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https://www.readbyqxmd.com/read/29331564/direct-renin-inhibition-is-not-enough-to-prevent-reactive-oxygen-species-generation-and-vascular-dysfunction-in-renovascular-hypertension
#1
Alisson Martins-Oliveira, Danielle A Guimaraes, Carla S Ceron, Elen Rizzi, Diogo M M Oliveira, Carlos R Tirapelli, Dulce E Casarini, Fernanda B Fernandes, Lucas C Pinheiro, Jose E Tanus-Santos
Renin-angiotensin system activation promotes oxidative stress and endothelial dysfunction. However, no previous study has examined the effects of the renin inhibitior aliskiren, either alone or combined with angiotensin II type 1 antagonists on alterations induced by two-kidney, one-clip (2K1C) hypertension. We compared the vascular effects of aliskiren (50mg/kg/day), losartan (10mg/kg/day), or both by gavage for 4 weeks in 2K1C and control rats. Treatment with losartan, aliskiren, or both exerted similar antihypertensive effects...
January 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29295576/intracellular-renin-inhibits-mitochondrial-permeability-transition-pore-via-activated-mitochondrial-extracellular-signal-regulated-kinase-erk-1-2-during-ischemia-in-diabetic-hearts
#2
Terumori Satoh, Masao Saotome, Hideki Katoh, Daishi Nonaka, Prottoy Hasan, Hideharu Hayashi, Yuichiro Maekawa
Although beneficial effects of non-secreting intracellular renin (ns-renin) against ischemia have been reported, the precise mechanism remains unclear. In this study, we investigated the roles of ns-renin and mitochondrial extracellular signal-related kinase (ERK) 1/2 on mitochondrial permeability transition pore (mPTP) opening during ischemia in diabetes mellitus (DM) hearts. When isolated hearts from Wistar rats (non-DM hearts) and Goto-Kakizaki rats (DM hearts) were subjected to ischemia for 70 min by left anterior descending coronary artery ligation, DM hearts exhibited higher left ventricular (LV) developed pressure and lower LV end-diastolic pressure than non-DM hearts, suggesting ischemic resistance...
December 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29230587/arterial-wall-hypertrophy-is-ameliorated-by-%C3%AE-2-adrenergic-receptor-antagonist-or-aliskiren-in-kidneys-of-angiotensinogen-knockout-mice
#3
Haruka Nakamori, Shin-Ichiro Yoshida, Hiroaki Ishiguro, Shota Suzuki, Hiroaki Yasuzaki, Tatsuo Hashimoto, Tomoaki Ishigami, Nobuhito Hirawa, Yoshiyuki Toya, Satoshi Umemura, Kouichi Tamura
BACKGROUND: Arterial hypertrophy and interstitial fibrosis are important characteristics in kidneys of angiotensinogen-knockout (Atg -/-) mice. In these mice, which exhibit polyuria and hypotension, sympathetic nerve signaling is estimated to be compensatorily hyperactive. Furthermore, transforming growth factor (TGF)-β1 is overexpressed in mice kidneys. To determine whether sympathetic nerve signaling and TGF-β1 exacerbate arterial hypertrophy and interstitial fibrosis, intervention studies of such signaling are required...
December 11, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29198406/comparison-of-the-effect-of-aliskiren-versus-negative-controls-on-aortic-stiffness-in-patients-with-marfan-syndrome-under-treatment-with-atenolol
#4
Ji-Won Hwang, Eun Kyoung Kim, Shin Yi Jang, Tae-Young Chung, Chang-Seok Ki, Kiick Sung, Sung Mok Kim, Joonghyun Ahn, Keumhee Carriere, Yeon Hyeon Choe, Sung-A Chang, Duk-Kyung Kim
INTRODUCTION AND OBJECTIVES: The aim of this study was to evaluate the effect of aliskiren on aortic stiffness in patients with Marfan syndrome (MS). METHODS: Twenty-eight MS patients (mean age ± standard deviation: 32.6 ± 10.6 years) were recruited from November 2009 to October 2014. All patients were receiving atenolol as standard beta-blocker therapy. A prospective randomization process was performed to assign participants to either aliskiren treatment (150-300mg orally per day) or no aliskiren treatment (negative control) in an open-label design...
November 29, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/29191768/interactions-of-aliskiren-a-direct-renin-inhibitor-with-antiepileptic-drugs-in-the-test-of-maximal-electroshock-in-mice
#5
Krzysztof Łukawski, Grzegorz Raszewski, Stanisław J Czuczwar
Experimental studies showed that certain angiotensin-converting enzyme inhibitors and angiotensin AT1 receptor antagonists can decrease seizure severity in rodents. Additionally, some of these blockers of the renin-angiotensin system have been documented to enhance the anticonvulsant activity of antiepileptic drugs against maximal electroshock-induced seizures. The aim of the current study was to investigate the effect of aliskiren, a direct renin inhibitor and a novel antihypertensive drug, on the protective action of numerous antiepileptic drugs (carbamazepine, valproate, clonazepam, phenobarbital, oxcarbazepine, lamotrigine, topiramate and pregabalin) in the test of maximal electroshock in mice...
