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Hypoxic pulmonary vasoconstriction

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https://www.readbyqxmd.com/read/28620066/mitochondrial-complex-iv-subunit-4-isoform-2-is-essential-for-acute-pulmonary-oxygen-sensing
#1
Natascha Sommer, Maik Huttemann, Oleg Pak, Susan Scheibe, Fenja Knöpp, Christopher Sinkler, Monika Malczyk, Mareike Gierhardt, Azadeh Esfandiary, Simone Kraut, Felix T Jonas, Christine Veith, Siddhesh Aras, Akylbek Sydykov, Nasim Alebrahimdehkordi, Klaudia Giehl, Matthias Hecker, Ralf P Brandes, Werner Seeger, Friedrich Grimminger, Hossein A Ghofrani, Ralph T Schermuly, Lawrence I Grossman, Norbert Weissmann
Rationale: Acute pulmonary oxygen sensing is essential to avoid life-threatening hypoxemia via hypoxic pulmonary vasoconstriction (HPV) which matches perfusion to ventilation. Hypoxia-induced mitochondrial superoxide release has been suggested as critical step in the signaling pathway underlying HPV. However, the identity of the primary oxygen sensor and mechanism of superoxide release in acute hypoxia, as well as its relevance for chronic pulmonary oxygen sensing remains unresolved. Objective: To investigate the role of the pulmonary specific isoform 2 of subunit 4 of mitochondrial complex IV (Cox4i2) and the subsequent mediators superoxide and hydrogen peroxide for pulmonary oxygen sensing and signaling...
June 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28533577/the-interaction-between-trolox-and-4-4-diisothiocyanatostilbene-2-2-disulfonic-acid-on-hypoxic-pulmonary-vasoconstriction-in-the-isolated-rabbit-lung
#2
Somayh Mansoori, Seyed Mostafa Shid Moosavi, Farzaneh Ketabchi
BACKGROUND: The mechanism of hypoxic pulmonary vasoconstriction (HPV) is still debatable. It has been proposed that reactive oxygen species (ROS) might be involved in HPV. However, there is no special transporter for superoxide anion in the cell membrane and it may release from the cells via anion exchanger. Therefore, the aim of this study was to investigate the interaction of ROS and anion exchanger in acute HPV. METHODS: The present study was performed in the isolated rabbit lung...
May 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28450284/eets-promote-hypoxic-pulmonary-vasoconstriction-via-constrictor-prostanoids
#3
Sharath Kandhi, Bin Zhang, Ghezal Froogh, Jun Qin, Norah Alruwali, Yicong Le, Yang-Ming Yang, Sung Hee Hwang, Bruce D Hammock, Michael S Wolin, An Huang, Dong Sun
To test the hypothesis that epoxyeicosatrienoic acids (EETs) facilitate pulmonary responses to hypoxia, male wild type (WT) and soluble epoxide hydrolase knockout (sEH-KO) mice, and WT mice chronically fed a sEH inhibitor (t-TUCB; 1mg/kg/day) were used. Right ventricular systolic pressure (RVSP) was recorded under control and hypoxic conditions. The control RVSP was comparable among all groups. However, hypoxia elicited increases in RVSP in all groups with predominance in sEH-KO and t-TUCB-treated mice. 14,15-EEZE (EET antagonist) attenuated the hypoxia-induced greater elevation of RVSP in sEH-deficient mice, suggesting an EET-mediated increment...
April 27, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28431421/sevoflurane-posttreatment-attenuates-lung-injury-induced-by-oleic-acid-in-dogs
#4
Guizhi Du, Shurong Wang, Zhuo Li, Jin Liu
BACKGROUND: In animal models, both sevoflurane and propofol protect against acute lung injury (ALI), especially when administered prior to ALI onset. We hypothesized that when compared to propofol, sevoflurane administration after the onset of acute respiratory distress syndrome would mitigate oleic acid (OA)-induced ALI in dogs. METHODS: Dogs were randomly assigned to receive intravenous OA to induce ALI (n = 7 for each OA group) or saline as an OA control (n = 6 for each control)...
