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Endothelin Receptor Antagonist

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https://www.readbyqxmd.com/read/30323613/endothelin-receptor-antagonists-in-the-management-of-pulmonary-arterial-hypertension-where-do-we-stand
#1
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
#2
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
#3
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
#4
Kedra Wallace, Krystal Chatman, Venessia Johnson, Alexis Brookins, John Rushing, Babbette LaMarca
CYR61 (cysteine-rich angiogenic inducer 61), an angiogenic factor whose expression is decreased in fibroids. The aim of this study was to determine if CYR61 secretion in smooth muscle cells is regulated by hypoxia and through the endothelin A (ETA ) receptor. Smooth muscle cells from fibroids (fSMC) and the adjacent myometrium smooth muscle cells (mSMC) were extracted from 10 women undergoing hysterectomy for uterine fibroids and cultured with or without 1.0µM of an ETA receptor antagonist for 24hrs under either normal or hypoxic oxygen conditions...
October 9, 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
#5
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
https://www.readbyqxmd.com/read/30266073/efficient-reconstitution-of-hepatic-microvasculature-by-endothelin-receptor-antagonism-in-liver-sinusoidal-endothelial-cells
#6
Neelam Yadav, Fadi Luc Jaber, Yogeshwar Sharma, Priya Gupta, Preeti Viswanathan, Sanjeev Gupta
Reconstitution of healthy endothelial cells in vascular beds offers opportunities for mechanisms in tissue homeostasis, organ regeneration, and correction of deficient functions. Liver sinusoidal endothelial cells express unique functions and their transplantation is relevant for disease models and for cell therapy. As molecular targets for improving transplanted cell engraftment and proliferation will be highly significant, we determined whether ETA/B receptor antagonism by the drug, bosentan, could overcome cell losses due to cell transplantation-induced cytotoxicity...
September 28, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/30244111/ct-perfusion-imaging-of-cerebral-microcirculatory-changes-following-subarachnoid-hemorrhage-in-rabbits-specific-role-of-endothelin-1-receptor-antagonist
#7
Quanyang Wu, Ruibin Zheng, Jiao Wang, Jiaqi Wang, Songbai Li
BACKGROUND: Cerebral vasospasm may lead to delayed ischemic neurological deficits following subarachnoid hemorrhage (SAH). Endothelin (ET-1) is an important factor participating in cerebral vasospasm underlying SAH. We used a specific endothelin receptor antagonist, BQ123 to assess the specific role of endothelin-1 receptor antagonist in cerebral vasospasm in a rabbit model of SAH by examining plasma ET-1 levels and the principal CT perfusion(CTP) parameters pertinent to the hemodynamic status of microcirculation following SAH...
September 20, 2018: Brain Research
https://www.readbyqxmd.com/read/30224253/pulmonary-vasodilator-therapies-are-of-no-benefit-in-pulmonary-hypertension-due-to-left-heart-disease-a-meta-analysis
#8
Jacob Y Cao, Kathryn M Wales, Rachael Cordina, Edmund M T Lau, David S Celermajer
BACKGROUND: Pulmonary hypertension complicating left heart disease (PH-LHD) is the most common cause of PH. Off-label use of pulmonary arterial hypertension (PAH) medications for PH-LHD is prevalent, despite a lack of clinical data supporting their use. METHODS: A systematic review and meta-analysis was performed. Comprehensive search of all available literature to date identified ten randomised, placebo controlled trials comprising 439 treated (Phosphodiesterase 5 inhibitors: n = 206; guanylate cyclase stimulators: n = 132; endothelin receptor antagonists: n = 101) and 338 placebo patients...
September 12, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/30198212/et-a-receptor-activation-contributes-to-t-cell-accumulation-in-the-kidney-following-ischemia-reperfusion-injury
#9
Erika I Boesen
Renal ischemia-reperfusion (IR) injury and acute kidney injury (AKI) increase the risk of developing hypertension, with T cells suspected as a possible mechanistic link. Endothelin promotes renal T cell infiltration in several diseases, predominantly via the ETA receptor, but its contribution to renal T cell infiltration following renal IR injury is poorly understood. To test whether ETA receptor activation promotes T cell infiltration of the kidney following IR injury, male C57BL/6 mice were treated with the ETA receptor antagonist ABT-627 or vehicle, commencing 2 days prior to unilateral renal IR injury...
