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https://www.readbyqxmd.com/read/27889788/inhibition-of-angiotensin-ii-production-increases-susceptibility-to-acute-ischemia-reperfusion-arrhythmia
#1
Eylem Taskin, Kadir Ali Tuncer, Celal Guven, Salih Tunc Kaya, Nurcan Dursun
BACKGROUND Myocardial ischemia and reperfusion lead to impairment of electrolyte balance and, eventually, lethal arrhythmias. The aim of this study was to investigate the effects of pharmacological inhibition of angiotensin-II (Ang-II) production on heart tissue with ischemia-reperfusion damage, arrhythmia, and oxidative stress. MATERIAL AND METHODS Rats were divided into 4 groups: only ischemia/reperfusion (MI/R), captopril (CAP), aliskiren (AL), and CAP+AL. The drugs were given by gavage 30 min before anesthesia...
November 27, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27859873/impact-of-an-intervention-on-the-prescription-of-aliskiren-after-new-evidence-on-safety-reported
#2
Isabel Rosich Martí, Alejandro Allepuz, Gemma Rodriguez Palomar, Francesca Ortin Font, Maria Soler Cera
PURPOSE: The purpose of the study is to analyze the impact of an intervention to disseminate safety alerts on the utilization of Aliskiren added to angiotensin converting enzyme inhibitor (ACEI) or an angiotensin-receptor blocker (ARB). METHODS: Quasi-experimental design (non-randomized intervention) comparing the utilization of Aliskiren + ACEI or ARB in a primary care area-intervention (PCA-I) with a primary care area-control (PCA-C) following a safety alert...
November 16, 2016: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/27809355/aliskiren-protects-against-myocardial-ischemia-reperfusion-injury-via-an-endothelial-nitric-oxide-synthase-dependent-manner
#3
Yu Chen, Guoliang Meng, Wenli Bai, Yan Ma, Liping Xie, Naila Altaf, Yanning Qian, Yi Han, Yong Ji
Aliskiren, a direct renin inhibitor, was shown potent ability to attenuate hypertension. Our previous research has found that aliskiren protected against myocardial ischemia-reperfusion (I/R) injury and enhanced phosphorylation of endothelial nitric oxide synthase (eNOS) in spontaneously hypertensive rats. However, whether the cardioprotective effect of aliskiren against myocardial I/R injury was eNOS-dependent is unknown. In the present study, 12-week-old male eNOS knockout (eNOS(-/-) ) and wild-type C57BL/6J mice (WT) were orally administrated with the dose of 50 mg/kg/day of aliskiren...
November 3, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27790455/efficacy-and-safety-of-complete-raas-blockade-with-aliskiren-in-patients-with-refractory-proteinuria-who-were-already-on-combined-ace-inhibitor-arb-and-aldosterone-antagonist
#4
Prabitha Panattil, M Sreelatha
INTRODUCTION: Proteinuria is always associated with intrinsic kidney disese and is a strong predictor of later development of End Stage Renal Disease (ESRD). As Renin Angiotensin Aldosterone System (RAAS) has a role in mediating proteinuria, inhibitors of this system are renoprotective and patients with refractory proteinuria are put on a combination of these agents. The routinely employed triple blockade of RAAS with Angiotensin Converting Enzyme (ACE) inhibitor, ARB and Aldosterone antagonist has many limitations...
September 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/27779587/the-renin-inhibitor-aliskiren-protects-rat-lungs-from-the-histopathological-effects-of-fat-embolism
#5
Amanda N Fletcher, Agostino Molteni, Rakesh Ponnapureddy, Chirag Patel, Mark Pluym, Alan M Poisner
BACKGROUND: Fat embolism (FE) and the consequent fat embolism syndrome (FES) occurring after trauma or surgery can lead to serious pulmonary injury, including ARDS and death. Current treatment of FES is limited to supportive therapy. We have shown in a rat model that the renin angiotensin system (RAS) plays a significant role in the pathophysiology of FE since drugs interfering with the RAS, captopril and losartan, reduce the histopathologic pulmonary damage. The purpose of the current study was to determine if inhibition of renin by aliskiren, an FDA-approved drug for treating hypertension, would produce effective protection in the same model...
