and the role of ovarian reserve markers in optimising ovarian response and reproductive ou

  10. Serotonin 2A receptor antagonists for treatment of schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Rasmussen, Hans; Arnt, Jørn;

    2011-01-01

    receptor antagonists is evaluated. Moreover, the investigational pipeline of major pharmaceutical companies is examined and an Internet search conducted to identify other pharmaceutical companies investigating 5-HT2A receptor antagonists for the treatment of schizophrenia. Expert opinion: 5-HT2A receptor...

  11. Antagonistic and Bargaining Games in Optimal Marketing Decisions

    Science.gov (United States)

    Lipovetsky, S.

    2007-01-01

    Game theory approaches to find optimal marketing decisions are considered. Antagonistic games with and without complete information, and non-antagonistic games techniques are applied to paired comparison, ranking, or rating data for a firm and its competitors in the market. Mix strategy, equilibrium in bi-matrix games, bargaining models with…

  12. 原发性醛固酮增多症患者血钾水平的影响因素分析%Analysis of related factors of blood potassium in patients with primary aldosteronism

    Institute of Scientific and Technical Information of China (English)

    邓西元; 李航; 叶大伟

    2015-01-01

    目的:分析原发性醛固酮增多症患者血钾水平的影响因素。方法回顾性分析原发性醛固酮增多症患者82例临床资料,将其分为正常血钾组和低血钾组。探讨原发性醛固酮增多症患者血钾与其血醛固酮、肾素、血管紧张素域及醛固酮肾素活性比值(ARR)的关系。结果原发醛固酮增多症患者血钾与醛固酮肾素活性比值(ARR)有相关性(P<0.05),正常血钾组与低血钾组ARR值差异有统计学意义(P<0.05)。结论在原发性醛固酮增多症患者中,醛固酮肾素活性比值反映其血钾水平。%Objective To analyse the related factors of blood potassium in patients with primary aldosteronism. Meth-ods Clinical date of 82 patients with primary aldosteronism were retrospectively analyzed. They were divided into normal blood potassium group and low blood potassium group, analysed the relationship of blood potassium with serum aldosterone, plasma renin activity, angiotensin II and aldosterone/plasma renin activity ratio (ARR). Results Blood potassium of patients with primary aldosteronism was significantly correlated with aldosterone/plasma renin activity ratio. There was statistical difference in ARR value between normal blood potassium group and low blood potassium group. Conclusion Aldosterone/plasma renin ac-tivity ratio reflects its potassium level in patients with primary aldosteronism.

  13. Pharmacokinetic interactions with calcium channel antagonists (Part I).

    Science.gov (United States)

    Schlanz, K D; Myre, S A; Bottorff, M B

    1991-11-01

    Calcium channel antagonists are a diverse class of drugs widely used in combination with other therapeutic agents. The potential exists for many clinically significant pharmacokinetic interactions between these and other concurrently administered drugs. The mechanisms of calcium channel antagonist-induced changes in drug metabolism include altered hepatic blood flow and impaired hepatic enzyme metabolising activity. Increases in serum concentrations and/or reductions in clearance have been reported for several drugs used with a number of calcium channel antagonists. A number of reports and studies of calcium channel antagonist interactions have yielded contradictory results and the clinical significance of pharmacokinetic changes seen with these agents is ill-defined. The first part of this article deals with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs. PMID:1773549

  14. Risk of ischemic stroke, hemorrhagic stroke, bleeding, and death in patients switching from vitamin K antagonist to dabigatran after an ablation

    DEFF Research Database (Denmark)

    Pallisgaard, Jannik Langtved; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian;

    2016-01-01

    BACKGROUND: Safety regarding switching from vitamin K antagonist (VKA) to dabigatran therapy in post-ablation patients has never been investigated and safety data for this is urgently needed. The objective of this study was to examine if switch from VKA to dabigatran increased the risk of stroke...

  15. Selective Allosteric Antagonists for the G Protein-Coupled Receptor GPRC6A Based on the 2-Phenylindole Privileged Structure Scaffold

    DEFF Research Database (Denmark)

    Johansson, Henrik; Boesgaard, Michael Worch; Nørskov-Lauritsen, Lenea;

    2015-01-01

    G protein-coupled receptors (GPCRs) represent a biological target class of fundamental importance in drug therapy. The GPRC6A receptor is a newly deorphanized class C GPCR that we recently reported for the first allosteric antagonists based on the 2-arylindole privileged structure scaffold (e.g., 1...

  16. Chronic psychosocial stress in tree shrews : effect of the substance P (NK1 receptor) antagonist L-760735 and clomipramine on endocrine and behavioral parameters

    NARCIS (Netherlands)

    van der Hart, MGC; de Biurrun, G; Czeh, B; Rupniak, NMJ; den Boer, JA; Fuchs, E

    2005-01-01

    Rationale: Substance P and its preferred receptor, the neurokinin 1 receptor (NK1R), have been proposed as possible targets for new antidepressant therapies, although results of a recently completed phase III trial failed to demonstrate that the NK1R antagonist MK-869 is more effective than placebo

  17. Vitamin K antagonists in heart disease: Current status and perspectives (Section III). Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease

    NARCIS (Netherlands)

    Caterina, R. de; Husted, S.; Wallentin, L.; Andreotti, F.; Arnesen, H.; Bachmann, F.; Baigent, C.; Huber, K.; Jespersen, J.; Kristensen, S.D.; Lip, G.Y.; Morais, J.; Rasmussen, L.H.; Siegbahn, A.; Verheugt, F.W.A.; Weitz, J.I.

    2013-01-01

    Oral anticoagulants are a mainstay of cardiovascular therapy, and for over 60 years vitamin K antagonists (VKAs) were the only available agents for long-term use. VKAs interfere with the cyclic inter-conversion of vitamin K and its 2,3 epoxide, thus inhibiting gamma-carboxylation of glutamate residu

  18. Feline primary hyperaldosteronism: an emerging endocrine disease

    Directory of Open Access Journals (Sweden)

    Daniel Diola Bento

    2016-04-01

    Full Text Available ABSTRACT: The primary hyperaldosteronism, an endocrine disease increasingly identified in cats, is characterized by adrenal gland dysfunction that interferes with the renin-angiotensin-aldosterone system, triggering the hypersecretion of aldosterone. Pathophysiological consequences of excessive aldosterone secretion are related to increased sodium and water retention, and increased excretion of potassium, which induce hypertension and severe hypokalemia, respectively. The most common clinical findings in cats include: polydipsia, nocturia, polyuria, generalized weakness, neck ventroflexion, syncope, anorexia, weight loss, pendulous abdomen and blindness. Diagnosis is based on the evidence of hormonal hypersecretion with suppression of renin release, imaging and histopathological evaluation of adrenal glands. Treatment may be curative with adrenalectomy, in cases of unilateral disease, or conservative, through administration of aldosterone antagonists, potassium supplementation and antihypertensives. Prognosis varies from fair to good with the appropriate therapy. This article reviews the main aspects of primary aldosteronism in cats, providing the clinician with important information for the diagnosis of this disease.

  19. Mineralocorticoid hypertension

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Hypertension affects about 10 - 25% of the population and is an important risk factor for cardiovascular and renal disease. The renin-angiotensin system is frequently implicated in the pathophysiology of hypertension, be it primary or secondary. The prevalence of primary aldosteronism increases with the severity of hypertension, from 2% in patients with grade 1 hypertension to 20% among resistant hypertensives. Mineralcorticoid hypertension includes a spectrum of disorders ranging from renin-producing pathologies (renin-secreting tumors, malignant hypertension, coarctation of aorta, aldosterone-producing pathologies (primary aldosteronism - Conns syndrome, familial hyperaldosteronism 1, 2, and 3, non-aldosterone mineralocorticoid producing pathologies (apparent mineralocorticoid excess syndrome, Liddle syndrome, deoxycorticosterone-secreting tumors, ectopic adrenocorticotropic hormones (ACTH syndrome, congenitalvadrenal hyperplasia, and drugs with mineraocorticoid activity (locorice, carbenoxole therapy to glucocorticoid receptor resistance syndromes. Clinical presentation includes hypertension with varying severity, hypokalemia, and alkalosis. Ratio of plasma aldosterone concentraion to plasma renin activity remains the best screening tool. Bilateral adrenal venous sampling is the best diagnostic test coupled with a CT scan. Treatment is either surgical (adrenelectomy for unilateral adrenal disease versus medical therapy for idiopathic, ambiguous, or bilateral disease. Medical therapy focuses on blood pressure control and correction of hypokalemia using a combination of anti-hypertensives (calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers and potassium-raising therapies (mineralcorticoid receptor antagonist or potassium sparing diuretics. Direct aldosterone synthetase antagonists represent a promising future therapy.

