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Aldosterone antagonist

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https://www.readbyqxmd.com/read/28814143/ly3045697-results-from-two-randomized-clinical-trials-of-a-novel-inhibitor-of-aldosterone-synthase
#1
Joanne Sloan-Lancaster, Eyas Raddad, Amy Flynt, Yan Jin, James Voelker, Jeffrey W Miller
INTRODUCTION: LY3045697 is a potent and selective aldosterone synthase (CYP11B2) inhibitor that was developed as a safer alternative to mineralocorticoid receptor antagonists. Effects of LY3045697 on aldosterone and cortisol synthesis, as well as potassium ion homeostasis, were evaluated in two clinical studies in healthy subjects. MATERIALS AND METHODS: Two incomplete, placebo-controlled crossover-design clinical studies examined safety, pharmacodynamics, and pharmacokinetics under single and repeated dose conditions in healthy subjects...
July 2017: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/28801620/a-novel-aldosterone-antagonist-limits-renal-injury-in-5-6-nephrectomy
#2
Clarice K Fujihara, M C Kowala, M D Breyer, Claudia R Sena, Mariliza V Rodrigues, Simone C A Arias, Camilla Fanelli, Denise M Malheiros, P K Jadhav, Chahrzad Montrose-Rafizadeh, Jose E Krieger, Roberto Zatz
Aldosterone antagonists slow the progression of chronic kidney disease (CKD), but their use is limited by hyperkalemia, especially when associated with RAS inhibitors. We examined the renoprotective effects of Ly, a novel non-steroidal mineralocorticoid receptor (MR) blocker, through two experimental protocols: In Protocol 1, male Munich-Wistar rats underwent 5/6 renal ablation (Nx), being divided into: Nx+V, receiving vehicle, Nx+Eple, given eplerenone, 150 mg/kg/day, and Nx+Ly, given Ly, 20 mg/kg/day...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28797006/amiloride-is-effective-in-the-management-of-abiraterone-induced-mineralocorticoid-excess-syndrome-without-interfering-with-its-antineoplastic-activity
#3
Francesca Bedussi, Diego Galli, Martina Fragni, Francesca Valcamonico, Elisa Rossini, Alberto Dalla Volta, Sara Vezzoli, Elisa Roca, Vittorio Ferrari, Barbara Lazzari, Maurizio Memo, Sandra Sigala, Alfredo Berruti
BACKGROUND: The administration of abiraterone acetate (abiraterone) leads to an adrenocorticotropic hormone (ACTH)-driven increase in mineralocorticoid hormones, requiring glucocorticoid supplementation that may stimulate the growth of prostate cancer (PCa). Amiloride is a drug that selectively reduces the aldosterone-sensitive Na+/K+ exchange and could be effective in the management of mineralocorticoid excess syndrome (MCES). METHODS: The efficacy of amiloride + hydrochlorothiazide (HCT) in the clinical management of abiraterone-induced MCES was assessed in 5 consecutive patients with castration-resistant PCa (CRPC)...
August 11, 2017: Pharmacology
https://www.readbyqxmd.com/read/28791529/effects-of-raas-inhibitors-in-patients-with-kidney-disease
#4
REVIEW
Fan Zhang, Hong Liu, Di Liu, Yexin Liu, Huiqiong Li, Xia Tan, Fuyou Liu, Youming Peng, Hongqing Zhang
Proteinuria and decline of renal function are associated with progression of kidney disease. The Renin Angiotensin Aldosterone System (RAAS) plays an important role in blood pressure regulation, fluid volume, and sodium balance. Overactivity of RAAS contributes to the pathogenesis of a variety of clinical conditions including progress of chronic kidney disease (CKD). This review summarizes the use of RAAS inhibitors as dual therapy or monotherapy in different stages of kidney disease. Experimental and clinical studies have demonstrated RAAS inhibitors prevent proteinuria, kidney fibrosis and slow decline of renal function and thus play a protective role in both early and end stages of kidney disease...
August 8, 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28780577/drug-treatment-effects-on-outcomes-in-heart-failure-with-preserved-ejection-fraction-a-systematic-review-and-meta-analysis
#5
Sean Lee Zheng, Fiona T Chan, Adam A Nabeebaccus, Ajay M Shah, Theresa McDonagh, Darlington O Okonko, Salma Ayis
BACKGROUND: Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. METHODS: We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality...
