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Endothelin inhibitor

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https://www.readbyqxmd.com/read/29165873/andrographolide-inhibits-hypoxia-induced-hypoxia-inducible-factor-1%C3%AE-and-endothelin-1-expression-through-the-heme-oxygenase-1-co-cgmp-mkp-5-pathways-in-ea-hy926-cells
#1
Hung-Chih Lin, Shih-Li Su, Wan-Chun Lin, Ai-Hsuan Lin, Ya-Chen Yang, Chong-Kuei Lii, Haw-Wen Chen
Andrographolide is a potent anti-inflammatory agent found in Andrographis paniculata. Endothelin 1 (ET-1) is an endothelium-derived vasoconstrictor with pro-inflammatory properties secreted in response to hypoxia. Mitogen-activated protein kinase phosphatase 5 (MKP-5) is a dual-specificity phosphatase that dephosphorylates threonine and tyrosine residues of MAPKs. We showed previously that hypoxia-induced HIF-1α expression and ET-1 secretion are dependent on p38 MAPK in EA.hy926 cells. Here, we investigate what role MKP-5 plays in andrographolide's inhibition of hypoxia-induced expression of HIF-1α and ET-1...
November 22, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29163807/macitentan-a-double-antagonist-of-endothelin-receptors-efficiently-impairs-migration-and-microenvironmental-survival-signals-in-chronic-lymphocytic-leukemia
#2
Rossana Maffei, Stefania Fiorcari, Tiziana Vaisitti, Silvia Martinelli, Stefania Benatti, Giulia Debbia, Davide Rossi, Patrizia Zucchini, Leonardo Potenza, Mario Luppi, Gianluca Gaidano, Silvia Deaglio, Roberto Marasca
The crosstalk between chronic lymphocytic leukemia (CLL) cells and tumor microenvironment is essential for leukemic clone maintenance, supporting CLL cells survival, proliferation and protection from drug-induced apoptosis. Over the past years, the role of several soluble factors involved in these processes has been studied. CLL cells express higher levels of endothelin 1 (ET-1) and ETA receptor as compared to normal B cells. Upon ET-1 stimulation, CLL cells improve their survival and proliferation and reduce their sensitivity to the phosphoinositide-3-kinase δ inhibitor idelalisib and to fludarabine...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29161233/swimming-but-not-vitamin-e-ameliorates-prothrombotic-state-and-hypofibrinolysis-in-a-rat-model-of-nonalcoholic-fatty-liver-disease
#3
Hussein F Sakr, Amr M Abbas, Mohamed A Haidara
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with a systemic procoagulant hypofibrinolysis state that is considered as a risk factor for microangiopathy and peripheral vascular diseases. Swimming exercise ameliorates the metabolic dysfunction in type 2 diabetes. Vitamin E is a natural antioxidant that reduces the risk of endothelial dysfunction in metabolic syndrome. The aim of the present study is to investigate the effect of combined swimming exercise with vitamin E on coagulation as well as blood fibrinolysis markers in rats with NAFLD...
November 21, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29158679/treatment-of-pulmonary-hypertension-with-left-heart-disease-a-concise-review
#4
REVIEW
Anish Desai, Shilpa A Desouza
Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure ≥ 25 mmHg, as determined by right heart catheterization. Pulmonary arterial hypertension (PAH) can no longer be considered an orphan disease given the increase in awareness and availability of new drugs. PH carries with it a dismal prognosis and leads to significant morbidity and mortality. Symptoms can range from dyspnea, fatigue and chest pain to right ventricular failure and death. PH is divided into five groups by the World Health Organization (WHO), based on etiology...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/29140729/gene-expression-and-gene-associations-during-the-development-of-heart-failure-with-preserved-ejection-fraction-in-the-dahl-salt-sensitive-model-of-hypertension
#5
Jeffrey Yim, Hyokeun Cho, Simon W Rabkin
Gene expression and associations were examined in a model of heart failure with preserved ejection fraction (HFpEF), a condition with minimal effective treatment. Genes with at least two studies showing significant changes in Dahl rat with heart failure were examined by meta-analysis. Significantly increased in expression were iNOS, p47phox, ADM, ANP, OPN, ACE, MCP-1, GP91PHOX, ICAM-1, TGF-β1, CTGF, ET-1, p22phox, ETB, BNP, ETA, MMP13, Col1a1, MMP2, TIMP1, Col3a1, Il-1β, β-MHC, ECE1, MMP14, AGT, and MMP9...
