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mineralocorticoid receptor

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https://www.readbyqxmd.com/read/28713285/amiloride-improves-endothelial-function-and-reduces-vascular-stiffness-in-female-mice-fed-a-western-diet
#1
Luis A Martinez-Lemus, Annayya R Aroor, Francisco I Ramirez-Perez, Guanghong Jia, Javad Habibi, Vincent G DeMarco, Brady Barron, Adam Whaley-Connell, Ravi Nistala, James R Sowers
Obese premenopausal women lose their sex related cardiovascular disease protection and develop greater arterial stiffening than age matched men. In female mice, we have shown that consumption of a Western diet (WD), high in fat and refined sugars, is associated with endothelial dysfunction and vascular stiffening, which occur via activation of mineralocorticoid receptors and associated increases in epithelial Na(+) channel (ENaC) activity on endothelial cells (EnNaC). Herein our aim was to determine the effect that reducing EnNaC activity with a very-low-dose of amiloride would have on decreasing endothelial and arterial stiffness in young female mice consuming a WD...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28713045/cortisol-elevation-post-hatch-affects-behavioural-performance-in-zebrafish-larvae
#2
Carol Best, Mathilakath M Vijayan
Maternal cortisol is essential for cortisol stress axis development and de novo production of this steroid commences only after hatch in zebrafish (Danio rerio). However, very little is known about the effect of elevated cortisol levels, during the critical period of stress axis activation, on larval performance. We tested the hypothesis that elevated cortisol levels post-hatch affect behavioural performance and this is mediated by glucocorticoid receptor activation in zebrafish larvae. The behavioural response included measuring larval activity in response to alternating light and dark cycles, as well as thigmotaxis...
July 13, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28710615/aldosterone-antagonist-therapy-and-its-relationship-with-inflammation-fibrosis-thrombosis-mineral-bone-disorder-and-cardiovascular-complications-in-peritoneal-dialysis-pd-patients
#3
Rafał Donderski, Paweł Stróżecki, Beata Sulikowska, Magdalena Grajewska, Ilona Miśkowiec, Anna Stefańska, Joanna Siódmiak, Grażyna Odrowąż-Sypniewska, Jacek Manitius
BACKGROUND: High aldosterone level may contribute to pathogenesis of hypertension, vessels damage and cardiovascular system deterioration in chronic kidney disease patients. Besides its classical action via mineralocorticoid receptor, aldosterone is also involved in cell growth, inflammation, oxidative stress, endothelial dysfunction and exerts fibroproliferative effects. The aim of the study was to assess whether aldosterone antagonist treatment may influence serum level of inflammatory, fibrosis, thrombosis and mineral-bone metabolism markers in peritoneal dialysis (PD) patients and blood pressure, aortic stiffness, echocardiographic indices after 12 months of treatment...
July 14, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28707341/impact-of-hyperkalemia-and-worsening-renal-function-on-the-use-of-renin-angiotensin-aldosterone-system-inhibitors-in-chronic-heart-failure-with-reduced-ejection-fraction
#4
B Pitt, P Rossignol
Patients with heart failure (HF) and reduced ejection fraction (HFREF) are at increased risk of death and hospitalizations for HF. Numerous registries have reported a large and persistent gap between real-life practice in the use of life-saving evidence-based therapies, such as renin angiotensin system inhibitors, beta blockers, mineralocorticoid receptor antagonists (MRAs), and recommended practices in international guidelines. The fears of inducing hyperkalemia and/or worsening renal function are the main triggers of this underuse...
July 14, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28702747/management-of-supine-hypertension-complicating-neurogenic-orthostatic-hypotension
#5
Jacquie Baker, Kurt Kimpinski
Neurogenic orthostatic hypotension (NOH) can be present in a number of disorders, including synucleinopathies, autoimmune disorders, and various genetic disorders. All are characterized by defective norepinephrine release from sympathetic terminals upon standing, resulting in impaired vasoconstriction. NOH is defined as a drop in systolic blood pressure ≥20 mmHg or diastolic blood pressure ≥10 mmHg, or both, within 3 minutes of standing or head up-tilt at a minimum of 60°. However, approximately 50% of patients have associated supine hypertension, which greatly complicates treatment...
