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https://www.readbyqxmd.com/read/27908837/angiotensin-type-1a-receptor-regulates-%C3%AE-arrestin-binding-of-the-%C3%AE-2-adrenergic-receptor-via-heterodimerization
#1
András D Tóth, Pál Gyombolai, Bence Szalai, Péter Várnai, Gábor Turu, László Hunyady
Heterodimerization between angiotensin type 1A receptor (AT1R) and β2-adrenergic receptor (β2AR) has been shown to modulate G protein-mediated effects of these receptors. Activation of G protein-coupled receptors (GPCRs) leads to β-arrestin binding, desensitization, internalization and G protein-independent signaling of GPCRs. Our aim was to study the effect of heterodimerization on β-arrestin coupling. We found that β-arrestin binding of β2AR is affected by activation of AT1Rs. Costimulation with angiotensin II and isoproterenol markedly enhanced the interaction between β2AR and β-arrestins, by prolonging the lifespan of β2AR-induced β-arrestin2 clusters at the plasma membrane...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27889505/candesartan-ameliorates-arsenic-induced-hypertensive-vascular-remodeling-by-regularizing-angiotensin-ii-and-tgf-beta-signaling-in-rats
#2
Maibam Wanta Khuman, Sankaran Kutty Harikumar, Abdul Sadam, Manickam Kesavan, Vattaparambil Sukumaran Susanth, Subhashree Parida, Karam Pal Singh, Souvendra Nath Sarkar
Arsenic exposure can cause several cardiovascular diseases, including hypertension, atherosclerosis and microvascular disease. Earlier, we reported that arsenic-mediated enhancement of angiotensin II (AngII) signaling can impair vascular physiology. Here, we investigated whether the AT1 receptor (AT1R) blocker candesartan can ameliorate the arsenic-induced hypertensive vascular remodeling in rats and whether the amelioration could relate to attenuation in vascular AngII and TGF-β signaling. Rats were exposed to sodium arsenite (50ppm) through drinking water for 90 consecutive days...
November 23, 2016: Toxicology
https://www.readbyqxmd.com/read/27856342/angiotensin-ii-at1-receptors-mediate-neuronal-sensitization-and-sustained-blood-pressure-response-induced-by-a-single-injection-of-amphetamine
#3
N A Marchese, M C Paz, X Caeiro, F M Dadam, G Baiardi, M F Perez, C Bregonzio
A single exposure to amphetamine induces neurochemical sensitization in striatal areas. The neuropeptide angiotensin II, through AT1 receptors (AT1-R) activation, is involved in these responses. However, amphetamine-induced alterations can be extended to extra-striatal areas involved in blood pressure control and their physiological outcomes. Our aim for the present study was to analyze the possible role for AT1-R in these events using a two-injection protocol and to further characterize the proposed AT1-R antagonism protocol...
November 14, 2016: Neuroscience
https://www.readbyqxmd.com/read/27846743/support-for-involvement-of-the-renin-angiotensin-system-in-dysplastic-barrett-s-esophagus
#4
Svein Olav Bratlie, Anna Casselbrant, Anders Edebo, Lars Fändriks
BACKGROUND AND AIM: Patients with dysplasia in Barrett's esophagus (BE) have a considerable risk of developing esophageal adenocarcinoma (EAC). The mucosal expression of the pro-inflammatory angiotensin II receptor type 1 (AT1R) is elevated in these patients, suggesting a role in carcinogenesis. The purpose of this study was to determine whether interference with the renin-angiotensin system (RAS) would influence downstream markers of carcinogenesis. METHODS: Endoscopic mucosal biopsies from BE patients with low-grade dysplasia (LGD) were sampled before and after a three-week period of RAS-interfering treatment...
November 16, 2016: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/27824680/angiotensin-ii-receptor-blockers-following-intravenous-nicardipine-administration-to-lower-blood-pressure-in-patients-with-hypertensive-intracerebral-hemorrhage-a-prospective-randomized-study
#5
Joji Inamasu, Shunsuke Nakae, Kazuhide Adachi, Yuichi Hirose
BACKGROUND AND OBJECTIVE: In patients with hypertensive intracerebral hemorrhage (HICH), intravenous nicardipine is primarily used to lower blood pressure (BP). However, there are few studies investigating the role of oral antihypertensives administered after intravenous nicardipine to prevent BP from rising. Angiotensin II receptor blockers (ARBs) may be beneficial in HICH patients not only as antihypertensives but also by lowering plasma catecholamine levels. A prospective randomized study was conducted between January 2015 and March 2016 to comparatively evaluate the efficacy of two ARBs (azilsartan vs...
