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Endothelin Receptor Antagonist

Xiao-Jing Sun, Min Chen, Ming-Hui Zhao
Background: Activation of coagulation system plays an important role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) pathogenesis. Thrombin, generated during coagulation could disrupt endothelial barrier integrity through protease-activated receptor 1 (PAR1). Our previous study found that sphingosine-1-phosphate (S1P) contributed to myeloperoxidase (MPO)-ANCA-positive IgG-induced glomerular endothelial cell (GEnC) activation through a S1P receptor (S1PR)-dependent route. In recent years, S1P signaling was reported to be involved in thrombin effects on endothelial cells...
2019: Frontiers in Immunology
Stéphanie Hostenbach, Ayla Pauwels, Veronique Michiels, Hubert Raeymaekers, Anne-Marie Van Binst, Annick Van Merhaeghen-Wieleman, Peter Van Schuerbeek, Jacques De Keyser, Miguel D'Haeseleer
BACKGROUND: Axonal degeneration is related to long-term disability in patients with multiple sclerosis (MS). The underlying mechanism remains ill understood but appears to involve axonal energetic dysfunction. A globally impaired cerebral blood flow (CBF) has been observed in the normal-appearing white matter (NAWM) of patients with MS, which is probably related to astrocytic overexpression of endothelin-1 (ET-1). Cerebral hypoperfusion has been associated with reduced mitochondrial activity and disabling symptoms (e...
March 14, 2019: Trials
Neeraj Dhaun, David J Webb
Cardiovascular disease is a major contributor to global morbidity and mortality and is the common end point of many chronic diseases. The endothelins comprise three structurally similar peptides of 21 amino acids in length. Endothelin 1 (ET-1) and ET-2 activate two G protein-coupled receptors - endothelin receptor type A (ETA ) and endothelin receptor type B (ETB ) - with equal affinity, whereas ET-3 has a lower affinity for ETA . ET-1 is the most potent vasoconstrictor in the human cardiovascular system and has remarkably long-lasting actions...
March 13, 2019: Nature Reviews. Cardiology
Venessa H M Tsang
PURPOSE OF REVIEW: Tyrosine kinase inhibitors (TKI), predominantly vandetanib and cabozantinib, are increasingly used for management of advanced medullary thyroid cancer. This review aims to discuss the major and serious adverse events associated with TKI. RECENT FINDINGS: The choice of TKI depends on the patient's existing comorbidities. Patients who have long QT interval should avoid vandetanib and those at risk of gastrointestinal perforation should avoid cabozantinib...
March 8, 2019: Current Opinion in Oncology
Julia Dolinina, Anna Rippe, Carl M Öberg
Emerging evidence indicates that endogenous production of endothelin 1 (ET-1), a 21-amino-acid peptide vasoconstrictor, plays an important role in proteinuric kidney disease. Previous studies in rats have shown that chronic administration of ET-1 leads to increased glomerular albumin leakage. The underlying mechanisms are however currently not known. Here we used size exclusion chromatography to measure glomerular sieving coefficients (θ) for neutral fluorescein isotiocyanate (FITC)-Ficoll (molecular Stokes-Einstein radius: 15-80 Å; MW 70 kDa/400kDa) in anesthetized male Sprague-Dawley rats (n=12) at baseline and at 5, 15, 30 and 60 minutes following intravenous administration of ET-1...
March 13, 2019: American Journal of Physiology. Renal Physiology
Nadir Planes, Michelle A Digman, Patrick P M L Vanderheyden, Enrico Gratton, Catherina Caballero-George
The angiotensin II AT1 and the endothelin 1 ETA receptors play a crucial role in the pathogenesis of cardiovascular diseases like hypertension, heart failure, stroke, pulmonary hypertension, and cardiac hypertrophy. Both receptors are members of the rhodopsion-like superfamily of G protein-coupled receptors which can exist as monomers, dimers, and higher order aggregates. Recently, oligomerization of these two receptors have been described by several biophysical methods based mainly on luminescence and fluorescence energy transfer...
March 6, 2019: Biochimica et Biophysica Acta. General Subjects
Arunachalam Muthuraman, Kamus Nafisa, Mysore Srinivasmurthy Sowmya, Bachahalli Madappa Arpitha, Nagdol Choedon, Crasta Denis Sandy, Narahari Rishitha, Islam Johurul
BACKGROUND: Cigarette smoke is exogenous modifiable factors to changes the neurovascular complication. The chronic exposure of cigarette smoke enhances neurocognitive dysfunction. AIMS: The present study is focused on evaluating the role of ambrisentan (selective endothelin-A receptor antagonist) on cigarette smoke-induced cognitive impairment in Danio rerio. MAIN METHODS: The cognitive dysfunction was developed by cigarette smoke exposure (CSE; 10 min in 25 ml of CSE per day) for five days...