September 2018: Physiological Reports
https://www.readbyqxmd.com/read/30190158/targeted-therapy-of-pulmonary-arterial-hypertension-updated-recommendations-from-the-cologne-consensus-conference-2018
#10
Marius M Hoeper, Christian Apitz, Ekkehard Grünig, Michael Halank, Ralf Ewert, Harald Kaemmerer, Hans-Joachim Kabitz, Christian Kähler, Hans Klose, Hanno Leuchte, Silvia Ulrich, Karen M Olsson, Oliver Distler, Stephan Rosenkranz, H Ardeschir Ghofrani
In the summer of 2016, delegates from the German Respiratory Society, the German Society of Cardiology and the German Society of Pediatric Cardiology met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary arterial hypertension (PAH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines and included new evidence, where available. The treatment algorithm for PAH was modified based on the observation that there are now many patients diagnosed with IPAH who are at an advanced age and have significant cardiopulmonary comorbidities...
August 25, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/30174784/sepsis-and-oxidative-stress-in-the-newborn-from-pathogenesis-to-novel-therapeutic-targets
#11
REVIEW
Chiara Poggi, Carlo Dani
Sepsis is at present one of the leading causes of morbidity and mortality in the neonatal population. Together with inflammation, oxidative stress is involved in detrimental pathways activated during neonatal sepsis, eventually leading to organ dysfunction and death. The redox cascade during sepsis is mainly initiated by IL-6 and IL-8 stimulation in newborns and includes multiple noxious processes, as direct cell damage induced by reactive oxygen species, activation of gene expression leading to amplification of inflammation and oxidative stress, and impairment of mitochondrial function...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/30166496/is-there-a-role-for-endothelin-1-receptor-antagonists-in-the-treatment-of-lung-fibrosis-associated-with-pulmonary-hypertension
#12
EDITORIAL
Jana Grune, Wolfgang M Kuebler
No abstract text is available yet for this article.
August 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/30149760/oleanolic-acid-a-novel-endothelin-a-receptor-antagonist-alleviated-high-glucose-induced-cardiomyocytes-injury
#13
Dewei Wu, Qiao Zhang, Yangyang Yu, Yuxin Zhang, Minyu Zhang, Qing Liu, Erli Zhang, Shiyou Li, Guangyuan Song
Endothelin-1 (ET-1) and its receptor endothelin A receptor (ET[Formula: see text] have been shown to be upregulated in a high glucose environment, which increase the incidence of diabetes-related heart failure. Our previous study demonstrated that oleanolic acid (OA), a natural compound found in Chinese herbs had ET-1 antagonistic effects. We aimed to verify whether OA could ameliorate diabetes mellitus (DM)-induced injury in cardiomyocytes by reducing the antagonistic effects of the ET-1 pathway. For the induction of high glucose-related injury in cardiomyocytes, neonatal rat ventricular cardiomyocytes (NRVMs) were subjected to culture medium containing 25[Formula: see text]mM of glucose...
2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/30144292/combined-hydroxyurea-and-et-a-receptor-blockade-reduces-renal-injury-in-the-humanized-sickle-cell-mouse
#14
Crystal Taylor, Malgorzata Kasztan, Binli Tao, Jennifer S Pollock, David M Pollock
AIM: The objective of this study is to determine if ambrisentan (ETA selective antagonist) and hydroxyurea (HU) treatment has a synergistic effect on renal injury in sickle cell nephropathy when compared to HU treatment alone. The premise of the study is based on recent studies showing that endothelin-1 (ET-1) contributes to the pathophysiology of nephropathy in sickle cell disease (SCD) and that ETA receptor blockade improves renal function and protects against renal injury. Hydroxyurea (HU) is commonly prescribed for the treatment of SCD and has been shown to reduce renal injury in patients with SCD...
August 24, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/30142162/the-direct-and-sustained-consequences-of-severe-placental-hypoxia-on-vascular-contractility
#15
Philippe Vangrieken, Salwan Al-Nasiry, Ger M J Janssen, Antje R Weseler, Marc E Spaanderman, Aalt Bast, Paul M H Schiffers
INTRODUCTION: Preeclampsia is a major health problem in human pregnancy, severely complicating 5-8% of all pregnancies. The emerging molecular mechanism is that conditions like hypoxic stress trigger the release of placental messengers into the maternal circulation, which causes preeclampsia. Our objective was to develop an in vitro model, which can be used to further elucidate the molecular mechanisms of preeclampsia and which might be used to find a remedy. METHODS: Human non-complicated term placentas were collected...
