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Aldosterone antagonist

Ning Xia, Huige Li
Under physiological conditions, perivascular adipose tissue (PVAT) attenuates agonist-induced vasoconstriction by releasing vasoactive molecules including hydrogen peroxide, angiotensin 1-7, adiponectin, methyl palmitate, hydrogen sulfide, nitric oxide (NO) and leptin. This anticontractile function of PVAT is lost under conditions of obesity. The central mechanism underlying PVAT dysfunction in obesity is likely to be an "obesity triad" (consisting of PVAT hypoxia, inflammation and oxidative stress) that leads to dysregulation of PVAT-derived vasoregulators...
October 20, 2016: British Journal of Pharmacology
Christian Cadeddu, Valentina Mercurio, Paolo Spallarossa, Savina Nodari, Marco Triggiani, Ines Monte, Roberta Piras, Rosalinda Madonna, Pasquale Pagliaro, Carlo G Tocchetti, Giuseppe Mercuro
Because of the recent advances in chemotherapeutic protocols, cancer survival has improved significantly, although cardiovascular disease has become a major cause of morbidity and mortality among cancer survivors: in addition to the well-known cardiotoxicity (CTX) from anthracyclines, biologic drugs that target molecules that are active in cancer biology also interfere with cardiovascular homeostasis.Pharmacological and non-pharmacological strategies to protect the cardiovascular structure and function are the best approaches to reducing the prevalence of cardiomyopathy linked to anticancer drugs...
May 2016: Journal of Cardiovascular Medicine
V V Muthusamy
Cardiovascular disease burden is increasing all over the world. The diagnosis of hypertension is considered when a person has persistently elevated BP (Systolic BP more than 140 mmHg and/or Diastolic BP more than 90 mmHg). Dyslipidemia denotes abnormal levels of lipids in the blood (Total Cholesterol >200 mg%, Low density lipoprotein (LDL) >100 mg%, Triglycerides (TGL) >150 mg% and High density lipoprotein (HDL) <40 mg in men and < 50 mg in women. Hypertension and Dyslipidemia constitute the important components of metabolic syndrome as per the definition of NCEP Guidelines-Adult Treatment Panel III (ATP III)...
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
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
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
Mitsuha Morisaki, Isao Kurihara, Sakiko Kobayashi, Kenichi Yokota, Ayano Murai-Takeda, Rie Jo, Yuko Mitsuishi, Toshifumi Nakamura, Nao Kohata, Yosuke Oshima, Hirotaka Shibata, Hiroshi Itoh
OBJECTIVE: It has been reported that obesity-related high blood pressure was partly associated with increased aldosterone secretion and/or activity, but detailed mechanisms are not known. Our previous study suggested that different salt contents in each diet would affect the aldosterone levels. In this study, we investigated the change of aldosterone secretion and MR sensitivity of obesity mice by high fat diet under equally-adjusted salt intake. DESIGN AND METHOD: We prepared normal fat diet (NFD, 10% lard) and high fat diet (HFD, 60% lard) with equal amount of salt based on the amount of food intake of C57BL/6J mice...
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
Matthew Weir, Martha Mayo, Dahlia Garza, Susan Arthur, Lance Berman, David Bushinsky, Daniel Wilson, Murray Epstein
OBJECTIVE: Diuretics, alone or in combination, are frequently prescribed in chronic kidney disease (CKD) and heart failure (HF) patients to reduce volume, blood pressure, and/or for symptom control. Clinicians may also use them to reduce the risk of hyperkalemia, but high doses of diuretics may lead to adverse events from intravascular volume depletion or gout. Patiromer is a non-absorbed K-binding polymer recently approved by the FDA for the treatment of hyperkalemia (HK). We compared patiromer's effects in RAASi-treated CKD patients with HK on different types of diuretics to patients not receiving diuretics in the treatment phase of OPAL-HK...
September 2016: Journal of Hypertension
Kaoru Yamashita, Atsuhiro Ichihara, Kentaro Ito, Naohiro Yoshida, Fumiko Mitani, Jin Endo, Motoaki Sano, Keiichi Fukuda, Satoshi Morimoto
OBJECTIVE: Numerous clinical trials demonstrated that renin-angiotensin-aldosterone system (RAAS) was involved in the pathogenesis of hypertension-induced heart failure. While RAS is a major machinery required for aldosterone production, multiple minor systems, including catecholamine, could give rise to the aberrant aldosterone production beyond the RAS activation. We investigated the mechanism underlying the RAS-independent aldosterone production in heart failure. DESIGN AND METHOD: Dahl-salt sensitive rats fed high salt diet developed malignant hypertension, resulting in heart failure with inappropriately increased plasma aldosterone level...