July 12, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28701888/pharmacological-treatment-of-heart-failure-with-preserved-ejection-fraction
#6
REVIEW
Kazuhiro Yamamoto
Heart failure with preserved ejection fraction is a socioeconomic burden in Japan as well as other developed countries. Diuretics are widely used to attenuate symptoms and signs of congestion in both heart failure with preserved and reduced ejection fraction, although their effects on long-term prognosis of both phenotypes of heart failure have not been demonstrated because of an ethical difficulty in designing a randomized and prospective clinical trial. Guidelines do not provide any guidance on therapy choice, and physicians blindly choose furosemide among loop diuretics in current clinical settings...
June 2017: Yonago Acta Medica
https://www.readbyqxmd.com/read/28700781/efficacy-and-safety-of-spironolactone-in-acute-heart-failure-the-athena-hf-randomized-clinical-trial
#7
Javed Butler, Kevin J Anstrom, G Michael Felker, Michael M Givertz, Andreas P Kalogeropoulos, Marvin A Konstam, Douglas L Mann, Kenneth B Margulies, Steven E McNulty, Robert J Mentz, Margaret M Redfield, W H Wilson Tang, David J Whellan, Monica Shah, Patrice Desvigne-Nickens, Adrian F Hernandez, Eugene Braunwald
Importance: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists administered at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF. Objective: To assess the effect of high-dose spironolactone and usual care on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with usual care alone. Design, Setting, and Participants: This double-blind and placebo (or low-dose)-controlled randomized clinical trial was conducted in 22 US acute care hospitals among patients with AHF who were previously receiving no or low-dose (12...
July 12, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28686058/genetic-associations-and-interactions-between-the-nr3c1-gr-and-nr3c2-mr-genes-and-aggressive-behavior-in-a-central-south-chinese-han-population
#8
Jianming Li, Liang Tang, Yan Wang, Fang Li, Meihua Bao, Ju Xiang, Deliang Lei, Beisha Tang
AIMS: The glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) play important roles in hypothalamic-pituitary-adrenal axis and stress regulation. The current study aimed to address the genetic association and gene-gene interactions between GR and MR gene polymorphisms and aggressive behavior. METHODS: A haplotype-based, case-control study was designed to examine the association between human MR and GR genes and aggressive behaviors, including robbery and intentional interpersonal injury, in a central south Chinese Han population...
July 7, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28684740/hur-dependent-editing-of-a-new-mineralocorticoid-receptor-splice-variant-reveals-an-osmoregulatory-loop-for-sodium-homeostasis
#9
Ingrid Lema, Larbi Amazit, Khadija Lamribet, Jérôme Fagart, Anne Blanchard, Marc Lombès, Nadia Cherradi, Say Viengchareun
Aldosterone and the Mineralocorticoid Receptor (MR) control hydroelectrolytic homeostasis and alterations of mineralocorticoid signaling pathway are involved in the pathogenesis of numerous human diseases, justifying the need to decipher molecular events controlling MR expression level. Here, we show in renal cells that the RNA-Binding Protein, Human antigen R (HuR), plays a central role in the editing of MR transcript as revealed by a RNA interference strategy. We identify a novel Δ6 MR splice variant, which lacks the entire exon 6, following a HuR-dependent exon skipping event...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28679089/declining-risk-of-sudden-death-in-heart-failure
#10
Li Shen, Pardeep S Jhund, Mark C Petrie, Brian L Claggett, Simona Barlera, John G F Cleland, Henry J Dargie, Christopher B Granger, John Kjekshus, Lars Køber, Roberto Latini, Aldo P Maggioni, Milton Packer, Bertram Pitt, Scott D Solomon, Karl Swedberg, Luigi Tavazzi, John Wikstrand, Faiez Zannad, Michael R Zile, John J V McMurray
BACKGROUND: The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to examine this trend in detail. METHODS: We analyzed data from 40,195 patients who had heart failure with reduced ejection fraction and were enrolled in any of 12 clinical trials spanning the period from 1995 through 2014...