November 15, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29131071/highly-selective-endothelin-1-receptor-a-inhibition-prevents-bleomycin-induced-pulmonary-inflammation-and-fibrosis-in-mice
#6
Nikolaos Manitsopoulos, Ioanna Nikitopoulou, Nikolaos A Maniatis, Christina Magkou, Anastasia Kotanidou, Stylianos E Orfanos
BACKGROUND: Pulmonary fibrosis is a chronic disease, which progressively leads to respiratory failure and ultimately death. Endothelin-1 (ET-1), a vasoconstrictor secreted by endothelial cells, promotes vasoconstriction by activation of its receptors A and B. OBJECTIVES: We addressed the role of highly selective ET-1 receptor A (ETA) inhibition in the pathogenesis of experimental pulmonary fibrosis by bleomycin (BLM). METHODS: BLM sulfate (2 U/mL) or saline was intratracheally administered to C57/Bl6 mice (4 groups; n = 5-11/group)...
November 9, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/29128622/efficacy-and-tolerability-of-pharmacological-interventions-for-pulmonary-arterial-hypertension-a-network-meta-analysis
#7
Hongjing Lin, Mupeng Wang, Ying Yu, Zeyu Qin, Xin Zhong, Jiahui Ma, Fangbo Zhao, Xueli Zhang
PURPOSE: This network meta-analysis (NMA) is designed to compare the efficacy and tolerability of various therapies and combinations for pulmonary arterial hypertension (PAH). METHOD: We conducted a systematic search in databases PubMed, Embase, and Cochrane Library. Treatment efficacy and tolerability were compared by synthesizing direct and indirect evidence. The surface under the curve ranking area was utilized to rank multiple interventions. RESULT: A total of 43 randomized clinical trials were included in our NMA...
November 8, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29126066/formaldehyde-regulates-vascular-tensions-through-nitric-oxide-cgmp-signaling-pathway-and-ion-channels
#8
Quanxi Zhang, Peiru Tian, Miaomiao Zhai, Xiaodong Lei, Zhenhua Yang, Yan Liu, Mengting Liu, Hao Huang, Xiri Zhang, Xu Yang, Yun Zhao, Ziqiang Meng
Formaldehyde (FA) has been linked to the detrimental cardiovascular effects. Here, we explored the effects and mechanisms of FA on rat aortas both in vivo and in vitro. The results presented that FA evidently lowered the blood pressures of rats. The expression levels of BKCa subunits α and β1 and iNOS of the aortas were up-regulated by FA in vivo. However, FA markedly reduced the levels of Cav1.2 and Cav1.3, which are the subunits of L-Ca(2+) channel. Furthermore, the contents of NO, cGMP and iNOS in the aortas were augmented by FA...
November 4, 2017: Chemosphere
https://www.readbyqxmd.com/read/29115394/high-glucose-upregulates-endothelin-type-b-receptors-in-vascular-smooth-muscle-cells-via-the-downregulation-of-sirt1
#9
Yan Lin, Yan Zhao, Enqi Liu
Silent information regulator family protein 1 (Sirt1) has recently gained attention for its protective effects against diabetic and cardiovascular diseases (CVDs). Vascular smooth muscle endothelin type B (ETB) receptors are involved in the pathogenesis of CVDs and diabetes. The aim of present study was to explore whether Sirt1 is involved in high glucose (HG)-mediated regulation of ETB receptors in rat superior mesenteric arteries (SMA). The rat SMA segments were cultured in the presence and absence of HG with or without the activator of Sirt1 and specific inhibitor for the extracellular signal-regulated protein kinase 1/2 (ERK1/2) for 24 h...