November 7, 2016: Blood Pressure Monitoring
https://www.readbyqxmd.com/read/27787557/potential-benefit-of-low-dose-candesartan-in-trastuzumab-induced-cardiotoxic-effects
#6
Seongseok Yun, Rostam Khoubyari, Ivo Abraham
No abstract text is available yet for this article.
October 27, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27787551/potential-benefit-of-low-dose-candesartan-in-trastuzumab-induced-cardiotoxic-effect-reply
#7
Jan H M Schellens
No abstract text is available yet for this article.
October 27, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27758802/in-individuals-at-intermediate-risk-for-cardiovascular-disease-treatment-with-rosuvastatin-but-not-candesartan-plus-hydrochlorothiazide-lowers-cardiovascular-disease-event-rates
#8
https://www.readbyqxmd.com/read/27754082/os-19-05-combination-of-arb-and-nifedipine-cr-reduces-microalbuminuria-in-association-with-reduction-of-serum-uric-acid-sub-analysis-of-nice-combi-study
#9
Naoki Nakagawa, Keisuke Maruyama, Motoki Matsuki, Nobuyuki Sato, Kenjiro Kikuchi, Naoyuki Hasebe
OBJECTIVE: Uric acid is a risk factor for cardiovascular disease. We investigated the relationship between the change of urinary albumin excretion (UAE) and the changes of serum uric acid (SUA) during antihypertensive treatment in hypertensive patients with microalbuminuria as a subanalysis of the results of the NICE Combi (Nifedipine and Candesartan Combination) Study. DESIGN AND METHOD: A total of 86 subjects with essential hypertension with microalbuminuria (UAE < 300 mg•g-1 creatinine) were randomly assigned in a double-blind manner to a combination therapy group (standard-dose candesartan at 8 mg/day plus controlled-release (CR) nifedipine 20 mg/day) (n = 42) or an up-titrated monotherapy group (candesartan 12 mg/day) (n = 44) for 8 weeks of continuous treatment after initially receiving standard-dose candesartan (8 mg/day) monotherapy for 8 weeks (initial treatment)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753835/sy-05-1-fibro-inflammatory-changes-during-progression-of-systolic-diastolic-dysfunction-in-the-hypertensive-heart
#10
Hisashi Kai
There is increasing evidence that fibro-inflammatory changes play a role in variety of cardiovascular diseases. We created new rat models to investigate the role of fibro-inflammatory changes in the pathophysiology of systolic and diastolic dysfunction in hypertensive heart. (1) a model of a blood pressure (BP) surge was created by performing abdominal aortic constriction in Wistar-Kyoto rats. Aortic constriction rapidly increased BP and the high BP levels sustained. A BP surge transiently induced MCP-1 and TGF-beta induction, angiotensin converting enzyme activation, and macrophage infiltration, followed by left ventricular (LV) hypertrophy and perivascular reactive fibrosis...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753282/pharmacokinetic-and-bioequivalence-studies-of-a-newly-developed-branded-generic-of-candesartan-cilextil-tablets-in-healthy-volunteers
#11
Rajesh Patel, Jonathan L Palmer, Shashidhar Joshi, Alejandro Di Ció Gimena, Florencia Esquivel
Two bioavailability/bioequivalence studies were carried out to evaluate the pharmacokinetics of candesartan cilexetil 16mg tablet formulations. A pilot study was used to optimise the formulation and manufacturing process prior to conducting the definitive study. The pilot study was a single dose, randomised two period crossover and the definitive study was a single dose randomised three period, 6 sequence cross over study in healthy adults. In the pilot study the test formulation was 24% and 18% greater for Cmax and AUC compared to the innovator product...
