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mineralocorticoid receptor

Cosmo Godino, Antonio Colombo, Alberto Margonato
Heart rate is an established prognostic marker for longevity and is an important contributor in the pathophysiology of various cardiovascular diseases, including ischemic heart disease and heart failure. Most ischemic episodes are triggered by an increase in heart rate, which causes an imbalance between myocardial oxygen delivery and consumption. In addition, increased heart rate is a modifiable risk factor for chronic heart failure. Ivabradine, an inhibitor of If ion channels, is an approved second-line anti-ischemic drug for the treatment of angina...
October 21, 2016: Clinical Drug Investigation
Amanda R de Oliveira, Adriano E Reimer, Fernando M C V Reis, Marcus L Brandão
Considering the complexity of aversive information processing and defensive response expression, a combined action of stress modulators may be required for an optimal performance during threatening situations. Dopamine is now recognized as one of the most active modulators underlying states of fear and anxiety. On the other hand, activation of hypothalamic-pituitary-adrenocortical (HPA) axis, which leads to the release of corticosterone in rodents, has been considered a key part of the stress response. The current study is an extension of prior work investigating modulatory effects of dopamine and corticosterone on conditioned fear expression...
October 20, 2016: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
Shigeru Shibata, Kenichi Ishizawa, Shunya Uchida
The kidney has a central role in long-term control of blood pressure, and decreased kidney function is a common but difficult-to-treat cause of hypertension. Conversely, elevated blood pressure contributes to the progression of chronic kidney disease. Steroid hormone aldosterone and its receptor mineralocorticoid receptor (MR) contribute to hypertension by increasing renal salt reabsorption and promote kidney dysfunction through direct effects on renal parenchymal cells. Accumulating data indicate that various mechanisms affect aldosterone-MR signaling...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Francesco Pichi, Paola Carrai, Antonio Ciardella, Francine Behar-Cohen, Paolo Nucci
PURPOSE: To evaluate the effect of oral spironolactone and eplerenone, two specific antagonists of the mineralocorticoid receptor, in central serous chorioretinopathy (CSCR). METHODS: In this prospective, placebo-controlled trial, sixty patients with persistent CSCR were assigned to three treatment group. Twenty patients in Group 1 were treated with 25 mg of spironolactone (Aldactone; Pfizer) for 1 week, then increased to 50 mg for the following 3 weeks, then shifted to eplerenone 50 mg for 1 month...
October 18, 2016: International Ophthalmology
Takuya Kanemitsu, Miho Sato, Miyuki Yoshida, Eisuke Ozasa, Michiko Miyazaki, Yuki Odanaka, Kazuhiro Nagata, Takashi Itoh
A highly enantioselective α-benzoyloxylation of malonic diester has been achieved by phase-transfer catalysis. The reaction of α-monosubstituted tert-butyl methyl malonate with benzoyl peroxide in the presence of aqueous KOH and N-(9-anthracenylmethyl)cinchoninium chloride afforded the corresponding α,α-disubstituted products in generally excellent chemical yields (up to 99% yield) with high enantioselectivities (up to 96% ee). In addition, the utility of this methodology was exhibited by the synthesis of a mineralocorticoid receptor antagonist...
October 18, 2016: Organic Letters
Jun Tao
OBJECTIVE: Hyperaldosteronemia exerts adverse effects on vascular endothelium except enhanceing blood pressure; however, the impacts and molecular mechanisms of hyperaldosteronemia on endothelial progenitor cell (EPC)-mediated endothelial repair are yet to be determined. The aim of this study was to investigate the endothelial repair capacity of EPCs from hypertensive patients with primary hyperaldosteronemia (PHA). DESIGN AND METHOD: In vivo endothelial repair capacity of EPCs from PHAs (n = 20), age- and blood pressure-matched essential hypertension patients (n = 20), and age-matched healthy subjects (n = 20) was evaluated by transplantation into nude mice with carotid artery denudation injury...
September 2016: Journal of Hypertension
Martin Wolley, Diane Cowley, Ashraf Ahmed, Richard Gordon, Michael Stowasser
OBJECTIVE: Obstructive sleep apnoea (OSA) is known to commonly co-exist with primary aldosteronism (PA), but it is unknown if treatment via mineralocorticoid receptor blockade or adrenalectomy (for aldosterone producing adenoma, APA), improves sleep apnoea parameters in these patients. We therefore aimed to determine if specific medical or surgical treatment of PA improves OSA, as measured by the apnoea hypopnoea index (AHI). DESIGN AND METHOD: Patients undergoing diagnostic workup for PA were recruited if they had symptoms suggestive of OSA...