October 25, 2016: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/27778035/-aliskiren-inhibits-proliferation-of-cardiac-fibroblasts-in-agt-ren-double-transgenic-hypertensive-mice-in-vitro
#6
Li-Ping Wang, Su-Jing Fan, Shu-Min Li, Xiao-Jun Wang, Na Sun
The purpose of the present study is to explore the effect of aliskiren on the proliferation of cardiac fibroblasts (CFs) in AGT-REN double transgenic hypertensive (dTH) mice. The cultured CFs from AGT-REN dTH mice were divided into AGT-REN group (dTH) and aliskiren group (ALIS). Cultured CFs from C57B6 mice were served as control (WT). The effect of different concentration of aliskiren (1 × 10(-6), 1 × 10(-7), 1 × 10(-8), 1 × 10(-9) mol/L) on CFs proliferation was determined by MTT assay. After treatment with 1 × 10(-7) mol/L aliskiren for 24 h, α-SMA, collagen I, III and NADPH oxidase (NOX) protein expression in CFs of AGT-REN dTH mice were detected by Western blot...
October 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/27773804/aliskiren-attenuates-the-effects-of-interleukin-6-on-endothelial-nitric-oxide-synthase-and-caveolin-1-in-human-aortic-endothelial-cells
#7
Ming-Jui Hung, Yu-Cheng Kao, Chun-Tai Mao, Tien-Hsin Chen, Wei-Siang Chen
Renin inhibitors enhance endothelial nitric oxide synthase (eNOS) bioavailability and have protective effects on endothelial function and atherosclerotic changes. This study was designed to investigate whether aliskiren attenuates the effects of interleukin-6 (IL-6) on eNOS and the eNOS-caveolin-1 interaction in human aortic endothelial cells (HAECs). In this study, we examined the effects of pretreatment with aliskiren on the changes of IL-6-induced expression and activation of eNOS and caveolin-1 in cultured HAECs...
October 20, 2016: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/27754863/selective-deletion-of-the-brain-specific-isoform-of-renin-causes-neurogenic-hypertension
#8
Keisuke Shinohara, Xuebo Liu, Donald A Morgan, Deborah R Davis, Maria Luisa S Sequeira-Lopez, Martin D Cassell, Justin L Grobe, Kamal Rahmouni, Curt D Sigmund
The renin-angiotensin system (RAS) in the brain is a critical determinant of blood pressure, but the mechanisms regulating RAS activity in the brain remain unclear. Expression of brain renin (renin-b) occurs from an alternative promoter-first exon. The predicted translation product is a nonsecreted enzymatically active renin whose function is unknown. We generated a unique mouse model by selectively ablating the brain-specific isoform of renin (renin-b) while preserving the expression and function of the classical isoform expressed in the kidney (renin-a)...
October 17, 2016: Hypertension
https://www.readbyqxmd.com/read/27748006/influence-of-atrial-fibrillation-on-post-discharge-natriuretic-peptide-trajectory-and-clinical-outcomes-among-patients-hospitalized-for-heart-failure-insights-from-the-astronaut-trial
#9
Stephen J Greene, Gregg C Fonarow, Scott D Solomon, Haris P Subacius, Andrew P Ambrosy, Muthiah Vaduganathan, Aldo P Maggioni, Michael Böhm, Eldrin F Lewis, Faiez Zannad, Javed Butler, Mihai Gheorghiade
AIMS: Change in NT-proBNP level is a common surrogate endpoint in early phase heart failure (HF) trials, but whether this endpoint is influenced by atrial fibrillation/flutter (AFF) is unclear. METHODS AND RESULTS: This analysis included 1358 patients from the ASTRONAUT trial, which randomized patients hospitalized for HF with EF ≤40% to aliskiren or placebo in addition to standard care. Patients were stratified by presence of AFF on baseline ECG. NT-proBNP was measured longitudinally by a core laboratory at baseline, 1 month, 6 months, and 12 months...
