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https://www.readbyqxmd.com/read/28432191/gene-expression-effects-of-glucocorticoid-and-mineralocorticoid-receptor-agonists-and-antagonists-on-normal-human-skeletal-muscle
#1
Jessica A Chadwick, James Spencer Hauck, Celso E Gomez-Sanchez, Elise P Gomez-Sanchez, Jill A Rafael-Fortney
Mineralocorticoid and glucocorticoid receptors are closely related steroid hormone receptors that regulate gene expression through many of the same hormone response elements. However, their transcriptional activities and effects in skeletal muscles are largely unknown. We recently identified mineralocorticoid receptors (MR) in skeletal muscles after finding that combined treatment with the angiotensin-converting enzyme inhibitor lisinopril and MR antagonist spironolactone was therapeutic in Duchenne muscular dystrophy mouse models...
April 21, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28430882/inhibition-of-the-cardiac-myocyte-mineralocorticoid-receptor-ameliorates-doxorubicin-induced-cardiotoxicity
#2
Achim Lother, Stella Bergemann, Jessica Kowalski, Michael Huck, Ralf Gilsbach, Christoph Bode, Lutz Hein
Aim: HASH(0x54c3db8) Anthracyclines such as doxorubicin are widely used in cancer therapy but their use is limited by cardiotoxicity. Up to date there is no established strategy for the prevention of anthracyclin-induced heart failure. In this study, we evaluated the role of the cardiac myocyte mineralocorticoid receptor (MR) during doxorubicin-induced cardiotoxicity. Methods and results: HASH(0x5475620) A single high-dose or repetitive low-dose doxorubicin administration lead to markedly reduced left ventricular function in mice...
April 18, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28430429/potential-glucocorticoid-and-mineralocorticoid-effects-of-nine-organophosphate-flame-retardants
#3
Quan Zhang, Jinghua Wang, Jianqiang Zhu, Jing Liu, Meirong Zhao
Organophosphate flame retardants (OPFRs), as alternatives of polybrominated diphenyl ethers (PBDEs), have been frequently detected in the environment and biota, and could pose adverse effects on organisms. However, information on the potential endocrine disruption of OPFRs, especially their effects on steroid hormone receptors, such as glucocorticoid and mineralocorticoid receptors (GR/MR), is limited. In this study, the dual-luciferase reporter gene assay via GR/MR and a H295R steroidogenesis assay were employed to evaluate the endocrine disruption of nine OPFRs...
April 21, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28427090/the-aldosterone-synthase-inhibitor-fad286-is-suitable-for-lowering-aldosterone-levels-in-zdf-rats-but-not-in-db-db-mice
#4
Anja Hofmann, Coy Brunssen, Mirko Peitzsch, Mariya Balyura, Jennifer Mittag, Annika Frenzel, Anett Jannasch, Nicholas F Brown, Steven M Weldon, Kristina K Gueneva-Boucheva, Graeme Eisenhofer, Stefan R Bornstein, Henning Morawietz
Inhibition of aldosterone synthase is an alternative treatment option to mineralocorticoid receptor antagonism to prevent harmful aldosterone actions. FAD286 is one of the best characterized aldosterone synthase inhibitors to date. FAD286 improves glucose tolerance and increases glucose-stimulated insulin secretion in obese and diabetic ZDF rats. However, there is limited knowledge about the dose-dependent effects of FAD286 on plasma aldosterone, corticosterone, and 11-deoxycorticosterone in ZDF rats and in db/db mice, a second important rodent model of obesity and type 2 diabetes...