November 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29114220/endothelin-1-regulation-of-exercise-induced-changes-in-flow-dynamic-regulation-of-vascular-tone
#10
Robert M Rapoport, Daphne Merkus
Although endothelin (ET)-1 is a highly potent vasoconstrictor with considerable efficacy in numerous vascular beds, the role of endogenous ET-1 in the regulation of vascular tone remains unclear. The perspective that ET-1 plays little role in the on-going regulation of vascular tone at least under physiologic conditions is supported by findings that potential ET-1 constriction is minimized by the release of the vasodilator and ET-1 synthesis inhibitor, nitric oxide (NO). Indeed, ET-1 release and constriction is self-limited by ET-1-induced, endothelial ETB receptor-mediated release of NO...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29113524/how-does-preeclampsia-affect-neonates-highlights-in-the-disease-s-immunity
#11
Lina R Marins, Leonardo B Anizelli, Ana L Sarquis, Mariana D Romanowski
INTRODUCTION: Preeclampsia (PE) is the primary obstetrical cause in one to four perinatal deaths. Although the etiology and pathogenesis of preeclampsia is not fully known, a proinflammatory immune state prevails and can disrupt fetal hematopoiesis. Some of the effects on the newborn include neonatal thrombocytopenia, neutropenia, a reduction in T regulatory cells and an increased cytotoxic natural killer cell profile. METHOD: Electronic databases were searched, and defined criteria were applied to select articles for review...
November 7, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/29109091/transcriptomic-profiling-of-mda-mb-231-cells-exposed-to-boswellia-serrata-and-3-o-acetyl-b-boswellic-acid-er-upr-mediated-programmed-cell-death
#12
REVIEW
Elizabeth A Mazzio, Charles A Lewis, Karam F A Soliman
BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is characterized by the absence of hormone receptors (estrogen, progesterone and human epidermal growth factor receptor-2) and a relatively poor prognosis due to inefficacy of hormone receptor-based chemotherapies. It is imperative that we continue to explore natural products with potential to impede growth and metastasis of TNBC. In this study, we screened over 1,000 natural products for capacity to induce cell death in TNBC (MDA-MB -231) cells...
November 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29055784/rac1-modulates-g-protein-coupled-receptor-induced-bronchial-smooth-muscle-contraction
#13
Hiroyasu Sakai, Yuki Kai, Ken Sato, Mitsuo Ikebe, Yohihiko Chiba
Increasing evidence suggests a functional role of RhoA/Rho-kinase signalling as a mechanism for smooth muscle contraction; however, little is known regarding the roles of Rac1 and other members of the Rho protein family. This study aimed to examine whether Rac1 modulates bronchial smooth muscle contraction. Ring preparations of bronchi isolated from rats were suspended in an organ bath, and isometric contraction of circular smooth muscle was measured. Immunoblotting was used to examine myosin light chain phosphorylation in bronchial smooth muscle...
October 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29049376/antioxidants-and-nox1-nox4-inhibition-blocks-tgf%C3%AE-1-induced-ccn2-and-%C3%AE-sma-expression-in-dermal-and-gingival-fibroblasts
#14
Hannah Murphy-Marshman, Katherine Quensel, Xu Shi-Wen, Rebecca Barnfield, Jacalyn Kelly, Alex Peidl, Richard J Stratton, Andrew Leask
TGFbeta induces fibrogenic responses in fibroblasts. Reactive oxygen species (ROS)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) may contribute to fibrogenic responses. Here, we examine if the antioxidant N-acetylcysteine (NAC), the NOX inhibitor diphenyleneiodonium (DPI) and the selective NOX1/NOX4 inhibitor GKT-137831 impairs the ability of TGFbeta to induce profibrotic gene expression in human gingival (HGF) and dermal (HDF) fibroblasts. We also assess if GKT-137831 can block the persistent fibrotic phenotype of lesional scleroderma (SSc) fibroblasts...
2017: PloS One
https://www.readbyqxmd.com/read/29034264/reducing-cardiac-fibrosis-na-k-atpase-signaling-complex-as-a-novel-target
#15
X Fan, J Xie, J Tian
Cardiac fibrosis is a common pathological process in cardiac disease and may lead to heart failure. It can also cause sudden death even in those without cardiac symptoms. Tissue fibrosis can be categorized into two categories: replacement fibrosis (also called reparative fibrosis) and reactive fibrosis. In replacement fibrosis, infiltration of inflammatory cells and accumulation of Extracellular Matrix (ECM) proteins are the initial steps in forming scarlike fibrotic tissue after acute cardiac injury and cardiac cell necrosis...
