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Endothelin Receptor Antagonist

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https://www.readbyqxmd.com/read/30549058/insights-into-the-pulmonary-vascular-complications-of-heart-failure-with-preserved-ejection-fraction
#1
Yen-Chun Lai, Longfei Wang, Mark T Gladwin
Pulmonary hypertension in the setting of heart failure with preserved ejection fraction (PH-HFpEF) is a growing public health problem that is increasing in prevalence. While PH-HFpEF is defined by a high mean pulmonary artery pressure, high left ventricular end-diastolic pressure and a normal ejection fraction, some HFpEF patients develop PH in the presence of pulmonary vascular remodeling with a high transpulmonary pressure gradient or pulmonary vascular resistance. Aging, increased left atrial pressure and stiffness, mitral regurgitation, as well as features of metabolic syndrome, which include obesity, diabetes, and hypertension, are recognized as risk factors for PH-HFpEF...
December 13, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/30527996/pulmonary-hypertension-associated-with-left-heart-disease-updated-recommendations-of-the-cologne-consensus-conference-2018
#2
Stephan Rosenkranz, Irene M Lang, Rüdiger Blindt, Diana Bonderman, Leonhard Bruch, Gerhard P Diller, Ralf Felgendreher, Christian Gerges, Wolfgang Hohenforst-Schmidt, Stephan Holt, Christian Jung, Ingrid Kindermann, Tilmann Kramer, Wolfgang M Kübler, Veselin Mitrovic, Andreas Riedel, Andreas Rieth, Alexander Schmeisser, Rolf Wachter, Joachim Weil, Christian F Opitz
In the summer of 2016, delegates from the German Society of Cardiology (DGK), the German Respiratory Society (DGP), and the German Society of Pediatric Cardiology (DGPK) met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary hypertension (PH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available...
August 27, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/30509118/managing-chronic-kidney-disease-in-diabetes-patients-with-the-latest-chemical-therapies
#3
Jingbo Hu, Yongzhong Du
During the years, while treatment strategy for diabetes mellitus has improved, the incidence of diabetes worldwide increases continuously. Chronic kidney disease (CKD) is one of the major diabetic microvascular complications, and a primary cause leading to end-stage renal disease (ESRD). The progression to ESRD, affected by hyperglycemia and hypertension, is characterized by microalbuminuria and macroalbuminuria. With advances in understanding the pathogenesis of CKD in diabetic patients, many novel therapeutic targets have been proposed, and the corresponding agents are being developed continually to prevent the progression of CKD...
December 3, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/30508597/clazosentan-for-aneurysmal-subarachnoid-hemorrhage-an-updated-meta-analysis-with-trial-sequential-analysis
#4
REVIEW
Steve S Cho, Sung-Eun Kim, Heung Cheol Kim, Won Jin Kim, Jin Pyeong Jeon
OBJECT: Clazosentan, an endothelin-receptor-antagonist, reduced vasospasm and delayed-ischemic-neurological-deficit (DIND) but did not improve outcome following subarachnoid hemorrhage (SAH) in clinical trials. However, a lack of dose-dependent analysis and potential overestimation of clazosentan's effect are concerning. We employ stratified analysis and trial-sequential-analysis (TSA) of existing data to investigate the effects of clazosentan on SAH outcome. METHODS: Studies from PubMed, EMBASE, and Cochrane were reviewed for eligibility...
November 30, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/30475252/review-of-evidence-for-bosentan-therapy-for-treatment-of-eisenmenger-syndrome
#5
Benjamin J Hartwig, Benjamin Schultze
BACKGROUND AND PURPOSE: Eisenmenger syndrome (ES) is a rare condition caused by a right-to-left cyanotic shunt. To date, only heart-lung transplant has been shown to be curative. Bosentan is the only medication studied with a double-blind placebo-controlled randomized trial for management of this condition. The intent of this article is to explore the literature surrounding bosentan in ES and assess its efficacy. METHODS: A literature review was conducted with no limitation on date...
November 19, 2018: Journal of the American Association of Nurse Practitioners
https://www.readbyqxmd.com/read/30448914/nano-medicine-and-vascular-endothelial-dysfunction-options-and-delivery-strategies
#6
REVIEW
Gaurav Taneja, Akash Sud, Narayan Pendse, Bishnu Panigrahi, Ashish Kumar, Arun K Sharma
The endothelium is a thin innermost layer of flat cells which release various mediators including endothelin-1 (ET-1), prostanoids, von Willebrand factor (vWF) and endothelium-derived relaxing factor (EDRF; nitric oxide) to regulate vascular tone. Endothelial nitric oxide synthase (eNOS) is a key enzyme that generates nitric oxide (NO). NO maintains vascular homeostasis and cardiac functions by influencing major vascular protective properties such as anti-platelet, anti-proliferative, anti-migratory, antioxidant and anti-inflammatory action in vessels...