September 2016: Journal of Hypertension
Toshifumi Nakamura, Isao Kurihara, Sakiko Kobayashi, Kenichi Yokota, Ayano Murai-Takeda, Yuko Mitsuishi, Mitsuha Morisaki, Nao Kohata, Yosuke Oshima, Gunther Schutz, Hirotaka Shibata, Hiroshi Itoh
OBJECTIVE: Recent studies have unveiled cardiovascular pathological roles of mineralocorticoid receptor (MR) in many types of cells. Although we have confirmed high expression of MR in intestinal epithelial cells (IEC), that role in progression of cardiovascular diseases is yet to be elucidated. As intestine is the first gate sensing sodium intake, MR of this organ is expected to have essential roles in blood pressure (BP) regulation. This study investigated the role of MR in IEC by using IEC-specific MR knockout mice (IEC-MR KO)...
September 2016: Journal of Hypertension
Toshiro Fujita
The aldosterone/mineralocorticoid receptor (MR) pathway regulate renal excretory function and control BP. Notably, we identified Rac1 as a novel ligand-independent modulator of MR (Nat Med 2008), and found involvement of the Rac1-MR pathway in rodent models of salt-sensitive hypertension (JCI 2011). In the clinical trial (EVALUATE study), effects of MR antagonist on urinary albumin excretion were assessed in 304 hypertensive CKD patients receiving renin-angiotensin system (RAS) inhibitors and sub-grouped according to the estimated dietary salt intake (Lancet Endo & Diabetes 2014)...
September 2016: Journal of Hypertension
InKyeom Kim
Histone deacetylases (HDACs) act as co-repressors in gene transcription by erasing the acetylation of histones, resulting in epigenetic gene silencing. Recent studies revealed that HDAC inhibitors attenuated blood pressure of several hypertensive animal models such as spontaneously hypertensive rats, hyperaldosteronism rats, angiotensin II-induced hypertensive rats and pulmonary hypertensive rats. Unexpectedly, microarray studies uncovered that administration of HDAC inhibitors decreased expression of some genes for example extracellular matrix proteins, oxidative stress-related proteins, cytokines, chemokines and ion transporters, mostly targets of corticoid receptors...
September 2016: Journal of Hypertension
Alexander Danser
Blockade of the renin-angiotensin-aldosterone system (RAAS) can be accomplished at the level of the angiotensin-generating enzymes renin and angiotensin-converting enzyme (ACE; using renin inhibitors or ACE inhibitors), the type 1 angiotensin II (AT1) receptor or mineralocorticoid receptor (MR; using angiotensin receptor blockers [ARBs] or MR blockers) and/or renin release (using beta-blockers). Several of these drugs are often combined-for example in heart failure-but such approaches may ultimately lead to RAAS annihilation with adverse consequences such as hypotension, renal dysfunction and hyperkalaemia...
September 2016: Journal of Hypertension
Suzanne Oparil
Heart disease, stroke, and kidney failure are leading causes of death worldwide, and hypertension is a significant risk factor for each. Hypertension is less common in women, compared to men, in those younger than 45 years of age. This trend is reversed in those 65 years and older. In the US between 2011-2014, the prevalence of hypertension in women and men by age group was 6% vs 8% (18-39 years), 30% vs 35% (40-59 years), and 67% vs 63% (60 years and over). Awareness, treatment, and control rates differ between genders with women being more aware of their diagnosis (85% vs 80%), more likely to take their medications (81% vs 71%) and more frequently having controlled hypertension (55% vs 49%)...
September 2016: Journal of Hypertension
Sverre Kjeldsen
There is a whole armament of good drugs for treatment of hypertension including diuretics, calcium antagonist, angiotensin receptor antagonists and angiotensin converting enzyme inhibitors. Secondary drugs mostly used for special indications include beta-blockers, alpha-blockers, mineralocorticoid receptor antagonists (aldosterone antagonists), renin-inhibitors, centrally acting drugs, direct vasodilators and others.A variety of new drugs targeting different pressor mechanism exist and have partly been studies experimentally but will unlikely make it to clinical use in human hypertension...
