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Endothelin Receptor Antagonist

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https://www.readbyqxmd.com/read/30118797/chst3-and-chst13-polymorphisms-as-predictors-of-bosentan-induced-liver-toxicity-in-japanese-patients-with-pulmonary-arterial-hypertension
#1
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 1,936 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...
August 14, 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
#2
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)...
August 8, 2018: Life Sciences
https://www.readbyqxmd.com/read/30095297/endotoxemia-enhanced-renal-vascular-reactivity-to-endothelin-1-in-cirrhotic-rats
#3
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 hypo-perfusion of kidneys resulting from intense renal vasoconstriction in response to generalized systemic arterial vasodilatation. Nevertheless, the mechanisms were 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 following lipopolysaccharide (LPS)...
August 10, 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
#4
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 Cidra-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
https://www.readbyqxmd.com/read/30031229/cardiomyocyte-specific-knockout-of-endothelin-receptor-a-attenuates-obesity-cardiomyopathy
#5
Asli F Ceylan, Shuyi Wang, Machender R Kandadi, Jie Chen, Yinan Hua, Zhaohui Pei, Sreejayan Nair, Jun Ren
Endothelin (ET)-1 is implicated in the pathophysiology of cardiovascular diseases although its role in obesity anomalies has not been fully elucidated. This study was designed to examine the impact of ET-1 receptor A (ETA ) ablation on obesity-induced changes in cardiac geometry and contractile function, as well as the mechanisms involved with a focus on autophagy. Cardiomyocyte-specific ETA receptor knockout (ETAKO) and WT mice were fed either low-fat (10% calorie from fat) or high-fat (45% calorie from fat) diet for 24 weeks...
July 18, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/30026513/involvement-of-endothelin-1-in-remote-preconditioning-induced-cardioprotection-through-connexin-43-and-akt-gsk-3%C3%AE-signaling-pathway
#6
Min Zhang, Wei Wei Gu, Xing Yu Hong
The present study was aimed to explore the role of endothelins in remote preconditioning (RP)-induced myocardial protection in ischemia-reperfusion (IR) injury. RP stimulus was given by subjecting hind limb to four cycles of ischemia and reperfuion (5 minutes each) using blood pressure cuff in male rats. Following RP, hearts were isolated and subjected to 30 minutes of ischemia and 120 minutes of reperfusion on Langendorff apparatus. The extent of myocardial injury was determined by measuring the levels of LDH-1, CK-MB and cardiac troponin T (cTnT) in coronary effluent; caspase-3 activity and Bcl 2 expression in heart (apoptosis); infarct size by triphenyl tetrazolium chloride and contractility parameters including left ventricular developed pressure, dp/dtmax dp/dtmin and heart rate...
July 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30020876/clinical-presentation-and-long-term-outcomes-of-systemic-sclerosis-portuguese-patients-from-a-single-centre-cohort-a-eustar-registration-initiative
#7
Carolina Vidal, Carina Ruano, Vera Bernardino, Pedro Lavado Carreira, Ana Lladó, Maria Céu Santos, Heidi Gruner, António Panarra, Nuno Riso, Maria Francisca Moraes-Fontes
INTRODUCTION: Systemic sclerosis is a complex disorder that requires systematic screening. Our objective is to report the European Scleroderma Trials and Research group centre affiliation and its impact in our clinical practice. MATERIAL AND METHODS: The European Scleroderma Trials and Research group affiliation process, database update and current patient evaluation, with respect to demographic and clinical features. Cumulative mortality was analysed. RESULTS: We identified 19 female patients (which met all the American College of Rheumatology/ European League Against Rheumatism 2013 criteria for systemic sclerosis) under current follow-up, divided according to the LeRoy classification into diffuse cutaneous (n = 5), limited cutaneous (n = 11) and limited (n = 3) types, followed for a median period of 5, 12 and 6 years, respectively...