October 18, 2016: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27670639/fixed-dose-combination-of-nifedipine-gastrointestinal-therapeutic-system-and-candesartan-cilexetil-in-patients-with-moderate-to-severe-essential-hypertension-an-open-label-long-term-safety-and-efficacy-study
#12
S E Kjeldsen, P Dzongowski, N Li, L Wang, A Radlmaier
WHAT IS KNOWN AND OBJECTIVE: The nifedipine gastrointestinal therapeutic system (GITS)/candesartan cilexetil (N/C) combination was demonstrated to be an effective, well-tolerated antihypertensive therapy in a short-term study. The current study investigated the long-term safety and efficacy of a fixed-dose combination (FDC) of N/C therapy in moderate-to-severe essential hypertension. METHODS: A multinational, 70-centre, open-label study of N/C treatment for 28 or 52 weeks at a target dose of N60 mg/C32 mg...
September 27, 2016: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/27651039/angiotensin-ii-receptor-blocker-combined-with-eplerenone-or-hydrochlorothiazide-for-hypertensive-patients-with-diabetes-mellitus
#13
Shigehiro Karashima, Takashi Yoneda, Mitsuhiro Kometani, Masashi Ohe, Shunsuke Mori, Toshitaka Sawamura, Kenji Furukawa, Masakazu Yamagishi, Yoshiyu Takeda
Experimental models recently suggested an interaction between aldosterone and adipose tissue, but clinical investigation has been limited. We studied the effects of eplerenone compared to hydrochlorothiazide (HCTZ) on blood pressure (BP), glucose, and lipid levels in 50 patients with essential hypertension (EHT) and type 2 diabetes mellitus whose BP failed to reach target levels with 8 mg of candesartan alone. BP improved similarly in both groups over the 12-month study period, but BMI, waist circumference, and LDL-cholesterol were decreased in the eplerenone group, while glycohemoglobin was elevated in the HCTZ group...
2016: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/27643003/os-19-05-combination-of-arb-and-nifedipine-cr-reduces-microalbuminuria-in-association-with-reduction-of-serum-uric-acid-sub-analysis-of-nice-combi-study
#14
Naoki Nakagawa, Keisuke Maruyama, Motoki Matsuki, Nobuyuki Sato, Kenjiro Kikuchi, Naoyuki Hasebe
OBJECTIVE: Uric acid is a risk factor for cardiovascular disease. We investigated the relationship between the change of urinary albumin excretion (UAE) and the changes of serum uric acid (SUA) during antihypertensive treatment in hypertensive patients with microalbuminuria as a subanalysis of the results of the NICE Combi (Nifedipine and Candesartan Combination) Study. DESIGN AND METHOD: A total of 86 subjects with essential hypertension with microalbuminuria (UAE < 300 mg•g-1 creatinine) were randomly assigned in a double-blind manner to a combination therapy group (standard-dose candesartan at 8 mg/day plus controlled-release (CR) nifedipine 20 mg/day) (n = 42) or an up-titrated monotherapy group (candesartan 12 mg/day) (n = 44) for 8 weeks of continuous treatment after initially receiving standard-dose candesartan (8 mg/day) monotherapy for 8 weeks (initial treatment)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27642888/sy-05-1-fibro-inflammatory-changes-during-progression-of-systolic-diastolic-dysfunction-in-the-hypertensive-heart
#15
Hisashi Kai
There is increasing evidence that fibro-inflammatory changes play a role in variety of cardiovascular diseases. We created new rat models to investigate the role of fibro-inflammatory changes in the pathophysiology of systolic and diastolic dysfunction in hypertensive heart. (1) a model of a blood pressure (BP) surge was created by performing abdominal aortic constriction in Wistar-Kyoto rats. Aortic constriction rapidly increased BP and the high BP levels sustained. A BP surge transiently induced MCP-1 and TGF-beta induction, angiotensin converting enzyme activation, and macrophage infiltration, followed by left ventricular (LV) hypertrophy and perivascular reactive fibrosis...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27634455/radioiodination-and-biological-evaluation-of-candesartan-as-a-tracer-for-cardiovascular-disorder-detection
#16
M H Sanad, Kh M Sallam, F A Marzook, S M Abd-Elhaliem
The goal of the study aims to evaluate newly radioiodinated candesartan (CAN) as a potential cardiovascular tracer. CAN was labeled using (125) I with chloramine-T (Ch-T) and N-bromosuccinimide (NBS) with full characterization of cold Iodo-candesartan. Factors such as pH, reaction temperature, reaction time, substrate, and oxidizing agent amounts were studied to optimize the radioiodination of CAN. The optimum radiochemical yield of (125) I-CAN was 98%. The labeled compound was separated and purified using high-pressure liquid chromatography...
