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https://www.readbyqxmd.com/read/28640888/mechanisms-of-acute-neurovascular-protection-with-at1-blockade-after-stroke-effect-of-prestroke-hypertension
#1
Ahmed Alhusban, Anna Kozak, Bindu Pillai, Heba Ahmed, Mohammed A Sayed, Maribeth H Johnson, Tauheed Ishrat, Adviye Ergul, Susan C Fagan
Stroke is a leading cause of adult disability worldwide. Improving stroke outcome requires an orchestrated interplay that involves up regulation of pro-survival pathways and a concomitant suppression of pro-apoptotic mediators. In this investigation, we assessed the involvement of eNOS in the AT1 blocker-mediated protective and pro-recovery effects in animals with hypertension. We also evaluated the effect of acute eNOS inhibition in hypertensive animals. To achieve these goals, spontaneously hypertensive rats (SHR) were implanted with blood pressure transmitters, and randomized to receive either an eNOS inhibitor (L-NIO) or saline one hour before cerebral ischemia induction...
2017: PloS One
https://www.readbyqxmd.com/read/28617574/synergistic-suppression-of-tumor-angiogenesis-by-co-delivering-of-vegf-targeted-sirna-and-candesartan-mediated-by-functionalized-carbon-nanovectors
#2
Xuefang Ding, Yujie Su, Cheng Wang, Fangrong Zhang, Kerong Chen, Yu Wang, Min Li, Wei Wang
Single-walled carbon nanotubes (SWNTs) with unique physicochemical properties have exhibited promising biomedical applications as drug/gene carrier. In this study, polyethyleneimine (PEI) modified SWNT conjugates linked with candesartan (CD) were developed to deliver vascular endothelial growth factor (VEGF) targeted siRNA (siVEGF) for synergistic and targeted treatment of tumor angiogenesis. The characterization results revealed that SWNT-PEI-CD conjugates were successfully synthesized, and exhibited desirable dispersibility and superior stability...
June 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28595131/a-precision-guided-mwnt-mediated-reawakening-the-sunk-synergy-in-ras-for-anti-angiogenesis-lung-cancer-therapy
#3
Yujie Su, Yahui Hu, Yu Wang, Xiangting Xu, Yang Yuan, Yunman Li, Zeyuan Wang, Kerong Chen, Fangrong Zhang, Xuefang Ding, Min Li, Jianping Zhou, Yuan Liu, Wei Wang
Multi-walled carbon nanotube (MWNT) with its versatility has exhibited tremendous superiority in drug delivery. Despite plenty of researches on MWNT based delivery systems, precision-guided assistances to maximize their profitable properties are still lacking in substantive progress. We developed here a dual-targeting and co-delivery system based on MWNT for antiangiogenesis therapy in lung cancer which aimed at renin-angiotensin system (RAS) dysregulation by synergistically conducting angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R) pathway...
September 2017: Biomaterials
https://www.readbyqxmd.com/read/28587581/ace-phenotyping-as-a-guide-toward-personalized-therapy-with-ace-inhibitors
#4
Sergei M Danilov, Stan I Tovsky, David E Schwartz, Randal O Dull
BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors (ACEI) are widely used in the management of cardiovascular diseases but with significant interindividual variability in the patient's response. OBJECTIVES: To investigate whether interindividual variability in the response to ACE inhibitors is explained by the "ACE phenotype"-for example, variability in plasma ACE concentration, activity, and conformation and/or the degree of ACE inhibition in each individual...
July 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28524699/comparison-of-ambulatory-blood-pressure-lowering-effects-of-higher-doses-of-different-calcium-antagonists-in-uncontrolled-hypertension-the-calcium-antagonist-controlled-release-high-dose-therapy-in-uncontrolled-refractory-hypertensive-patients-carillon-study
#5
Hiroyuki Mizuno, Satoshi Hoshide, Naoko Tomitani, Kazuomi Kario
BACKGROUND: Data are sparse regarding ambulatory blood pressure (BP) reduction of up-titration from a standard dose to a high dose in both nifedipine controlled-release (CR) and amlodipine. This was a prospective, randomized, multicenter, open-label trial. PATIENTS AND METHODS: Fifty-one uncontrolled hypertensives medicated by two or more antihypertensive drugs including a renin-angiotensin system inhibitor and a calcium antagonist were randomly assigned to either the nifedipine CR (80 mg)/candesartan (8 mg) group or the amlodipine (10 mg)/candesartan (8 mg) group...