  20. Gingival hyperplasia in renal allograft recipients receiving cyclosporin-A and calcium antagonists.

    Science.gov (United States)

    King, G N; Fullinfaw, R; Higgins, T J; Walker, R G; Francis, D M; Wiesenfeld, D

    1993-04-01

    Although it is established that the immunosuppressant cyclosporin-A (CsA) and calcium antagonists [Nifedipine (Nif) and Diltiazem (Dz)] can independently induce gingival enlargement, little has been documented on the significance of the salivary CsA levels and the combined effect of CsA and a calcium antagonist upon gingival tissues. In the present cross-sectional investigation, clinical periodontal parameters and the pharmacologic profiles of CsA, Nif, and Dz were determined for 66 renal transplant recipients. Subjects were divided into the following groups: Group (Gp) 1: CsA [n = 18]; Gp 2: CsA + Nif [n = 15]; Gp 3: CsA + Dz [n = 12] and a negative Control Gp 4: azathioprine [n = 21]. A gingival enlargement score was assessed for each patient from study models using a hyperplastic index (HI). Pharmacologic profiles included CsA whole blood and whole saliva levels as measured by fluorescence polarization immunoassay. The HI scores between Gp 1, 2 and 3 were not significantly different. However, when compared with controls (Gp 4), there was a significant difference in HI and all individual groups (Gp 1, 2, 3) (p < 0.05). Gingival hyperplasia was only weakly related to plaque and calculus but was unrelated to CsA dose (mg/kg/day), duration of CsA therapy (months), CsA blood or saliva levels (ng/ml), or the concurrent administration of a Nif or Dz. Gingival enlargement was found to occur in 49% of subjects who were either on CsA or CsA and a calcium antagonist. It is concluded that CsA alone or in combination with a calcium antagonist caused a significant increase in gingival enlargement compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Advance of research on application of renin-angiotensin-aldosterone system blockers in elderly patients with chronic kidney disease%RAAS阻滞剂在老年慢性肾脏病中应用的研究进展

    Institute of Scientific and Technical Information of China (English)

    张琪; 倪兆慧

    2014-01-01

    全球老龄人(年龄≥65岁)所占的人口比例正逐步上升。老年人由于其特殊的生理状态更易被一些慢性病如,高血压、糖尿病、慢性肾脏病( CKD)所困扰。肾素-血管紧张素-醛固酮系统( RAAS)的过分活跃可导致高血压、心血管事件及CKD的发生。因此,针对RAAS的治疗具有可行性。但老年患者在使用RAAS阻滞剂[主要包括血管紧张素转换酶抑制剂( ACEI)、血管紧张素受体阻滞剂( ARB)、肾素抑制剂、醛固酮拮抗剂]类药物时更易出现肾小球滤过率( GFR)下降、高钾血症、低血压等不良反应,所以临床使用时,需要特别平衡使用该类药物的利弊。尽管目前对老年人使用RAAS阻滞剂药物有限的研究大多获得了肯定的结论,但是,仍需要更多、更长周期的研究结果来探寻老年CKD患者使用RAAS阻滞剂的疗效和安全性,以及是否确实能减缓CKD的进展。%Theproportionofglobalolderpeople(age≥65years)isgraduallyincreasing.Because of their special physiological state,older people are more easily troubled by some chronic diseases such as hypertension,diabetes,and chronic kidney disease( CKD). Overactivity of renin-angiotensin-aldosterone system( RAAS)can lead to hypertension,cardiovascular events,as well as CKD. Therefore,the treatment targeting RAAS is feasible. However,while using RAAS blockers including angiotensin converting enzyme inhibitors( ACEI),angiotensin receptor blockers( ARB),renin inhibitors,and aldosterone antagonists, elderly patients are more likely to be subjected to decrease of glomerular filtration rate ( GFR ), hyperkalemia,and hypotension,etc,indicating that it is specially required to weigh the pros and cons before clinical use of such drugs. Although most limited researches on efficacy of RAAS blocker drugs in elderly patients obtained positive conclusions,more long-term studies are still needed to explore the therapeutic efficacy

  2. 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

  3. 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...

  4. 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...

  5. Rivaroxaban and other non-vitamin K antagonist oral anticoagulants in the emergency treatment of thromboembolism.

    Science.gov (United States)

    Goldstein, Patrick; Elalamy, Ismaïl; Huber, Kurt; Danchin, Nicolas; Wiel, Eric

    2013-01-01

    Pulmonary embolism (PE) is potentially fatal and often requires emergency management. Because PE associated with shock and/or hypotension carries a high risk of sudden death, emergency clinicians must rapidly make a diagnosis and initiate appropriate therapeutic strategies, usually involving anticoagulant treatment. Traditional anticoagulants, such as heparins and vitamin K antagonists, although effective and recommended by guidelines, are associated with limitations. Several targeted, orally administered anticoagulants that may overcome some of these constraints have been developed recently and undergone analysis in randomised, phase III clinical trials. Rivaroxaban, a direct factor Xa inhibitor, was non-inferior to standard therapy with enoxaparin plus a vitamin K antagonist for the prevention of recurrent, symptomatic venous thromboembolism (VTE) in patients with acute PE and led to a 50% reduction in major bleeding. Dabigatran, a direct thrombin inhibitor, was also non-inferior to standard therapy for the prevention of recurrent VTE or VTE-related death when given after a parenteral anticoagulant and had a similar incidence of major bleeding. The results of a phase III study of apixaban, another direct factor Xa inhibitor, for the acute treatment of VTE are expected in the near future. Rivaroxaban is now approved in Europe and the US for the treatment of acute PE and prevention of recurrent VTE. This article reviews the current guidance on the treatment of PE with special focus on the emergency setting, and considers data regarding rivaroxaban and the other non-vitamin K antagonist oral anticoagulants and their potential role, including patients who are and are not appropriate for treatment with these agents. Issues such as drug interactions, reversal of anticoagulant effect and coagulation monitoring are also discussed. PMID:23866080

  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. MDM2 antagonist Nutlin-3a potentiates antitumour activity of cytotoxic drugs in sarcoma cell lines

    Directory of Open Access Journals (Sweden)

    Lothe Ragnhild A

    2011-05-01

    Full Text Available Abstract Background Frequent failure and severe side effects of current sarcoma therapy warrants new therapeutic approaches. The small-molecule MDM2 antagonist Nutlin-3a activates the p53 pathway and efficiently induces apoptosis in tumours with amplified MDM2 gene and overexpression of MDM2 protein. However, the majority of human sarcomas have normal level of MDM2 and the therapeutic potential of MDM2 antagonists in this group is still unclear. We have investigated if Nutlin-3a could be employed to augment the response to traditional therapy and/or reduce the genotoxic burden of chemotherapy. Methods A panel of sarcoma cell lines with different TP53 and MDM2 status were treated with Nutlin-3a combined with Doxorubicin, Methotrexate or Cisplatin, and their combination index determined. Results Clear synergism was observed when Doxorubicin and Nutlin-3a were combined in cell lines with wild-type TP53 and amplified MDM2, or with Methotrexate in both MDM2 normal and amplified sarcoma cell lines, allowing for up to tenfold reduction of cytotoxic drug dose. Interestingly, Nutlin-3a seemed to potentiate the effect of classical drugs as Doxorubicin and Cisplatin in cell lines with mutated TP53, but inhibited the effect of Methotrexate. Conclusion The use of Nutlin in combination with classical sarcoma chemotherapy shows promising preclinical potential, but since clear biomarkers are still lacking, clinical trials should be followed up with detailed tumour profiling.