November 27, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29184499/aliskiren-improves-ischemia-and-oxygen-glucose-deprivation-induced-cardiac-injury-through-activation-of-autophagy-and-amp-activated-protein-kinase
#6
Ming-Hsien Chiang, Chan-Jung Liang, Chen-Wei Liu, Bo-Jhih Pan, Wen-Ping Chen, Yi-Fan Yang, I-Ta Lee, Jaw-Shiun Tsai, Chiang-Wen Lee, Yuh-Lien Chen
Aliskiren is a direct renin inhibitor that has been effective in anti-hypertension. We investigated whether aliskiren could improve the ischemia-induced cardiac injury and whether the autophagy was involved in this effect. A myocardial infarction (MI) model was created by the ligation of the left anterior coronary artery in C57J/BL6 mice. They were treated for 1, 3, 7, and 14 days with vehicle or aliskiren (25 mg/kg/day via subcutaneous injection). In vivo, the MI mice exhibited worse cardiac function by echocardiographic assessment and showed larger myocardial scarring by light microscopy, whereas aliskiren treatment reversed these effects, which were also associated with the changes in caspase-3 and Bcl-2 expression as well as in the number of apoptotic cells...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29179525/aliskiren-therapy-in-hypertension-and-cardiovascular-disease-a-systematic-review-and-a-meta-analysis
#7
REVIEW
Shufang Fu, Xin Wen, Fei Han, Yin Long, Gaosi Xu
The efficacy and safety of aliskiren combination therapy with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in patients with hypertension and cardiovascular disease remains attractive attention. We searched the Cochrane Central Register, the Clinical Trials Registry, EMBASE, MEDLINE and PubMed for relevant literatures up to January 2017. A total of 13 randomized controlled trials (RCTs) with 12222 patients were included in this study, and the combined results indicated that aliskiren in combination therapy with ACEIs or ARBs had remarkable effects in reducing systolic blood pressure (SBP) [weighted mean differences (WMD), -4...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29172824/aliskiren-and-valsartan-in-combination-is-a-promising-therapy-for-hypertensive-renal-injury-in-rats
#8
Hala Salah Abdel Kawy
Neither ACEI nor ARBs completely repress the RAAS. Aliskiren is a newer agent that inhibits renin. However, it increases the biosynthesis and secretion of renin and prorenin, that might induce renal tissue damage. This study was conducted to investigate the renoprotective effects of aliskiren and valsartan the ARB, either alone or in combination, on hypertensive nephropathy induced by L-NAME. Aliskiren (50 mg/kg/daily i.p.), valsartan (10 mg/kg daily i.p.) alone or in half dose combination were administered with L-NAME (30-40 mg daily in drinking water) for 8 weeks...
November 27, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29152151/aliskiren-for-heart-failure-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#9
Hongzhi Liu, Hongxing Luo, Suqin Wang, Cong Zhang, Jialiang Hao, Chuanyu Gao
Objective: To systematically review and synthesize the currently available evidence of aliskiren for the treatment of heart failure. Materials and Methods: We systematically searched the Cochrane, Embase and PubMed databases to identify the randomized controlled trials (RCT) on the effects of aliskiren on heart failure. Data were synthesized with random effects model and presented in forest plot. Publication bias was evaluated with funnel plot. Heterogeneity was evaluated with Begg's test and Egger's test...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29145948/type-of-atrial-fibrillation-and-outcomes-in%C3%A2-patients-with-heart-failure-and-reduced%C3%A2-ejection%C3%A2-fraction
#10
RANDOMIZED CONTROLLED TRIAL
Ulrik M Mogensen, Pardeep S Jhund, William T Abraham, Akshay S Desai, Kenneth Dickstein, Milton Packer, Jean L Rouleau, Scott D Solomon, Karl Swedberg, Michael R Zile, Lars Køber, John J V McMurray
BACKGROUND: Atrial fibrillation (AF) is common in heart failure (HF), but the outcome by type of AF is largely unknown. OBJECTIVES: This study investigated outcomes related to type of AF (paroxysmal, persistent or permanent, or new onset) in 2 recent large trials in patients with HF with reduced ejection fraction. METHODS: The study analyzed patients in the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure) trials...
