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Endothelin inhibitor

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https://www.readbyqxmd.com/read/28326642/neprilysin-inhibition-in-heart-failure-mechanisms-and-substrates-beyond-modulating-natriuretic-peptides
#1
REVIEW
Emilia D'Elia, Attilio Iacovoni, Muthiah Vaduganathan, Ferdinando L Lorini, Stefano Perlini, Michele Senni
The autonomic nervous system, the renin-angiotensin-aldosterone system, and the natriuretic peptide system represent critical regulatory pathways in heart failure and as such have been the major targets of pharmacological development. The introduction and approval of angiotensin receptor neprilysin inhibitors (ARNi) have broadened the available drug treatments of patients with chronic heart failure with reduced ejection fraction. Neprilysin catalyses the degradation of a number of vasodilator peptides, including the natriuretic peptides, bradykinin, substance P, and adrenomedullin, as well as vasoconstrictor peptides, including endothelin-1 and angiotensin I and II...
March 21, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28323857/myocardial-ischemia-reperfusion-enhances-transcriptional-expression-of-endothelin-1-and-vasoconstrictor-etb-receptors-via-the-protein-kinase-mek-erk1-2-signaling-pathway-in-rat
#2
Gry Freja Skovsted, Lars Schack Kruse, Lukas Adrian Berchtold, Anne-Sofie Grell, Karin Warfvinge, Lars Edvinsson
BACKGROUND: Coronary artery remodelling and vasospasm is a complication of acute myocardial ischemia and reperfusion. The underlying mechanisms are complex, but the vasoconstrictor peptide endothelin-1 is suggested to have an important role. This study aimed to determine whether the expression of endothelin-1 and its receptors are regulated in the myocardium and in coronary arteries after experimental ischemia-reperfusion. Furthermore, we evaluated whether treatment with a specific MEK1/2 inhibitor, U0126, modified the expression and function of these proteins...
2017: PloS One
https://www.readbyqxmd.com/read/28303689/non-healing-ischaemic-digital-ulcer-in-a-systemic-sclerosis-patient-a-challenging-clinical-case
#3
Sophie Blaise, Matthieu Roustit, Alexandra Forli, Bernard Imbert, Jean-Luc Cracowski
Ischaemic digital ulcers (DUs) are an indicator of the severity of the microangiopathy in patients with systemic sclerosis (SSc). DUs are a frequent complication, affecting about 50% of patients with SSc, and are often recurrent. In cross-sectional studies involving patients with SSc, the frequency of ischaemic DUs was 12-16% with a major impact on hand function and quality of life. Effective therapy for DUs remains elusive. Intravenous iloprost has been demonstrated to have a positive effect on healing of active DUs...
March 16, 2017: International Wound Journal
https://www.readbyqxmd.com/read/28298655/dual-nep-ece-inhibition-improves-endothelial-function-in-mesenteric-resistance-arteries-of-32-week-old-shr
#4
Pieter Lemkens, Leon Ja Spijkers, Merlijn J Meens, Jelly Nelissen, Ben Janssen, Stephan Lm Peters, Paul Mh Schiffers, Jo Gr De Mey
Endothelin 1 (ET-1), a potent vasoconstrictor, pro-mitogenic and pro-inflammatory peptide, may promote development of endothelial dysfunction and arterial remodeling. ET-1 can be formed through cleavage of big-ET-1 by endothelin-converting enzyme (ECE) or neutral endopeptidase (NEP). We investigated whether chronic treatment with the novel dual NEP/ECE inhibitor SOL1 improves functional and structural properties of resistance-sized arteries of 32-week-old male spontaneously hypertensive rats (SHR). SHR received a chronic 4-week treatment with SOL1, losartan or hydralazine...