  9. Non-vitamin K antagonist oral anticoagulants for the prevention of recurrent venous thromboembolism.

    Science.gov (United States)

    Bauersachs, Rupert

    2016-08-01

    Venous thromboembolism (VTE) is associated with a risk of recurrence that depends on factors specific to index event and patient. A first unprovoked VTE increases the risk of a recurrent event, particularly during the first year after anticoagulation cessation. Determining a strategy for the long-term prevention of recurrent VTE poses challenges that stem from a lack of agreement on recommended therapy duration and varying treatment burden for the patient. Oral anticoagulants, including vitamin K antagonists and non-vitamin K antagonist oral anticoagulants (NOACs), are the main treatment options for the long-term prevention of recurrent VTE. However, the risk of VTE recurrence must be balanced against the risk of bleeding in each patient. Phase III clinical trials have evaluated rivaroxaban, apixaban and dabigatran for extended treatment and prevention of VTE versus placebo, and versus warfarin in the case of dabigatran. Compared with placebo treatment, each NOAC showed superior efficacy together with an acceptable safety profile during extended treatment periods of 6-18months. Patients receiving long-term NOAC therapy will still require regular risk factor assessment, but these agents may permit longer treatment duration with an improved benefit-risk profile. PMID:27263046

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

    Directory of Open Access Journals (Sweden)

    Natalia Muñoz-Durango

    2016-06-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-06-23

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

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

    Directory of Open Access Journals (Sweden)

    Yi-Chun Chen

    2013-01-01

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

  14. 原发性醛固酮增多症遗传学研究进展%Genetics advances in primary aldosteronism

    Institute of Scientific and Technical Information of China (English)

    谢利芳; 欧阳金芝; 母义明

    2015-01-01

    原发性醛固酮增多症(primary aldosteronism,PA)是一种常见的、可治愈的继发性高血压的原因之一,主要由醛固酮瘤(aldosterone-producing adenoma,APA)或特发性醛固酮增多症(idiopathic hyperaldosteronism,IHA)引起,只有小部分的PA是家族性醛固酮增多症(familial hyperaldosteronism,FH)。基因组学技术的发展,使得人们逐步阐明了与APA、IHA和FH发生有关的部分异常基因。本文主要描述了与PA有关的异常基因,以期为PA分型诊断和继发性高血压的治疗提供新的方向。%Primary aldosteronism (PA) is the most common and curable form of secondary hypertension which is primarily caused by either aldosterone-producing adenoma (APA) or by idiopathic hyperaldosteronism (IHA). Only a tiny part of PA patients are familial hyperaldosteronism (FH). Recent advances in genome technology have allowed researchers to unravel part of the genetic abnormalities of APA, IHA and FH. In this review, we mainly describe the genetic abnormalities associated with PA and may offer a new direction for diagnosis of PA and treatment in secondary hypertension.

  15. 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

  16. Simultaneous measurement of aldosterone and cortisol by high-performance liquid chromatography-tandem mass spectrometry: application to dehydration-rehydration studies.

    Science.gov (United States)

    Taylor, Paul J; van Rosendal, Simon P; Coombes, Jeff S; Gordon, Richard D; Stowasser, Michael

    2010-05-01

    Aldosterone and cortisol are useful biomarkers of dehydration and stress, respectively. The aim of this study was to develop an HPLC-tandem mass spectrometric method for the simultaneous measurement of aldosterone and cortisol in human plasma that could be applied to the study of athletes undergoing exercise and rehydration. Samples were prepared and analysed using an on-line sample preparation/HPLC system coupled to a triple quadrupole tandem-mass spectrometer. Samples (200 microL) were pre-treated and extracted on Hysphere C18 HD cartridges (7 microm, Spark Holland). Chromatography was performed on a Sunfire C18 analytical column (50 mm x 3.0 mm, 3 microm, Waters) under isocratic conditions at a flow rate of 0.3 mL/min. The mobile phase consisted of 35% acetonitrile/water. Mass spectrometric detection was by selected reaction monitoring using negative electrospray ionization conditions. The assay had an analytical range of 25-500 pg/mL and 25-500 ng/mL for aldosterone and cortisol, respectively (r(2)>0.992, n=22). Inter-day accuracy and imprecision for quality control samples was 99.4-106% and dehydration, rehydration and exercise when measured by this method. The reported method is suitable to facilitate the study of athletes undergoing dehydration and rehydration protocols.

  17. Behavioural effects of histamine and its antagonists: a review.

    Science.gov (United States)

    White, J M; Rumbold, G R

    1988-01-01

    This review focuses on the behavioural effects of histamine and drugs which affect histaminergic function, particularly the H1- and H2-receptors antagonists. Research in this area has assumed considerable importance with increasing interest in the role of brain histamine, the clinical use of both H1 and H2 antagonists and evidence of nonmedical use of H1 antagonists. Results from a number of studies show that H1 and H2 antagonists have clear, but distinct subjective effects and that H1 antagonists have discriminative effects in animals. While H1 antagonists are reinforcers in certain conditions, histamine itself is a punisher. Moderate doses of H1 antagonists affect psychomotor performance in some situations, but the results are variable. The exceptions are terfenadine and astemizole, which do not seem to penetrate the blood-brain barrier readily. In studies of schedule-controlled behaviour, marked changes in response rate have been observed following administration of H1 antagonists, with the magnitude and direction dependent on the dose and the baseline behaviour. Histamine reduces avoidance responding, an effect mediated via H1-receptors. Changes in drinking and aggressive behaviour have also been observed following histamine administration and distinct roles for H1- and H2-receptors have been delineated. Separate H1- and H2-receptor mechanisms have also been suggested to account for changes in activity level. While the H2 antagonists do not always have strong behavioural effects when administered peripherally, there is evidence that cimetidine has a depressant effect on sexual function. These and other findings reveal an important role for histaminergic systems in a wide range of behaviour. PMID:3133686

  18. Effective management of venous thromboembolism in the community: non-vitamin K antagonist oral anticoagulants

    Directory of Open Access Journals (Sweden)

    Patel R

    2016-05-01

    Full Text Available Raj Patel Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital, London, UK Abstract: Anticoagulation therapy is essential for the effective treatment and secondary prevention of venous thromboembolism (VTE. For many years, anticoagulation for acute VTE was limited to the use of initial parenteral heparin, overlapping with and followed by a vitamin K antagonist. Although highly effective, this regimen has several limitations and is particularly challenging when given in an ambulatory setting. Current treatment pathways for most patients with deep-vein thrombosis typically involve initial hospital or community-based ambulatory care with subsequent follow-up in a secondary care setting. With the introduction of non-vitamin K antagonist oral anticoagulants (NOACs into routine clinical practice, it is now possible for the initial acute management of patients with deep-vein thrombosis to be undertaken by primary care. As hospital admissions associated with VTE become shorter, primary care will play an increasingly important role in the long-term management of these patients. Although the NOACs can potentially simplify patient management and improve clinical outcomes, primary care physicians may be less familiar with these new treatments compared with traditional therapy. To assist primary care physicians in further understanding the role of the NOACs, this article outlines the main differences between NOACs and traditional anticoagulation therapy and discusses the benefit–risk profile of the different NOACs in the treatment and secondary prevention of recurrent VTE. Key considerations for the use of NOACs in the primary care setting are highlighted, including dose transition, risk assessment and follow-up, duration of anticoagulant therapy, how to minimize bleeding risks, and the importance of patient education and counseling. Keywords: venous thromboembolism, oral anticoagulant, prevention, treatment, primary

  19. Leukotriene Receptor Antagonists and Related Compounds

    Directory of Open Access Journals (Sweden)

    Sally E Wenzel

    1999-01-01

    Full Text Available Leukotrienes (LTs, lipid mediators of inflammation, have proved to be important biochemicals involved in the symptoms and physiological changes of asthma. In the past year and a half, the development of three new drugs that modulate the LT pathway has been completed. The first subclass of these drugs, leukotriene receptor antagonists (LTRA (zafirlukast and montelukast, blocks the interaction of the cysteinyl form of the LTs with the cell type bearing the receptor. The second subclass, the 5-lipoxygenase (5-LO inhibitors (zileuton inhibits the 5-LO enzyme, which prevents the formation of both cysteinyl LTs and LTB4. The LT modulators have shown efficacy in inhibiting the physiological changes occurring after allergen, acetylsalicylic acid and exercise challenge in asthmatics. In addition, they have shown efficacy in improving symptoms, beta-agonist use and forced expiratory volume in 1 s (FEV1 in chronic, ‘day-to-day’ asthma in patients with mild disease. Comparison studies with low doses of inhaled corticosteroids suggest that LT modulators may have similar effects on symptom scores and beta-agonist use, but have lesser effects on FEV1. Finally, emerging data suggest that these drugs are beneficial in decreasing the dose of inhaled corticosteroids necessary to control more moderate to severe asthma. While long term studies will be helpful in determining the ‘disease modifying’ effects of these drugs, data suggest that these drugs are useful in the treatment of a broad range of asthmatic patients.