June 29, 2018: Acta Médica Portuguesa
https://www.readbyqxmd.com/read/30012496/attenuation-of-oxidative-stress-and-hypertension-in-an-animal-model-of-hellp-syndrome
#8
Rachael Morris, Shauna-Kay Spencer, Allison Barnes, Teylor Bowles, Patrick B Kyle, Kedra Wallace
HELLP (hemolysis elevated liver enzyme low platelet) syndrome is associated with hypertension, inflammation, oxidative stress and endothelial activation. The objective of this study was to determine if oxygen scavenging or endothelin A receptor antagonism improved hypertension and oxidative stress. sFlt-1 and sEndoglin were infused via mini-osmotic pump into normal pregnant rats (NP) on gestational day 12 to create HELLP syndrome. On gestational day 18 arterial catheters were inserted and on gestational day 19 mean arterial pressure was analyzed in rats; serum, urine and tissues were collected for molecular analysis...
July 24, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/30005860/therapy-of-scleroderma-renal-crisis-state-of-the-art
#9
REVIEW
Elisabetta Zanatta, Pamela Polito, Maria Favaro, Maddalena Larosa, Piero Marson, Franco Cozzi, Andrea Doria
Scleroderma renal crisis (SRC) is an uncommon but still life-threatening manifestation of systemic sclerosis (SSc). The incidence of SRC has decreased in the last few decades, probably due to a widespread use of vasodilators in SSc patients. It is well-recognized that exposure to different drugs can trigger SRC (corticosteroids, cyclosporine) or might prevent its occurrence (iloprost, calcium channel blockers). The prognosis of this life-threatening manifestation has not substantially improved since 1980s, when ACE-inhibitors were introduced in its treatment...
July 10, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29999581/ovarian-hormones-modulate-endothelin-1-receptor-responses-in-young-women
#10
Kelly N Sebzda, Andrew V Kuczmarski, Ryan T Pohlig, Shannon L Lennon, David G Edwards, Megan M Wenner
OBJECTIVE: We recently demonstrated ETBR mediate vasodilation in young but not postmenopausal women; it is unclear if this is related to age or a decline in ovarian hormones. The purpose of this study was to test the hypothesis that ETBR responses are modulated by ovarian hormones. METHODS: We measured cutaneous vasodilatory responses in 12 young women (22 ± 1 years, 23 ± 1 kg/m2 ) during the ML (days 20-25) and EF (days 2-5) phases of the menstrual cycle...
July 12, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/29950821/elicitation-of-health-state-utilities-associated-with-the-mode-of-administration-of-drugs-acting-on-the-prostacyclin-pathway-in-pulmonary-arterial-hypertension
#11
Evan W Davies, Samuel Llewellyn, Amélie Beaudet, Charlotte E Kosmas, Wendy Gin-Sing, Helen A Doll
Introduction: Pulmonary arterial hypertension (PAH) is a rare, incurable disease associated with decreased life expectancy and a marked impact on quality of life (QoL). There are three classes of drugs available for treatment: endothelin receptor antagonists (ERA), drugs acting on nitric oxide pathway (riociguat and phosphodiesterase type 5 inhibitors [PDE5i]), and drugs acting on prostacyclin pathway. The latter have widely different modes of administration - continuous intravenous infusion, continuous subcutaneous infusion, inhaled, and oral - each associated with variable treatment burden, and implications for health economic assessment...
2018: Patient Preference and Adherence
https://www.readbyqxmd.com/read/29947543/endothelin-1-inhibition-improves-the-mbdnf-probdnf-ratio-in-endothelial-cells-and-ht22-neurons-under-high-glucose-palmitate-growth-conditions
#12
R Ward, Y Abdul, A Ergul
Diabetes increases the risk and worsens the progression of cognitive impairment. The hippocampus is an important domain for learning and memory. We previously showed that endothelin-1 (ET-1) reduced diabetes-induced inflammation in hippocampal neurons, suggesting a neuroprotective effect. Given that neurons and endothelial cells within the neurovascular unit depend on each other for proper function, we investigated the effect of ET-1 on brain-derived neurotrophic factor (BDNF) synthesis, a key neurotrophin and prosurvival factor, in neuronal (HT22 hippocampal neurons) and brain microvascular endothelial (BMEC-5i) cells under normal and diabetes-mimicking (high glucose plus palmitate) conditions...