November 17, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/30442035/a-bayesian-network-meta-analysis-on-the-efficacy-and-safety-of-eighteen-targeted-drugs-or-drug-combinations-for-pulmonary-arterial-hypertension
#7
Sumei Wang, Miao Yu, Xiangchun Zheng, Shangjuan Dong
Pulmonary arterial hypertension (PAH) can be relieved by pharmacological interventions, especially the targeted drug, which is classified into endothelin receptor antagonist, phosphodiesterase 5 inhibitor, prostaglandin I2 , soluble guanylate cyclase stimulator and selective non-prostanoid prostacyclin receptor agonist. To solve the contradictions existing in reported trials and provide a comprehensive guideline for clinical practice. PubMed, Embase, Cochrane library, and clinicaltrials.gov were searched. The basic information about the article, trial, arm, intervention, and the detailed data of outcome, including 6 minutes walking distance (6MWD) change, WHO functional class (FC) improvement, Borg dyspnea score (BDS) change, cardiac index (CI) change, mean pulmonary arterial pressure (mPAP) change, mean right arterial pressure (mRAP) change, pulmonary vascular resistance (PVR) change, clinical worsening, hospitalization, death, severe adverse events (SAEs), and withdrawal were extracted...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/30428543/topical-administration-of-bosentan-prevents-retinal-neurodegeneration-in-experimental-diabetes
#8
Patricia Bogdanov, Olga Simó-Servat, Joel Sampedro, Cristina Solà-Adell, Marta Garcia-Ramírez, Hugo Ramos, Marta Guerrero, Josep Maria Suñé-Negre, Josep Ramon Ticó, Bruno Montoro, Vicente Durán, Luís Arias, Cristina Hernández, Rafael Simó
Experimental evidence suggests that endothelin 1 (ET-1) is involved in the development of retinal microvascular abnormalities induced by diabetes. The effects of ET-1 are mediated by endothelin A- and B-receptors (ETA and ETB). Endothelin B-receptors activation mediates retinal neurodegeneration but there are no data regarding the effectiveness of ETB receptor blockage in arresting retinal neurodegeneration induced by diabetes. The main aim of the present study was to assess the usefulness of topical administration of bosentan (a dual endothelin receptor antagonist) in preventing retinal neurodegeneration in diabetic (db/db) mice...
November 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30417231/long-term-effects-of-bosentan-on-cardiovascular-events-in-hispanic-patients-with-intermittent-claudication-four-year-follow-up-of-the-clau-trial-the-clau-randomized-trial-long-term-outcome
#9
Joaquin De Haro, Silvia Bleda, Carmen Gonzalez-Hidalgo, Ignacio Michel, Francisco Acin
INTRODUCTION: The Clinical and Endothelial Function Assessment after Endothelin Receptor Antagonist (CLAU) trial demonstrated the effect of bosentan on the endothelial function, inflammatory status and claudication distance in Hispanic patients with incipient peripheral arterial disease (PAD). Our aim was to assess the protective effect on cardiovascular events of bosentan versus conventional anti-atherosclerosis therapy. METHODS: CLAU included 56 patients with intermittent claudication, randomized 1:1 to receive bosentan for 12 weeks (n = 27) or placebo (n = 29), associating the best medical treatment...
November 12, 2018: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/30408737/blockade-of-peripheral-endothelin-receptors-abolishes-heat-hyperalgesia-and-spontaneous-nociceptive-behavior-in-a-rat-model-of-facial-cancer
#10
Caroline Machado Kopruszinski, Renata Cristiane Dos Reis, Giles Alexander Rae, Juliana Geremias Chichorro
OBJECTIVE: To improve understanding of the pathophysiology of cancer-induced facial nociception, by evaluating the contribution of peripheral endothelin receptors in tumor-induced facial heat hyperalgesia, increased spontaneous grooming, as well as ongoing nociception in a rat model of facial cancer. DESIGN: The study was conducted using 396 rats. Facial cancer was induced by inoculating a suspension of Walker-256 cells into the rats' right vibrissal pad. Facial heat hyperalgesia and spontaneous grooming were assessed on day 6, while the conditioned place preference (CPP) test was performed on days 3-6 after tumor cells inoculation...