2017: Cardiovascular Pharmacology: Open Access
https://www.readbyqxmd.com/read/29025575/biomarkers-in-pulmonary-vascular-disease-gauging-response-to-therapy
#16
REVIEW
Timothy J McMahon, Nathan S Bryan
Biomarkers are increasingly being investigated in the treatment of pulmonary vascular disease. In particular, the signaling pathways targeted by therapies for pulmonary arterial hypertension provide biomarkers that potentially can be used to guide therapy and to assess clinical response as an alternative to invasive procedures such as right-sided cardiac catheterization. Moreover, the growing use of combination therapy for both the initial and subsequent treatment of pulmonary arterial hypertension highlights the need for biomarkers in this treatment approach...
October 15, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28982333/cerebral-artery-vasoconstriction-is-endothelin-1-dependent-requiring-neurogenic-and-adrenergic-crosstalk
#17
Roel H L Haeren, Sieuwke A Hartmans, Jo De Mey, Govert Hoogland, Jim Dings, Olaf E M G Schijns, Sander M J van Kuijk, Kim Rijkers, Paul Schiffers, Koo J van Overbeeke
BACKGROUND: The regulation of cerebral arterial vasomotor tone involves several mechanisms. The role of sympathetic nerves and the adrenergic neurotransmitter, noradrenaline (NA), has been subject of debate for decades. Moreover, the specific role of endothelin-1 (ET-1) in cerebral arterial vasoconstriction has not been elucidated to date. In this study, we evaluated the contribution of NA and ET-1 to cerebral artery vasoconstriction. METHODS: Arterial responses of rat middle cerebral arteries, and human pial cerebral arteries to cumulative concentrations of NA and ET-1, and to electrical field stimulation (EFS), were evaluated...
October 5, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28981444/central-mediators-of-the-zymosan-induced-febrile-response
#18
Amanda Leite Bastos-Pereira, Daniel Fraga, Arturo Alejandro Dreifuss, Aleksander Roberto Zampronio
BACKGROUND: Zymosan is a fungal cell wall protein-carbohydrate complex that is known to activate inflammatory pathways through the Toll-like receptors and is commonly used to induce fever. Nevertheless, the central mediators that are involved in the zymosan-induced febrile response are only partially known. METHODS: The present study evaluated the participation of prostaglandins, substance P, endothelin-1 (ET-1), and endogenous opioids (eOPs) in the zymosan-induced febrile response by using inhibitors and antagonists in male Wistar rats...
November 27, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28977677/signaling-cascades-activated-by-uvb-in-human-melanocytes-lead-to-the-increased-expression-of-melanocyte-receptors-endothelin-b-receptor-and-c-kit-%C3%A2
#19
Shuko Terazawa, Genji Imokawa
A single exposure of normal human melanocytes (NHMs) to ultraviolet B (UVB) radiation induces a distinct increase in the expression of c-KIT and endothelin B receptor (EDNRB) and up-regulates the expression of microphthalmia-associated transcription factor (MITF). In this review, we clarify the signaling mechanisms by which UVB stimulates the expression of MITF in NHMs, thus leading to up-regulation of those two important melanogenic receptors. The increased expression of MITF in UVB-exposed NHMs is accompanied by a markedly stimulated and prolonged phosphorylation of p38/CREB...
October 4, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28964752/inhibition-of-nkcc1-promotes-axonal-growth-and-motor-recovery-in-ischemic-rats
#20
X P Mu, H B Wang, X Cheng, L Yang, X Y Sun, H L Qu, S S Zhao, Z K Zhou, T T Liu, T Xiao, B Song, J Jolkkonen, C S Zhao
Bumetanide is a selective inhibitor of the Na(+)-K(+)-Cl(-)-co-transporter 1(NKCC1). We studied whether bumetanide could affect axonal growth and behavioral outcome in stroke rats. Adult male Wistar rats were randomly assigned to four groups: sham-operated rats treated with vehicle or bumetanide, and ischemic rats treated with vehicle or bumetanide. Endothelin-1 was used to induce focal cerebral ischemia. Bumetanide administration (i.c.v.) started on postoperative day 7 and continued for 3 weeks. Biotinylated dextran amine (BDA) was injected into the right imotor cortex on postoperative day 14 to trace corticospinal tract (CST) fibers sprouting into the denervated cervical spinal cord...
December 4, 2017: Neuroscience
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