November 14, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29143416/plasma-renin-activity-response-to-aliskiren-and-clinical-outcomes-in-patients-hospitalized-for-heart-failure-the-astronaut-trial
#11
Muthiah Vaduganathan, Baljash Cheema, Erin Cleveland, Kamya Sankar, Haris Subacius, Gregg C Fonarow, Scott D Solomon, Eldrin F Lewis, Stephen J Greene, Aldo P Maggioni, Michael Böhm, Faiez Zannad, Javed Butler, Mihai Gheorghiade
AIMS: The direct renin inhibitor, aliskiren, is known to reduce plasma renin activity (PRA), but whether the efficacy of aliskiren varies based on an individual's baseline PRA in patients hospitalized for heart failure (HF) is presently unknown. We characterized the prognostic value of PRA and determined if this risk is modifiable with use of aliskiren. METHODS AND RESULTS: This pre-specified neurohormonal substudy of ASTRONAUT analysed all patients hospitalized for HF with ejection fraction (EF) ≤40% with available baseline PRA data (n = 1306, 80...
November 16, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29141857/contemporary-characteristics-and-outcomes-in-chagasic-heart-failure-compared-with-other-nonischemic-and-ischemic-cardiomyopathy
#12
Li Shen, Felix Ramires, Felipe Martinez, Luiz Carlos Bodanese, Luis Eduardo Echeverría, Efraín A Gómez, William T Abraham, Kenneth Dickstein, Lars Køber, Milton Packer, Jean L Rouleau, Scott D Solomon, Karl Swedberg, Michael R Zile, Pardeep S Jhund, Claudio R Gimpelewicz, John J V McMurray
BACKGROUND: Chagas' disease is an important cause of cardiomyopathy in Latin America. We aimed to compare clinical characteristics and outcomes in patients with heart failure (HF) with reduced ejection fraction caused by Chagas' disease, with other etiologies, in the era of modern HF therapies. METHODS AND RESULTS: This study included 2552 Latin American patients randomized in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure) trials...
November 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29105958/additivity-of-nebivolol-valsartan-single-pill-combinations-versus-other-single-pill-combinations-for-hypertension
#13
Jack Ishak, Michael Rael, Henry Punzi, Alan Gradman, Lynn M Anderson, Mehul Patel, Sanjida Ali, William Ferguson, Joel Neutel
The single-pill combination (SPC) comprising nebivolol (5 mg), a vasodilatory β1 -selective antagonist/β3 -agonist, and valsartan (80 mg), a renin-angiotensin-aldosterone system inhibitor, is the only Food and Drug Administration-approved β-blocker/renin-angiotensin-aldosterone system inhibitor SPC for hypertension. Additive effects of four nebivolol/valsartan SPC doses (5 mg/80 mg, 5/160 mg, 10/160 mg, 10/320 mg nebivolol/valsartan) were compared with five Food and Drug Administration-approved non-β-blocker/renin-angiotensin-aldosterone system inhibitor SPCs (aliskiren/hydrochlorothiazide, aliskiren/amlodipine, valsartan/amlodipine, aliskiren/valsartan, and telmisartan/amlodipine)...
November 5, 2017: Journal of Clinical Hypertension
https://www.readbyqxmd.com/read/29098323/three-question-set-from-michigan-neuropathy-screening-instrument-adds-independent-prognostic-information-on-cardiovascular-outcomes-analysis-of-altitude-trial
#14
Jelena P Seferovic, Marc A Pfeffer, Brian Claggett, Akshay S Desai, Dick de Zeeuw, Steven M Haffner, John J V McMurray, Hans-Henrik Parving, Scott D Solomon, Nish Chaturvedi
AIMS/HYPOTHESIS: The self-administered Michigan Neuropathy Screening Instrument (MNSI) is used to diagnose diabetic peripheral neuropathy. We examined whether the MNSI might also provide information on risk of death and cardiovascular outcomes. METHODS: In this post hoc analysis of the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial, we divided 8463 participants with type 2 diabetes and chronic kidney disease (CKD) and/or cardiovascular disease (CVD) into independent training (n = 3252) and validation (n = 5211) sets...
November 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/29069238/urinary-cytokine-profiles-according-to-the-site-of-blockade-of-the-renin-angiotensin-system-in-nephrectomized-rats
#15
Nilo César do Vale Baracho, Kátia Daniela da Silveira, Natália Pessoa Rocha, Thiago Macedo Cordeiro, Victor Feracin, Regina Maria Pereira, Marconi Augusto Aguiar Dos Reis, Mauro Martins Teixeira, Ana Cristina Simões E Silva
INTRODUCTION: It is still unknown how the pharmacological inhibition of the Renin Angiotensin System (RAS) impacts the levels of inflammation and fibrosis biomarkers. OBJECTIVE: This study sought to evaluate the effect of enalapril, candesartan and aliskiren on urinary levels of cytokines in a model of chronic kidney disease (CKD). METHODS: Male Wistar rats were submitted to surgical removal of ¾ of renal parenchyma to induce CKD (¾ nephrectomy), or subjected to sham surgery (control)...