July 6, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28672951/hypothalamic-pituitary-adrenal-axis-hypersensitivity-in-female-rats-on-a-post-weaning-high-fat-diet-after-chronic-mild-stress
#11
Lian Liu, Junqiang Yang, Feng Qian, Chengbiao Lu
A high-fat diet (HFD) is highly correlated to obesity, metabolic diseases and certain behavioral changes. However, the effects of post-weaning HFD in rats during puberty and the role of the hypothalamic-pituitary-adrenal (HPA) axis in this process have remained elusive. The present study hypothesized that the HPA axis mediates the behavioral alterations induced by a post-weaning HFD. To investigate this, female rats were divided into two groups, one of which was fed a HFD from postnatal weeks (PWs) 4-12, while the other group received standard chow...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28668826/inhibition-of-erg-activity-in-patient-derived-prostate-cancer-xenografts-by-yk-4-279
#12
Brian Winters, Lisha Brown, Ilsa Coleman, Holly Nguyen, Tsion Zewdu Minas, Lori Kollath, Valeri Vasioukhin, Peter Nelson, Eva Corey, Aykut Üren, Colm Morrissey
BACKGROUND/AIM: The aim of the current study was to determine the effects of the ERG small-molecule inhibitor YK-4-279 on ERG(+) prostate cancer patient-derived xenografts (PDX). MATERIALS AND METHODS: ERG activity was blocked using YK-4-279 in three subcutaneously-implanted ERG(+) (LuCaP 23.1, 86.2 and 35) and one ERG(-) (LuCaP 96) PDX. Treated animals tumor volume (TV), body weight (BW) and serum prostate-specific antigen (PSA) were compared to vehicle-treated control animals...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28661412/risk-of-new-onset-diabetes-mellitus-in-primary-aldosteronism-a-population-study-over-5-years
#13
Vin-Cent Wu, Shih-Chieh J Chueh, Likwang Chen, Chia-Hui Chang, Ya-Hui Hu, Yen-Hung Lin, Kwan-Dun Wu, Wei-Shiung Yang
OBJECTIVE: Abnormal glucose metabolism due to insulin resistance has been linked to aldosterone overproduction. However, the long-term incidence of new-onset diabetes mellitus (NODM) among patients with primary aldosteronism after targeted treatment has not been well documented. METHODS: The diagnosis of primary aldosteronism and essential hypertension were identified, and then the occurrence of NODM, all-cause mortality among these patients, was ascertained by a validated algorithm from a 23-million population insurance registry...
August 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28656517/treatment-of-hyperkalemia-in-heart-failure
#14
REVIEW
Ersilia M DeFilippis, Akshay S Desai
PURPOSE OF REVIEW: The aim of this paper is to discuss strategies for prevention and management of hyperkalemia in patients with heart failure, including the role of novel therapies. RECENT FINDINGS: Renin-angiotensin-aldosterone system (RAAS) antagonists, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and mineralocorticoid receptor antagonists (MRA) decrease mortality and morbidity in heart failure but increase the risk of hyperkalemia, especially when used in combination...
June 27, 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28647918/designing-future-clinical-trials-in-heart-failure-with-preserved-ejection-fraction-lessons-from-topcat
#15
REVIEW
Ravi B Patel, Sanjiv J Shah, Gregg C Fonarow, Javed Butler, Muthiah Vaduganathan
PURPOSE OF REVIEW: Spironolactone did not demonstrate benefit with respect to the primary composite endpoint in the global TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial in patients with chronic heart failure with preserved ejection fraction (HFpEF). We identify key lessons from the TOPCAT experience that can be applied to future HFpEF trials. RECENT FINDINGS: Subsequent analyses of TOPCAT have revealed marked regional heterogeneity in patient profiles, event rates, drug adherence, and treatment effects...
