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mineralocorticoid receptor

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https://www.readbyqxmd.com/read/28324065/neurod-factors-discriminate-mineralocorticoid-from-glucocorticoid-receptor-dna-binding-in-the-male-rat-brain
#1
Lisa T C M van Weert, Jacobus C Buurstede, Ahmed Mahfouz, Pamela S M Braakhuis, J Annelies E Polman, Hetty C M Sips, Benno Roozendaal, Judit Balog, E Ronald de Kloet, Nicole A Datson, Onno C Meijer
In the limbic brain, mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) both function as receptors for the naturally occurring glucocorticoids (corticosterone/cortisol), but mediate distinct effects on cellular physiology via transcriptional mechanisms. The transcriptional basis for specificity of these MR- versus GR-mediated effects is unknown. To address this conundrum we have identified the extent of MR/GR DNA binding selectivity in the rat hippocampus using chromatin immunoprecipitation followed by sequencing (ChIP-seq)...
January 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323995/renin-phenotypes-characterize-vascular-disease-autonomous-aldosteronism-and-mineralocorticoid-receptor-activity
#2
Gregory L Hundemer, Rene Baudrand, Jenifer M Brown, Gary Curhan, Gordon H Williams, Anand Vaidya
Context: Mild cases of autonomous aldosterone secretion may go unrecognized using current diagnostic criteria for primary aldosteronism (PA). Objective: To investigate whether the inability to stimulate renin serves as a biomarker for unrecognized autonomous aldosterone secretion and mineralocorticoid receptor (MR) activation. Participants: 663 normotensive and mildly hypertensive participants, who were confirmed to not have PA using current guideline criteria and were on no antihypertensive medications...
February 17, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28303624/effect-of-eplerenone-in-patients-with-heart-failure-and-reduced-ejection-fraction-potential-effect-modification-by-abdominal-obesity-insight-from-the-emphasis-hf-trial
#3
Arnaud Olivier, Bertram Pitt, Nicolas Girerd, Zohra Lamiral, Jean-Loup Machu, John J V McMurray, Karl Swedberg, Dirk J van Veldhuisen, Timothy J Collier, Stuart J Pocock, Patrick Rossignol, Faiez Zannad, Anne Pizard
AIMS: An excessive production of aldosterone influences outcome in patients with heart failure (HF) and in obese patients. Findings from laboratory studies suggest that chronic aldosterone blockade maybe more beneficial in abdominally obese HF-prone rats. In the current study, we investigated if the clinical response to a mineralocorticoid receptor antagonist in mildly symptomatic HF patients varied by abdominal obesity. METHODS AND RESULTS: A total of 2587 NYHA class II, reduced ejection fraction HF (HFrEF) patients enrolled in the EMPHASIS-HF trial were randomly assigned to eplerenone and placebo...
March 16, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28298295/t-cell-mineralocorticoid-receptor-controls-blood-pressure-by-regulating-interferon-gamma
#4
Xue Nan Sun, Chao Li, Yuan Liu, Lin-Juan Du, Meng-Ru Zeng, Xiao Jun Zheng, Wu Chang Zhang, Yan Liu, Mingjiang Zhu, Deping Kong, Li Zhou, Limin Lu, Zhu-Xia Shen, Yi Yi, Lili Du, Mu Qin, Xu Liu, Zichun Hua, Shuyang Sun, Huiyong Yin, Bin Zhou, Ying Yu, Zhiyuan Zhang, Sheng-Zhong Duan
Rationale: Hypertension remains to be a global public health burden and demands novel intervention strategies such as targeting T cells and T cell-derived cytokines. Mineralocorticoid receptor (MR) antagonists have been clinically used to treat hypertension. However, the function of T cell MR in blood pressure (BP) regulation has not been elucidated. Objective: We aim to determine the role of T cell MR in BP regulation and to explore the mechanism. Methods and Results: Using T cell MR knockout (TMRKO) mouse in combination with angiotensin II (AngII)-induced hypertensive mouse model, we demonstrated that MR deficiency in T cells strikingly decreased both systolic and diastolic BP, and attenuated renal and vascular damage...