  20. Identification of a novel conformationally constrained glucagon receptor antagonist.

    Science.gov (United States)

    Lee, Esther C Y; Tu, Meihua; Stevens, Benjamin D; Bian, Jianwei; Aspnes, Gary; Perreault, Christian; Sammons, Matthew F; Wright, Stephen W; Litchfield, John; Kalgutkar, Amit S; Sharma, Raman; Didiuk, Mary T; Ebner, David C; Filipski, Kevin J; Brown, Janice; Atkinson, Karen; Pfefferkorn, Jeffrey A; Guzman-Perez, Angel

    2014-02-01

    Identification of orally active, small molecule antagonists of the glucagon receptor represents a novel treatment paradigm for the management of type 2 diabetes mellitus. The present work discloses novel glucagon receptor antagonists, identified via conformational constraint of current existing literature antagonists. Optimization of lipophilic ligand efficiency (LLE or LipE) culminated in enantiomers (+)-trans-26 and (-)-trans-27 which exhibit good physicochemical and in vitro drug metabolism profiles. In vivo, significant pharmacokinetic differences were noted with the two enantiomers, which were primarily driven through differences in clearance rates. Enantioselective oxidation by cytochrome P450 was ruled out as a causative factor for pharmacokinetic differences.

  1. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Mohammad eKhanfar

    2016-05-01

    Full Text Available With the very recent market approval of pitolisant (Wakix®, the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.

  2. Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years

    DEFF Research Database (Denmark)

    Knorr, B; Franchi, L M; Bisgaard, H;

    2001-01-01

    BACKGROUND: The greatest prevalence of asthma is in preschool children; however, the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index, long-term tolerability, and frequency and/or difficulty of administration. Inhaled corticosteroids and inhaled...... cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma, although very young patients may have difficulty using inhalers, and dose delivery can be variable. Moreover, reduced compliance with inhaled therapy relative to orally administered therapy has been....... To our knowledge, this represents the first large, multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma, as well as one of the few asthma studies that incorporated end points validated for use in preschool children...

  3. Effects of 2,3-benzodiazepine AMPA receptor antagonists on dopamine turnover in the striatum of rats with experimental parkinsonism.

    Science.gov (United States)

    Megyeri, Katalin; Marko, Bernadett; Sziray, Nora; Gacsalyi, Istvan; Juranyi, Zsolt; Levay, Gyorgy; Harsing, Laszlo G

    2007-03-15

    Although levodopa is the current "gold standard" for treatment of Parkinson's disease, there has been disputation on whether AMPA receptor antagonists can be used as adjuvant therapy to improve the effects of levodopa. Systemic administration of levodopa, the precursor of dopamine, increases brain dopamine turnover rate and this elevated turnover is believed to be essential for successful treatment of Parkinson's disease. However, long-term treatment of patients with levodopa often leads to development of dyskinesia. Therefore, drugs that feature potentiation of dopamine turnover rate and are able to reduce daily levodopa dosages might be used as adjuvant in the treatment of patients suffering from Parkinson's disease. To investigate such combined treatment, we have examined the effects of two non-competitive AMPA receptor antagonists, GYKI-52466 and GYKI-53405, alone or in combination with levodopa on dopamine turnover rate in 6-hydroxydopamine-lesioned striatum of the rat. We found here that repeated administration of levodopa, added with the peripheral DOPA decarboxylase inhibitor carbidopa, increased dopamine turnover rate after lesioning the striatum with 6-hydroxydopamine. Moreover, combination of levodopa with GYKI-52466 or GYKI-53405 further increased dopamine turnover enhanced by levodopa administration while the AMPA receptor antagonists by themselves failed to influence striatal dopamine turnover. We concluded from the present data that potentiation observed between levodopa and AMPA receptor antagonists may reflect levodopa-sparing effects in clinical treatment indicating the therapeutic potential of such combination in the management of Parkinson's disease.

  4. Effect of the selective vasopressin V2 receptor antagonists in hepatic cirrhosis patients with ascites: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Shao-hui TANG

    2013-07-01

    The selective vasopressin V2 receptor antagonists may improve ascites and increase serum sodium in patients with hepatic cirrhosis and ascites. No significant changes are observed in heart and kidney function, and the incidence of adverse reaction is relatively less. It could be a novel therapy for the treatment of ascites due to liver cirrhosis.

  5. The muscarinic antagonists scopolamine and atropine are competitive antagonists at 5-HT3 receptors.

    Science.gov (United States)

    Lochner, Martin; Thompson, Andrew J

    2016-09-01

    Scopolamine is a high affinity muscarinic antagonist that is used for the prevention of post-operative nausea and vomiting. 5-HT3 receptor antagonists are used for the same purpose and are structurally related to scopolamine. To examine whether 5-HT3 receptors are affected by scopolamine we examined the effects of this drug on the electrophysiological and ligand binding properties of 5-HT3A receptors expressed in Xenopus oocytes and HEK293 cells, respectively. 5-HT3 receptor-responses were reversibly inhibited by scopolamine with an IC50 of 2.09 μM. Competitive antagonism was shown by Schild plot (pA2 = 5.02) and by competition with the 5-HT3 receptor antagonists [(3)H]granisetron (Ki = 6.76 μM) and G-FL (Ki = 4.90 μM). The related molecule, atropine, similarly inhibited 5-HT evoked responses in oocytes with an IC50 of 1.74 μM, and competed with G-FL with a Ki of 7.94 μM. The reverse experiment revealed that granisetron also competitively bound to muscarinic receptors (Ki = 6.5 μM). In behavioural studies scopolamine is used to block muscarinic receptors and induce a cognitive deficit, and centrally administered concentrations can exceed the IC50 values found here. It is therefore possible that 5-HT3 receptors are also inhibited. Studies that utilise higher concentrations of scopolamine should be mindful of these potential off-target effects. PMID:27108935

  6. Addition of a renin-angiotensin-aldosterone system inhibitor to a calcium channel blocker ameliorates arterial stiffness

    Directory of Open Access Journals (Sweden)

    Kiuchi S

    2015-10-01

    Full Text Available Shunsuke Kiuchi,1 Shinji Hisatake,1 Muneyasu Kawasaki,2 Osamu Hirashima,2 Takayuki Kabuki,1 Junichi Yamazaki,1 Takanori Ikeda1 1Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, 2Division of Cardiology and Cardiovascular Surgery, Misato Central General Hospital, Saitama, JapanBackground: The aim of controlling hypertension is to protect against arteriosclerosis. Calcium channel blockers (CCBs and renin-angiotensin-aldosterone system (RAAS inhibitors have been reported to have antihypertensive effects, but their effect on the progression of arteriosclerosis is not fully understood. The cardio-ankle vascular index (CAVI was developed to estimate arterial stiffness, which reflects arteriosclerosis. In this study, we investigated the longer term effects of CCBs and RAAS inhibitors on the progression of arteriosclerosis by monitoring the CAVI.Methods: Our subjects were 115 consecutive, non-smoking hypertensive patients on oral treatment with a CCB and/or RAAS inhibitor for at least 3 years in whom the CAVI was measured on two occasions approximately 1 year apart during the period from January 2009 to December 2011. Changes in CAVI were evaluated in patients administered a CCB alone (group C, an RAAS inhibitor (group R alone, or both drugs together (group B. Changes in laboratory findings, blood pressure, and ankle-brachial index were similarly evaluated.Results: No significant change in laboratory findings, blood pressure, or ankle-brachial index was noted in any of the groups. The CAVI decreased slightly in group R (first recording 8.80±1.03, second recording 8.57±0.97, P=0.517 and increased significantly in group C (first 8.45±0.92, second 8.95±1.04, P=0.038, but showed no significant change in group B (first 9.01±1.26, second 9.05±1.35, P=0.851.Conclusion: Long-term administration of a CCB alone increased the CAVI, but this effect was offset by the concomitant use of a RAAS inhibitor, indicating that a RAAS