May 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28430879/role-of-phosphatase-and-tensin-homolog-pten-in-hypoxic-pulmonary-vasoconstriction
#5
Adrienn Krauszman, Tak Mak, Katalin Szaszi, Wolfgang M Kuebler
AIMS: Hypoxic pulmonary vasoconstriction (HPV) redistributes blood flow from poorly ventilated to better aerated areas in the lung, thereby optimizing ventilation-perfusion ratio (V/Q). Pulmonary artery smooth muscle cell (PASMC) contraction in response to hypoxia is triggered by Ca2+ influx via transient receptor potential canonical 6 (TRPC6) cation channels that have translocated to caveolae in the plasma membrane. Since phosphatase and tensin homolog (PTEN) was suggested to regulate TRPC6 in endothelial cells, we aimed to define its role in the hypoxic response of PASMCs and as a putative mediator of HPV...
April 18, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28424078/interleukin-6-displays-lung-anti-inflammatory-properties-and-exerts-protective-hemodynamic-effects-in-a-double-hit-murine-acute-lung-injury
#6
Guillaume Voiriot, Keyvan Razazi, Valérie Amsellem, Jeanne Tran Van Nhieu, Shariq Abid, Serge Adnot, Armand Mekontso Dessap, Bernard Maitre
BACKGROUND: Interleukin 6 (IL-6) is a predictive factor of poor prognosis in patients with acute respiratory distress syndrome (ARDS). However, its acute pulmonary hemodynamic effects and role in lung injury have not been investigated in a clinically relevant murine model of ARDS. METHODS: We used adult C57Bl6 wild-type (WT) and IL-6 knock-out (IL-6KO) mice. The animals received intravenous recombinant human IL-6 (rHuIL-6) or vehicle followed by intratracheal lipopolysaccharide (LPS) or saline before undergoing low tidal volume mechanical ventilation (MV) for 5 h...
April 19, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28339017/sirt1-is-required-for-mitochondrial-biogenesis-reprogramming-in-hypoxic-human-pulmonary-arteriolar-smooth-muscle-cells
#7
Pengyun Li, Yan Liu, Nana Burns, Ke-Seng Zhao, Rui Song
Although recent studies have reported that mitochondria are putative oxygen sensors underlying hypoxic pulmonary vasoconstriction, little is known concerning the sirtuin 1 (SIRT1)-mediated mitochondrial biogenesis regulatory program in pulmonary arteriolar smooth muscle cells (PASMCs) during hypoxia/reoxygenation (H/R). We investigated the epigenetic regulatory mechanism of mitochondrial biogenesis and function in human PASMCs during H/R. Human PASMCs were exposed to hypoxia of 24-48 h and reoxygenation of 24-48 h...
May 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28301582/task-1-potassium-channel-is-not-critically-involved-in-mediating-hypoxic-pulmonary-vasoconstriction-of-murine-intra-pulmonary-arteries
#8
Ghulam Murtaza, Petra Mermer, Anna Goldenberg, Uwe Pfeil, Renate Paddenberg, Nobert Weissmann, Guenter Lochnit, Wolfgang Kummer
The two-pore domain potassium channel KCNK3 (TASK-1) is expressed in rat and human pulmonary artery smooth muscle cells. There, it is associated with hypoxia-induced signalling, and its dysfunction is linked to pathogenesis of human pulmonary hypertension. We here aimed to determine its role in hypoxic pulmonary vasoconstriction (HPV) in the mouse, and hence the suitability of this model for further mechanistic investigations, using appropriate inhibitors and TASK-1 knockout (KO) mice. RT-PCR revealed expression of TASK-1 mRNA in murine lungs and pre-acinar pulmonary arteries...
2017: PloS One
https://www.readbyqxmd.com/read/28267435/-the-right-ventricle-in-acute-respiratory-distress-syndrome
#9
REVIEW
Vasileios Zochios, Ken Parhar, William Tunnicliffe, Andrew Roscoe, Fang Gao
Acute respiratory distress syndrome is associated with poor clinical outcomes with a pooled mortality rate of approximately 40% despite best standards of care. Current therapeutic strategies are based upon improving oxygenation and pulmonary compliance while minimizing ventilator induced lung injury. It has been demonstrated that relative hypoxemia can be well tolerated and improvements in oxygenation do not necessarily translate into survival benefit. Cardiac failure, in particular right ventricular dysfunction, is commonly encountered in moderate to severe acute respiratory distress syndrome and is reported to be one of the major determinants of mortality...