June 24, 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28645352/r%C3%A3-sistances-aux-hormones-st%C3%A3-ro%C3%A3-des-physiologie-et-pathologie-pathophysiology-of-steroid-resistance-syndrome
#16
N Ramos, M Lombès
Steroid resistance syndrome (mineralocorticoids, glucocorticoids, estrogens, androgens) is a rare clinical disorder, androgen insensitivity syndrome being the most commonly described. Resistance syndromes are characterized by elevated steroid hormone levels, secondary to an impaired signal transduction and a lack of negative feedback, without any specific clinical signs of steroid excess. In most cases, steroid hormone resistance is generally caused by steroid receptor mutations. Several nonsense and missense mutations or deletions have already been described for all steroid receptors, except for the progesterone receptor...
October 2016: Annales D'endocrinologie
https://www.readbyqxmd.com/read/28637706/endothelial-mineralocorticoid-receptor-contributes-to-systolic-dysfunction-induced-by-pressure-overload-without-modulating-cardiac-hypertrophy-or-inflammation
#17
Ane M Salvador, M Elizabeth Moss, Mark Aronovitz, Kathleen B Mueller, Robert M Blanton, Iris Z Jaffe, Pilar Alcaide
Heart Failure (HF) is associated with increased circulating levels of aldosterone and systemic inflammation. Mineralocorticoid receptor (MR) antagonists block aldosterone action and decrease mortality in patients with congestive HF However, the molecular mechanisms underlying the therapeutic benefits of MR antagonists remain unclear. MR is expressed in all cell types in the heart, including the endothelial cells (EC), in which aldosterone induces the expression of intercellular adhesion molecule 1 (ICAM-1)...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28634268/30-years-of-the-mineralocorticoid-receptor-mineralocorticoid-receptor-antagonists-60-years-of-research-and-development
#18
REVIEW
Peter Kolkhof, Lars Bärfacker
The cDNA of the mineralocorticoid receptor (MR) was cloned 30 years ago, in 1987. At that time, spirolactone, the first generation of synthetic steroid-based MR antagonists (MRAs), which was identified in preclinical in vivo models, had already been in clinical use for 30 years. Subsequent decades of research and development by Searle & Co., Ciba-Geigy, Roussel Uclaf and Schering AG toward identifying a second generation of much more specific steroidal MRAs were all based on the initial 17-spirolactone construct...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28634267/30-years-of-the-mineralocorticoid-receptor-the-role-of-the-mineralocorticoid-receptor-in-the-vasculature
#19
REVIEW
Jennifer J DuPont, Iris Z Jaffe
Since the mineralocorticoid receptor (MR) was cloned 30 years ago, it has become clear that MR is expressed in extra-renal tissues, including the cardiovascular system, where it is expressed in all cells of the vasculature. Understanding the role of MR in the vasculature has been of particular interest as clinical trials show that MR antagonism improves cardiovascular outcomes out of proportion to changes in blood pressure. The last 30 years of research have demonstrated that MR is a functional hormone-activated transcription factor in vascular smooth muscle cells and endothelial cells...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28634266/30-years-of-the-mineralocorticoid-receptor-the-brain-mineralocorticoid-receptor-a-saga-in-three-episodes
#20
REVIEW
Marian Joëls, E Ronald de Kloet
In 1968, Bruce McEwen discovered that (3)H-corticosterone administered to adrenalectomised rats is retained in neurons of hippocampus rather than those of hypothalamus. This discovery signalled the expansion of endocrinology into the science of higher brain regions. With this in mind, our contribution highlights the saga of the brain mineralocorticoid receptor (MR) in three episodes. First, the precloning era dominated by the conundrum of two types of corticosterone-binding receptors in the brain, which led to the identification of the high-affinity corticosterone receptor as the 'promiscuous' MR cloned in 1987 by Jeff Arriza and Ron Evans in addition to the classical glucocorticoid receptor (GR)...
July 2017: Journal of Endocrinology
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