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Angiotensin II and endothelin

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https://www.readbyqxmd.com/read/28416805/a-new-inhibitor-of-the-%C3%AE-arrestin-ap2-endocytic-complex-reveals-interplay-between-gpcr-internalization-and-signalling
#1
Alexandre Beautrait, Justine S Paradis, Brandon Zimmerman, Jenna Giubilaro, Ljiljana Nikolajev, Sylvain Armando, Hiroyuki Kobayashi, Lama Yamani, Yoon Namkung, Franziska M Heydenreich, Etienne Khoury, Martin Audet, Philippe P Roux, Dmitry B Veprintsev, Stéphane A Laporte, Michel Bouvier
In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes...
April 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28393188/a-heptameric-peptide-purified-from-spirulina%C3%A2-sp-gastrointestinal-hydrolysate-inhibits-angiotensin-i-converting-enzyme-and-angiotensin%C3%A2-ii-induced-vascular-dysfunction-in-human-endothelial-cells
#2
Seong-Yeong Heo, Seok-Chun Ko, Chang Su Kim, Gun-Woo Oh, Bomi Ryu, Zhong-Ji Qian, Geunhyung Kim, Won Sun Park, Il-Whan Choi, Thi Tuong Vy Phan, Soo-Jin Heo, Do-Hyung Kang, Myunggi Yi, Won-Kyo Jung
In this study, a marine microalga Spirulina sp.-derived protein was hydrolyzed using gastrointestinal enzymes to produce an angiotensin I (Ang I)-converting enzyme (ACE) inhibitory peptide. Following consecutive purification, the potent ACE inhibitory peptide was composed of 7 amino acids, Thr-Met‑Glu‑Pro‑Gly‑Lys-Pro (molecular weight, 759 Da). Analysis using the Lineweaver-Burk plot and molecular modeling suggested that the purified peptide acted as a mixed non-competitive inhibitor of ACE...
April 4, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28362327/the-salutary-influence-of-forest-bathing-on-elderly-patients-with-chronic-heart-failure
#3
Genxiang Mao, Yongbao Cao, Bozhong Wang, Sanying Wang, Zhuomei Chen, Jirong Wang, Wenmin Xing, Xiaoxu Ren, Xiaoling Lv, Jianhua Dong, Shasha Chen, Xiuyuan Chen, Guofu Wang, Jing Yan
The aim of the current study was to test the hypothesis that forest bathing would be beneficial for elderly patients with chronic heart failure (CHF) as an adjunctive therapy. Two groups of participants with CHF were simultaneously sent to the forest or an urban control area for a four-day trip, respectively. Subjects exposed to the forest site showed a significant reduction of brain natriuretic peptide (BNP) in comparison to that of the city group and their own baseline levels. The values for the cardiovascular disease related pathological factors, including endothelin-1 (ET-1), and constituents of the renin-angiotensin system (RAS), including renin, angiotensinogen (AGT), angiotensin II (ANGII), and ANGII receptor type 1 or 2 (AT1 or AT2) in subjects exposed to the forest environment were lower than those in the urban control group...
March 31, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28344559/cyclooxygenase-2-inhibition-limits-angiotensin-ii-induced-dna-oxidation-and-protein-nitration-in-humans
#4
Vincent Pialoux, Marc J Poulin, Brenda R Hemmelgarn, Daniel A Muruve, Erica N Chirico, Camille Faes, Darlene Y Sola, Sofia B Ahmed
Compared to other cyclooxygenase-2 inhibitors, celecoxib is associated with a lower cardiovascular risk, though the mechanism remains unclear. Angiotensin II is an important mediator of oxidative stress in the pathophysiology of vascular disease. Cyclooxygenase-2 may modify the effects of angiotensin II though this has never been studied in humans. The purpose of the study was to test the effects of selective cyclooxygenase-2 inhibition on plasma measures of oxidative stress, the vasoconstrictor endothelin-1, and nitric oxide metabolites, both at baseline and in respose to Angiotensin II challenge in healthy humans...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28329261/effects-of-noise-on-vascular-function-oxidative-stress-and-inflammation-mechanistic-insight-from-studies-in-mice
#5
Thomas Münzel, Andreas Daiber, Sebastian Steven, Lan P Tran, Elisabeth Ullmann, Sabine Kossmann, Frank P Schmidt, Matthias Oelze, Ning Xia, Huige Li, Antonio Pinto, Philipp Wild, Kai Pies, Erwin R Schmidt, Steffen Rapp, Swenja Kröller-Schön
Aims: Epidemiological studies indicate that traffic noise increases the incidence of coronary artery disease, hypertension and stroke. The underlying mechanisms remain largely unknown. Field studies with nighttime noise exposure demonstrate that aircraft noise leads to vascular dysfunction, which is markedly improved by vitamin C, suggesting a key role of oxidative stress in causing this phenomenon. Methods and results: We developed a novel animal model to study the vascular consequences of aircraft noise exposure...