October 17, 2016: European Journal of Heart Failure
https://www.readbyqxmd.com/read/27713608/aliskiren-inhibits-neointimal-matrix-metalloproteinases-in-experimental-atherosclerosis
#10
Tao-Cheng Wu, Chiu-Yang Lee, Shing-Jong Lin, Jaw-Wen Chen
BACKGROUND: The renin-angiotensin system (RAS) plays an important role in atherosclerosis. Acting via the angiotensin II receptor, type 1, oxidative stress increases and contributes to endothelial dysfunction and vascular inflammation. Renin exerts effects through a renin receptor causing an increase in the efficiency of angiotensinogen cleavage and facilitates angiotensin II (Ang II) generation and action on cell surfaces. Ang II enhances proliferation and migration of vascular smooth muscle cells, indicating a direct involvement of the RAS in smooth muscle cell proliferation during neointimal formation...
September 2016: Acta Cardiologica Sinica
https://www.readbyqxmd.com/read/27695972/aliskiren-decreases-oxidative-stress-and-angiogenic-markers-in-retinal-pigment-epithelium-cells
#11
Sónia Simão, Daniela F Santos, Gabriela A Silva
There is growing evidence on the role of ocular renin-angiotensin system (RAS) in the development of diabetic retinopathy (DR), particularly due to the trigger of oxidative stress and angiogenesis. Despite this there is no effective RAS-based therapy in DR capable of preventing retinal damage induced by RAS activation. We recently described that retinal pigment epithelium (RPE) cells express the main components of the RAS. We here propose to investigate the role of glucose upon the retinal RAS and whether aliskiren, a direct renin inhibitor, protects RPE cells from angiogenesis and oxidative stress...
October 1, 2016: Angiogenesis
https://www.readbyqxmd.com/read/27667116/aliskiren-targets-multiple-systems-to-alleviate-cancer-cachexia
#12
Chaoyi Wang, Dunwei Guo, Qiang Wang, Song You, Zhongpeng Qiao, Yong Liu, Hang Dai, Hua Tang
To examine the effects of aliskiren, a small-molecule renin inhibitor, on cancer cachexia and to explore the underlying mechanisms. A cancer cachexia model was established by subcutaneously injecting C26 mouse colon carcinoma cells into isogenic BALB/c mice. Aliskiren was administered intragastrically [10 mg/kg body weight (BW)] on day 5 (as a preventive strategy, AP group) or on day 12 (as a therapeutic strategy, AT group) after C26 injection. Mice that received no C26 injection (healthy controls, HC group) or only C26 injection but not aliskiren (cancer, CA group) were used as controls...
September 21, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27645307/inhibiting-renin-angiotensin-system-in-rate-limiting-step-by-aliskiren-as-a-new-approach-for-preventing-indomethacin-induced-gastric-ulcers
#13
Zekai Halici, Beyzagul Polat, Elif Cadirci, Atilla Topcu, Emre Karakus, Duygu Kose, Abdulmecit Albayrak, Yasin Bayir
PURPOSE: Previously blocking the renin angiotensin system (RAAS) has been effective in the prevention of gastric damage. Therefore, the aim of this study was to investigate the effects of aliskiren, and thus, direct renin blockage, in indomethacin-induced gastric damage model. METHODS: Effects of aliskiren were evaluated in indomethacin-induced gastric damage model on Albino Wistar rats. Effects of famotidine has been investigated as standard antiulcer agent. Stereological analyses for ulcer area determination, biochemical analyses for oxidative status determination and molecular analyses for tissue cytokine and cyclooxygenase determination were performed on stomach tissues...
October 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27612855/anti-diabetic-and-renoprotective-effects-of-aliskiren-in-streptozotocin-induced-diabetic-nephropathy-in-female-rats
#14
Amal M Mahfoz, Hekma A Abd El-Latif, Lamiaa A Ahmed, Nahed M Hassanein, Afaf A Shoka
Since chronic kidney disease due to diabetic nephropathy (DN) is becoming an ever larger health burden worldwide, more effective therapies are desperately needed. In the present study, the anti-diabetic and renoprotective effects of aliskiren have been evaluated in streptozotocin (STZ)-induced DN in rats. DN was induced by a single intraperitoneal injection of STZ (65 mg/kg). Three weeks after STZ, rats were divided into four groups; normal, diabetic, diabetic treated with gliclazide (10 mg/kg/day) for 1 month, and diabetic treated with aliskiren (50 mg/kg/day) for 1 month...