2018: PloS One
https://www.readbyqxmd.com/read/30131231/pulmonary-hypertension-due-to-lung-diseases-updated-recommendations-from-the-cologne-consensus-conference-2018
#16
Horst Olschewski, Jürgen Behr, Hinrich Bremer, Martin Claussen, Philipp Douschan, Michael Halank, Matthias Held, Marius M Hoeper, Stephan Holt, Hans Klose, Stephan Krüger, Tobias J Lange, Frank Reichenberger, Dirk Skowasch, Silvia Ulrich, Heinrike Wilkens, Werner Seeger
The 2015 European Guidelines on Pulmonary Hypertension did not only cover pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) associated with chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase‑5 inhibitors, sGC stimulators) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH...
August 11, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/30118797/chst3-and-chst13-polymorphisms-as-predictors-of-bosentan-induced-liver-toxicity-in-japanese-patients-with-pulmonary-arterial-hypertension
#17
Kennosuke Yorifuji, Yuko Uemura, Shinji Horibata, Goh Tsuji, Yoko Suzuki, Kazuya Miyagawa, Kazuhiko Nakayama, Ken-Ichi Hirata, Shunichi Kumagai, Noriaki Emoto
Bosentan, an endothelin receptor antagonist, has been widely used as a first-line drug for the treatment of pulmonary arterial hypertension (PAH). In addition, bosentan is approved for patients with digital ulcers related to systemic sclerosis. Liver dysfunction is a major adverse effect of bosentan and may lead to discontinuation of therapy. The purpose of this study was to identify genomic biomarkers to predict bosentan-induced liver injury. A total of 69 PAH patients were recruited into the study. An exploratory analysis of 1936 single-nucleotide polymorphisms (SNPs) in 231 genes involved in absorption, distribution, metabolism, and elimination of multiple medications using Affimetrix DMET™ (Drug Metabolism Enzymes and Transporters) chips was performed...
September 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30098343/regulation-of-blood-pressure-is-influenced-by-gender-a-study-in-obese-zucker-rats
#18
Mohadetheh Moulana, Rodrigo O Maranon
AIM: The present study determined the role of renin-angiotensin system (RAS), endothelin system, and eicosanoid system in the blood pressure (BP) regulation in male and female Zucker rats, and whether the pressor response change similarly in lean and obese animals. MATERIAL AND METHODS: In female (f) and male (m), lean (L) and obese (O) Zucker rats (ZR) at 22 weeks old, we evaluated the role of the 3 mentioned systems using the following treatments: 1) enalapril (angiotensin I converting enzyme inhibitor), 2) the ABT-627 (endothelin receptor A (ETA ) antagonist), and 3) the 1-aminobenzotriazol (1-ABT: eicosanoid synthesis inhibitor)...
September 15, 2018: Life Sciences
https://www.readbyqxmd.com/read/30095297/endotoxemia-enhanced-renal-vascular-reactivity-to-endothelin-1-in-cirrhotic-rats
#19
Chiao-Lin Chuang, Ching-Chih Chang, Shao-Jung Hsu, Hui-Chun Huang, Fa-Yauh Lee, Ling-Ju Huang, Shou-Dong Lee
Hepatorenal syndrome (HRS), a severe complication of advanced cirrhosis, is defined as hypoperfusion of kidneys resulting from intense renal vasoconstriction in response to generalized systemic arterial vasodilatation. Nevertheless, the mechanisms have been barely investigated. Cumulative studies demonstrated renal vasodilatation in portal hypertensive and compensated cirrhotic rats. Previously, we identified that blunted renal vascular reactivity of portal hypertensive rats was reversed after lipopolysaccharide (LPS)...
November 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30094478/electroacupuncture-induces-antihyperalgesic-effect-through-endothelin-b-receptor-in-the-chronic-phase-of-a-mouse-model-of-complex-regional-pain-syndrome-type-i
#20
Leidiane Mazzardo-Martins, Daiana Cristina Salm, Elisa C Winkelmann-Duarte, Júlia Koerich Ferreira, Daniela Dero Lüdtke, Kamilla Pamplona Frech, Luiz Augusto Oliveira Belmonte, Verônica Vargas Horewicz, Anna Paula Piovezan, Francisco José Cidral-Filho, Ari Ojeda Ocampo Moré, Daniel Fernandes Martins
Complex regional pain syndrome (CRPS) is a disorder that involves abnormal inflammation and nerve dysfunction frequently resistant to a broad range of treatments. Peripheral nerve stimulation with electroacupuncture (EA) has been widely used in different clinical conditions to control pain and inflammation; however, the use of EA in the treatment of CRPS is under investigation. In this study, we explore the effects of EA on hyperalgesia and edema induced in an animal model of chronic post-ischemia pain (CPIP model) and the possible involvement of endothelin receptor type B (ETB ) in this effect...
August 10, 2018: Pflügers Archiv: European Journal of Physiology
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