May 19, 2017: Blood Pressure
https://www.readbyqxmd.com/read/28501349/potential-health-impact-and-cost-effectiveness-of-drug-therapy-for-prehypertension
#6
Tao Chen, Dahai Yu, Victoria Cornelius, Rui Qin, Yamei Cai, Zhixin Jiang, Zhanzheng Zhao
BACKGROUND: Studies have reported that pharmacologic interventions with candesartan or ramipril could reduce the risk of hypertension among prehypertensive subjects free of clinical cardiovascular disease (CVD), however, the cost-effectiveness and long-term cardiovascular risk of drug treatment among these population is unclear. METHOD: A Markov state-transition model was developed to simulate a hypothetical cohort of Chinese adults with high-range prehypertension (130-139/85-89mmHg) but without CVD...
May 5, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28468966/protein-disulfide-isomerase-regulates-renal-at1-receptor-function-and-blood-pressure-in-rats
#7
Xitao Wang, Mohammad Asghar
Role and mechanism of renal PDI in blood pressure (BP) regulation has not been tested before. Here, we are testing this possibility in Sprague-Dawley (SD) rats. Rats were treated with PDI inhibitor bacitracin (100mg/kg, i.p./day for 14 days) followed by determining BP and renal AT1 receptor (AT1R) function in anesthetized rats. Renal AT1R function was determined as the ability of candesartan (an AT1R blocker) to increase diuresis and natriuresis. Second set of vehicle and bacitracin treated rats were used to determine biochemical parameters...
May 3, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28449313/neurovascular-unit-alteration-in-somatosensory-cortex-and-enhancement-of-thermal-nociception-induced-by-amphetamine-involves-central-at1-receptor-activation
#8
Victoria Belén Occhieppo, Natalia Andrea Marchese, Iara Diamela Rodríguez, Osvaldo Martin Basmadjian, Gustavo Baiardi, Claudia Bregonzio
The use of psychostimulants, such as amphetamine (Amph), is associated with inflammatory processes, involving glia and vasculature alterations. Brain Angiotensin II (Ang II), through AT1 -receptors (AT1 -R), modulates neurotransmission and plays a crucial role in inflammatory responses in brain vasculature and glia. Our aim for the present work was to evaluate the role of AT1 -R in long-term alterations induced by repeated exposure to Amph. Astrocyte reactivity, neuronal survival and brain microvascular network were analysed at the somatosensory cortex...
April 27, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28448185/addition-of-spironolactone-in-patients-with-resistant-hypertension-a-meta-analysis-of-randomized-controlled-trials
#9
Liping Liu, Bing Xu, Yunfeng Ju
This study was designed to assess the effect of additional spironolactone on blood pressure in patients with resistant hypertension. MEDLINE, EMBASE, and Cochrane Library were searched to identify randomized controlled trials (RCTs) that determined the effect of add-on spironolactone on blood pressure in patients with resistant hypertension compared with a control group. A total of five RCTs met the inclusion criteria. Spironolactone reduced office systolic blood pressure (SBP) by 15.73 mmHg (95% CI -20.45 to -11...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28426886/risk-of-stroke-in-chronic-heart-failure-patients-with-preserved-ejection-fraction-but-without-atrial-fibrillation-analysis-of-the-charm-preserved-and-i-preserve-trials
#10
Azmil H Abdul-Rahim, Ana-Cristina Perez, Rachael L MacIsaac, Pardeep S Jhund, Brian L Claggett, Peter E Carson, Michel Komajda, Robert S McKelvie, Michael R Zile, Karl Swedberg, Salim Yusuf, Marc A Pfeffer, Scott D Solomon, Gregory Y H Lip, Kennedy R Lees, John J V McMurray
Aims: The incidence and predictors of stroke in patients with heart failure and preserved ejection fraction (HF-PEF), but without atrial fibrillation (AF), are unknown. We described the incidence of stroke in HF-PEF patients with and without AF and predictors of stroke in those without AF. Methods and results: We pooled data from the CHARM-Preserved and I-Preserve trials. Using Cox regression, we derived a model for stroke in patients without AF in this cohort and compared its performance with a published model in heart failure patients with reduced ejection fraction (HF-REF)-predictive variables: age, body mass index, New York Heart Association class, history of stroke, and insulin-treated diabetes...