April 20, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28422753/steroid-metabolome-analysis-reveals-prevalent-glucocorticoid-excess-in-primary-aldosteronism
#5
Wiebke Arlt, Katharina Lang, Alice J Sitch, Anna S Dietz, Yara Rhayem, Irina Bancos, Annette Feuchtinger, Vasileios Chortis, Lorna C Gilligan, Philippe Ludwig, Anna Riester, Evelyn Asbach, Beverly A Hughes, Donna M O'Neil, Martin Bidlingmaier, Jeremy W Tomlinson, Zaki K Hassan-Smith, D Aled Rees, Christian Adolf, Stefanie Hahner, Marcus Quinkler, Tanja Dekkers, Jaap Deinum, Michael Biehl, Brian G Keevil, Cedric H L Shackleton, Jonathan J Deeks, Axel K Walch, Felix Beuschlein, Martin Reincke
BACKGROUND: Adrenal aldosterone excess is the most common cause of secondary hypertension and is associated with increased cardiovascular morbidity. However, adverse metabolic risk in primary aldosteronism extends beyond hypertension, with increased rates of insulin resistance, type 2 diabetes, and osteoporosis, which cannot be easily explained by aldosterone excess. METHODS: We performed mass spectrometry-based analysis of a 24-hour urine steroid metabolome in 174 newly diagnosed patients with primary aldosteronism (103 unilateral adenomas, 71 bilateral adrenal hyperplasias) in comparison to 162 healthy controls, 56 patients with endocrine inactive adrenal adenoma, 104 patients with mild subclinical, and 47 with clinically overt adrenal cortisol excess...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28420172/subtype-diagnosis-of-primary-aldosteronism-is-adrenal-vein-sampling-always-necessary
#6
REVIEW
Fabrizio Buffolo, Silvia Monticone, Tracy A Williams, Denis Rossato, Jacopo Burrello, Martina Tetti, Franco Veglio, Paolo Mulatero
Aldosterone producing adenoma and bilateral adrenal hyperplasia are the two most common subtypes of primary aldosteronism (PA) that require targeted and distinct therapeutic approaches: unilateral adrenalectomy or lifelong medical therapy with mineralocorticoid receptor antagonists. According to the 2016 Endocrine Society Guideline, adrenal venous sampling (AVS) is the gold standard test to distinguish between unilateral and bilateral aldosterone overproduction and therefore, to safely refer patients with PA to surgery...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28414302/increased-salt-consumption-induces-body-water-conservation-and-decreases-fluid-intake
#7
Natalia Rakova, Kento Kitada, Kathrin Lerchl, Anke Dahlmann, Anna Birukov, Steffen Daub, Christoph Kopp, Tetyana Pedchenko, Yahua Zhang, Luis Beck, Bernd Johannes, Adriana Marton, Dominik N Müller, Manfred Rauh, Friedrich C Luft, Jens Titze
BACKGROUND: The idea that increasing salt intake increases drinking and urine volume is widely accepted. We tested the hypothesis that an increase in salt intake of 6 g/d would change fluid balance in men living under ultra-long-term controlled conditions. METHODS: Over the course of 2 separate space flight simulation studies of 105 and 205 days' duration, we exposed 10 healthy men to 3 salt intake levels (12, 9, or 6 g/d). All other nutrients were maintained constant...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28414294/salt-and-water-not-so-simple
#8
Mark L Zeidel
It has long been viewed that the maintenance of osmotic balance in response to high salt intake is a passive process that is mediated largely by increased water consumption to balance the salt load. Two studies in this issue of the JCI challenge this notion and demonstrate that osmotic balance in response to high salt intake involves a complex regulatory process that is influenced by hormone fluctuation, metabolism, food consumption, water intake, and renal salt and water excretion. Rakova et al. report the unexpected observation that long-term high salt intake did not increase water consumption in humans but instead increased water retention...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28413970/optimizing-the-management-of-uncontrolled-resistant-hypertension-the-importance-of-sleep-apnoea-syndrome
#9
Jacek Wolf, Krzysztof Narkiewicz
Obstructive sleep apnoea (OSA) constitutes the most prevalent form of abnormal respiratory control during sleep in adults. Evidence linked OSA to cardiovascular disease, and the role of OSA in abnormal blood pressure (BP) control has been extensively studied. Although longitudinal trials suggest a causative role of OSA in the development of hypertension, the evidence is not fully consistent. Nasal continuous positive airway pressure (nCPAP) applied during sleep is well documented and a highly efficient therapeutic aid to eliminate OSA...
April 14, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28411834/glucocorticoids-inhibit-wound-healing-novel-mechanism-of-action
#10
Andrzej T Slominski, Michal A Zmijewski
Jozic et al. describe mechanisms of glucocorticoid (GC) downregulation of wound healing by interaction with the membrane bound GC receptor, followed by stimulation of β-catenin and c-myc pathways. Targeting the membrane bound GC receptor or the recently discovered interaction of GC with mineralocorticoid receptors may counteract negative effects of GC on the skin barrier and potentially could serve as a remedy for age-related skin atrophy.