March 16, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28287881/renin-angiotensin-system-blockade-alone-or-combined-with-eta-receptor-blockade-effects-on-the-course-of-chronic-kidney-disease-in-5-6-nephrectomized-ren-2-transgenic-hypertensive-rats
#5
Lenka Sedláková, Věra Čertíková Chábová, Šárka Doleželová, Petra Škaroupková, Libor Kopkan, Zuzana Husková, Lenka Červenková, Soňa Kikerlová, Ivana Vaněčková, Janusz Sadowski, Elzbieta Kompanowska-Jezierska, Petr Kujal, Herbert J Kramer, Luděk Červenka
BACKGROUND: Early addition of endothelin (ET) type A (ETA) receptor blockade to complex renin-angiotensin system (RAS) blockade has previously been shown to provide better renoprotection against progression of chronic kidney disease (CKD) in Ren-2 transgenic hypertensive rats (TGR) after 5/6 renal ablation (5/6 NX). In this study, we examined if additional protection is provided when ETA blockade is applied in rats with already developed CKD. METHODS: For complex RAS inhibition, an angiotensin-converting enzyme inhibitor along with angiotensin II type 1 receptor blocker was used...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28286190/outcome-of-adults-with-eisenmenger-syndrome-treated-with-drugs-specific-to-pulmonary-arterial-hypertension-a-french-multicentre-study
#6
Sebastien Hascoet, Emmanuelle Fournier, Xavier Jaïs, Lauriane Le Gloan, Claire Dauphin, Ali Houeijeh, Francois Godart, Xavier Iriart, Adelaïde Richard, Jelena Radojevic, Pascal Amedro, Gilles Bosser, Nathalie Souletie, Yvette Bernard, Pamela Moceri, Hélène Bouvaist, Pierre Mauran, Elise Barre, Adeline Basquin, Clement Karsenty, Damien Bonnet, Laurence Iserin, Olivier Sitbon, Jérôme Petit, Elie Fadel, Marc Humbert, Magalie Ladouceur
BACKGROUND: The relationship between pulmonary arterial hypertension-specific drug therapy (PAH-SDT) and mortality in Eisenmenger syndrome (ES) is controversial. AIMS: To investigate outcomes in patients with ES, and their relationship with PAH-SDT. METHODS: Retrospective, observational, nationwide, multicentre cohort study. RESULTS: We included 340 patients with ES: genetic syndrome (n=119; 35.3%); pretricuspid defect (n=75; 22...
March 9, 2017: Archives of Cardiovascular Diseases
https://www.readbyqxmd.com/read/28283735/in-vitro-and-in-vivo-evaluation-of-dasatinib-and-imatinib-on-physiological-parameters-of-pulmonary-arterial-hypertension
#7
Bethany Baumgart, Mausumee Guha, James Hennan, Julia Li, Jochen Woicke, Damir Simic, Michael Graziano, Nicola Wallis, Thomas Sanderson, Roderick Todd Bunch
PURPOSE: Pulmonary arterial hypertension (PAH) results from occlusion or vasoconstriction of pulmonary vessels, leading to progressive right ventricular failure. Dasatinib, a BCR-ABL1 tyrosine kinase inhibitor (TKI) approved for the treatment of chronic myelogenous leukemia, has been associated with PAH. In contrast, the BCR-ABL1 TKI imatinib has demonstrated anti-vasoproliferative properties and has been investigated as a potential treatment for PAH. Here we describe studies evaluating the effects of dasatinib and imatinib on cardiovascular and pulmonary functions to understand the reported differential consequences of the two TKIs in a clinical setting...
March 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28283234/endothelin-inhibitors-lower-pulmonary-vascular-resistance-and-improve-functional-capacity-in-patients-with-fontan-circulation
#8
Gabriella Agnoletti, Simona Gala, Francesca Ferroni, Roberto Bordese, Lorenzo Appendini, Carlo Pace Napoleone, Laura Bergamasco
OBJECTIVES: To evaluate the effects of endothelin inhibitors (ERAs) on hemodynamic and functional parameters in patients post-Fontan procedure with high pulmonary vascular resistance (PVR). METHODS: Among our cohort of patients with Fontan circulation, 8 children, 8 adolescents, and 8 adults had PVR ≥2 WU*m(2). These patients were treated with ERAs (minors with bosentan, adults with macitentan) and reevaluated after 6 months. Pre- and posttreatment hemodynamic variables were assessed by cardiac catheterization...
February 10, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28242818/characterization-of-flow-regulated-cortical-collecting-duct-endothelin-1-production
#9
Nirupama Ramkumar, Yang Gao, Donald E Kohan
Collecting duct (CD) endothelin-1 (ET-1) is an autocrine inhibitor of Na(+) and water reabsorption. Salt or water loading increases CD ET-1 production; this is likely due, at least in part, to increased tubule fluid flow. The mechanisms by which flow stimulates CD ET-1 production are incompletely understood. In particular, flow induction of cortical CD (CCD) and inner medullary CD (IMCD) ET-1 synthesis may occur via different mechanisms. Since flow-mediated ET-1 production in IMCD has been more extensively characterized than in the CCD, this study was undertaken to further examine putative signaling pathways involved in flow-stimulated CCD ET-1 production...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28237536/early-experience-of-macitentan-for-pulmonary-arterial-hypertension-in-adult-congenital-heart-disease
#10
S Herbert, W Gin-Sing, L Howard, R M R Tulloh
BACKGROUND: Endothelin receptor antagonists (ERA) have been recognised as effective therapy for pulmonary arterial hypertension in congenital heart disease (CHD-PH), and Eisenmenger syndrome (ES) since the Breathe 5 study. A new dual receptor antagonist - Macitentan - is currently undergoing trials to determine its efficacy in simple ES. To date there is little information on this therapy in CHD and we report our first experience, some with more complex diseases. METHODS: Data was collected prospectively from September 2014...
