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https://www.readbyqxmd.com/read/28191524/renin-angiotensin-aldosterone-system-in-insulin-resistance-and-metabolic-syndrome
#1
Undurti N Das
Obesity and its consequent complications such as hypertension and metabolic syndrome are increasing in incidence in almost all countries. Insulin resistance is common in obesity. Renin- angiotensin system (RAS) is an important target in the treatment of hypertension and drugs that act on RAS improve insulin resistance and decrease the incidence of type 2 diabetes mellitus, explaining the close association between hypertension and type 2 diabetes mellitus. RAS influences food intake by modulating the hypothalamic expression of neuropeptide Y and orexins via AMPK dephosphorylation...
June 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28185171/neprilysin-inhibitors-in-cardiovascular-disease
#2
REVIEW
Guson Kang, Dipanjan Banerjee
Mortality from heart failure remains high despite advances in medical therapy over the last three decades. Angiotensin receptor-neprilysin inhibitor (ARNI) combinations are the latest addition to the heart failure medical armamentarium, which is built on the cornerstone regimen of beta blockers, angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers, and aldosterone antagonists. Recent trial data have shown a significant mortality benefit from ARNIs, which, as of May 2016, have now received a class I recommendation for use in patients with heart failure and reduced ejection fraction from the major American and European cardiology societies...
February 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28176630/novel-drugs-for-hypertension-and-heart-failure-struggling-for-a-place-under-the-sun
#3
Charles Faselis, Chrysoula Boutari, Michael Doumas, Konstantinos Imprialos, Konstantinos Stavropoulos, Peter Kokkinos
BACKGOUND: Current drug therapy for the management of arterial hypertension and heart failure has provided substantial benefits but has also some limitations. LCZ696, a dual inhibitor of angiotensin receptor blockers and neprilysin, and finerenone, a non-steroidal mineralocorticoid receptor antagonist, are two recently developed novel agents for the management of these conditions. METHODS: This review aims to present the pathophysiological basis for the use of these two novel drugs, critically discuss available clinical data, and provide future perspectives...
February 6, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28144958/population-pharmacokinetics-of-ly2623091-in-patients-with-hypertension-and-chronic-kidney-disease
#4
Evan B Wang, Archana Chaudhary, Timothy H Waterhouse, Gemma L Dickinson
LY2623091 is a selective, orally active, nonsteroidal, competitive mineralocorticoid receptor antagonist that blocks the actions of aldosterone and other mineralocorticoid receptor ligands at the receptor level. The aim of this work was to explore and establish a population pharmacokinetic model, quantify the degree of interindividual variability, and identify significant disease-, patient-, and study-specific covariates that alter the disposition of LY2623091. The data included concentrations from 294 healthy subjects and patients with hypertension and/or chronic kidney disease (CKD), sampled in 5 phase 1 and 2 studies...
February 1, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28133468/changing-the-treatment-of-heart-failure-with-reduced-ejection-fraction-clinical-use-of-sacubitril-valsartan-combination
#5
REVIEW
Edgardo Kaplinsky
Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk of morbidity and mortality. Sacubitril valsartan (previously known as LCZ696) is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the first in class angiotensin receptor neprilysin inhibitor (ARNI) since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides (NPs), bradykinin, endothelin and angiotensin II (Ang-II)...
November 2016: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/28129699/advances-in-the-pharmacotherapy-of-chronic-heart-failure-with-preserved-ejection-fraction-an-ideal-opportunity-for-precision-medicine
#6
Vincenzo B Polsinelli, Sanjiv J Shah
Heart failure with preserved ejection fraction (HFpEF), which comprises approximately 50% of all heart failure patients, is a challenging and complex clinical syndrome that is often thought to lack effective treatments. Areas covered: Despite the common mantra that HFpEF has no effective treatments, closer inspection of HFpEF clinical trials reveals that several of the drugs tested are associated with benefits in exercise capacity and quality of life, and reduction in heart failure hospitalization. Here we review major randomized controlled trials in HFpEF, focusing on renin-angiotensin-aldosterone system antagonists, organic nitrates, digoxin, beta-blockers, and phosphodiesterase-5 inhibitors...