  7. On the top of ARB N/L type Ca channel blocker leads to less elevation of aldosterone

    Science.gov (United States)

    Konoshita, Tadashi; Kaeriyama, Saori; Urabe, Machi; Nakaya, Takahiro; Yamada, Mika; Ichikawa, Mai; Yamamoto, Katsushi; Sato, Satsuki; Imagawa, Michiko; Fujii, Miki; Makino, Yasukazu; Zenimaru, Yasuo; Wakahara, Shigeyuki; Suzuki, Jinya; Ishizuka, Tamotsu; Nakamura, Hiroyuki

    2016-01-01

    The activation of the renin–angiotensin system (RAS) is one of the unfavourable characteristics of calcium channel blocker (CCB). N type calcium channel is thought to be involved in renin gene transcription and adrenal aldosterone release. Accordingly, N/L type CCB has a possibility of less elevation of plasma aldosterone concentrations (PAC) among CCBs. In a monotherapy study, we had already demonstrated that N/L type CCB leads to less activation of the RAS compared with L type CCB. The objective of this study is to substantiate the hypothesis that at the condition of additive administration on the top of an angiotensin receptor blocker (ARB), still N/L type CCB leads to less elevation of PAC compared with L type one. Subjects were 60 hypertensives administered with valsartan. As an open label study, amlodipine (L type) or cilnidipine (N/L type) were administered on the top of valsartan (ARB) in a cross-over manner. Results were as follows (valsartan+amlodipine compared with valsartan+cilnidipine): systolic blood pressure (SBP)/diastolic blood pressure (DBP) (mmHg): 132±10/76±10 compared with 131±10/77±9, P=0.95/0.48, plasma renin activity (PRA) (ng/ml·h): 2.41±2.67 compared with 2.00±1.50 P=0.20, PAC (pg/ml): 77.3±31.0 compared with 67.4±24.8, P<0.05, urinary albumin excretion (UAE) (mg/gCr): 105.9±216.1 compared with 73.9±122.2, P<0.05. Thus, PAC at cilnidipine was significantly lower than those at amlodipine in spite of the comparable BP reductions. Besides, UAE was significantly lower at cilnidipine. In conclusion, on the top of the ARB, it is suggested that cilnidipine administration might lead to less elevation of PAC and reduction in UAE compared with amlodipine. PMID:27515419

  8. 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

  9. 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

  10. 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

  11. “Nihilism” of chronic heart failure therapy in children and why effective therapy is withheld

    OpenAIRE

    Schranz, Dietmar; Voelkel, Norbert F.

    2016-01-01

    Major advances in chronic heart failure (cHF) therapy have been achieved and documented in adult patients, while research regarding the mechanisms and therapy of cHF in children has lagged behind. Based on receptor physiological studies and pharmacological knowledge, treatment with specific ß1-adrenergic receptor blocker (ARB), tissue angiotensin-converting enzyme inhibitor (ACE-I), and mineralocorticoid antagonists have to be recommended in children despite lack of sufficient data derived fr...

  12. Secondary prevention with calcium antagonists after acute myocardial infarction

    DEFF Research Database (Denmark)

    Hansen, J F

    1992-01-01

    Experimental studies have demonstrated that the 3 calcium antagonists nifedipine, diltiazem, and verapamil have a comparable effect in the prevention of myocardial damage during ischaemia. Secondary prevention trials after acute myocardial infarction, which aimed at improving survival...

  13. Aldosterone induces aortic smooth muscle cell apoptosis%醛固酮诱导大鼠主动脉平滑肌细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    闫永吉; 李炯明; 刘建和; 陈戬; 姜永明; 张劲松

    2012-01-01

    目的 观察醛固酮在体内能否诱导主动脉平滑肌细胞凋亡.方法 将24只SD大鼠随机分为3组,每组8只:(1)空白溶剂设为对照组;(2)醛固酮组;(3)醛固酮+血管扩张剂组.渗透泵内分别注入醛固酮(1 μg/h)或空白溶剂,然后埋于大鼠背部皮下.肼苯哒嗪[25 mg/(kg·d)]溶于引用水,每日灌胃1次.8周后脱氧核苷酸末端转移介导的缺口末端标记法(TUNEL)检测凋亡的主动脉平滑肌细胞.结果 醛固酮组和醛固酮+血管扩张剂组大鼠主动脉TUNEL阳性的平滑肌细胞分别占(18.0±1.5)%和(16.5±2.0)%,与对照组(4.7±1.0)%比较,差异有统计学意义(P<0,05);后两组之间差异无统计学意义(P>0.05).结论 醛固酮在体内可以直接诱导主动脉平滑肌细胞凋亡.%Objective To determine whether aldosterone induces aortic smooth muscle cell apoptosis in vivo.Methods 24 Sprague-Dawley rats were randomly divided into 3 groups:vehicle as control; aldosterone and aldosterone plus hydralazine.All animals were then implanted with an osmotic mini-pump containing either aldosterone ( 1 μg/h) or vehicle.Hydralazine [ 25 mg/(kg·d) ] was resolved in drinking water and gavaged once daily.After 8 weeks,aortic smooth muscle cell (ASMC) apoptosis was examined by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay.Results TUNEL-positive aortic smooth muscle cells in aldosterone-infused and aldosterone plus hydralazine rats were ( 18.0± 1.5 ) % and ( 16.5 ± 2.0) % respectively; compared with control rats (4.7 ± 1.0 ) %,there was signifi-cant difference (P < 0.05 ). In contrast,no significant difference was achieved between the latter twogroups (P > 0.05).Conclusion This study' s findings suggest that aldosterone induces aortic smooth muscle cell apoptosis by its direct effect on the aorta.

  14. The Apolipoprotein E Antagonistic Pleiotropy Hypothesis: Review and Recommendations

    OpenAIRE

    Tuminello, Elizabeth R.; S Duke Han

    2011-01-01

    Research on apolipoprotein E (APOE) has consistently revealed a relationship between the gene's ε 4 allele and risk for development of Alzheimer's disease (AD). However, research with younger populations of ε 4 carriers has suggested that the APOE ε 4 allele may in fact be beneficial in earlier ages and may only confer risk of cognitive decline later in life. Accordingly, we and others have proposed that APOE may represent an example of antagonistic pleiotropy. Antagonistic pleiotropy is an e...

  15. Bradykinin antagonists modified with dipeptide mimetic beta-turn inducers.

    Science.gov (United States)

    Alcaro, Maria C; Vinci, Valerio; D'Ursi, Anna M; Scrima, Mario; Chelli, Mario; Giuliani, Sandro; Meini, Stefania; Di Giacomo, Marcello; Colombo, Lino; Papini, Anna Maria

    2006-05-01

    Bradykinin (BK) is involved in a wide variety of pathophysiological processes. Potent BK peptide antagonists can be developed introducing constrained unnatural amino acids, necessary to force the secondary structure of the molecule. In this paper, we report a structure-activity relationship study of two peptide analogues of the potent B2 antagonist HOE 140 by replacing the D-Tic-Oic dipeptide with conformationally constrained dipeptide mimetic beta-turn inducers. PMID:16504505

  16. Identification of M-CSF agonists and antagonists

    Science.gov (United States)

    Pandit, Jayvardhan; Jancarik, Jarmila; Kim, Sung-Hou; Koths, Kirston; Halenbeck, Robert; Fear, Anna Lisa; Taylor, Eric; Yamamoto, Ralph; Bohm, Andrew

    2000-02-15

    The present invention is directed to methods for crystallizing macrophage colony stimulating factor. The present invention is also directed to methods for designing and producing M-CSF agonists and antagonists using information derived from the crystallographic structure of M-CSF. The invention is also directed to methods for screening M-CSF agonists and antagonists. In addition, the present invention is directed to an isolated, purified, soluble and functional M-CSF receptor.