August 5, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28771453/nonsteroidal-mineralocorticoid-antagonists-in-diabetic-kidney-disease
#6
Farheen K Dojki, George Bakris
PURPOSE OF REVIEW: Current data highlight the pathological aspects of excess aldosterone in promoting glomerular hypertrophy, glomerulosclerosis, and proteinuria in diabetic kidney disease (DKD). The role of nonsteroidal mineralocorticoid receptor antagonists (MRAs) in DKD is being evaluated in ongoing clinical trials. RECENT FINDINGS: Recent studies demonstrate beneficial effects of adding MRAs to the treatment regimen of patients with type 2 diabetes with nephropathy...
September 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28746811/the-acute-effects-of-different-spironolactone-doses-on-cardiac-function-in-streptozotocin-induced-diabetic-rats
#7
Aleksandra Vranic, Stefan Simovic, Petar Ristic, Tamara R Nikolic, Isidora Stojic, Ivan M Srejovic, Vladimir I Zivkovic, Vladimir Jakovljevic, Dusan Djuric
Currently, cardiovascular diseases are leading cause of global mortality, while diabetes mellitus remains an important cause of cardiovascular morbidity. Findings suggest that obesity and diabetes mellitus are closely interconnected with high aldosterone levels, while mineralocorticoid receptors antagonist therapy has shown positive effects on cardiovascular complications associated with diabetes mellitus. A recent study showed that patients with diabetes mellitus treated with mineralocorticoid receptors antagonist have improved coronary microvascular function, leading to improved diastolic dysfunction...
July 26, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28734243/caveolin-1-related-autophagy-initiated-by-aldosterone-induced-oxidation-promotes-liver-sinusoidal-endothelial-cells-defenestration
#8
Xiaoying Luo, Dan Wang, Xuan Luo, Xintao Zhu, Guozhen Wang, Zuowei Ning, Yang Li, Xiaoxin Ma, Renqiang Yang, Siyi Jin, Yun Huang, Ying Meng, Xu Li
Aldosterone, with pro-oxidation and pro-autophagy capabilities, plays a key role in liver fibrosis. However, the mechanisms underlying aldosterone-promoted liver sinusoidal endothelial cells (LSECs) defenestration remain unknown. Caveolin 1 (Cav1) displays close links with autophagy and fenestration. Hence, we aim to investigate the role of Cav1-related autophagy in LSECs defenestration. We found the increase of aldosterone/MR (mineralocorticoid receptor) level, oxidation, autophagy, and defenestration in LSECs in the human fibrotic liver, BDL or hyperaldosteronism models; while antagonizing aldosterone or inhibiting autophagy relieved LSECs defenestration in BDL-induced fibrosis or hyperaldosteronism models...
July 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/28733447/mineralocorticoid-receptor-antagonists-attenuate-exaggerated-exercise-pressor-reflex-responses-in-hypertensive-rats
#9
Ryan M Downey, Masaki Mizuno, Jere Holloway Mitchell, Wanpen Vongpatanasin, Scott A Smith
Exaggerated heart rate (HR) and blood pressure responses to exercise in hypertension are mediated, in part, by overactivity of the exercise pressor reflex (EPR). The mechanisms underlying this EPR dysfunction have not been fully elucidated. Previous studies have shown that stimulation of mineralocorticoid receptors (MR) with exogenous administration of aldosterone in normal, healthy rats reproduces the EPR overactivity characteristic of hypertensive animals. Conversely, the purpose of this study was to examine whether antagonizing MR with spironolactone (SPIR) or eplerenone (EPL) in decerebrated hypertensive rats ameliorates abnormal EPR function...
July 21, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28725324/cardiorenal-syndrome-role-of-arginine-vasopressin-and-vaptans-in-heart-failure
#10
REVIEW
Poornima Vinod, Vinod Krishnappa, Abigail M Chauvin, Anshika Khare, Rupesh Raina
Heart and kidney failure continued to be of increasing prevalence in today's society, and their comorbidity has synergistic effect on the morbidity and mortality of patients. Cardiorenal syndrome (CRS) is a complex disease with multifactorial pathophysiology. Better understanding of this pathophysiological network is crucial for the successful intervention to prevent advancement of the disease process. One of the major factors in this process is neurohormonal activation, predominantly involving renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP)...