January 27, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28126566/rapid-actions-of-aldosterone-revisited-receptors-in-the-limelight
#7
Martin Wehling
Steroid hormones like aldosterone have been conclusively shown to elicit both late genomic and rapid, nongenomically initiated responses. Aldosterone was among the first for which rapid, clinically relevant effects were even shown in humans. Yet, after over 30 years of research, the nature of receptors involved in rapid actions of aldosterone is still unclear. Such effects may be assigned to the classical, intracellular steroid receptors, in this case mineralocorticoid receptors (MR, class IIa action Mannheim classification)...
January 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28104456/rapid-stimulation-of-sodium-intake-combining-aldosterone-into-the-4th-ventricle-and-the-blockade-of-the-lateral-parabrachial-nucleus
#8
S Gasparini, M R Melo, G F Leite, P A Nascimento, G M F Andrade-Franzé, J V Menani, E Colombari
Chronic infusion of aldosterone into the 4th ventricle (4th V) induces robust daily sodium intake, whereas acute injection of aldosterone into the 4th V produces no sodium intake. The inhibitory mechanism of the lateral parabrachial nucleus (LPBN) restrains sodium intake induced by different natriorexigenic stimuli and might affect the acute response to aldosterone into the 4th V. In the present study, 1.8% NaCl and water intake was tested in rats treated with acute injections of aldosterone into the 4th V combined with the blockade of the inhibitory mechanisms with injections of moxonidine (α2 adrenergic/imidazoline agonist) or methysergide (a serotonergic antagonist) into the LPBN...
January 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28103616/l-lysine-acts-as-a-serotonin-type-4-receptor-antagonist-to-counteract-in-vitro-and-in-vivo-the-stimulatory-effect-of-serotonergic-agents-on-aldosterone-secretion-in-man
#9
C Duparc, C André, J Ménard, B Godouet-Getti, J Wils, A F Cailleux, L Moreau-Grangé, E Louiset, H Lefebvre
In the normal human adrenal gland, serotonin (5-HT) stimulates aldosterone secretion through the 5-HT4 receptor (5-HT4R). However, the physiological role of the serotonergic control of adrenocortical function is not known. In the present study, we have investigated the ability of l-Lysine, which has been shown to act as a 5-HT4 receptor antagonist, to counteract in vitro and in vivo the stimulatory effect of 5-HT4R agonists on aldosterone production. l-Lysine was found to inhibit aldosterone production induced by 5-HT and the 5-HT4R agonists BIMU8 from cultured human adrenocortical cells...
January 19, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28100428/heart-failure-with-preserved-ejection-fraction-has-a-better-long-term-prognosis-than-heart-failure-with-reduced-ejection-fraction-in-old-patients-in-a-5-year-follow-up-retrospective-study
#10
Silvana Kontogeorgos, Erik Thunström, Magnus C Johansson, Michael Fu
BACKGROUND: The issue of whether prognosis is similar between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) remains unresolved. Because of the problem of inconsistency in the diagnostic criteria and because there is currently no lifesaving therapy available for HFpEF, it seems to be the right time to study the outcome of a clearly defined HFpEF compared with HFrEF in contemporary heart failure (HF) therapy. This study investigates 5-year-mortality and its prognostic factors in old patients with HFpEF compared with those with HFrEF...
April 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28096435/regulation-of-aldosterone-secretion-by-mineralocorticoid-receptor-mediated-signaling
#11
Cherish Chong, Anis Hamid, Tham Yao, Amanda E Garza, Luminita H Pojoga, Gail K Adler, Jose R Romero, Gordon H Williams
We posit the existence of a paracrine/autocrine negative feedback loop, mediated by the mineralocorticoid receptor (MR), regulating aldosterone secretion. To assess this hypothesis, we asked whether altering MR activity in zona glomerulosa (ZG) cells affects aldosterone production. To this end, we studied ex vivo ZG cells isolated from male Wistar rats fed chow containing either high (1.6% Na(+) (HS)) or low (0.03% Na(+) (LS)) amount of sodium. Western blot analyses demonstrated that MR was present in both the ZG and zona fasciculata/zona reticularis (ZF/ZR/ZR)...