March 3, 2017: Chest
https://www.readbyqxmd.com/read/28217180/hypoxic-pulmonary-vasoconstriction-in-humans-tale-or-myth
#10
REVIEW
A Hussain, M S Suleiman, S J George, M Loubani, A Morice
Hypoxic Pulmonary vasoconstriction (HPV) describes the physiological adaptive process of lungs to preserves systemic oxygenation. It has clinical implications in the development of pulmonary hypertension which impacts on outcomes of patients undergoing cardiothoracic surgery. This review examines both acute and chronic hypoxic vasoconstriction focusing on the distinct clinical implications and highlights the role of calcium and mitochondria in acute versus the role of reactive oxygen species and Rho GTPases in chronic HPV...
2017: Open Cardiovascular Medicine Journal
https://www.readbyqxmd.com/read/28155615/the-protective-effect-of-dl0805-derivatives-on-pulmonary-artery-cells-and-the-underlying-mechanisms-study
#11
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/28143879/acute-high-altitude-sickness
#12
REVIEW
Andrew M Luks, Erik R Swenson, Peter Bärtsch
At any point 1-5 days following ascent to altitudes ≥2500 m, individuals are at risk of developing one of three forms of acute altitude illness: acute mountain sickness, a syndrome of nonspecific symptoms including headache, lassitude, dizziness and nausea; high-altitude cerebral oedema, a potentially fatal illness characterised by ataxia, decreased consciousness and characteristic changes on magnetic resonance imaging; and high-altitude pulmonary oedema, a noncardiogenic form of pulmonary oedema resulting from excessive hypoxic pulmonary vasoconstriction which can be fatal if not recognised and treated promptly...
January 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28096303/down-regulation-of-epas1-transcription-and-genetic-adaptation-of-tibetans-to-high-altitude-hypoxia
#13
Yi Peng, Chaoying Cui, Yaoxi He, Ouzhuluobu, Hui Zhang, Deying Yang, Qu Zhang, Bianbazhuoma, Lixin Yang, Yibo He, Kun Xiang, Xiaoming Zhang, Sushil Bhandari, Peng Shi, Yangla, Dejiquzong, Baimakangzhuo, Duojizhuoma, Yongyue Pan, Cirenyangji, Baimayangji, Gonggalanzi, Caijuan Bai, Bianba, Basang, Ciwangsangbu, Shuhua Xu, Hua Chen, Shiming Liu, Tianyi Wu, Xuebin Qi, Bing Su
Tibetans are well adapted to the hypoxic environments at high altitude, yet the molecular mechanism of this adaptation remains elusive. We reported comprehensive genetic and functional analyses of EPAS1, a gene encoding hypoxia inducible factor 2α (HIF-2α) with the strongest signal of selection in previous genome-wide scans of Tibetans. We showed that the Tibetan-enriched EPAS1 variants down-regulate expression in human umbilical endothelial cells and placentas. Heterozygous EPAS1 knockout mice display blunted physiological responses to chronic hypoxia, mirroring the situation in Tibetans...
April 1, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28090300/bk-channels-in-rat-and-human-pulmonary-smooth-muscle-cells-are-bk%C3%AE-%C3%AE-1-functional-complexes-lacking-the-oxygen-sensitive-stress-axis-regulated-exon-insert
#14
Neil D Detweiler, Li Song, Samantha J McClenahan, Rachel J Versluis, Sujay V Kharade, Richard C Kurten, Sung W Rhee, Nancy J Rusch
A loss of K(+) efflux in pulmonary arterial smooth muscle cells (PASMCs) contributes to abnormal vasoconstriction and PASMC proliferation during pulmonary hypertension (PH). Activation of high-conductance Ca(2+)-activated (BK) channels represents a therapeutic strategy to restore K(+) efflux to the affected PASMCs. However, the properties of BK channels in PASMCs-including sensitivity to BK channel openers (BKCOs)-are poorly defined. The goal of this study was to compare the properties of BK channels between PASMCs of normoxic (N) and chronic hypoxic (CH) rats and then explore key findings in human PASMCs...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28057815/susceptibility-to-high-altitude-pulmonary-edema-is-associated-with-a-more-uniform-distribution-of-regional-specific-ventilation
#15
Michael D Patz, Rui C Sá, Chantal Darquenne, Ann R Elliott, Amran K Asadi, Rebecca J Theilmann, David J Dubowitz, Erik R Swenson, G Kim Prisk, Susan R Hopkins
High-altitude pulmonary edema (HAPE) is a potentially fatal condition affecting high-altitude sojourners. The biggest predictor of HAPE development is a history of prior HAPE. Magnetic resonance imaging (MRI) shows that HAPE-susceptible (with a history of HAPE), but not HAPE-resistant (with a history of repeated ascents without illness) individuals develop greater heterogeneity of regional pulmonary perfusion breathing hypoxic gas (O2 = 12.5%), consistent with uneven hypoxic pulmonary vasoconstriction (HPV)...