June 27, 2018: Physiological Research
https://www.readbyqxmd.com/read/29947537/endothelin-a-receptor-blockade-improves-endothelium-dependent-relaxation-in-obese-woman
#13
K Gradin, B Persson
Hypertension in obesity is associated with increased insulin resistance, vascular mass and body mass index (BMI). The purpose of the study was to visualize endothelin-1 (ET-1) mediated constriction in arteries isolated from subcutaneous adipose tissue from obese hypertensive women previously operated by gastric bypass. Functional studies were conducted in a microvascular myograph. Expressed as percentage of contraction elicited by 124 mM KCl concentration-response curves for ET-1 were shifted leftward in arteries from obese hypertensive patients compared to healthy normotensive subjects...
June 27, 2018: Physiological Research
https://www.readbyqxmd.com/read/29947528/renoprotective-effects-of-et-a-receptor-antagonists-therapy-in-experimental-non-diabetic-chronic-kidney-disease-is-there-still-hope-for-the-future
#14
I Vaněčková, S Hojná, M Kadlecová, Z Vernerová, L Kopkan, L Červenka, J Zicha
Chronic kidney disease (CKD) is a life-threatening disease arising as a frequent complication of diabetes, obesity and hypertension. Since it is typically undetected for long periods, it often progresses to end-stage renal disease. CKD is characterized by the development of progressive glomerulosclerosis, interstitial fibrosis and tubular atrophy along with a decreased glomerular filtration rate. This is associated with podocyte injury and a progressive rise in proteinuria. As endothelin-1 (ET-1) through the activation of endothelin receptor type A (ET(A)) promotes renal cell injury, inflammation, and fibrosis which finally lead to proteinuria, it is not surprising that ET(A) receptors antagonists have been proven to have beneficial renoprotective effects in both experimental and clinical studies in diabetic and non-diabetic CKD...
June 27, 2018: Physiological Research
https://www.readbyqxmd.com/read/29947527/new-drugs-and-emerging-therapeutic-targets-in-the-endothelin-signaling-pathway-and-prospects-for-personalized-precision-medicine
#15
A P Davenport, R E Kuc, C Southan, J J Maguire
During the last thirty years since the discovery of endothelin-1, the therapeutic strategy that has evolved in the clinic, mainly in the treatment of pulmonary arterial hypertension, is to block the action of the peptide either at the ET(A) subtype or both receptors using orally active small molecule antagonists. Recently, there has been a rapid expansion in research targeting ET receptors using chemical entities other than small molecules, particularly monoclonal antibody antagonists and selective peptide agonists and antagonists...
June 27, 2018: Physiological Research
https://www.readbyqxmd.com/read/29944850/intravitreal-administration-of-endothelin-type-a-receptor-or-endothelin-type-b-receptor-antagonists-attenuates-hypertensive-and-diabetic-retinopathy-in-rats
#16
Saeed F Alrashdi, Devy Deliyanti, Jennifer L Wilkinson-Berka
Hypertension is an independent risk factor for diabetic retinopathy, yet anti-hypertensive medications such as blockade of angiotensin II do not completely protect against vision-threatening vascular disease. We hypothesized that the potent vasoactive factor, endothelin (ET), is up-regulated in diabetic retinopathy and antagonism of the ET type A receptor (ETRA) or ET type B receptor (ETRB) ameliorates retinal vascular leakage independently of any blood pressure lowering effects. Spontaneously hypertensive rats (SHR) and their normotensive and genetic controls, Wistar Kyoto rats, were randomized to become diabetic or non-diabetic and studied for 8 weeks...