September 9, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27570581/the-effect-of-aliskiren-on-the-renal-dysfunction-following-unilateral-ureteral-obstruction-in-the-rat
#15
Fayez T Hammad, Loay Lubbad
PURPOSE: To investigate the effect of blocking renin-angiotensin system by direct renin inhibition using aliskiren on the renal dysfunction following reversible unilateral ureteral obstruction (UO). METHODS: Wistar rats underwent reversible left UO for 72 hours. Group-Alsk (n=12) received aliskiren (30 mg/kg/day) dissolved in water starting one day before creating UO and continued until the terminal experiment five days post reversal when renal functions were measured using clearance techniques...
2016: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/27568833/mechanistic-insight-of-diabetic-nephropathy-and-its-pharmacotherapeutic-targets-an-update
#16
Niloy Bhattacharjee, Sujata Barma, Nandita Konwar, Saikat Dewanjee, Prasenjit Manna
Diabetic nephropathy (DN), a chronic complication of diabetes, is charecterized by glomerular hypertrophy, proteinuria, decreased glomerular filtration, and renal fibrosis resulting in the loss of renal function. Although the exact cause of DN remains unclear, several mechanisms have been postulated, such as hyperglycemia-induced renal hyper filtration and renal injury, AGEs-induced increased oxidative stress, activated PKC-induced increased production of cytokines, chemokines, and different inflammatory and apoptotic signals...
August 25, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27560625/aliskiren-regulates-neonatal-fc-receptor-and-igg-metabolism-with-attenuation-of-anti-gbm-glomerulonephritis-in-mice
#17
Ju Hyung Kang, Haing Woon Baik, Seung-Min Yoo, Joo Heon Kim, Hae Il Cheong, Chung-Gyu Park, Hee Gyung Kang, Il-Soo Ha
BACKGROUND: Renin, in addition to its activation of the renin-angiotensin system, binds to the (pro)renin receptor (PRR) and triggers inflammatory and fibrogenic signaling in tissue. In addition, aliskiren, a direct renin inhibitor, has been shown to affect IgG metabolism by altering PRR and neonatal Fc receptors (FcRns). METHODS: We investigated the effect of aliskiren on proteinuria, glomerular extracellular matrix, expressions of fibronectin, transforming growth factor β1 (TGF-β1), PRR, FcRn and renal metabolism of IgG in a mice model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN)...
August 25, 2016: Nephron
https://www.readbyqxmd.com/read/27545826/intracellular-renin-increases-the-inward-calcium-current-in-smooth-muscle-cells-of-mesenteric-artery-of-shr-implications-for-hypertension-and-vascular-remodeling
#18
Walmor De Mello
UNLABELLED: The influence of intracellular renin on the inward calcium current in isolated smooth muscle cells from SHR mesenteric arteries was investigated. Measurements of calcium current were performed using the whole cell configuration of pCLAMP. The results indicated that: 1) renin (100nM) dialyzed into smooth muscle cells, increased the inward calcium current; 2) verapamil (10-9M) administered to the bath inhibited the effect of renin on the inward calcium current; 3) concurrently with the increase of calcium current a depolarization of 6...
October 2016: Peptides
https://www.readbyqxmd.com/read/27533118/therapeutic-modulation-of-tissue-kallikrein-expression
#19
Duncan J Campbell
The kallikrein kinin system has cardioprotective actions and mediates in part the cardioprotection produced by angiotensin converting enzyme inhibitors and angiotensin type 1 receptor blockers. Additional approaches to exploit the cardioprotective effects of the kallikrein kinin system include the administration of tissue kallikrein and kinin receptor agonists. The renin inhibitor aliskiren was recently shown to increase cardiac tissue kallikrein expression and bradykinin levels, and to reduce myocardial ischemia-reperfusion injury by bradykinin B2 receptor- and angiotensin AT2 receptor-mediated mechanisms...
August 17, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27532844/aliskiren-enalapril-or-both-in-heart-failure
#20
LETTER
Alessandra R Silva, Alexandre Martini, Francisco A R Neves
No abstract text is available yet for this article.
August 18, 2016: New England Journal of Medicine
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