  17. Monitoring Oral Anticoagulant Therapy: Measuring Coagulant Activity

    DEFF Research Database (Denmark)

    Attermann, Jorn

    Life-long oral anticoagulant therapy (OAT) with vitamin K antagonists is offered to patients with increased risk of thrombosis, e.g. patients with artificial heart valves or with atrial fibrillation. It is estimated that in 1992 in the Nordic countries 0.3 – 0.5% of the population was undergoing...... daily anticoagulant therapy. The therapy necessitates close monitoring of coagulant activity, since excess doses of anticoagulant medicine may lead to life-threatening bleedings. Traditionally, patients on OAT are required to pay regular visits to a physician, who decides on drug dosage adjustments...

  18. 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

  19. EFFECT OF ELECTROACUPUNCTURE ON PLASMA ANGIOTENSIN-ALDOSTERONE AND ATRIAL NATRIURETIC POLYPEPTIDE IN RABBITS WITH ACUTE CEREBRAL INFARCTION

    Institute of Scientific and Technical Information of China (English)

    吴绪平; 王述菊; 刘玲; 周华

    2004-01-01

    Objective: To observe the therapeutic effect of electroacupuncture (EA) on plasma angiotensin (Ang*.Ⅱ), aldosterone (ALD) and atrial natriuretic polypeptide (ANP) contents in experimental cerebral infarction rabbits for analyzing the underlying mechanism of acupuncture in ameliorating blood supply of the brain tissue. Methods: A total of 80 rabbits were randomized into control (n=8), pseudo-operation (n=24), model (n=24) and EA (n=24) groups. Cerebral infarction model was established by infusion of self-thrombus into the carotid artery. EA (1 mA, 2 Hz) was applied to "Baihui"(百会GV 20) and "Shuigou"(水沟GV 26) for 30 min, once every 12 hours. Plasma Ang-II, ALD and ANP contents were detected with radioimmunoassay method. In the later 3 groups, blood samples were taken at 6 h, 24 h and 48 h after cerebral ischemia. Results: Compared with control and pseudo-operation groups, Ang-II and ALD contents of model group at 6 h, 24 h and 48 h after cerebral ischemia increased significantly while plasma ANP of the 3 time-courses of model group decreased considerably (P<0.01). In comparison with model group, results showed that Ang-II and ALD contents of EA group decreased significantly whereas ANP level of EA group increased strikingly (P<0.01). Conclusion: Electroacupuncture has the effects of raising plasma ANP level and lowering plasma Ang-II and ALD in cerebral infarction rabbits.

  20. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Yongue, B.G.

    1985-01-01

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

  2. 应用ROC曲线评价醛固酮肾素比值对原发性醛固酮增多症诊断的临床意义%Significance of aldosterone/plasma renin activity ratio in diagnosis of primary aldosteronism with ROC curve

    Institute of Scientific and Technical Information of China (English)

    邓西元; 庞欣欣; 张旭

    2011-01-01

    目的 应用接受者操作特性曲线(ROC曲线)选择术前诊断原发醛固酮增多症(原醛症)的醛固酮肾素比值(ARR)的最佳切点,并探讨醛固酮肾素比值在诊断原醛症方面的临床意义.方法 从2004年1月到2007年6月在同济医院行手术治疗的肾上腺肿瘤病例133例分为总原醛症组、醛固酮瘤组、肾上腺增生组和非原醛组,用ROC工作曲线选择醛固酮肾素比值的最佳切点.结果 总原醛症组和醛固酮瘤组的醛固酮肾素比值的最佳切点为40,而肾上腺增生组的最佳切点为20,醛固酮肾素比值与肾素活性(r=0.615,P<0.01)和血管紧张素Ⅱ(r=0.527,P<0.01)有负相关性.结论 运用醛固酮肾素比值来诊断原醛有很大价值,但还存在不足.%Objective To choose the best cut-off value and to evaluate the clinical significance of aldosterone/plasma renin activity ratio(ARR) for preoperative diagnosis of primary aldosteronism by ROC curve. Methods Data of 133 adrenal tumor cases treated surgically at Tongji Hospital from Jan. 2004 to June 2007 were retrospectively analyzed. The cases were divided into total primary aldosteronism group, APA group, adrenal hyperplasia group and non- primary aldosteronism group,and the best out-off value of ARR was detected by ROC. Results The best cut-off value of ARR was 40 in the total primary aldosteronism group and APA group, and was 20 in the adrenal hyperplasia group. The cut-off value of ARR was negatively correlated with plasma renin activity ratio( r= -0. 615 P<0. 01) and Angiotensin Ⅱ ( r= -0. 527 P<0.01) . Conclusions The use of ARR for diagnosis of primary aldosteronism is significant although it's not perfect.

  3. The Role of Nonvitamin K Antagonist Oral Anticoagulants (NOACs) in Stroke Prevention in Patients with Atrial Fibrillation.

    Science.gov (United States)

    Kuznetsov, Sofya; Barcelona, Robert; Josephson, Richard A; Mohan, Sri K Madan

    2016-05-01

    Anticoagulation is important in stroke prevention in patients with atrial fibrillation. Until recently, heparins and vitamin K antagonists were the only available therapy for stroke reduction in atrial fibrillation (AF) patients. Non-vitamin K antagonist oral anticoagulants (NOACs) including direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) are now available and offer new options for stroke prevention. This article reviews the available data on the use of NOACs for primary and secondary stroke prevention in AF patients and describes specific patient populations to guide clinician in making the informed decision regarding appropriate use of those agents. It also addresses the use of NOACs early after acute stroke and use of thrombolysis while on NOAC. PMID:27023335

  4. Proton Therapy

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Proton Therapy Proton therapy delivers radiation to tumor tissue ... feel during and after the procedure? What is proton therapy and how is it used? Protons are ...

  5. Oxygen Therapy

    Science.gov (United States)

    Oxygen therapy is a treatment that provides you with extra oxygen. Oxygen is a gas that your body ... machine in your home. A different kind of oxygen therapy is called hyperbaric oxygen therapy. It uses oxygen ...

  6. Blocking S1P interaction with S1P{sub 1} receptor by a novel competitive S1P{sub 1}-selective antagonist inhibits angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Yasuyuki, E-mail: y.fujii@po.rd.taisho.co.jp [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Igarashi, Yasuyuki [Laboratory of Biomembrane and Biofunctional Chemistry, Hokkaido University, Sapporo, Hokkaido 060-0812 (Japan); Goitsuka, Ryo [Division of Development and Aging, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022 (Japan)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer The effect of a newly developed S1P{sub 1}-selective antagonist on angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1} is a critical component of VEGF-related angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vitro activity to inhibit angiogenesis. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vivo activity to inhibit angiogenesis. Black-Right-Pointing-Pointer The efficacy of S1P{sub 1}-selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P{sub 1}) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P{sub 1} and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P{sub 1}-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P{sub 1} antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P{sub 1} is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  7. Novel class of medications, orexin receptor antagonists, in the treatment of insomnia - critical appraisal of suvorexant.