June 23, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29924890/targeting-matrix-metalloproteinase-13-in-bronchial-epithelial-repair
#17
Christopher Howell, James R Smith, Janis K Shute
BACKGROUND: Viral infection of the bronchial epithelium disrupts the barrier properties of the epithelium in healthy individuals and those with lung disease. Repair of the bronchial epithelium is dependent of the formation of a provisional fibrin matrix and migration of epithelial cells to cover denuded areas, followed by proliferation and differentiation. OBJECTIVE: The objective was to test the hypothesis that poly I:C, a model of viral infection, limits epithelial repair through the stimulated release of matrix metalloproteinase-13 (MMP-13)...
June 20, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29896159/blockade-of-endothelin-1-receptor-type-b-ameliorates-glucose-intolerance-and-insulin-resistance-in-a-mouse-model-of-obstructive-sleep-apnea
#18
Jan Polak, Naresh M Punjabi, Larissa A Shimoda
Obstructive sleep apnea (OSA) is associated with insulin resistance (IR) and glucose intolerance. Elevated endothelin-1 (ET-1) levels have been observed in OSA patients and in mice exposed to intermittent hypoxia (IH). We examined whether pharmacological blockade of type A and type B ET-1 receptors (ETA and ETB ) would ameliorate glucose intolerance and IR in mice exposed to IH. Subcutaneously implanted pumps delivered BQ-123 (ETA antagonist; 200 nmol/kg/day), BQ-788 (ETB antagonist; 200 nmol/kg/day) or vehicle (saline or propyleneglycol [PG]) for 14 days in C57BL6/J mice (10/group)...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29888323/circulating-neurotoxic-5-ht2a-receptor-agonist-autoantibodies-in-adult-type-2-diabetes-with-parkinson-s-disease
#19
Mark B Zimering
Aims: To test whether circulating neurotoxic autoantibodies increase in adult type 2 diabetes mellitus with Parkinson's disease (PD) or dementia. To identify the G-protein coupled receptor on neuroblastoma cells mediating neural inhibitory effects in diabetic Parkinson's disease plasma autoantibodies. To determine the mechanism of accelerated neuroblastoma cell death and acute neurite retraction induced by diabetic Parkinson's disease and dementia autoantibodies. Methods: Protein-A eluates from plasma of twelve older adult male diabetic patients having Parkinson's disease (n=10) or dementia (n=2), and eight age-matched control diabetic patients were tested for ability to cause accelerated N2A neuroblastoma cell death and acute neurite retraction...
2018: Journal of Endocrinology and Diabetes
https://www.readbyqxmd.com/read/29886166/attenuation-of-the-degenerative-effects-of-endothelin-1-on-cartilaginous-endplate-cells-by-the-endothelin-receptor-antagonist-bq-123-via-the-wnt-%C3%AE-catenin-signaling-pathway
#20
Wei Yuan, Zhen-Xi Li, Cheng-Long Zhao, Tian-Hui Hou, Si-Wang Hu, Wei-Bo Liu, Feng-Lai Yuan, Jian-Ru Xiao
BACKGROUND: Context: Endothelin-1 (ET-1) is an inflammatory mediator associated with cartilage endplate (CEP) degeneration in the intervertebral disc. SOX9 is down-regulated during CEP degeneration, along with its targets, collagen II and aggrecan. Wnt/β-catenin signaling is associated with CEP degeneration and a downstream target of SOX9; however, the precise mechanism of CEP degeneration and the role of ET-1 are largely unknown. PURPOSE: The purpose of the study was to evaluate the influence of the endothelin A receptor antagonist, BQ-123, on ET-1-induced effects on cartilaginous endplate cells (CECs) associated with CEP degeneration via the Wnt/β-catenin signaling pathway...
June 7, 2018: Spine Journal: Official Journal of the North American Spine Society
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