February 6, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28216625/endothelial-overexpression-of-endothelin-1-modulates-aortic-carotid-iliac-and-renal-arterial-responses-in-obese-mice
#11
Oliver Baretella, Sookja K Chung, Aimin Xu, Paul M Vanhoutte
Endothelin-1 (ET-1) is essential for mammalian development and life, but it has also been implicated in increased cardiovascular risk under pathophysiological conditions. The aim of this study was to determine the impact of endothelial overexpression of the prepro-endothelin-1 gene on endothelium-dependent and endothelium-independent responses in the conduit and renal arteries of lean and obese mice. Obesity was induced by high-fat-diet (HFD) consumption in mice with Tie-1 promoter-driven, endothelium-specific overexpression of the prepro-endothelin-1 gene (TET(het)) and in wild-type (WT) littermates on a C57BL/6N background...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28214885/signaling-pathway-for-endothelin-1-and-phenylephrine-induced-camp-response-element-binding-protein-activation-in-rat-ventricular-myocytes-role-of-inositol-1-4-5-trisphosphate-receptors-and-camkii
#12
Krishna P Subedi, Min-Jeong Son, Bojjibabu Chidipi, Seong-Woo Kim, Jun Wang, Kyeong-Hee Kim, Joon-Chul Kim, Sun-Hee Woo
BACKGROUND/AIMS: Endothelin-1 (ET-1) and the α1-adrenoceptor agonist phenylephrine (PE) activate cAMP response element binding protein (CREB), a transcription factor implicated in cardiac hypertrophy. The signaling pathway involved in CREB activation by these hypertrophic stimuli is poorly understood. We examined signaling pathways for ET-1- or PE-induced cardiac CREB activation. METHODS: Western blotting was performed with pharmacological and genetic interventions in rat ventricular myocytes...
January 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28195067/the-effect-of-short-term-treatment-with-probiotic-vsl-3-on-various-clinical-and-biochemical-parameters-in-patients-with-liver-cirrhosis
#13
W Marlicz, E Wunsch, M Mydlowska, M Milkiewicz, K Serwin, M Mularczyk, P Milkiewicz, J Raszeja-Wyszomirska
The evidence is mounting that alterations of innate immunity and gut microbiota contribute to chronic liver disease and its complications. Modulation of intestinal microbiota is an emerging therapeutic strategy in hepatology. Probiotics through modulation of intestinal milieu have the potential to affect the course of liver disease. The data concerning the influence of probiotics on various plasma molecules and compounds involved in the pathogenesis of hyperdynamic circulatory state in liver cirrhosis is still not confluent and require further evaluation...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28190786/survival-in-portopulmonary-hypertension-outcomes-of-the-united-kingdom-national-pulmonary-arterial-hypertension-registry
#14
Sasiharan Sithamparanathan, Arun Nair, Logan Thirugnanasothy, J Gerry Coghlan, Robin Condliffe, Konstantinos Dimopoulos, Charlie A Elliot, Andrew J Fisher, Sean Gaine, J Simon R Gibbs, Michael A Gatzoulis, Clive E Handler, Luke S Howard, Martin Johnson, David G Kiely, James L Lordan, Andrew J Peacock, Joanna Pepke-Zaba, Benjamin E Schreiber, Karen K K Sheares, Stephen J Wort, Paul A Corris
BACKGROUND: Portopulmonary hypertension (PoPH) is a rare condition associated with poor survival, and the effect of modern therapies that target pulmonary arterial hypertension (PAH) on long-term outcome is unknown. This study investigated the baseline characteristics and survival in the cohort of patients diagnosed with PoPH in the United Kingdom National Pulmonary Hypertension Service. METHODS: A retrospective review was conducted of all incident treatment-naïve patients with PoPH within the United Kingdom national registry diagnosed between January 2001 and December 2010...
December 31, 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28183818/normalization-of-hemoglobin-based-oxygen-carrier-201-induced-vasoconstriction-roles-of-nitric-oxide-scavenging-and-endothelin
#15
Yannick J Taverne, Daphne P M de Wijs-Meijler, Maaike Te Lintel Hekkert, Paula F Moon-Massat, Greg P Dubé, Dirk Jan Duncker, Daphne Merkus
BACKGROUND: Hemoglobin-based oxygen carrier (HBOC)-201 is a cell-free modified hemoglobin solution potentially facilitating oxygen uptake and delivery in cardiovascular disorders and hemorrhagic shock. Clinical use has been hampered by vasoconstriction in the systemic and pulmonary beds. Therefore we aimed to 1) determine the possibility of counteracting HBOC-201-induced pressor effects with adenosine (ADO), 2) assess the potential roles of nitric oxide (NO) scavenging, reactive oxygen species (ROS) and endothelin (ET) in mediating the observed vasoconstriction and 3) compare these effects in resting and exercising swine...