February 17, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28326642/neprilysin-inhibition-in-heart-failure-mechanisms-and-substrates-beyond-modulating-natriuretic-peptides
#6
REVIEW
Emilia D'Elia, Attilio Iacovoni, Muthiah Vaduganathan, Ferdinando L Lorini, Stefano Perlini, Michele Senni
The autonomic nervous system, the renin-angiotensin-aldosterone system, and the natriuretic peptide system represent critical regulatory pathways in heart failure and as such have been the major targets of pharmacological development. The introduction and approval of angiotensin receptor neprilysin inhibitors (ARNi) have broadened the available drug treatments of patients with chronic heart failure with reduced ejection fraction. Neprilysin catalyses the degradation of a number of vasodilator peptides, including the natriuretic peptides, bradykinin, substance P, and adrenomedullin, as well as vasoconstrictor peptides, including endothelin-1 and angiotensin I and II...
March 21, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28289180/beneficial-effects-of-apelin-on-vascular-function-in-patients-with-central-obesity
#7
Francesca Schinzari, Augusto Veneziani, Nadia Mores, Angela Barini, Nicola Di Daniele, Carmine Cardillo, Manfredi Tesauro
Patients with central obesity have impaired insulin-stimulated vasodilation and increased ET-1 (endothelin 1) vasoconstriction, which may contribute to insulin resistance and vascular damage. Apelin enhances insulin sensitivity and glucose disposal but also acts as a nitric oxide (NO)-dependent vasodilator and a counter-regulator of AT1 (angiotensin [Ang] II type 1) receptor-induced vasoconstriction. We, therefore, examined the effects of exogenous (Pyr(1))apelin on NO-mediated vasodilation and Ang II- or ET-1-dependent vasoconstrictor tone in obese patients...
March 13, 2017: Hypertension
https://www.readbyqxmd.com/read/28287881/renin-angiotensin-system-blockade-alone-or-combined-with-eta-receptor-blockade-effects-on-the-course-of-chronic-kidney-disease-in-5-6-nephrectomized-ren-2-transgenic-hypertensive-rats
#8
Lenka Sedláková, Věra Čertíková Chábová, Šárka Doleželová, Petra Škaroupková, Libor Kopkan, Zuzana Husková, Lenka Červenková, Soňa Kikerlová, Ivana Vaněčková, Janusz Sadowski, Elzbieta Kompanowska-Jezierska, Petr Kujal, Herbert J Kramer, Luděk Červenka
BACKGROUND: Early addition of endothelin (ET) type A (ETA) receptor blockade to complex renin-angiotensin system (RAS) blockade has previously been shown to provide better renoprotection against progression of chronic kidney disease (CKD) in Ren-2 transgenic hypertensive rats (TGR) after 5/6 renal ablation (5/6 NX). In this study, we examined if additional protection is provided when ETA blockade is applied in rats with already developed CKD. METHODS: For complex RAS inhibition, an angiotensin-converting enzyme inhibitor along with angiotensin II type 1 receptor blocker was used...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28271726/molecular-mechanisms-of-atrial-fibrosis-implications-for-the-clinic
#9
REVIEW
Shivshankar Thanigaimani, Dennis H Lau, Thomas Agbaedeng, Adrian D Elliott, Rajiv Mahajan, Prashanthan Sanders
Recent research has unravelled an increasing list of cardiac conditions and risk factors that may be responsible for the abnormal underlying atrial substrate that predisposes to atrial fibrillation (AF). Atrial fibrosis has been demonstrated as the pivotal structural abnormality underpinning conduction disturbances that promote AF in different disease models. Despite the advancement in our discoveries of the molecular mechanisms involved in the profibrotic milieu, targeted therapeutics against atrial fibrosis remain lacking...