March 7, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28415046/cost-benefit-effectiveness-of-angiotensin-ii-receptor-blockers-in-patients-with-uncomplicated-hypertension-a-comparative-analysis
#11
Alberto Mazza, Antonella Paola Sacco, Danyelle M Townsend, Gianni Bregola, Edgardo Contatto, Isabella Cappello, Laura Schiavon, Emilio Ramazzina, Domenico Rubello
OBJECTIVE: The treatment of hypertensive patients (HTs) requires a long-term commitment of compliance for the patient and resources by the healthcare system. This poses an economic dilemma in countries where universal healthcare is standard. The aim of this study was to evaluate the costs/health benefit and effectiveness of treatment with angiotensin-II receptor blockers (ARBs) in uncomplicated essential hypertension. DESIGN AND METHODS: The daily and annual economic commitment for treating patients with ARBs was estimated using pharmacy dispensing records and the BP-lowering effects of candesartan, irbesartan, losartan, olmesartan, telmisartan and valsartan was evaluated retrospectively...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28405886/pharmacokinetic-variability-of-drugs-used-for-prophylactic-treatment-of-migraine
#12
REVIEW
Peer Tfelt-Hansen, Frederik Nybye Ågesen, Agniezka Pavbro, Jacob Tfelt-Hansen
In this review, we evaluate the variability in the pharmacokinetics of 11 drugs with established prophylactic effects in migraine to facilitate 'personalized medicine' with these drugs. PubMed was searched for 'single-dose' and 'steady-state' pharmacokinetic studies of these 11 drugs. The maximum plasma concentration was reported in 248 single-dose and 115 steady-state pharmacokinetic studies, and the area under the plasma concentration-time curve was reported in 299 single-dose studies and 112 steady-state pharmacokinetic studies...
May 2017: CNS Drugs
https://www.readbyqxmd.com/read/28400916/angiotensin-receptor-blocker-drugs-and-inhibition-of-adrenal-beta-arrestin-1-dependent-aldosterone-production-implications-for-heart-failure-therapy
#13
EDITORIAL
Anastasios Lymperopoulos, Beatrix Aukszi
Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II (AngII). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure (HF), is induced by AngII type 1 receptors (AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1 (βarr1) or -2 (βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 protein-independent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated...
March 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28374982/angiotensin-ii-receptor-blockers-inhibit-the-generation-of-epoxyeicosatrienoic-acid-from-arachidonic-acid-in-recombinant-cyp2c9-cyp2j2-and-human-liver-microsomes
#14
Asuna Senda, Yuji Mukai, Toru Hayakawa, Yuka Kato, Erik Eliasson, Anders Rane, Takaki Toda, Nobuo Inotsume
Cytochrome P450 (CYP) 2C9, CYP2C8 and CYP2J2 enzymes, which metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs), have cardioprotective effects including anti-inflammation and vasodilation. We have recently shown that some angiotensin II receptor blockers (ARBs) may inhibit AA metabolism via CYP2C8. Using recombinant CYP2C9, CYP2J2, and human liver microsomes (HLMs), the aim was now to compare the ability of six different clinically used ARBs to inhibit AA metabolism in vitro. The rank order of the ARBs for the 50% inhibitory concentration (IC50 ) of AA metabolism was losartan < telmisartan < irbesartan < candesartan < olmesartan < valsartan via CYP2C9, and telmisartan < irbesartan < olmesartan < losartan < candesartan and valsartan via CYP2J2...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28290850/-prevention-of-cardiovascular-complications-in-patients-with-arterial-hypertension-while-use-of-angiotensin-ii-receptor-antagonists-possibilities-of-candesartan
#15
N M Savina
The article demonstrates advantages of angiotensin II receptor antagonists in treatment of arterial hypertension (AH). Subjects for consideration are evidences of antihypertensive efficacy of candesartan and possibilities of the product in prevention of cardiovascular complications in patients with AH.