March 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28290905/-therapy-of-high-risk-patients-after-decompensation-of-heart-failure-under-nt-probnp-control-main-results
#5
A A Skvortsov, D E Koshkina, O Yu Narusov, V N Protasov, V P Masenko, S N Tereshchenko
AIM: to compare efficacy of treatment of high risk patients after acute decompensation (AD) of chronic heart failure (CHF) based on monitoring of NT-proBNP concentration and standard treatment. MATERIAL AND METHODS: Patients (n=100) with class III-IV CHF and left ventricular ejection fraction (LV EF) <40% due to ischemic heart disease (IHD), dilated cardiomyopathy (DCMP), or arterial hypertension (AH) after compensation of HF before discharge were distributed into groups of low (NT-proBNP <1400 picog/ml, n=30) or high (NT-proBNP more or equal 1400 picog/ml, n=70) risk...
July 2016: Kardiologiia
https://www.readbyqxmd.com/read/28289182/continuum-of-renin-independent-aldosteronism-in-normotension
#6
Rene Baudrand, Francisco J Guarda, Carlos Fardella, Gregory Hundemer, Jenifer Brown, Gordon Williams, Anand Vaidya
Primary aldosteronism is a severe form of autonomous aldosteronism. Milder forms of autonomous and renin-independent aldosteronism may be common, even in normotension. We characterized aldosterone secretion in 210 normotensives who had suppressed plasma renin activity (<1.0 ng/mL per hour), completed an oral sodium suppression test, received an infusion of angiotensin II, and had measurements of blood pressure and renal plasma flow. Continuous associations between urinary aldosterone excretion rate, renin, and potassium handling were investigated...
March 13, 2017: Hypertension
https://www.readbyqxmd.com/read/28289181/hypokalemia-and-pendrin-induction-by-aldosterone
#7
Ning Xu, Daigoro Hirohama, Kenichi Ishizawa, Wen Xiu Chang, Tatsuo Shimosawa, Toshiro Fujita, Shunya Uchida, Shigeru Shibata
Aldosterone plays an important role in regulating Na-Cl reabsorption and blood pressure. Epithelial Na(+) channel, Na(+)-Cl(-) cotransporter, and Cl(-)/HCO3(-) exchanger pendrin are the major mediators of Na-Cl transport in the aldosterone-sensitive distal nephron. Existing evidence also suggests that plasma K(+) concentration affects renal Na-Cl handling. In this study, we posited that hypokalemia modulates the effects of aldosterone on pendrin in hyperaldosteronism. Chronic aldosterone infusion in mice increased pendrin levels at the plasma membrane, and correcting hypokalemia in this model almost completely blocked pendrin upregulation...
March 13, 2017: Hypertension
https://www.readbyqxmd.com/read/28286996/understanding-the-economic-burden-of-heart-failure-in-china-impact-on-disease-management-and-resource-utilization
#8
Jun Huang, Hongjun Yin, Milun Zhang, Qian Ni, Jianwei Xuan
INTRODUCTION AND OBJECTIVES: This study has two objectives: (1) to examine healthcare resource utilization in heart failure (HF) patients; and (2) to examine the treatment costs associated with HF in China. METHODS: The data used in this study was from the 2014 national insurance database sponsored by the China Health Insurance Research Association (CHIRA), that covers national urban employees and residents. ICD-10 codes and keywords indicating heart failure diagnoses were used to identify patients with heart failure...
March 12, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28279521/recombinant-human-ace2-and-the-angiotensin-1-7-axis-as-potential-new-therapies-for-heart-failure
#9
Vaibhav B Patel, Judith N Lezutekong, Xueyi Chen, Gavin Y Oudit
Heart failure (HF) is a common cause of death and disability and a major economic burden in industrialized nations. Heart disease remains the leading cause of death in North America, with ischemic and hypertensive heart disease as the leading cause of HF. Various basic and clinical studies have established the role of an activated renin-angiotensin (Ang) system and Ang II generation in the progression of HF. Inhibition of an activated renin-Ang system using Ang-converting enzyme inhibitors, Ang II type 1 receptor blockers, and mineralocorticoid receptors antagonists have shown clinical benefits in patients with HF, although, largely limited to HF with reduced ejection fraction (HF-rEF)...
December 23, 2016: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28277988/therapy-rationale-for-mineralocorticoid-receptor-antagonists-acetazolamide-and-a-switch-of-therapy-in-nonresponders-in-central-serous-chorioretinopathy
#10
Anne Rübsam, Claudia E Thieme, Juliane Schlomberg, Sibylle Winterhalter, Bert Müller, Antonia M Joussen, Nicole Stübiger
PURPOSE: To evaluate the efficacy of mineralocorticoid-receptor antagonists in comparison to acetazolamide and observation in the treatment of central serous chorioretinopathy. METHODS: Retrospective, interventional cohort study on 93 patients with acute or chronic central serous chorioretinopathy (37 patients: acetazolamide group, 20 patients: mineralocorticoid-receptor antagonist group, 8 patients: observation group, and 27 patients with a therapy switch between both medications)...