November 2, 2018: Archives of Oral Biology
https://www.readbyqxmd.com/read/30406063/neuroprotective-effect-of-irl-1620-an-endothelin-b-receptor-agonist-on-a-pediatric-rat-model-of-middle-cerebral-artery-occlusion
#11
Enrique G Cifuentes, Mary G Hornick, Suresh Havalad, Ramona L Donovan, Anil Gulati
Objective: The purpose of this study was to determine the potential neuroprotective effect of endothelin B (ETB ) receptor agonist IRL-1620 treatment in a pediatric model of ischemic stroke. Design: A prospective, animal model study. Setting: An experimental laboratory. Subjects: Three-month-old male Wistar Han rats. Interventions: The rats underwent permanent middle cerebral artery occlusion (MCAO). At 2, 4, and 6 h post MCAO, they were treated with saline, IRL-1620 (5 μg/kg, IV), and/or ETB antagonist BQ788 (1 mg/kg, IV)...
2018: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/30372743/constriction-of-retinal-venules-to-endothelin-1-obligatory-roles-of-eta-receptors-extracellular-calcium-entry-and-rho-kinase
#12
Yen-Lin Chen, Yi Ren, Wenjuan Xu, Robert H Rosa, Lih Kuo, Travis W Hein
Purpose: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide implicated in retinal venous pathologies such as diabetic retinopathy and retinal vein occlusion. However, underlying mechanisms contributing to venular constriction remain unknown. Thus, we examined the roles of ET-1 receptors, extracellular calcium (Ca2+), L-type voltage-operated calcium channels (L-VOCCs), Rho kinase (ROCK), and protein kinase C (PKC) in ET-1-induced constriction of retinal venules. Methods: Porcine retinal venules were isolated and pressurized for vasoreactivity study using videomicroscopic techniques...
October 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/30367951/regulation-of-extracellular-matrix-degradation-and-metastatic-spread-by-iqgap1-through-endothelin-1-receptor-signalling-in-ovarian-cancer
#13
Lidia Chellini, Valentina Caprara, Francesca Spadaro, Rosanna Sestito, Anna Bagnato, Laura Rosanò
The invasive phenotype of serous ovarian cancer (SOC) cells is linked to the formation of actin-based protrusions, invadopodia, operating extracellular matrix (ECM) degradation and metastatic spread. Growth factor receptors might cause engagement of integrin-related proteins, like the polarity protein IQ-domain GTPase-activating protein 1 (IQGAP1), to F-actin core needed for invadopodia functions. Here, we investigated whether IQGAP1 forms a signalosome with endothelin-1 (ET-1)/β-arrestin1 (β-arr1) network, as signal-integrating module for adhesion components, cytoskeletal remodelling and ECM degradation...
October 25, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/30361325/duet-a-phase-2-study-evaluating-the-efficacy-and-safety-of-sparsentan-in-patients-with-fsgs
#14
Howard Trachtman, Peter Nelson, Sharon Adler, Kirk N Campbell, Abanti Chaudhuri, Vimal Kumar Derebail, Giovanni Gambaro, Loreto Gesualdo, Debbie S Gipson, Jonathan Hogan, Kenneth Lieberman, Brad Marder, Kevin Edward Meyers, Esmat Mustafa, Jai Radhakrishnan, Tarak Srivastava, Miganush Stepanians, Vladimír Tesar, Olga Zhdanova, Radko Komers
BACKGROUND: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA ) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS. METHODS: In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 years with biopsy-proven FSGS, eGFR>30 ml/min per 1...
November 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/30352269/endothelin-and-the-heart-in-health-and-diseases
#15
Takashi Miyauchi, Satoshi Sakai
Endothelin-1 (ET-1), a 21-amino acid peptide, was initially identified in 1988 as a potent vasoconstrictor and pressor substance isolated from the culture supernatant of porcine aortic endothelial cells. From human genomic DNA analysis, two other family peptides, ET-2 and ET-3, were found. They showed different effects and distribution, suggesting that each peptide may play separate roles in different organs. In the heart, ET-1 also causes positive inotropic and chronotropic responses and hypertrophic activity of the cardiomyocytes...