April 1, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28057053/a-pig-model-of-acute-right-ventricular-afterload-increase-by-hypoxic-pulmonary-vasoconstriction
#16
Kathrine Knai, Nils Kristian Skjaervold
BACKGROUND: The aim of this study was to construct a non-invasive model for acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction. Intact animal models are vital to improving our understanding of the pathophysiology of acute right ventricular failure. Acute right ventricular failure is caused by increased afterload of the right ventricle by chronic or acute pulmonary hypertension combined with regionally or globally reduced right ventricular contractile capacity...
January 3, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/27886864/an-autopsy-case-of-refractory-pulmonary-hypertension-with-sarcoidosis
#17
Hiroki Ota, Keishi Sugino, Toshimasa Uekusa, Tamiko Takemura, Sakae Homma
A 63-year-old man with sarcoidosis-associated pulmonary hypertension (SAPH) died suddenly of decompensated right heart failure. At autopsy, microscopy showed subpleural and interlobular fibrosis in both upper lobes, with marked broncho-bronchiolectasis, as well as bronchovascular bundle fibrosis and fibrotic organization in alveolar lumens, which are consistent with pulmonary sarcoidosis. Intimal fibrosis and medial hypertrophy were noted in the proximal elastic to distal muscular pulmonary arteries (Heath-Edwards, grades II-III) within intensive fibrotic lesions...
November 2016: Respiratory Investigation
https://www.readbyqxmd.com/read/27847441/hypoxic-pulmonary-vasoconstriction-and-vascular-contractility-in-monocrotaline-induced-pulmonary-arterial-hypertensive-rats
#18
Hae Jin Kim, Hae Young Yoo
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling of pulmonary arteries (PAs) and increased vascular resistance in the lung. Monocrotaline (MCT), a toxic alkaloid, is widely used for developing rat models of PAH caused by injury to pulmonary endothelial cells; however, characteristics of vascular functions in MCT-induced PAH vary and are not fully understood. Here, we investigated hypoxic pulmonary vasoconstriction (HPV) responses and effects of various vasoconstrictors with isolated/perfused lungs of MCT-induced PAH (PAH-MCT) rats...
November 2016: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/27815261/soluble-epoxide-hydrolase-deficiency-or-inhibition-enhances-murine-hypoxic-pulmonary-vasoconstriction-after-lipopolysaccharide-challenge
#19
Martin Wepler, Arkadi Beloiartsev, Mary D Buswell, Dipak Panigrahy, Rajeev Malhotra, Emmanuel S Buys, Peter Radermacher, Fumito Ichinose, Donald B Bloch, Warren M Zapol
Hypoxic pulmonary vasoconstriction (HPV) is the response of the pulmonary vasculature to low levels of alveolar oxygen. HPV improves systemic arterial oxygenation by matching pulmonary perfusion to ventilation during alveolar hypoxia and is impaired in lung diseases such as the acute respiratory distress syndrome (ARDS) and in experimental models of endotoxemia. Epoxyeicosatrienoic acids (EETs) are pulmonary vasoconstrictors, which are metabolized to less vasoactive dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH)...
December 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27806595/technical-note-contrast-free-angiography-of-the-pulmonary-vasculature-in-live-mice-using-a-laboratory-x-ray-source
#20
Chaminda R Samarage, Richard Carnibella, Melissa Preissner, Heather D Jones, James T Pearson, Andreas Fouras, Stephen Dubsky
PURPOSE: In vivo imaging of the pulmonary vasculature in small animals is difficult yet highly desirable in order to allow study of the effects of a host of dynamic biological processes such as hypoxic pulmonary vasoconstriction. Here the authors present an approach for the quantification of changes in the vasculature. METHODS: A contrast free angiography technique is validated in silico through the use of computer-generated images and in vivo through microcomputed tomography (μCT) of live mice conducted using a laboratory-based x-ray source...
November 2016: Medical Physics
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