May 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28409833/dietary-salt-blunts-vasodilation-by-stimulating-epithelial-sodium-channels-in-endothelial-cells-from-salt-sensitive-rats
#11
Zi-Rui Wang, Hui-Bin Liu, Ying-Ying Sun, Qing-Qing Hu, Yu-Xia Li, Wei-Wan Zheng, Chang-Jiang Yu, Xin-Yuan Li, Ming-Ming Wu, Bin-Lin Song, Jian-Jun Mu, Zu-Yi Yuan, Zhi-Ren Zhang, He-Ping Ma
BACKGROUND AND PURPOSE: Our recent studies show that the reduced activity of epithelial sodium channels (ENaC) in endothelial cells accounts for the adaptation of vasculature to salt in Sprague-Dawley (SD) rats. The present study examines a hypothesis that enhanced ENaC activity mediates the loss of vasorelaxation in Dahl salt-sensitive (SS) rats. EXPERIMENTAL APPROACH: We used the cell-attached patch-clamp technique to record ENaC activity in split-open mesenteric arteries...
April 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28409010/specialist-intervention-is-associated-with-improved-patient-outcomes-in-patients-with-decompensated-heart-failure-evaluation-of-the-impact-of-a-multidisciplinary-inpatient-heart-failure-team
#12
Jayne Masters, Geraint Morton, Isabel Anton, Jane Szymanski, Elizabeth Greenwood, Joanna Grogono, Andrew S Flett, John G F Cleland, Peter J Cowburn
OBJECTIVE: The study aimed to evaluate the impact of a multidisciplinary inpatient heart failure team (HFT) on treatment, hospital readmissions and mortality of patients with decompensated heart failure (HF). METHODS: A retrospective service evaluation was undertaken in a UK tertiary centre university hospital comparing 196 patients admitted with HF in the 6 months prior to the introduction of the HFT (pre-HFT) with all 211 patients seen by the HFT (post-HFT) during its first operational year...
2017: Open Heart
https://www.readbyqxmd.com/read/28408456/correction-to-identification-of-a-retinal-aldosterone-system-and-the-protective-effects-of-mineralocorticoid-receptor-antagonism-on-retinal-vascular-pathology
#13
(no author information available yet)
No abstract text is available yet for this article.
April 14, 2017: Circulation Research
https://www.readbyqxmd.com/read/28406245/nanomechanics-of-the-endothelial-glycocalyx-contribute-to-na-induced-vascular-inflammation
#14
Florian Schierke, Margot J Wyrwoll, Martin Wisdorf, Leon Niedzielski, Martina Maase, Tobias Ruck, Sven G Meuth, Kristina Kusche-Vihrog
High dietary salt (NaCl) is a known risk factor for cardiovascular pathologies and inflammation. High plasma Na(+) concentrations (high Na(+)) have been shown to stiffen the endothelial cortex and decrease nitric oxide (NO) release, a hallmark of endothelial dysfunction. Here we report that chronic high Na(+) damages the endothelial glycocalyx (eGC), induces release of inflammatory cytokines from the endothelium and promotes monocyte adhesion. Single cell force spectroscopy reveals that high Na(+) enhances vascular adhesion protein-1 (VCAM-1)-dependent adhesion forces between monocytes and endothelial surface, giving rise to increased numbers of adherent monocytes on the endothelial surface...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28402979/the-inhibitory-effect-of-eplerenone-on-cell-proliferation-in-the-contralateral-kidneys-of-rats-with-unilateral-ureteral-obstruction
#15
Cong-Hui Wang, Zheng Wang, Li-Juan Liang, Xiang-Ting Wang, Xue-Lian Ma, Bei-Bei Liu, Jia-Qi He, Tatsuo Shimosawa, Qing-You Xu
BACKGROUND: The unilateral ureteral obstruction (UUO) model not only induces renal interstitial fibrosis in the obstructed kidney but also induces injury in the contralateral kidney. We hypothesized that activation of the mineralocorticoid receptor (MR) may induce fibrosis in the early stage of UUO. METHODS: Thirty male Sprague-Dawley rats weighting 200 ± 10 g were used in this study and randomly divided into 3 groups: a UUO group, a UUO and eplerenone group, and a sham group...