October 20, 2018: Peptides
https://www.readbyqxmd.com/read/30323613/endothelin-receptor-antagonists-in-the-management-of-pulmonary-arterial-hypertension-where-do-we-stand
#16
REVIEW
Michele Correale, Armando Ferraretti, Ilenia Monaco, Davide Grazioli, Matteo Di Biase, Natale Daniele Brunetti
Pulmonary arterial hypertension, a disease largely neglected until a few decades ago, is presently the object of intense studies by several research teams. Despite considerable progress, pulmonary arterial hypertension remains a major clinical problem, because it is not always easy to diagnose, treat, and prevent. The disease was considered incurable until the late 1990s, when Epoprostenol was introduced as the first tool against this illness. More recently, therapy for pulmonary arterial hypertension gained momentum after publication of the SERAPHIN and AMBITION trials, which also highlighted the importance of upfront therapy...
2018: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/30318105/pulmonary-arterial-pressure-management-based-on-oral-medicine-for-pediatric-living-donor-liver-transplant-with-portopulmonary-hypertension
#17
T Ueno, S Hiwatashi, R Saka, H Yamanaka, Y Takama, Y Tazuke, K Bessho, S Kogaki, T Yonekura, H Okuyama
Pediatric living donor liver transplantation (LDLT) in patients with advanced portopulmonary hypertension (PoPH) is associated with poor prognoses. Recently, novel oral medications, including endothelin receptor antagonists (ERAs), phosphodiesterase 5 (PDE5) inhibitors, and oral prostacyclin (PGI2) have been used to treat PoPH. Pediatric patients with PoPH who underwent LDLT from 2006 to 2016 were enrolled. Oral pulmonary hypertension (PH) medication was administered to control pulmonary arterial pressure (PAP)...
March 15, 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/30303741/endothelin-receptor-a-and-p66shc-regulate-spontaneous-ca-2-oscillations-in-smooth-muscle-cells-controlling-renal-arterial-spontaneous-motion
#18
Oleg Palygin, Bradley S Miller, Yoshinori Nishijima, David X Zhang, Alexander Staruschenko, Andrey Sorokin
Adaptor protein p66Shc is overexpressed in smooth muscle cells of renal resistance vessels of hypertensive salt-sensitive rats and is involved in the regulation of renal vascular tone. We applied 2-photon laser scanning fluorescence microscopy to analyze spontaneous dynamic fluctuations in intracellular calcium concentrations ([Ca2+ ]i ) in smooth muscle cells embedded in the walls of freshly isolated renal resistance arteries. The amplitude, number of events, and frequency of spontaneous [Ca2+ ]i oscillations triggered by endogenously released endothelin-1 were recorded in smooth muscle cells of the renal arteries...
October 10, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30301761/novel-treatment-avenues-for-uterine-leiomyoma-a-new-implication-for-endothelin
#19
Kedra Wallace, Krystal Chatman, Venessia Johnson, Alexis Brookins, John Rushing, Babbette LaMarca
Cysteine-rich angiogenic inducer 61 (CYR61), an angiogenic factor whose expression is decreased in fibroids. The aim of the present study was to determine if CYR61 secretion in smooth muscle cells (SMCs) is regulated by hypoxia and through the endothelin A (ETA ) receptor. SMCs from fibroids (fSMC) and the adjacent myometrium smooth muscle cells (mSMCs) were extracted from ten women undergoing hysterectomy for uterine fibroids and cultured with or without 1.0 µM of an ETA receptor antagonist for 24 h under either normal or hypoxic oxygen conditions...
October 31, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/30279475/dysregulation-of-the-endothelin-pathway-in-lymphangioleiomyomatosis-with-no-direct-effect-on-cell-proliferation-and-migration
#20
Nader Chebib, Fabienne Archer, Alexandra Bobet-Erny, Caroline Leroux, Vincent Cottin
LAM is a rare low-grade metastasizing lung neoplasm. Inhibitors of mTOR improve clinical outcome of LAM patients by preventing loss of lung function. Nevertheless, other cell targets may be of interest for drug development. Therefore, we explored the potential role of EDN1 (endothelin) in LAM. We report an increased endothelin blood level in LAM patients as well as EDN1 overexpression and EDN1 receptor downregulation in LAM-derived primary cells and in TSC2NEG cells mutated in TSC2. We evidenced EDN pathway dysregulation based on EDN1, EDNRA, EDNRB and ARRB1 mRNA expression in LAM-derived primary cells...
October 2, 2018: Scientific Reports
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