June 2017: Cardiology Research
https://www.readbyqxmd.com/read/28724838/csk-regulates-blood-pressure-by-controlling-the-synthetic-pathways-of-aldosterone
#11
Sung-Moon Kim, Ji-One Kang, Ji Eun Lim, Sue-Yun Hwang, Bermseok Oh
BACKGROUND: Blood pressure is regulated by a network of diverse physiological pathways. The C-terminal Src kinase (CSK) locus (15q24) is associated with blood pressure in various ethnic groups. It was recently reported thatCskinsufficiency increases blood pressure through Src. The mechanisms of hypertension inCsk(+/-)mice are examined further in this study.Methods and Results:To identify a causal component responsible for hypertension inCsk(+/-), the heart rate was measured by electrocardiogram and plasma volume by Evans blue dilution...
July 20, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
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
#12
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
#13
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...
September 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28699986/diagnosis-and-management-of-primary-aldosteronism
#14
Leticia A P Vilela, Madson Q Almeida
Primary aldosteronism (PA) is the most common form of secondary hypertension (HTN), with an estimated prevalence of 4% of hypertensive patients in primary care and around 10% of referred patients. Patients with PA have higher cardiovascular morbidity and mortality than age- and sex-matched patients with essential HTN and the same degree of blood pressure elevation. PA is characterized by an autonomous aldosterone production causing sodium retention, plasma renin supression, HTN, cardiovascular damage, and increased potassium excretion, leading to variable degrees of hypokalemia...
May 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28690496/dynamic-changes-in-the-renin-angiotensin-aldosterone-system-and-the-beneficial-effects-of-renin-angiotensin-aldosterone-inhibitors-on-spatial-learning-and-memory-in-a-rat-model-of-chronic-cerebral-ischemia
#15
Xinwu Huang, Guozhou Lu, Guochun Li, Hua Li, Beihua Li, Jiazhen Yin, Shousong Cao
Renin-angiotensin-aldosterone system (RAAS) plays an important role in the regulation of blood pressure and brain function. Therefore, we studied the dynamic changes in the RAAS in the blood, cerebral cortex, and hippocampus and the effects of RAAS inhibitors on spatial learning and memory and hippocampal apoptosis in a rat model of chronic cerebral ischemia (CCI) established by bilateral ligation of the common carotid arteries of rats. The levels of renin, angiotensin II (Ang II), and aldosterone (ALD) in the plasma, and the homogenates of the left side of cerebral cortex and whole hippocampus of rats were detected on day 1, 3, 7, 14, 21, and 30 by radioimmunoassay...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28680167/efficiency-and-specificity-of-raas-inhibitors-in-cardiovascular-diseases-how-to-achieve-better-end-organ-protection
#16
REVIEW
Ali Nehme, Kazem Zibara
RAAS, a major pharmacological target in cardiovascular medicine, is inhibited by pharmacological classes including angiotensin converting enzyme (ACE) inhibitors (ACEIs), angiotensin-II type 1 blockers (ARBs) and aldosterone receptors antagonists, in addition to the recently introduced direct renin inhibitors (DRIs). However, currently used RAAS inhibitors still cannot achieve their desired effects and are associated with certain drawbacks, such as adverse side effects, incomplete blockage of the system and poor end-organ protection...
July 6, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28661412/risk-of-new-onset-diabetes-mellitus-in-primary-aldosteronism-a-population-study-over-5-years
#17
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/28660991/insulin-resistance-in-endocrine-disorders-treatment-options
#18
Anita Rogowicz-Frontczak, Anna Majchrzak, Dorota Zozulińska-Ziółkiewicz
Changes in sensitivity to insulin occur in the course of a number of endocrine disorders. Most of the hormones through their antagonistic action to insulin lead to increased hepatic glucose output and its decreased utilisation in peripheral tissues. Carbohydrate disorders observed in endocrine diseases result from the phenomenon of insulin resistance, and in some cases also a reduction in insulin secretion is present. Abnormalities of glucose metabolism are observed in acromegaly, but also in growth hormone deficiency, hypercortisolism in the course of Cushing's syndrome, hyper- or hypothyroidism, primary hyperparathyroidism, aldosteronism, pheochromocytoma, congenital hypertrophy of the adrenal glands, polycystic ovaries syndrome, hypogonadism, or other hormonally active neuroendocrine tumours...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28656517/treatment-of-hyperkalemia-in-heart-failure
#19
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...
August 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
#20
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...
August 2017: Current Heart Failure Reports
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