April 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28264495/the-endothelin-type-a-receptor-as-a-potential-therapeutic-target-in-preeclampsia
#10
REVIEW
Bhavisha Bakrania, Jeremy Duncan, Junie P Warrington, Joey P Granger
Preeclampsia (PE) is a disorder of pregnancy typically characterized by new onset hypertension after gestational week 20 and proteinuria. Although PE is one of the leading causes of maternal and perinatal morbidity and death worldwide, the mechanisms of the pathogenesis of the disease remain unclear and treatment options are limited. However, there is increasing evidence to suggest that endothelin-1 (ET-1) plays a critical role in the pathophysiology of PE. Multiple studies report that ET-1 is increased in PE and some studies report a positive correlation between ET-1 and the severity of symptoms...
February 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28241704/-influence-of-n-hexane-on-vascular-endothelial-active-substances-in-brain-tissue-in-mice
#11
L Lin, Z Q Zhang, C Z Zhang
Objective: To investigate the influence of n-hexane on vascular endothelial active substances in brain tissue in mice and its significance. Methods: A total of 48 healthy Kunming mice were randomly divided into high-dose exposure group, middle-dose exposure group, low-dose exposure group, and control group, with 12 mice in each group. All groups except the control group were exposed to n-hexane via static inhalation (0.035 g/L, 0.018 g/L, and 0.009 g/L for the high-, middle-, and low-dose exposure groups, respectively) 4 hours a day for 21 days...
January 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/28133468/changing-the-treatment-of-heart-failure-with-reduced-ejection-fraction-clinical-use-of-sacubitril-valsartan-combination
#12
REVIEW
Edgardo Kaplinsky
Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk of morbidity and mortality. Sacubitril valsartan (previously known as LCZ696) is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the first in class angiotensin receptor neprilysin inhibitor (ARNI) since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides (NPs), bradykinin, endothelin and angiotensin II (Ang-II)...
November 2016: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/28116728/isolation-and-culture-of-endothelial-cells-from-large-vessels
#13
Augusto C Montezano, Karla B Neves, Rheure A M Lopes, Francisco Rios
The endothelium, which is at the interface between circulating blood and the vascular wall, comprises a simple squamous layer of cells that lines the inner surface of all blood vessels. Endothelial cells are highly metabolically active and play an important role in many physiological functions, including control of vasomotor tone, blood cell trafficking, vascular permeability, and maintenance of vascular integrity (Mensah, Vascul Pharmacol 46(5):310-314, 2007; Yetik-Anacak and Catravas, Vascul Pharmacol 45(5):268-276, 2006)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28013061/voltage-and-receptor-mediated-activation-of-a-non-selective-cation-channel-in-rat-carotid-body-glomus-cells
#14
Jiaju Wang, James O Hogan, Donghee Kim
A recent study showed that hypoxia activates a Ca(2+)-sensitive, Na(+)-permeable non-selective cation channel (NSC) in carotid body glomus cells. We studied the effects of mitochondrial inhibitors that increase Ca(2+) influx via Ca(2+) channel (Cav), and receptor agonists that release Ca(2+) from endoplasmic reticulum (ER) on NSC. Mitochondrial inhibitors (NaCN, FCCP, H2S, NO) elevated [Ca(2+)]i and activated NSC. Angiotensin II and acetylcholine that elevate [Ca(2+)]i via the Gq-IP3 pathway activated NSC. However, endothelin-1 (Gq) and 5-HT (Gq) showed little or no effect on [Ca(2+)]i and did not activate NSC...
March 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28012855/prostanoids-counterbalance-the-synergism-between-endothelin-1-and-angiotensin-ii-in-mesenteric-veins-of-trained-rats
#15
Agnaldo Bruno Chies, Priscilla Bianca de Oliveira, Patrícia de Souza Rossignoli, Rafaela de Fátima Ferreira Baptista, Roger William de Lábio, Spencer Luiz Marques Payão
Exercise-induced adaptations of the modulating mechanisms that influence the angiotensin (Ang II) responses assume different features depending on the venous bed. In femoral veins, exercise mobilizes vasodilator prostanoids to cooperate with NO in order to maintain reduced Ang II responses. On the other hand, exercise's influence on the Ang II responses in veins that drain blood from the mesenteric region has been poorly described. Therefore, the present study aimed to identify the effects of a single bout of exercise, as well as exercise training, on the Ang II responses in mesenteric veins...