March 4, 2019: Life Sciences
Maryam Khoramzadeh, Amirreza Dehghanian, Farzaneh Ketabchi
INTRODUCTION: Hepatopulmonary syndrome and portopulmonary hypertension are common complications of liver disorders. This study aimed to determine roles of ET-B receptors and endothelial-derived NO synthase in the regulation of pulmonary hemodynamic in cirrhotic rats. METHODS: Male Sprague-Dawley rats were divided into the Sham and common bile duct ligation (CBDL) groups. After 28 days, animals were anesthetized, and the right ventricle, femoral artery, and vein cannulated...
March 2019: Journal of Cardiovascular Pharmacology
Markus Hoenicka, Svitlana Golovchenko, Leonie Englert, Mirjam Spaeth, Levani Shoshiashvili, Christian Großer, Hans-Stefan Hofmann, Michael Ried
PURPOSE: Treatment of pulmonary arterial hypertension (PAH) by vasodilator drug monotherapy is often limited in its effectiveness. Combination therapy may help to improve treatment and to reduce drug toxicity. This study assessed the combination of the endothelin receptor antagonist macitentan and the phosphodiesterase-5 inhibitor vardenafil in a human ex vivo model. METHODS: Study patients did not suffer from PAH. Human pulmonary arteries (PA) and veins (PV) were harvested from resected pulmonary lobes...
March 2, 2019: Cardiovascular Drugs and Therapy
Humberto Morales-Loredo, David T Jones, Adelaeda Barrera, Perenkita Mendiola, Joshua Garcia, Carolyn E Pace, Minerva Murphy, Nancy L Kanagy, Laura V Gonzalez Bosc
Obstructive sleep apnea (OSA) is characterized by recurrent episodes of pharyngeal collapse during sleep resulting in intermittent hypoxia (IH), and is associated with high incidence of hypertension and accelerated renal failure. In rodents, endothelin-1 (ET-1) contributes to IH-induced hypertension, and ET-1 levels inversely correlate with glomerular filtration rate (GFR) in end-stage chronic kidney disease (CKD) patients. Therefore, we hypothesized that a dual ET receptor antagonist, macitentan (Actelion Pharmaceuticals) will attenuate and reverse hypertension and renal dysfunction in a rat model of combined IH and CKD...
February 27, 2019: American Journal of Physiology. Renal Physiology
Faezeh Seif, Peter J Little, Reyhaneh Niayesh-Mehr, Masoumeh Zamanpour, Hossein Babaahmadi-Rezaei
OBJECTIVES: TGF-β through hyperelongation of glycosaminoglycan (GAG) chains leads to binding of low-density lipoproteins to the proteoglycans. The vasoactive peptide, endothelin-1 (ET-1), plays a key role in the development of atherosclerosis. This study addressed the question whether ET-1 by activating the Rho kinase and cytoskeletal rearrangement can transactivate the TGF-β receptor leading to phosphorylation of the transcription factor Smad2 and increased expression of the GAG chain synthesizing enzyme such as chondroitin synthase-1 (CHSY-1) in bovine aortic endothelial cells (BAECs)...
February 27, 2019: Journal of Pharmacy and Pharmacology
Alejandro Gutiérrez, Cristina Contreras, Ana Sánchez, Dolores Prieto
Insulin resistance plays a key role in the pathogenesis of type 2 diabetes and is also related to other health problems like obesity, hypertension, and metabolic syndrome. Imbalance between insulin vascular actions via the phosphatidylinositol 3-Kinase (PI3K) and the mitogen activated protein kinase (MAPK) signaling pathways during insulin resistant states results in impaired endothelial PI3K/eNOS- and augmented MAPK/endothelin 1 pathways leading to endothelial dysfunction and abnormal vasoconstriction. The role of PI3K, MAPK, and protein kinase C (PKC) in Ca2+ handling of resistance arteries involved in blood pressure regulation is poorly understood...
2019: Frontiers in Physiology
Ryosuke Saigusa, Takashi Yamashita, Shunsuke Miura, Megumi Hirabayashi, Kouki Nakamura, Takuya Miyagawa, Yuki Fukui, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano
BACKGROUNDS: Stratified epithelia have caught much attention as potential contributors to the development of dermal and esophageal fibrosis in systemic sclerosis (SSc). Galectin-7 is a marker of all types of stratified epithelia, which is involved in the maintenance of epidermal homeostasis. So far, the role of galectin-7 has not been studied in SSc. OBJECTIVES: To investigate the potential contribution of galectin-7 to the development of clinical manifestations in SSc...