    Science.gov (United States)

    Norman, Jessica L; Anderson, Sarah L

    2016-01-01

    Insomnia, a highly prevalent disorder, can be detrimental to patients' overall health and worsen existing comorbidities. Patients may have acute episodes of insomnia related to a traumatic event, but more commonly insomnia occurs chronically. While proper sleep hygiene and behavioral therapy play important roles in the nonpharmacologic management of short-term and chronic insomnia, medications may also be required. Historically, insomnia has been treated with agents such as benzodiazepines, nonbenzodiazepine receptor agonists, and melatonin agonists. Dual orexin receptor antagonists represent a new class of medications for the treatment of insomnia, which block the binding of wakefulness-promoting neuropeptides orexin A and orexin B to their respective receptor sites. Suvorexant (Belsomra) is the first dual orexin receptor antagonist to be approved in the US and Japan and has demonstrated efficacy in decreasing time to sleep onset and increasing total sleep time. Its unique mechanism of action, data to support efficacy and safety over 12 months of use, and relative lack of withdrawal effects when discontinued may represent an alternative for patients with chronic insomnia who cannot tolerate or do not receive benefit from more traditional sleep agents. Suvorexant is effective and well tolerated, but precautions exist for certain patient populations, including females, obese patients, and those with respiratory disease. Suvorexant has only been studied vs placebo, and hence it is unknown how it directly compares with other medications approved by the US Food and Drug Administration for insomnia. Suvorexant is not likely to replace benzodiazepines or nonbenzodiazepine receptor antagonists as a first-line sleep agent but does represent a novel option for the treatment of patients with chronic insomnia. PMID:27471419

  8. Novel agents for anti-platelet therapy

    Directory of Open Access Journals (Sweden)

    Ji Xuebin

    2011-11-01

    Full Text Available Abstract Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti-platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12 receptor antagonists (e.g., clopidogrel, prasugrel, cangrelor, and ticagrelor are being used in clinical settings for their pronounced protective effects. The new protease-activated receptor antagonists, vorapaxar and atopaxar, potentially decrease the risk of ischemic events without significantly increasing the rate of bleeding. Some other new anti-platelet drugs undergoing clinical trials have also been introduced. Indeed, the number of new anti-platelet drugs is increasing. Consequently, the efficacy of these anti-platelet agents in actual patients warrants scrutiny, especially in terms of the hemorrhagic risks. Hopefully, new selective platelet inhibitors with high anti-thrombotic efficiencies and low hemorrhagic side effects can be developed.

  9. 血浆醛固酮/肾素活性比值在原发性醛固酮增多症诊断中的价值%The Diagnosis Value of Plasma Aldosterone/renin Activity Ratio in Primary Aldosteronism

    Institute of Scientific and Technical Information of China (English)

    刘慧光; 任建伟; 陈彦民

    2011-01-01

    目的:探讨血浆醛固酮/肾素活性比值(ARR)在原发性醛固酮增多症(PA)诊断中的临床价值.方法:选择我院收治的高血压患者460例,空腹采血后采用放射免疫法测定患者醛固酮和肾素水平,并计算血浆醛固酮/肾素活性比值.对其中疑诊为原发性醛固酮增多症的患者再行肾上腺薄层CT扫描,并行血液生化和血清钾检测.结果:460例患者中,ARR>25者56例,经肾上腺薄层CT扫描、血液生化和血清钾检测后确诊为原发性醛固酮增多症者48例.ARR应用于原发性醛固酮增多症的检出率为10.43%,诊断符合率为85.71%.48例患者中合并低血钾者18例,占37.5%.结论:血浆醛固酮/肾素活性比值在临床的应用可使高血压人群中原发性醛固酮增多症的检出率明显增加,具有重要的临床价值,应作为重度高血压和难治性高血压患者的常规检查项目.%Objective: To investigate the diagnosis value of plasma aldosterone/renin activity ratio (ARR) in primary aldosteronism.Methods: 460 patients with hypertension were collected, after fasting blood measured by radioimmunoassay in patients with aldosterone and renin levels, and calculate the plasma aldosterone/renin activity ratio.Checking the patients which was suspected with primary aldosteronism by CT scan of adrenal thin, blood biochemistry and serum potassium.Results: In 460 patients, there were 56 patients' ARR>25.The CT scan, adrenal thin layer blood biochemical and potassium diagnosed after detecting primary aldosteronism in 48 cases.Detection rate was 10.43%, diagnostic rate was 85.71%.18 patients combined hypokalemia in 48 patients (37.5%).Conclusion: Plasma aldosterone/renin activity ratio in the clinical application can significantly increase the detection rate in hypertensives with primary aldosteronism, it has important clinical value, should be severe hypertension and refractory hypertension in patients with routine examination project.

  10. Combination pharmacological therapies for the management of benign prostatic hyperplasia.

    Science.gov (United States)

    Cohen, Seth A; Parsons, J Kellogg

    2012-04-01

    Benign prostatic hyperplasia (BPH) is a highly prevalent condition of older men caused by unregulated growth of the prostate gland. Clinical trials of medical therapy for BPH have consistently demonstrated that combined therapy with an α(1)-adrenergic receptor (AR) antagonist and a 5α-reductase inhibitor is superior to either agent alone. The addition of anticholinergic therapy to a treatment regimen could effectively improve symptoms in men with persistent storage lower urinary tract symptoms (LUTS) who have not seen a benefit with an α(1)-AR antagonist or 5α-reductase inhibitor. Among α(1)-AR antagonists, doxazosin, terazosin, tamsulosin, and alfuzosin, although with slight differences in adverse event profiles, are equivalent in effectiveness and efficacy. No data in the form of direct comparator trials exist to suggest a difference in clinical efficacy of finasteride and dutasteride, the two 5α-reductase inhibitors currently available. Current American Urological Association guidelines do not recommend phytotherapy or dietary supplements in any combination for the medical management of BPH. The current literature supports the safety and efficacy of the combination of an α(1)-AR antagonist and a 5α-reductase inhibitor in the treatment of symptomatic BPH and, in select patients, the use of an α(1)-AR antagonist and anticholinergic medication in the treatment of LUTS suggestive of BPH. PMID:22428659

  11. Clinical value of posture test in subtype differentiation of primary aldosteronism%体位试验对鉴别原发性醛固酮增多症分型的价值

    Institute of Scientific and Technical Information of China (English)

    邢玉微; 邹俊杰; 石勇铨; 刘志民

    2016-01-01

    Objective To evaluate the value of posture test in the subtype differentiation of primary aldosteronism.Methods In total,91 patients with primary aldosteronism were divided into the aldosterone-producing adenoma (n =43)and idiopathic hyperaldosteronism groups (IHA,n =48).General characteris-tics,renin activity and aldosterone changes after posture test were statistically compared between two groups.Results Age,gender constitution,systolic and diastolic pressure and plasma potassium did not significantly differ between two groups (all P >0.05).Compared with IHA group,renin activity was significantly lower whereas aldosterone changes and the ratio of aldosterone /renin activity were significantly higher after saline ad-ministration in the aldosterone-producing adenoma group (all P 30% eleva-tion.In the IHA group,aldosterone level in a standing posture was elevated compared with that in a lying pos-ture including 8 cases with 30% elevation.The percentage of patients with 0.05).Conclusions Posture test contributes to directly identif-ying the aldosterone-producing adenoma with decreasing aldosterone level in a standing posture.For those with elevated aldosterone level after a standing posture,comprehensive tests are required to differentiate the subtype of primary aldosteronism.%目的:探讨体位试验对鉴别原发性醛固酮增多症分型的价值。方法将91例原发性醛固酮增多症患者分为醛固酮瘤组(43例)及特发性醛固酮增多症(IHA)组(48例),比较2组的一般特征及体位试验后肾素活性、醛固酮的变化特点。结果2组的年龄、性别构成比、收缩压、舒张压、血钾比较差异无统计学意义(P 均>0.05),醛固酮瘤组滴注生理盐水后肾素活性低于 IHA组,而滴注生理盐水后血浆醛固酮及醛固酮与肾素活性比值均高于 IHA 组(P 均<0.05)。体位试验显示醛固酮瘤组患者立位血浆醛固酮较卧位下降的有19例,升高的有24

  12. P2Y12 Receptor Antagonists and Morphine: A Dangerous Liaison?

    Science.gov (United States)

    Giannopoulos, Georgios; Deftereos, Spyridon; Kolokathis, Fotios; Xanthopoulou, Ioanna; Lekakis, John; Alexopoulos, Dimitrios

    2016-09-01

    P2Y12 receptor antagonists, concurrently administered with aspirin in what has come to be commonly called dual antiplatelet therapy, are a mainstay of treatment for patients with acute coronary syndromes. Morphine, on the contrary, is a commonly used drug in the acute phase of acute coronary syndromes to relieve pain-with the added potential benefit of attenuating acutely raised sympathetic tone. In current guidelines, though, morphine is recommended with decreasing strength of recommendation. One reason is that it raises concern regarding the potentially significant interaction with antiplatelet agents, leading to impaired inhibition of platelet activation. In any case, it is still considered a mandatory part of the inventory of available medications in prehospital acute myocardial infarction management. The goal of the present review is to present published evidence on morphine and its potential interactions with P2Y12 receptor antagonists, as well as on the central issue of whether such interactions may underlie clinically significant effects on patient outcomes. PMID:27586412