February 2017: Peptides
https://www.readbyqxmd.com/read/27996266/blueberry-anthocyanin-enriched-extracts-attenuate-fine-particulate-matter-pm2-5-induced-cardiovascular-dysfunction
#16
Ziyu Wang, Wei Pang, Congcong He, Yibo Li, Yugang Jiang, Changjiang Guo
Blueberry anthocyanin-enriched extracts (BAE) at three doses (0.5, 1.0, and 2.0 g/kg) were administered by oral gavage to rats exposed to 10 mg/kg fine particulate matter (PM2.5) three times a week. A positive control group was exposed to PM2.5 without BAE treatment. We analyzed heart rate (HR), electrocardiogram (ECG), and histopathology, and biomarkers of cardiovascular system injuries, systemic inflammation, oxidative stress, endothelial function, and apoptosis. Results indicated that BAE, particularly at 1...
January 11, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27884701/cardiac-inositol-1-4-5-trisphosphate-receptors
#17
REVIEW
M Iveth Garcia, Darren Boehning
Calcium is a second messenger that regulates almost all cellular functions. In cardiomyocytes, calcium plays an integral role in many functions including muscle contraction, gene expression, and cell death. Inositol 1,4,5-trisphosphate receptors (IP3Rs) are a family of calcium channels that are ubiquitously expressed in all tissues. In the heart, IP3Rs have been associated with regulation of cardiomyocyte function in response to a variety of neurohormonal agonists, including those implicated in cardiac disease...
November 22, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27837397/from-arb-to-arni-in-cardiovascular-control
#18
REVIEW
Estrellita Uijl, Lodi C W Roksnoer, Ewout J Hoorn, A H Jan Danser
Coexistence of hypertension, diabetes mellitus and chronic kidney disease synergistically aggravates the risk of cardiovascular and renal morbidity and mortality. These high-risk, multi-morbid patient populations benefit less from currently available anti-hypertensive treatment. Simultaneous angiotensin II type 1 receptor blockade and neprilysin inhibition ('ARNI') with valsartan/sacubitril (LCZ696) might potentiate the beneficial effects of renin-angiotensin-aldosterone inhibition by reinforcing its endogenous counterbalance, the natriuretic peptide system...
December 2016: Current Hypertension Reports
https://www.readbyqxmd.com/read/27836671/glycine-prevents-pressure-overload-induced-cardiac-hypertrophy-mediated-by-glycine-receptor
#19
Yan Lu, Xudong Zhu, Jinjie Li, Ru Fang, Zhuoyun Wang, Jing Zhang, Kexue Li, Xiaoyu Li, Hui Bai, Qing Yang, Jingjing Ben, Hanwen Zhang, Qi Chen
As a major amino acid, glycine has multiple functions in metabolism, growth, immunity, cytoprotection, and survival. The aim of this study was to determine the effects of glycine on pathologic cardiac hypertrophy and the mechanism underlying it. Pre-treatment with glycine significantly attenuated murine cardiac hypertrophy induced by transverse aortic constriction or by administration of angiotensin II (Ang II). This action was associated with a suppressive extracellular signal-regulated kinase 1/2 phosphorylation in myocardium...
January 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27825364/mid-regional-pro-adrenomedullin-mr-proadm-a-marker-of-positive-fluid-balance-in-critically-ill-patients-results-of-the-envol-study
#20
Bernard Vigué, Pierre-Etienne Leblanc, Frédérique Moati, Eric Pussard, Hussam Foufa, Aurore Rodrigues, Samy Figueiredo, Anatole Harrois, Jean-Xavier Mazoit, Homa Rafi, Jacques Duranteau
BACKGROUND: The optimal control of blood volume without fluid overload is a main challenge in the daily care of intensive care unit (ICU) patients. Accordingly this study focused on the identification of biomarkers to help characterize fluid overload status. METHODS: Sixty-seven patients were studied from ICU admission to day 7 (D7). Blood and urine samples were taken daily and sodium and water balance strictly calculated resulting in a total cumulative assessment of ∆Na(+) and ∆H2O...
November 9, 2016: Critical Care: the Official Journal of the Critical Care Forum
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