April 2017: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/29066168/patterns-and-predictors-of-physician-adoption-of-new-cardiovascular-drugs
#16
Timothy S Anderson, Wei-Hsuan Lo-Ciganic, Walid F Gellad, Rouxin Zhang, Haiden A Huskamp, Niteesh K Choudhry, Chung-Chou H Chang, Seth Richards-Shubik, Hasan Guclu, Bobby Jones, Julie M Donohue
BACKGROUND: Little is known about physicians' approaches to adopting new cardiovascular drugs and how adoption varies between drugs of differing novelty. METHODS: Using data on dispensed prescriptions from IMS Health's Xponent™ database, we created a cohort of all primary care physicians (PCPs) and cardiologists in Pennsylvania who regularly prescribed anticoagulants, antihypertensives and statins from 2007 to 2011. We examined prescribing of three new cardiovascular drugs of differing novelty: dabigatran, aliskiren and pitavastatin...
October 21, 2017: Healthcare
https://www.readbyqxmd.com/read/29061718/inhibition-of-aneurysm-progression-by-direct-renin-inhibition-in-a-rabbit-model
#17
Takashi Miyake, Tetsuo Miyake, Hideo Shimizu, Ryuichi Morishita
Angiotensin II is thought to participate in aneurysm formation, because of its ability to induce and perpetuate inflammation in the aortic wall. Because activation of renin is the first step of the renin-angiotensin system, renin inhibition could inhibit all components of this system effectively. Therefore, we examined the hypothesis that direct inhibition of renin activity could decrease the expansion of aortic aneurysm using a rabbit model. Aortic dilatation was induced by incubation with elastase around the rabbit abdominal aorta...
October 23, 2017: Hypertension
https://www.readbyqxmd.com/read/29046730/aliskiren-effect-on-non-alcoholic-steatohepatitis-in-metabolic-syndrome
#18
F N Ramalho, S C Sanches, M C Foss, M J Augusto, D M Silva, A M Oliveira, L N Ramalho
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is highly associated with metabolic syndrome, a major cause of morbidity in the globalized society. The renin-angiotensin system (RAS) influences hepatic fatty acid metabolism, inflammation and fibrosis. Thus, in the present study, we aimed to evaluate the effect of aliskiren, a direct renin inhibitor, on metabolic syndrome-related NASH. METHODS: C57BL/6 male mice (n = 45) were divided into three groups: controls; animals inoculated with streptozotocin (STZ) (40 mg/kg/day) for 5 days and fed with high fat diet (HFD) for 8 weeks; and animals inoculated with STZ for 5 days, fed with HFD for 8 weeks and treated with aliskiren (100 mg/kg/day) for the final 2 weeks...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/29021226/attenuation-of-accelerated-renal-cystogenesis-in-pkd1-mice-by-renin-angiotensin-system-blockade
#19
Wayne R Fitzgibbon, Yujing Dang, Marlene A Bunni, Catalin F Baicu, Michael R Zile, Adam E Mullick, Takamitsu Saigusa
BACKGROUND: The intrarenal renin angiotensin system (RAS) is activated in polycystic kidney disease. We have recently shown in the Pkd1 mouse that Gen 2 antisense oligonucleotide (ASO), which suppresses angiotensinogen (Agt) synthesis, is efficacious in slowing kidney cyst formation compared to lisinopril. The aim of this current study was to determine 1) if unilateral nephrectomy accelerates cystogenesis in Pkd1 mice (as previously shown in cilia knockout mice), and 2) whether Agt ASO can slow the progression in this accelerated cystic mouse model...
October 11, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29018174/prognostic-value-of-n-terminal-pro-b-type-natriuretic-peptide-levels-in-heart-failure-patients-with-and-without-atrial-fibrillation
#20
Søren Lund Kristensen, Pardeep S Jhund, Ulrik M Mogensen, Rasmus Rørth, William T Abraham, Akshay Desai, Kenneth Dickstein, Jean L Rouleau, Michael R Zile, Karl Swedberg, Milton Packer, Scott D Solomon, Lars Køber, John J V McMurray
BACKGROUND: Patients with heart failure (HF) and atrial fibrillation (AF) have higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) than HF patients without AF. There is uncertainty about the prognostic importance of a given concentration of NT-proBNP in HF patients with and without AF. We investigated this question in a large cohort of patients with HF and reduced ejection fraction. METHODS AND RESULTS: We studied 14 737 patients with HF and reduced ejection fraction and a measurement of NT-proBNP at time of screening, enrolled in either the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG...
October 2017: Circulation. Heart Failure
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