September 2016: Journal of Hypertension
Yoshitsugu Iwakura, Ryo Morimoto, Kumi Kikuchi, Yoshikiyo Ono, Yuta Tezuka, Yasuko Tsukada, Masahiro Nezu, Yasuhiro Igarashi, Masataka Kudo, Akira Nishiyama, Sadayoshi Ito, Fumitoshi Satoh
OBJECTIVE: High prevalence of renal damage has been demonstrated in patients with primary aldosteronism (PA). However, the original mechanism and onset still be elucidated. The purpose of this study is to investigate the possible original mechanisms of renal damages in PA. DESIGN AND METHOD: Consecutive 72 patients with aldosterone producing adenoma (APA) and 70 patients with essential hypertension (EH) participated. No patients had renal damages defined as eGFR (based on Cystatin C) < 60 ml/min/1...
September 2016: Journal of Hypertension
Anastasia Mihailidou, Anthony Ashton
OBJECTIVE: Myocardial infarction (MI) continues to be a major burden of disease, despite rapid reperfusion interventions. Reperfusion of ischemic hearts (reperfusion injury) induces free radical generation, activation of early stress responses and apoptosis, which contributes to ventricular remodeling and dysfunction, which may lead to developing heart failure. Mineralocorticoid receptor (MR) antagonists have been shown clinically to reduce blood pressure, particularly in resistant hypertension, and substantially increase survival in heart failure...
September 2016: Journal of Hypertension
David John Webb
Treatment-resistant hypertension (TRH) is defined as the failure to achieve an office BP target of <140/90 mmHg (<130/80 mmHg in patients with chronic kidney disease (CKD) or diabetes) in patients with hypertension (HT), despite adherence to at least 3 antihypertensive medications at optimal tolerated doses, ideally including a diuretic (Calhoun et al., Circulation 2008). TRH identifies patients with hard-to-treat HT, who might benefit from specialist investigation and treatment. Although some studies put the prevalence of TRH as >10%, these levels may be inflated by white-coat hypertension and poor adherence...
September 2016: Journal of Hypertension
Brandi Wynne, Trinity Kronk, Otor Al-Khalili, Benjamin Ko, Franziska Theilig, Douglas Eaton, Robert Hoover
OBJECTIVE: Hypertension is characterized by increased sodium reabsorption along the aldosterone-sensitive distal nephron (ASDN) and systemic inflammation. Interleukin-6 (IL-6) is a possible mediator, signaling via the transmembrane IL-6 receptor alpha (IL-6Rα); however, whether IL-6Rα is present in the distal convoluted tubule (DCT) is unknown. Increased sodium reabsorption is not always correlated with increased aldosterone (Aldo). Thus, understanding how Aldo-independent sodium reabsorption occurs is critical...
September 2016: Journal of Hypertension
Toshiro Fujita
The aldosterone/mineralocorticoid receptor (MR) pathway regulate renal excretory function and control BP. Notably, we identified Rac1 as a novel ligand-independent modulator of MR (Nat Med 2008), and found involvement of the Rac1-MR pathway in rodent models of salt-sensitive hypertension (JCI 2011). In the clinical trial (EVALUATE study), effects of MR antagonist on urinary albumin excretion were assessed in 304 hypertensive CKD patients receiving renin-angiotensin system (RAS) inhibitors and sub-grouped according to the estimated dietary salt intake (Lancet Endo & Diabetes 2014)...
September 2016: Journal of Hypertension
Omar Al Dhaybi, George Bakris
PURPOSE OF REVIEW: Current evidence showcases the pathologic effects of excess aldosterone in promoting glomerular and tubulointerstitial inflammation and fibrosis through various pathways. The place for mineralocorticoid receptor antagonists (MRAs) in chronic kidney disease (CKD) progression is unclear. RECENT FINDINGS: MRAs further reduce albuminuria and blood pressure in CKD patients when used in conjunction with angiotensin-converting enzyme inhibitor or angiotensin receptor blockers...
October 7, 2016: Current Opinion in Nephrology and Hypertension
Sankar N Maity, Mark A Titus, Revekka Gyftaki, Guanglin Wu, Jing-Fang Lu, S Ramachandran, Elsa M Li-Ning-Tapia, Christopher J Logothetis, John C Araujo, Eleni Efstathiou
Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) is a validated treatment target for the treatment of metastatic castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA) inhibits both 17α-hydroxylase (hydroxylase) and 17,20-lyase (lyase) reactions catalyzed by CYP17A1 and thus depletes androgen biosynthesis. However, coadministration of prednisone is required to suppress the mineralocorticoid excess and cortisol depletion that result from hydroxylase inhibition. VT-464, a nonsteroidal small molecule, selectively inhibits CYP17A1 lyase and therefore does not require prednisone supplementation...
October 17, 2016: Scientific Reports
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