March 9, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28275946/a-network-meta-analysis-of-clinical-management-strategies-for-treatment-resistant-hypertension-making-optimal-use-of-the-evidence
#11
Peter Makai, Joanna IntHout, Jaap Deinum, Kevin Jenniskens, Gert Jan van der Wilt
BACKGROUND: With the addition of surgical interventions to current medicinal treatments, it is increasingly challenging for clinicians to rationally choose among the various options for treating patients with apparent treatment-resistant hypertension (ATRHTN). This study aims to establish the comparative effectiveness of mineralocorticoid receptor antagonists (MRA), renal denervation (RDN), darusentan and central arteriovenous anastomosis (CAA) for patients with ATRHTN by performing a network meta-analysis...
March 8, 2017: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/28275643/a-translational-approach-to-clinical-practice-via-stress-responsive-glucocorticoid-receptor-signaling
#12
COMMENT
Mario F Juruena, Bruno Agustini, Anthony J Cleare, Allan H Young
A recent article by Kwan and colleagues could elegantly demonstrate the necessary interaction between neuronal serotonin (5-HT) systems and the hypothalamic-pituitary-adrenal (HPA) axis through glucocorticoid receptors (GR), producing an adequate stress response, in this case, responding to hypoxia with an increase in hematopoietic stem and progenitor cells (HSPC). There is an intricate system connecting brain, body and mind and this exchange is only possible when all these systems-nervous, endocrine, and immune-have receptors on critical cells to receive information (via messenger molecules) from each of the other systems...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28272757/aldosterone-activates-the-oncogenic-signals-erk1-2-and-stat3-via-redox-regulated-mechanisms
#13
Nina Queisser, Nicole Schupp, Eva Schwarz, Christina Hartmann, Gerardo G Mackenzie, Patricia I Oteiza
Epidemiological studies found an increased risk for kidney cancer in hypertensive patients, of which a subgroup has high aldosterone (Ald) levels. We recently showed that Ald is genotoxic both in kidney tubular cells and in rats with mineralocorticoid-mediated hypertension. The present work investigated in vitro and in vivo, if the oxidative stress-mediated activation of the ERK1/2 pathway, and its downstream target STAT3, could be one mechanism involved in the potential oncogenic potential of excess Ald exposure...
March 8, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28271625/clinical-characteristics-of-patients-from-the-worldwide-registry-on-peripartum-cardiomyopathy-ppcm-eurobservational-research-programme-in-conjunction-with-the-heart-failure-association-of-the-european-society-of-cardiology-study-group-on-ppcm
#14
Karen Sliwa, Alexandre Mebazaa, Denise Hilfiker-Kleiner, Mark C Petrie, Aldo P Maggioni, Cecile Laroche, Vera Regitz-Zagrosek, Maria Schaufelberger, Luigi Tavazzi, Peter van der Meer, Jolien W Roos-Hesselink, Petar Seferovic, Karin van Spandonck-Zwarts, Amam Mbakwem, Michael Böhm, Frederic Mouquet, Burkert Pieske, Roger Hall, Piotre Ponikowski, Johann Bauersachs
AIMS: The purpose of this study is to describe disease presentation, co-morbidities, diagnosis and initial therapeutic management of patients with peripartum cardiomyopathy (PPCM) living in countries belonging to the European Society of Cardiology (ESC) vs. non-ESC countries. METHODS AND RESULTS: Out of 500 patients with PPCM entered by 31 March 2016, we report on data of the first 411 patients with completed case record forms (from 43 countries) entered into this ongoing registry...
