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https://www.readbyqxmd.com/read/28107310/the-renin-inhibitor-aliskiren-protects-rat-lungs-from-the-histopathologic-effects-of-fat-embolism
#1
Amanda N Fletcher, Agostino Molteni, Rakesh Ponnapureddy, Chirag Patel, Mark Pluym, Alan M Poisner
BACKGROUND: Fat embolism (FE) and the consequent FE syndrome occurring after trauma or surgery can lead to serious pulmonary injury, including ARDS and death. Current treatment of FE syndrome is limited to supportive therapy. We have shown in a rat model that the renin angiotensin system plays a significant role in the pathophysiology of FE because drugs interfering with the renin angiotensin system, 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...
February 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28096205/effect-of-prepublication-results-on-trends-in-prescribing-of-antihypertensive-medication-impact-of-the-altitude-aliskiren-trial-in-type-2-diabetes-using-cardio-renal-disease-endpoints-trial-on-aliskiren-prescribing
#2
Sahar S Othman, Peter C Austin, Jack V Tu, Douglas S Lee
No abstract text is available yet for this article.
January 2017: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/28040266/angiotensin-ii-at1-receptor-signaling-is-necessary-for-cyclooxygenase-2-dependent-postnatal-nephron-generation
#3
Stefanie Frölich, Patrick Slattery, Dominique Thomas, Itamar Goren, Nerea Ferreiros, Boye L Jensen, Rolf M Nüsing
Deletion of cyclooxygenase-2 (COX-2) causes impairment of postnatal kidney development. Here we tested whether the renin angiotensin system contributes to COX-2-dependent nephrogenesis in mice after birth and whether a rescue of impaired renal development and function in COX-2(-/-) mice was achievable. Plasma renin concentration in mouse pups showed a birth peak and a second peak around day P8 during the first 10 days post birth. Administration of the angiotensin II receptor AT1 antagonist telmisartan from day P1 to P3 did not result in cortical damage...
December 28, 2016: Kidney International
https://www.readbyqxmd.com/read/28002889/variability-in-response-to-albuminuria-lowering-drugs-true-or-random
#4
S I Petrykiv, D de Zeeuw, F Persson, P Rossing, R T Gansevoort, G D Laverman, H J L Heerspink
AIMS: Albuminuria lowering drugs have shown different effect size in different individuals. Since urine albumin levels are known to vary considerably from day-to-day, we questioned whether the between-individual variability in albuminuria response after therapy initiation reflects a random variability or a true response variation to treatment. In addition, we questioned whether the response variability is drug dependent. METHODS: To determine whether the response to treatment is random or a true drug response, we correlated in six clinical trials the change in albuminuria during placebo or active treatment (on-treatment) with the change in albuminuria during wash-out (off-treatment)...
December 21, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27936941/comparison-of-direct-renin-inhibitor-and-angiotensin-ii-receptor-blocker-on-clinic-and-ambulatory-blood-pressure-profiles-in-hypertension-with-chronic-kidney-disease
#5
RANDOMIZED CONTROLLED TRIAL
Kazushi Uneda, Kouichi Tamura, Hiromichi Wakui, Kengo Azushima, Sona Haku, Ryu Kobayashi, Kohji Ohki, Kotaro Haruhara, Sho Kinguchi, Masato Ohsawa, Tetsuya Fujikawa, Satoshi Umemura
We compared the therapeutic effects of aliskiren (direct renin inhibitor (DRI) group) with angiotensin II (Ang II) type 1 receptor blockers (ARBs) (ARB group) on clinic blood pressure (BP) and ambulatory BP in 36 hypertensive chronic kidney disease (CKD) patients. The baseline clinic BP levels and the after-treatment/baseline (A/B) ratios of clinic BP levels, estimated after 24-week treatment period, were similar in DRI group (n = 18) and ARB group (n = 18). With respect to the effects on ambulatory BP, the A/B ratios of the daytime and nighttime systolic BP in DRI group were significantly higher than those in ARB group...
2016: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/27889788/inhibition-of-angiotensin-ii-production-increases-susceptibility-to-acute-ischemia-reperfusion-arrhythmia
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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)...
December 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
#14
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
#15
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
#16
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
#17
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...
November 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
#18
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
#19
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
#20
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
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