  13. The Role of Interferon Antagonist, Non-Structural Proteins in the Pathogenesis and Emergence of Arboviruses

    Directory of Open Access Journals (Sweden)

    Samantha S. Soldan

    2011-06-01

    Full Text Available A myriad of factors favor the emergence and re-emergence of arthropod-borne viruses (arboviruses, including migration, climate change, intensified livestock production, an increasing volume of international trade and transportation, and changes to ecosystems (e.g., deforestation and loss of biodiversity. Consequently, arboviruses are distributed worldwide and represent over 30% of all emerging infectious diseases identified in the past decade. Although some arboviral infections go undetected or are associated with mild, flu-like symptoms, many are important human and veterinary pathogens causing serious illnesses such as arthritis, gastroenteritis, encephalitis and hemorrhagic fever and devastating economic loss as a consequence of lost productivity and high mortality rates among livestock. One of the most consistent molecular features of emerging arboviruses, in addition to their near exclusive use of RNA genomes, is the inclusion of viral, non-structural proteins that act as interferon antagonists. In this review, we describe these interferon antagonists and common strategies that arboviruses use to counter the host innate immune response. In addition, we discuss the complex interplay between host factors and viral determinants that are associated with virus emergence and re-emergence, and identify potential targets for vaccine and anti-viral therapies.

  14. Antagonistic Effects of Sodium Butyrate and N-(4-Hydroxyphenyl-retinamide on Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Rainer Kuefer

    2007-03-01

    Full Text Available Butyrates and retinoids are promising antineoplastic agents. Here we analyzed effects of sodium butyrate and N-(4-hydroxyphenyl-retinamide (4-HPR on prostate cancer cells as monotherapy or in combination in vitro and in vivo. Sodium butyrate and 4-HPR induced concentration-dependent growth inhibition in prostate cancer cells in vitro. The isobologram analysis revealed that sodium butyrate and 4-HPR administered together antagonize effects of each other. For the in vivo studies, a water-soluble complex (4-HPR with a cyclodextrin was created. A single dose of sodium butyrate and 4-HPR showed a peak level in chicken plasma within 30 minutes. Both compounds induced inhibition of proliferation and apoptosis in xenografts of the chicken chorioallantoic membrane. Analysis of the cytotoxic effects of the drugs used in combination demonstrated an antagonistic effect on inhibition of proliferation and on induction of apoptosis. Prolonged jun N-terminal kinase phosphorylation induced by sodium butyrate and 4-HPR was strongly attenuated when both compounds were used in combination. Both compounds induced inhibition of NF-κ,B. This effect was strongly antagonized in LNCaP cells when the compounds were used in combination. These results indicate that combinational therapies have to be carefully investigated due to potential antagonistic effects in the clinical setting despite promising results of a monotherapy.

  15. Oleoylethanolamide: A Novel Potential Pharmacological Alternative to Cannabinoid Antagonists for the Control of Appetite

    Directory of Open Access Journals (Sweden)

    Adele Romano

    2014-01-01

    Full Text Available The initial pharmaceutical interest for the endocannabinoid system as a target for antiobesity therapies has been restricted by the severe adverse effects of the CB1 antagonist rimonabant. This study points at oleoylethanolamide (OEA, a monounsaturated analogue, and functional antagonist of anandamide, as a potential and safer antiobesity alternative to CB1 antagonism. Mice treated with equal doses (5 or 10 mg/kg, i.p. of OEA or rimonabant were analyzed for the progressive expression of spontaneous behaviors (eating, grooming, rearing, locomotion, and resting occurring during the development of satiety, according to the paradigm called behavioral satiety sequence (BSS. Both drugs reduced food (wet mash intake to a similar extent. OEA treatment decreased eating activity within the first 30 min and caused a temporary increase of resting time that was not accompanied by any decline of horizontal, vertical and total motor activity. Besides decreasing eating activity, rimonabant caused a marked increase of the time spent grooming and decreased horizontal motor activity, alterations that might be indicative of aversive nonmotivational effects on feeding. These results support the idea that OEA suppresses appetite by stimulating satiety and that its profile of action might be predictive of safer effects in humans as a novel antiobesity treatment.

  16. 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

  17. 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.

  18. Guanylyl cyclase/natriuretic peptide receptor-A gene disruption causes increased adrenal angiotensin II and aldosterone levels.

    Science.gov (United States)

    Zhao, Di; Vellaichamy, Elangovan; Somanna, Naveen K; Pandey, Kailash N

    2007-07-01

    Disruption of the guanylyl cyclase-A/natriuretic peptide receptor-A (GC-A/NPRA) gene leads to elevated arterial blood pressure and congestive heart failure in mice lacking NPRA. This study was aimed at determining whether Npr1 (coding for GC-A/NPRA) gene copy number affects adrenal ANG II and aldosterone (Aldo) levels in a gene-dose-dependent manner in Npr1 gene-targeted mice. Adrenal ANG II and Aldo levels increased in 1-copy mice compared with 2-copy mice, but decreased in 3-copy and 4-copy mice. In contrast, renal ANG II levels decreased in 1-copy (25%), 3-copy (38%), and 4-copy (39%) mice compared with 2-copy mice. The low-salt diet stimulated adrenal ANG II and Aldo levels in 1-copy (20 and 2,441%), 2-copy (15 and 2,339%), 3-copy (20 and 424%), and 4-copy (31 and 486%) mice, respectively. The high-salt diet suppressed adrenal ANG II and Aldo levels in 1-copy (46 and 29%) and 2-copy (38 and 17%) mice. On the other hand, the low-salt diet stimulated renal ANG II levels in 1-copy (45%), 2-copy (45%), 3-copy (59%), and 4-copy (48%) mice. However, the high-salt diet suppressed renal ANG II levels in 1-copy (28%) and 2-copy (27%) mice. In conclusion, NPRA signaling antagonizes adrenal ANG II and Aldo levels in a gene-dose dependent manner. Increased adrenal ANG II and Aldo levels may play an important role in elevated arterial blood pressure and progressive hypertension, leading to renal and vascular injury in Npr1 gene-disrupted mice.

  19. 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.

  20. Baseline Serum Aldosterone-to-Renin Ratio is Associated with the Add-on Effect of Thiazide Diuretics in Non-Diabetic Essential Hypertensives

    Science.gov (United States)

    Huang, Chin-Chou; Leu, Hsin-Bang; Huang, Po-Hsun; Wu, Tao-Cheng; Lin, Shing-Jong; Chen, Jaw-Wen

    2013-01-01

    Background The baseline status of renin-angiotensin-aldosterone system (RAAS) might modify the blood pressure (BP) lowering effects of thiazide diuretics. This study aimed to determine if baseline RAAS indicated by serum aldosterone-to-renin ratio (ARR) could be associated with the add-on effects of thiazide on BP lowering in patients with other concomitant antihypertensive medication. Methods Non-diabetic hypertensive patients, either untreated or unsatisfactorily treated, were enrolled if their office systolic BP was ≥ 140 or diastolic BP ≥ 90 mmHg. After 2 weeks of diet control and lifestyle modification, patients with persistently elevated BP were prospectively given hydrochlorothiazide 50 mg daily for 2 weeks. Serum aldosterone-to-renin ratio (ARR) was determined before thiazide treatment. Patients with a significant (≥ 10%) reduction of office mean artery pressure (MAP) by thiazide treatment were defined as responders. Results Among the 66 patients studied, 27 were defined as responders after a 2-week hydrochlorothiazide treatment. Baseline serum renin level was reduced and ARR increased (p = 0.009) in the responders as compared with the non-responders. A similar pattern was also apparent in patients with or without concomitant medications. Furthermore, baseline renin level was inversely and ARR positively correlated to the MAP reduction both in the whole patient group and in patients with concomitant medications. By stepwise multiple linear regression analysis, ARR was the only independent predictor for the response to thiazide treatment (β = 0.051, p = 0.007). Conclusions Baseline ARR could be associated with the add-on effects of hydrochlorothiazide on BP reduction in patients with other concomitant antihypertensive treatment. PMID:27122683