October 2016: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/27612496/differential-renal-effects-of-candesartan-at-high-and-ultra-high-doses-in-diabetic-mice-potential-role-of%C3%A2-ace2-at2r-mas
#17
Glaucia Callera, Tayze Antunes, Jose Correa, Danielle Moorman, Alexey Gutsol, Ying He, Aurelie Nguyen Dinh Cat, Ana M Briones, Augusto C Montezano, Kevin Burns, Rhian M Touyz
High doses of AngII receptor (AT1R) blockers (ARBs) are reno-protective in diabetes. Underlying mechanisms remain unclear. We evaluated whether high/ultra-high doses of candesartan (ARB) upregulate ACE2/Ang II type 2 receptor (AT2R)/Mas receptor (protective axis of the of the renin-angiotensin-system (RAS)) in diabetic mice. Systolic blood pressure (SBP), albuminuria, and expression/activity of RAS components were assessed in diabetic db/db and control db/+mice treated with increasing candesartan doses (intermediate, 1 mg/Kg/d; high, 5 mg/Kg/d; ultra-high, 25 and 75 mg/Kg/d; 4 weeks)...
September 9, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27598921/-pharmacological-primary-prevention-of-myocardial-infarction-stroke-and-death-a-possible-task
#18
Christian Keller, Jochen Müller-Ehmsen
The HOPE-3-Trial investigated the effect of primary prevention on cardio- and neurovascular events in patients without known atherosclerotic disease, but with intermediate risk. In a factorial design Rosuvastatin 10 mg, Candesartan 16 mg/HCT 12.5 mg or both were compared with placebo. Rosuvastatin effectively lowered LDL-cholesterol and the rate of cardio- and neurovascular complications with a NNT of approximately 500/year without detectable effect on mortalitiy. Candesartan 16 mg/HCT 12.5 mg did not influence any endpoint, however, the predefined subgroup of patients with hypertension level I had a benefit...
September 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27594177/severity-of-renal-impairment-in-patients-with-heart-failure-and-atrial-fibrillation-implications-for-non-vitamin-k-antagonist-oral-anticoagulant-dose-adjustment
#19
Nathaniel M Hawkins, Pardeep S Jhund, Andrea Pozzi, Eileen O'Meara, Scott D Solomon, Christopher B Granger, Salim Yusuf, Marc A Pfeffer, Karl Swedberg, Mark C Petrie, Sean Virani, John J V McMurray
AIMS: The non-vitamin K antagonist oral anticoagulants (NOACs) have varying degrees of renal elimination which may be challenging in patients with heart failure (HF) and atrial fibrillation (AF). We examined the severity and variation in renal impairment, and the proportion of patients requiring NOAC cessation or dose reduction. METHODS AND RESULTS: A retrospective analysis of patients with HF and AF in the Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity programme was carried out...
September 2016: European Journal of Heart Failure
https://www.readbyqxmd.com/read/27590905/combined-statin-and-angiotensin-converting-enzyme-ace-inhibitor-treatment-increases-the-lifespan-of-long-lived-f1-male-mice
#20
Stephen R Spindler, Patricia L Mote, James M Flegal
Statins, such as simvastatin, and ACE inhibitors (ACEis), such as ramipril, are standard therapies for the prevention and treatment of cardiovascular diseases. These types of drugs are commonly administered together. More recently, angiotensin II type 1 receptor (AT1R) antagonists, such as candesartan cilexetil (candesartan), have been used in the place of, or in combination with, ACEis. Here, we investigated the effects of simvastatin and ramipril single and combination therapy, and candesartan treatment on the lifespan of isocalorically fed, long-lived, B6C3F1 mice...
September 2, 2016: Age (2005-)
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