March 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28090229/the-impact-exerted-on-clinical-outcomes-of-patients-with-chronic-heart-failure-by-aldosterone-receptor-antagonists-a-meta-analysis-of-randomized-controlled-trials
#12
Renato De Vecchis, Claudio Cantatrione, Damiana Mazzei, Augusto Barone, Nicola Maurea
BACKGROUND: Aldosterone receptor antagonists (ARAs) have been associated with improved clinical outcomes in patients with heart failure with reduced left ventricular ejection fraction (HFREF), but not in those with heart failure with preserved left ventricular ejection fraction (HFpEF). With the aim to study this topic more deeply, we carried out a meta-analysis of selective and non-selective ARAs in HFREF and HFpEF. METHODS: We searched PubMed and Scopus databases...
February 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28089144/essential-role-of-icam-1-in-aldosterone-induced-atherosclerosis
#13
Vincenzo Marzolla, Andrea Armani, Caterina Mammi, Mary E Moss, Vittoria Pagliarini, Laura Pontecorvo, Antonella Antelmi, Andrea Fabbri, Giuseppe Rosano, Iris Z Jaffe, Massimiliano Caprio
OBJECTIVE: Elevated aldosterone is associated with increased risk of atherosclerosis complications, whereas treatment with mineralocorticoid receptor (MR) antagonists decreases the rate of cardiovascular events. Here we test the hypothesis that aldosterone promotes early atherosclerosis by modulating intercellular adhesion molecule-1 (ICAM-1) expression and investigate the molecular mechanisms by which aldosterone regulates ICAM-1 expression. METHODS AND RESULTS: Apolipoprotein-E (ApoE)(-/-) mice fed an atherogenic diet and treated with aldosterone for 4weeks showed increased vascular expression of ICAM-1, paralleled by enhanced atherosclerotic plaque size in the aortic root...
January 5, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28075105/heart-failure-due-to-reduced-ejection-fraction-medical-management
#14
William E Chavey, Robrt V Hogikyan, R Van Harrison, John M Nicklas
Heart failure is an increasingly common condition resulting in high rates of morbidity and mortality. For patients who have heart failure and reduced ejection fraction, randomized clinical trials demonstrate consistent mortality benefit from angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, direct-acting vasodilators, beta blockers, and aldosterone antagonists. Additionally, some data show benefits from two new classes of drugs: angiotensin receptor blocker/neprilysin inhibitor and sinus node modulator...
January 1, 2017: American Family Physician
https://www.readbyqxmd.com/read/28073769/aldosterone-does-not-predict-cardiovascular-events-following-acute-coronary-syndrome-in-patients-initially-without-heart-failure
#15
Reynaria Pitts, Elise Gunzburger, Christie M Ballantyne, Philip J Barter, David Kallend, Lawrence A Leiter, Eran Leitersdorf, Stephen J Nicholls, Prediman K Shah, Jean-Claude Tardif, Anders G Olsson, John J V McMurray, John Kittelson, Gregory G Schwartz
BACKGROUND: Aldosterone may have adverse effects in the myocardium and vasculature. Treatment with an aldosterone antagonist reduces cardiovascular risk in patients with acute myocardial infarction complicated by heart failure (HF) and left ventricular systolic dysfunction. However, most patients with acute coronary syndrome do not have advanced HF. Among such patients, it is unknown whether aldosterone predicts cardiovascular risk. METHODS AND RESULTS: To address this question, we examined data from the dal-OUTCOMES trial that compared the cholesteryl ester transfer protein inhibitor dalcetrapib with placebo, beginning 4 to 12 weeks after an index acute coronary syndrome...
January 10, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28062142/aldosterone-pathway-blockade-to-prevent-atrial-fibrillation-a-systematic-review-and-meta-analysis
#16
J Neefs, N W E van den Berg, J Limpens, W R Berger, S M Boekholdt, P Sanders, J R de Groot
BACKGROUND: Despite advances in therapeutic interventions AF remains a progressive and symptomatic disease. Therefore, novel therapeutic interventions targeting the underlying arrhythmogenic substrate for AF is needed. Atrial fibrosis is an important component of the arrhythmogenic substrate of AF and may be initiated by aldosterone binding to the mineralocorticoid receptor. We hypothesized that aldosterone pathway blockade with mineralocorticoid receptor antagonists (MRA) reduces atrial fibrosis, and thus AF...
