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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
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
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 Cardiol Sin
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
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
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
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
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
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
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
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
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
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
R de O Caminhotto, R A L Sertié, S Andreotti, A B Campaãa, F B Lima
Due to the presence of the renin-angiotensin system (RAS) in tissues and its specific influence on white adipose tissue, fat cells are possible targets of pharmacological RAS blockers commonly used as anti-hypertensive drugs. In the present study, we investigated the effects of different RAS blockers on fat cell metabolism, more specifically on lipolysis, lipogenesis and oxidation of energy substrates. Isolated primary adipocytes were incubated with different RAS blockers (aliskiren, captopril and losartan) in vitro for 24 h and lipolysis, lipogenesis and glucose oxidation capacities were determined in dose-response assays to a β-adrenergic agonist and to insulin...
July 28, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Frederik Persson, Simone Theilade, Jesper Eugen-Olsen, Peter Rossing, Hans-Henrik Parving
Soluble urokinase plasminogen activator receptor (suPAR) is associated with faster decline in kidney function and the pathogenesis of diabetic nephropathy. However, little is known about the impact of treatment on plasma and urinary levels of suPAR. We aimed to investigate the impact of renin angiotensin system (RAS) single and dual blockade on suPAR levels in patients with type 2 diabetes and albuminuria. We conducted a post-hoc analysis of a randomized controlled crossover trial. Urine and plasma samples were analyzed for suPAR levels...
November 2016: Journal of Diabetes and its Complications
Zachary A Marcum, Johanna E Bellon, Jie Li, Walid F Gellad, Julie M Donohue
BACKGROUND: Medications to treat and prevent chronic disease have substantially reduced morbidity and mortality; however, their diffusion has been uneven. Little is known about prescribing of chronic disease medications by nurse practitioners (NPs) and physician assistants (PAs), despite their increasingly important role as primary care providers. Thus, we sought to conduct an exploratory analysis to examine prescribing of new chronic disease medications by NPs and PAs compared to primary care physicians (PCPs)...
2016: BMC Health Services Research
Chien-Ning Hsu, Kay L H Wu, Wei-Chia Lee, Steve Leu, Julie Y H Chan, You-Lin Tain
UNLABELLED: Key points summary Maternal high-fructose (HF) induces programmed hypertension in adult offspring.Early aliskiren administration prevents HF-induced hypertension in both sexes of adult offspring.HF regulates RAS components in the offspring kidney in a sex-specific manner.HF alters renal transcriptome, with female offspring being more sensitive.Deprogramming strategy to prevent hypertension might be sex-specific. BACKGROUND: Maternal high fructose (HF) intake induced renal programming and hypertension in male adult offspring...
2016: Frontiers in Physiology
O B Kuzmin, N V Buchneva, L N Landar
Propranolol injection (0.5 mg/kg, s.c.) in anesthetized rats increases diuresis 1.60 times (p < 0.05) with simultaneous 1.54- and 1.62-fold increase (p < 0.05) in sodium and potassium excretion, respectively. Preliminary inhibition of renin-angiotensin system (RAS) activity using ACE inhibitor enalapril (1 mg/kg, orally, 7 days) increases the sensitivity of rat kidney to drug, increasing its diuretic effect 2.33 times, natriuresis 2.49 times, and urine potassium excretion 1.80 times (p < 0.05). After the preliminary insertion of AT1 angiotensin receptor antagonist losartan (1 mg/kg, orally, 7 days), propranolol causes 1...
2016: Eksperimental'naia i Klinicheskaia Farmakologiia
Sheila Flavahan, Fumin Chang, Nicholas A Flavahan
Aging impairs endothelium-dependent NO-mediated dilatation, which results from increased production of reactive oxygen species (ROS). The local generation of angiotensin II (ANG II) is increased in aging arteries and contributes to inflammatory and fibrotic activity of smooth muscle cells and arterial wall remodeling. Although prolonged in vivo ANG II inhibition improves the impaired endothelial dilatation of aging arteries, it is unclear whether this reflects inhibition of intravascular or systemic ANG II systems...
September 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Manuela Ciocoiu, Magda Badescu, Oana Badulescu, Laurentiu Badescu
CONTEXT: The health effects of Sambucus nigra L. (Caprifoliaceae) could be due to polyphenols whose modes of action differ from the traditional one proposed for exogenous antioxidants. OBJECTIVE: The study emphasizes the effects of the association between the renin inhibitor and the polyphenolic extract on biochemical parameters and systolic (TAS) and diastolic (TAD) blood pressure within an L NAME-induced experimental model of arterial hypertension (AHT). MATERIALS AND METHODS: The polyphenols are extracted with ethanol from isolated and purified vegetable material represented by the mature fruit of the S...
July 14, 2016: Pharmaceutical Biology
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