February 9, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28178968/imatinib-relaxes-the-pulmonary-venous-bed-of-guinea-pigs
#16
Nina A Maihöfer, Said Suleiman, Daniela Dreymüller, Paul W Manley, Rolf Rossaint, Stefan Uhlig, Christian Martin, Annette D Rieg
BACKGROUND: Recently, the IMPRES study revealed that systemic imatinib improves exercise capacity in patients with advanced pulmonary arterial hypertension. Imatinib blocks the tyrosine kinase activity of the platelet-derived growth factor (PDGF)-receptor (PDGFR), acts antiproliferative and relaxes pulmonary arteries. However so far, the relaxant effects of imatinib on pulmonary veins (PVs) and on the postcapillary resistance are unknown, although pulmonary hypertension (PH) due to left heart disease (LHD) is most common and primarily affects PVs...
February 8, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28155615/the-protective-effect-of-dl0805-derivatives-on-pulmonary-artery-cells-and-the-underlying-mechanisms-study
#17
Tianyi Yuan, Huifang Zhang, Yucai Chen, Xiaozhen Jiao, Ping Xie, Lianhua Fang, Guanhua Du
Pulmonary hypertension (PH) is a severe disease characterized by a progressive increase in pulmonary vascular resistance, initially due to abnormal pulmonary vasoconstriction in response to endothelial and smooth muscle cells injury. The discovery of new chemical entities having a protective effect on pulmonary artery cells could be meaningful for the treatment of PH. We evaluated the protective effect of DL0805 derivatives (DL0805-1 and DL0805-2) on pulmonary artery vascular cells, including human pulmonary artery endothelial cells (HPAECs) and human pulmonary artery smooth muscle cells (HPASMCs)...
February 1, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28153500/endothelin-causes-transactivation-of-the-egfr-and-her2-in-non-small-cell-lung-cancer-cells
#18
Terry W Moody, Irene Ramos-Alvarez, Paula Moreno, Samuel A Mantey, Lisa Ridnour, David Wink, Robert T Jensen
Endothelin (ET)-1 is an important peptide in cancer progression stimulating cellular proliferation, tumor angiogenesis and metastasis. ET-1 binds with high affinity to the ETA receptor (R) and ETBR on cancer cells. High levels of tumor ET-1 and ETAR are associated with poor survival of lung cancer patients. Here the effects of ET-1 on epidermal growth factor (EGF)R and HER2 transactivation were investigated using non-small cell lung cancer (NSCLC) cells. ETAR mRNA was present in all 10 NSCLC cell lines examined...
January 31, 2017: Peptides
https://www.readbyqxmd.com/read/28152298/salubrinal-alleviates-pressure-overload-induced-cardiac-hypertrophy-by-inhibiting-endoplasmic-reticulum-stress-pathway
#19
Shilpa Rani, Pradeep Kumar Sreenivasaiah, Chunghee Cho, Do Han Kim
Pathological hypertrophy of the heart is closely associated with endoplasmic reticulum stress (ERS), leading to maladaptations such as myocardial fibrosis, induction of apoptosis, and cardiac dysfunctions. Salubrinal is a known selective inhibitor of protein phosphatase 1 (PP1) complex involving dephosphorylation of phospho-eukaryotic translation initiation factor 2 subunit (p-eIF2)-α, the key signaling process in the ERS pathway. In this study, the effects of salubrinal were examined on cardiac hypertrophy using the mouse model of transverse aortic constriction (TAC) and cell model of neonatal rat ventricular myocytes (NRVMs)...
January 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28139522/ovarian-fibrosis-a-phenomenon-of-concern
#20
REVIEW
Feng Zhou, Li-Bing Shi, Song-Ying Zhang
OBJECTIVE: Ovarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition of extracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review aimed to investigate the pathogenetic mechanism of ovarian fibrosis and to clarify the relationship between ovarian diseases and fibrosis. DATA SOURCES: We searched PubMed for English language articles published up to November 2016. The search terms included ovarian fibrosis OR fibrosis, ovarian chocolate cyst OR ovarian endometrioma, polycystic ovarian syndrome (PCOS), premature ovarian failure, ECM, matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), transforming growth factor-beta 1 (TGF-β1), connective tissue growth factor (CTGF), peroxisome proliferator-activated receptor gamma (PPAR-γ), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and combinations of these terms...
February 5, 2017: Chinese Medical Journal
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