March 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28052869/nlrp3-inflammasome-activation-contributes-to-aldosterone-induced-podocyte-injury
#17
Mi Bai, Ying Chen, Min Zhao, Yue Zhang, John Cijiang He, Songming Huang, Zhanjun Jia, Aihua Zhang
Aldosterone (Aldo) has been shown as an important contributor of podocyte injury. However, the underlying molecular mechanisms are still elusive. Recently, the pathogenic role of NLRP3 inflammasome in mediating renal tubular damage was identified while its role in podocyte injury still needs evidence. Thus the present study was undertaken to investigate the role of NLRP3 inflammasome in Aldo-induced podocyte damage. In vitro, exposure of podocytes to Aldo enhanced NLRP3, caspase-1 and IL-18 expressions in dose- and time-dependent manners, indicating an activation of NLRP3 inflammasome, which was significantly blocked by a mineralocorticoid receptor antagonist Eplerenone (EPL) or an antioxidant NAC...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28045409/turkish-registry-for-diagnosis-and-treatment-of-acute-heart-failure-taktik-study
#18
Mehmet Eren, Mehdi Zoghi, Mustafa Tuncer, Yüksel Çavuşoğlu, Recep Demirbağ, Mahmut Şahin, Osman Akın Serdar, Ersel Onrat, Haşim Mutlu, Dursun Dursunoğlu, Mehmet Birhan Yılmaz, Ahmet Temizhan
OBJECTIVE: The goal of this study was to develop a national database of patients hospitalized in Turkey with acute heart failure (AHF) using evaluations of diagnostic and therapeutic approaches. METHODS: Patient data were collected using an Internet-based survey. A total of 588 patients were enrolled from 36 participating medical centers across the country. RESULTS: Mean age was 62±13 years and 38% of the patients were female. Ratio of de novo AHF to study cohort was 24%...
December 2016: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/27992114/the-role-of-spironolactone-on-myocardial-oxidative-stress-in-rat-model-of-streptozotocin-induced-diabetes
#19
Fadia Mayyas, Karem H Alzoubi, Ruwidah Bonyan
BACKGROUND: Diabetes mellitus (DM) is linked to cardiovascular diseases development and progression. Aldosterone contributes to cardiac oxidative stress and remodeling. AIM: to evaluate the impact of spironolactone (an aldosterone antagonist) on markers of myocardial redox status in a rat model of streptozotocin (STZ) induced DM. METHOD: Adult Sprague Dawley rats were randomized into four groups; controls, spironolactone treated rats (Spir), diabetic rats (DM), and diabetic rats treated with spironolactone (DM+Spir) for 4 weeks...
December 19, 2016: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/27958695/aldosterone-receptor-antagonists-decrease-mortality-and-cardiovascular-hospitalizations-in-chronic-heart-failure-chf-with-reduced-left-ventricular-ejection-fraction-lvef-but-not-in-chf-with-preserved-lvef-a-meta-analysis-of-randomized-controlled-trials
#20
Renato DE Vecchis, Carmelina Ariano
INTRODUCTION: Aldosterone receptor antagonists (ARAs) were introduced in the treatment of chronic heart failure (CHF), as a result of the demonstration of their protective effect on the failing heart. However, important questions remain unanswered regarding the clinical efficacy of the ARAs on the clinical and echocardiographic phenotype of heart failure, called heart failure with preserved left ventricular ejection fraction( HFpEF). EVIDENCE ACQUISITION: The aim of the present meta-analysis was to verify the impact of the ARAs on some hard endpoints, such as all - cause death and hospitalizations from cardiovascular cause, making a comparative evaluation of these outcomes in CHF patients with reduced left ventricular ejection fraction (HFREF) and in those with HFpEF, respectively...
December 13, 2016: Minerva Cardioangiologica
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