April 13, 2017: Nephron
https://www.readbyqxmd.com/read/28401618/tailoring-mineralocorticoid-receptor-antagonist-therapy-in-heart-failure-patients-are-we-moving-towards-a-personalized-approach
#16
REVIEW
João Pedro Ferreira, Robert J Mentz, Anne Pizard, Bertram Pitt, Faiez Zannad
The aim of personalized medicine is to offer a tailored approach to each patient in order to provide the most effective therapy, while reducing risks and side effects. The use of mineralocorticoid receptor antagonists (MRAs) has demonstrated major benefits in heart failure with reduced ejection fraction (HFrEF), results with challenging inconsistencies in heart failure with preserved ejection fraction (HFpEF), and 'neutral' preliminary results in acute heart failure. Data derived from landmark trials are generally applied in a 'one size fits all' manner and the development and implementation of more personalized MRA management would offer the potential to improve outcomes and reduce side effects...
April 12, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28382959/treatment-of-primary-aldosteronism-is-associated-with-a-reduction-in-the-severity-of-obstructive-sleep-apnoea
#17
M J Wolley, E Pimenta, D Calhoun, R D Gordon, D Cowley, M Stowasser
Obstructive sleep apnoea (OSA) is known to commonly co-exist with primary aldosteronism (PA), but it is unknown if treatment of PA improves sleep apnoea parameters in these patients. We therefore aimed to determine whether specific medical or surgical treatment of PA improves OSA, as measured by the apnoea-hypopnoea index (AHI). We recruited patients undergoing diagnostic workup for PA if they had symptoms suggestive of OSA. Patients with confirmed PA underwent polysomnography (PSG) at baseline and again at least 3 months after specific treatment for PA...
April 6, 2017: Journal of Human Hypertension
https://www.readbyqxmd.com/read/28382926/aldosterone-induces-inflammatory-cytokines-in-penile-corpus-cavernosum-by-activating-the-nf-%C3%AE%C2%BAb-pathway
#18
Fei Wu, Zu-Quan Xiong, Shan-Hua Mao, Ji-Meng Hu, Jian-Qing Wang, Hao-Wen Jiang, Qiang Ding
Emerging evidence indicates that aldosterone and mineralocorticoid receptors (MRs) are associated with the pathogenesis of erectile dysfunction. However, the molecular mechanisms remain largely unknown. In this study, freshly isolated penile corpus cavernosum tissue from rats was treated with aldosterone, with or without MRs inhibitors. Nuclear factor (NF)-kappa B (NF-κB) activity was evaluated by real-time quantitative PCR, luciferase assay, and immunoblot. The results demonstrated that mRNA levels of the NF-κB target genes, including inhibitor of NF-κB alpha (IκB-α), NF-κB1, tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6), were higher after aldosterone treatment...
April 4, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/28382468/role-of-hyperkalemia-in-heart-failure-and-the-therapeutic-use-of-potassium-binders
#19
Chaudhry M S Sarwar, Aditi A Bhagat, Stefan D Anker, Javed Butler
Hyperkalemia can be a life-threatening disorder, especially for at-risk patients with heart failure, chronic kidney disease, with diabetes, and patients on certain drugs like renin-angiotensin-aldosterone system antagonists and mineralocorticoid receptor antagonists. There are limited therapeutic options available for hyperkalemia, and they have narrow effectiveness because of their unfavorable side effects profile in long-term and high cost utilization requiring inpatient care. Patiromersorbitex calcium and sodium zirconium cyclosilicate are novel potassium-lowering compounds for the treatment and prevention of hyperkalemia in at-risk population...
April 6, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28381250/transcriptional-signatures-of-steroid-hormones-in-the-striatal-neurons-and-astrocytes
#20
Marcin Piechota, Michał Korostynski, Slawomir Golda, Joanna Ficek, Danuta Jantas, Ziolkowska Barbara, Ryszard Przewlocki
BACKGROUND: The mechanisms of steroids actions in the brain mainly involve the binding and nuclear translocation of specific cytoplasmic receptors. These receptors can act as transcription factors and regulate gene expression. However, steroid-dependent transcriptional regulation in different types of neural cells is not yet fully understood. The aim of this study was to evaluate and compare transcriptional alterations induced by various steroid receptor agonists in primary cultures of astrocytes and neurons from mouse brain...
April 5, 2017: BMC Neuroscience
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