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
Hae-Young Lee, Chan-Soon Park, Sang-Hoon Na, Kyung-Jin Kim, Chan Joo Lee, Sungha Park
A 47-year-old woman was admitted via emergency department due to dyspnea NYHA Fc II-III aggravated for 2 months after upper respiratory infection. Her height and body weight were 161 cm / 67 kg. Initial vital signs were 110/70 mmHg - 112 BPM - 24/min - 36.5°C. Chest PA showed cardiomegaly and pulmonary congestion (Figure 1). B-natriuretic peptide level was markedly increased (2002 pg/mL, normal range ≤ 100 pg/mL). The echocardiographic examination showed severely dilated LV cavity (61/72 mm) and severe LV systolic dysfunction (EF 28%) with normal left ventricular wall thickness (9/11 mm) (Figure 2)...
September 2016: Journal of Hypertension
Colin Johnston
Aldosterone's deleterious pathophysiological effects on the cardiovascular system if blocked by mineralcorticord antagonists (MRAs) logically should lead to improvement in heart function and outcomes in heart failure (HF). The first trial to test this hypothesis was tthe RALES trial in 1999 which treated patients with class III-IV HF with spironolactone. It showed significant reduction in mortality and cardiovascular hospitalzation rates. This was confirmed & extended in EMHASIS-HF RCT with classs II-III being treated with ACEIs & BB who received placebo or elperinone (a MRA) with again a statistically significant fall in mortality & hospitalization...
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
Hisashi Kai
There is increasing evidence that fibro-inflammatory changes play a role in variety of cardiovascular diseases. We created new rat models to investigate the role of fibro-inflammatory changes in the pathophysiology of systolic and diastolic dysfunction in hypertensive heart. (1) a model of a blood pressure (BP) surge was created by performing abdominal aortic constriction in Wistar-Kyoto rats. Aortic constriction rapidly increased BP and the high BP levels sustained. A BP surge transiently induced MCP-1 and TGF-beta induction, angiotensin converting enzyme activation, and macrophage infiltration, followed by left ventricular (LV) hypertrophy and perivascular reactive fibrosis...
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
Trinath Kumar Mishra, Biswajit Das
BACKGROUND: Coronary artery disease (CAD) is rising in epidemic proportions with India not being an exception. CAD in Indian scenario has its onset at a younger age with multitude of risk factors. OBJECTIVE: This study was carried out to obtain complete information about demographic profile, risk factors, clinical scenario, therapeutic modalities, natural course, outcome and changing profile of acute ST-segment elevated myocardial infarction (STEMI) patients. METHODS: This cross-sectional study was conducted in 45,122 acute STEMI patients admitted 1st March 1990 to 1st March 2014...
June 2016: Journal of the Association of Physicians of India
David A Calhoun
Resistant hypertension has for many decades been defined as difficult-to-treat hypertension in order to identify patients who may benefit from special diagnostic and/or therapeutic considerations. Recently, the term "refractory hypertension" has been proposed as a novel phenotype of antihypertensive failure, that is, patients whose blood pressure cannot be controlled with maximal treatment. Early studies of this phenotype indicate that it is uncommon, affecting less than 5% of patients with resistant hypertension...
September 2016: Korean Circulation Journal
Olivier Malaise, Biserka Relic, Edith Charlier, Mustapha Zeddou, Sophie Neuville, Céline Deroyer, Philippe Gillet, Edouard Louis, Michel G Malaise, Dominique de Seny
BACKGROUND: Glucocorticoid-induced leucine zipper (GILZ) is a mediator of the anti-inflammatory activities of glucocorticoids. However, GILZ deletion does not impair the anti-inflammatory activities of exogenous glucocorticoids in mice arthritis models and GILZ could also mediate some glucocorticoid-related adverse events. Osteoarthritis (OA) is a metabolic disorder that is partly attributed to adipokines such as leptin, and we previously observed that glucocorticoids induced leptin secretion in OA synovial fibroblasts...
October 4, 2016: Arthritis Research & Therapy
M Cioboata, C Alexandrescu, C A Hopinca, M C Pienaru, A Merticariu, S Schmitzer
We report the case of a 46-year-old patient, medical doctor with a relapsing unilateral CRSC-Central Serous Chorioretinopathy who was treated after an initial medical therapy (oral carbonic anhydrase inhibitor, oral antihistamines, non-steroidal anti-inflammatory drugs - systemic and topical), with an oral aldosterone antagonist-Eplerenone (Inspra), resulted in significant anatomic and visual improvements. Abbreviations: CRSC = Central Serous Chorioretinopathy, R.E. = right eye, L.E. = left eye, BCVA = best corrected visual acuity, RPE = retinal pigment epithelium, OCT = optical coherence tomography, FDA = food and drug administration...
January 2016: Journal of Medicine and Life
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