June 2016: Kardiologiia
https://www.readbyqxmd.com/read/28274926/%C3%AE-arrestin-biased-at1r-stimulation-promotes-extracellular-matrix-synthe-sis-in-renal-fibrosis
#16
Yandao Wang, Jieli Huang, Xi Liu, Yangyang Niu, Liqin Zhao, Ying Yu, Li Zhou, Limin Lu, Chen Yu
BACKGROUND: Renin-angiotensin system (RAS) plays a critical role in the progression of renal fibrosis. Angiotensin II type 1 receptor (AT1R) belongs to the B family of G protein coupled receptors (GPCRs) family. β-arrestins are known as negative regula-tors of GPCRs. Recently, β-arrestins have been found to regulate multiple intracellu-lar signaling pathways independent of G proteins. In this study we investigated the role of β-arrestins in regulating extracellular matrix (ECM) synthesis in renal fibrosis...
March 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28239165/antihypertensive-agents-do-not-prevent-blood-brain-barrier-dysfunction-and-cognitive-deficits-in-dietary-induced-obese-mice
#17
J C L Mamo, V Lam, C Giles, S H Coulson, N Fimognari, A Mooranian, H Al-Salami, R Takechi
BACKGROUND: While vascular risk factors including Western-styled diet and obesity are reported to induce cognitive decline and increase dementia risk, recent reports consistently suggest that compromised integrity of cerebrovascular blood-brain barrier (BBB) may have an important role in neurodegeneration and cognitive deficits. A number of studies report that elevated blood pressure increases the permeability of BBB. METHODS: In this study, we investigated the effects of antihypertensive agents, candesartan or ursodeoxycholic acid (UDCA), on BBB dysfunction and cognitive decline in wild-type mice maintained on high fat and fructose (HFF) diet for 24 weeks...
June 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28230330/comparing-six-antihypertensive-medication-classes-for-preventing-new-onset-diabetes-mellitus-among-hypertensive-patients-a-network-meta-analysis
#18
Yang Yang, Huilan Xu
Hypertensive patients usually have a higher risk of new-onset diabetes mellitus (NOD) which may trigger cardiovascular diseases. In this study, the effectiveness of six antihypertensive agents with respect to NOD prevention in hypertensive patients was assessed. A network meta-analysis was conducted to compare the efficacy of specific drug classes. PubMed and Embase databases were searched for relevant articles. Results of the pairwised meta-analysis were illustrated by odd ratios (OR) and a corresponding 95% confidence interval (CI)...
February 23, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28220370/the-effect-of-candesartan-on-pentraxin-3-plasma-levels-as-marker-of-endothelial-dysfunction-in-patients-with-essential-arterial-hypertension
#19
V Buda, M Andor, C Cristescu, M Voicu, F Cochera, P Tuduce, L Petrescu, M C Tomescu
BACKGROUND: In the last decades, the studies performed on the field of endothelial dysfunction confirmed the fact that the starting point of this pathology is the inflammation. Several inflammatory biomarkers had been discovered and studied, ones showing systemic inflammation, and others being more specific biomarkers and showing the local inflammation. Pentraxin-3 (PTX3) is a new inflammatory biomarker, from the same family as high-selectivity C-reactive protein (hs-CRP), but it is a more specific biomarker, due to its local production: the endothelial cells and not the liver like in the case of hs-CRP...
February 21, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28215000/angiotensin-ii-receptor-blockers-attenuate-lipopolysaccharide-induced-memory-impairment-by-modulation-of-nf-%C3%AE%C2%BAb-mediated-bdnf-creb-expression-and-apoptosis-in-spontaneously-hypertensive-rats
#20
Ruby Goel, Shahnawaz Ali Bhat, Kashif Hanif, Chandishwar Nath, Rakesh Shukla
Clinical studies demonstrated a positive correlation between hypertension and cognitive decline. Beneficial effects of angiotensin II receptor blockers on cognitive functions have also been reported earlier; however, its role in chronic neuroinflammation-induced memory impairment in the hypertensive state is not well understood. Therefore, in the present study, we investigated the effect of angiotensin II receptor blockers on memory impairment induced by lipopolysaccharide (LPS) in spontaneously hypertensive rats (SHRs)...
February 18, 2017: Molecular Neurobiology
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