March 8, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28270594/aldosterone-does-not-alter-endothelin-b-receptor-signaling-in-the-inner-medullary-collecting-duct
#15
Nirupama Ramkumar, Deborah Stuart, Tianxin Yang, Donald E Kohan
Recent studies suggest that aldosterone-mediated sulfenic acid modification of the endothelin B receptor (ETB) promotes renal injury in an ischemia/reperfusion model through reduced ETB-stimulated nitric oxide production. Similarly, aldosterone inactivation of ETB signaling promotes pulmonary artery hypertension. Consequently, we asked whether aldosterone inhibits collecting duct ETB signaling; this could promote fluid retention since CD ETB exerts natriuretic and diuretic effects. A mouse inner medullary collecting duct cell line (IMCD3) was treated with aldosterone for 48 h followed by sarafotoxin-6c, an ETB-selective agonist, and extracellular signal-related kinase 1/2 (ERK) phosphorylation assessed...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28251412/insight-into-the-orientational-versatility-of-steroid-substrates-a-docking-and-molecular-dynamics-study-of-a-steroid-receptor-and-steroid-monooxygenase
#16
Anna Panek, Alina Świzdor, Natalia Milecka-Tronina, Jarosław J Panek
Numerous steroids are essential plant, animal, and human hormones. The medical and industrial applications of these hormones require the identification of new synthetic routes, including biotransformations. The metabolic fate of a steroid can be complicated; it may be transformed into a variety of substituted derivatives. This may be because a steroid molecule can adopt several possible orientations in the binding pocket of a receptor or an enzyme. The present study, based on docking and molecular dynamics, shows that it is indeed possible for a steroid molecule to bind to a receptor binding site in two or more orientations (normal, head-to-tail reversed, upside down)...
March 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28249922/clinical-manifestation-and-molecular-analysis-of-three-korean-patients-with-the-renal-form-of-pseudohypoaldosteronism-type-1
#17
Hyo-Kyoung Nam, Myung-Hyun Nam, Hye Ryun Kim, Young-Jun Rhie, Kee Hwan Yoo, Kee-Hyoung Lee
Pseudohypoaldosteronism (PHA) type 1 is a rare, heterogeneous disease characterized by hyponatremia and hyperkalemia due to mineralocorticoid resistance. The clinical features of PHA are usually failure to thrive, vomiting, and dehydration in the neonatal period. Heterozygous mutations in the Nuclear receptor subfamily 3, group C, member 2 (NR3C2) gene result in the dominant renal form of PHA type 1. Mutations in the epithelial sodium channel gene result in the more severe, recessive, systemic form of PHA type 1...
January 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28245785/vascular-consequences-of-aldosterone-excess-and-mineralocorticoid-receptor-antagonism
#18
Sophocles Chrissobolis
Aldosterone binds to mineralocorticoid receptors (MRs) on renal epithelial cells to regulate sodium and water reabsorption, and therefore blood pressure. Recently, the actions of aldosterone outside the kidney have been extensively investigated, with numerous reports of aldosterone having detrimental actions, including in the vasculature. Notably, elevated aldosterone levels are an independent cardiovascular risk factor, and in addition to causing an increase in blood pressure, aldosterone can have blood pressure-dependent and -independent effects commonly manifested in the vasculature in cardiovascular diseases, including vascular oxidative stress, endothelial dysfunction, inflammation, remodeling, stiffening, and plaque formation...
February 28, 2017: Current Hypertension Reviews
https://www.readbyqxmd.com/read/28220108/adaptations-in-basal-and-hypothalamic-pituitary-adrenal-activated-deoxycorticosterone-responses-following-ethanol-self-administration-in-cynomolgus-monkeys
#19
Vanessa A Jimenez, Patrizia Porcu, A Leslie Morrow, Kathleen A Grant
Acute ethanol activates the hypothalamic-pituitary-adrenal (HPA) axis, while long-term exposure results in a blunted neuroendocrine state, particularly with regards to the primary endpoint, cortisol, the primary glucocorticoid produced in the adrenal cortex. However, it is unknown if this dampened neuroendocrine status also influences other adrenocortical steroids. Plasma concentration of the mineralocorticoid and neuroactive steroid precursor deoxycorticosterone (DOC) is altered by pharmacological challenges of the HPA axis in cynomolgus monkeys...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28196143/iron-restricted-pair-feeding-affects-renal-damage-in-rats-with-chronic-kidney-disease
#20
Yoshiro Naito, Aya Senchi, Hisashi Sawada, Makiko Oboshi, Tetsuo Horimatsu, Keisuke Okuno, Seiki Yasumura, Masaharu Ishihara, Tohru Masuyama
BACKGROUND: We have previously shown that dietary iron restriction prevents the development of renal damage in a rat model of chronic kidney disease (CKD). However, iron deficiency is associated with appetite loss. In addition, calorie restriction is reported to prevent the development of end-stage renal pathology in CKD rats. Thus, the beneficial effect of iron restriction on renal damage may depend on calorie restriction. Here, we investigate the effect of pair-feeding iron restriction on renal damage in a rat model of CKD...
2017: PloS One
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