February 9, 2019: Experimental Dermatology
Briony Labram, Sara Namvar, Tracy Hussell, Sarah E Herrick
BACKGROUND: Asthma is a chronic inflammatory condition of the airways and patients sensitised to airborne fungi such as Aspergillus fumigatus have more severe asthma. Thickening of the bronchial subepithelial layer is a contributing factor to asthma severity for which no current treatment exists. Airway epithelium acts as an initial defence barrier to inhaled spores, orchestrating an inflammatory response and contributing to subepithelial fibrosis. OBJECTIVE: We aimed to analyse the production of profibrogenic factors by airway epithelium in response to A...
February 8, 2019: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Catharina Belge, Marion Delcroix
Macitentan (10 mg once daily orally), a dual endothelin receptor antagonist (ERA) developed by modifying the structure of bosentan to increase the efficacity and safety, is approved for the treatment of pulmonary arterial hypertension (PAH). The pivotal SERAPHIN trial, (a landmark trial in the history of PAH trials because of the large number of included patients, the long-term follow up and the first trial with morbidity/mortality as the primary endpoint) showed a reduction of the risk of a morbidity or mortality event by 45% over the treatment time compared with placebo...
January 2019: Therapeutic Advances in Respiratory Disease
Mevlut Albayrak, Alptug Atıla, Elif Yılmazel Ucar, Omer Araz, Yucel Kadıoglu
Macitentan is an endothelin receptor antagonist commonly used in the treatment of pulmonary arterial hypertension (PAH). A novel, rapid, simple and sensitive UPLC-MS/MS method was developed and validated for pharmacokinetic study and the determination of macitentan in PAH patients. Macitentan and bosentan which is used as internal standard were detected using APCI in positive ion and MRM mode by monitoring the mass transitions m/z 589.1→203.3 and 552.6→311.5, respectively. Chromatographic separation was performed on reverse phase C18 column (5 μm, 4...
February 6, 2019: Biomedical Chromatography: BMC
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No abstract text is available yet for this article.
February 5, 2019: Circulation
T V Martynyuk, S N Nakonechnikov, I Ye Chazova
Since 2015, macitentan, the new oral dual endothelin receptors antagonist (ERA), has been successfully introduced into clinical practice in the Russian Federation for the treatment of pulmonary arterial hypertension (PAH) patients. It has improved physicochemical properties, which provides tissue specificity. Among ERA and other drugs of specific therapy, macitentan is the only one with indication-prevention of PAH progression. In the randomized, placebo-controlled study SERAPHIN in 742 PAH patients aged >12 years, macitentan 10 mg compared with placebo reduced the risk of morbidity and mortality by 45%...
April 19, 2018: Terapevticheskiĭ Arkhiv
Hayley Barnes, Zoe Brown, Andrew Burns, Trevor Williams
BACKGROUND: Pulmonary hypertension (PH) comprises a group of complex and heterogenous conditions, characterised by elevated pulmonary artery pressure, and which left untreated leads to right-heart failure and death. PH includes World Health Organisation (WHO) Group 1 pulmonary arterial hypertension (PAH); Group 2 consists of PH due to left-heart disease (PH-LHD); Group 3 comprises PH as a result of lung diseases or hypoxia, or both; Group 4 includes PH due to chronic thromboembolic occlusion of pulmonary vasculature (CTEPH), and Group 5 consists of cases of PH due to unclear and/or multifactorial mechanisms including haematological, systemic, or metabolic disorders...
January 31, 2019: Cochrane Database of Systematic Reviews
I Rachdi, M Tougorti, F Daoud, Z Aydi, H Zoubeidi, B Ben Dhaou, F Boussema
PURPOSE: There are authentic observations of combination of systemic lupus erythematosus (SLE) with systemic sclerosis (SS) and with polymyositis defined as overlap syndromes. The prevalence of pulmonary hypertension is unknown in SS-SLE overlap syndrome because of its rarity. The aim of our study was to precise clinical, paraclinical and evolutive features of pulmonary hypertension in patients with systemic sclerosis-systemic lupus erythematosus (SS-SLE) overlap syndrome. METHODS: Sixteen cases of SS-SLE overlap syndrome were retrospectively studied in a period of 16 years (2000-2015)...
January 23, 2019: Annales de Cardiologie et D'angéiologie
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