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Hypoxic vasoconstriction

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https://www.readbyqxmd.com/read/29433570/role-of-atp-sensitive-potassium-channels-on-hypoxic-pulmonary-vasoconstriction-in-endotoxemia
#1
Maurizio Turzo, Julian Vaith, Felix Lasitschka, Markus A Weigand, Cornelius J Busch
BACKGROUND: ATP-regulated potassium channels (KATP) regulate pulmonary vascular tone and are involved in hypoxic pulmonary vasoconstriction (HPV). In patients with inflammation like sepsis or ARDS, HPV is impaired, resulting in a ventilation-perfusion mismatch and hypoxia. Since increase of vascular KATP channel Kir6.1 has been reported in animal models of endotoxemia, we studied the expression and physiological effects of Kir6.1 in murine endotoxemic lungs. We hypothesized that inhibition of overexpressed Kir6...
February 13, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29425776/the-effects-of-hemoglobin-glutamer-200-and-ino-on-pulmonary-vascular-tone-and-arterial-oxygenation-in-an-experimental-acute-respiratory-distress-syndrome
#2
Maria Theresa Voelker, Andreas Bergmann, Thilo Busch, Nora Jahn, Sven Laudi, Katharina Noreikat, Philipp Simon, Sven Bercker
INTRODUCTION: Hemoglobin-based oxygen carriers (HBOC) have been developed as an alternative to blood transfusions. Their nitric-oxide-scavenging properties HBOC also induce vasoconstriction. In acute lung injury, an excess of nitric oxide results in a general vasodilation, reducing oxygenation by impairing the hypoxic pulmonary vasoconstriction. Inhaled nitric oxide (iNO) is used to correct the ventilation perfusion mismatch. We hypothesized that the additional use of HBOC might increase this effect...
February 6, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29419444/impact-of-the-mitochondria-targeted-antioxidant-mitoq-on-hypoxia-induced-pulmonary-hypertension
#3
Oleg Pak, Susan Scheibe, Azadeh Esfandiary, Mareike Gierhardt, Akylbek Sydykov, Angela Logan, Athanasios Fysikopoulos, Florian Veit, Matthias Hecker, Florian Kroschel, Karin Quanz, Alexandra Erb, Katharina Schäfer, Mirja Fassbinder, Nasim Alebrahimdehkordi, Hossein A Ghofrani, Ralph T Schermuly, Ralf P Brandes, Werner Seeger, Michael P Murphy, Norbert Weissmann, Natascha Sommer
Increased mitochondrial reactive oxygen species (ROS), particularly superoxide have been suggested to mediate hypoxic pulmonary vasoconstriction (HPV), chronic hypoxia-induced pulmonary hypertension (PH) and right ventricular (RV) remodelling.We determined ROS in acute, chronic hypoxia and investigated the effect of the mitochondria-targeted antioxidant MitoQ under these conditions.The effect of MitoQ or its inactive carrier substance, decyltriphenylphosphonium (TPP+), on acute HPV (1% O2 for 10 minutes) was investigated in isolated blood-free perfused mouse lungs...
February 1, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29388468/plc%C3%AE-1-pkc%C3%AE%C2%B5-ip3r1-plays-an-important-role-in-hypoxia-induced-calcium-response-in-pulmonary-artery-smooth-muscle-cells
#4
Vishal R Yadav, Tengyao Song, Lin Mei, Leroy Joseph, Yun-Min Zheng, Yong-Xiao Wang
Hypoxia-induced pulmonary vasoconstriction (HPV) is attributed to an increase in intracellular Ca2+ concentration ([Ca2+]i) in pulmonary artery smooth muscle cells (PASMCs). We have reported that phospholipase C-γ1 (PLCγ1) plays a significant role in the hypoxia-induced increase in [Ca2+]i in PASMCs and attendant HPV. In this study, we intended to determine molecular mechanisms for hypoxic Ca2+ and contractile responses in PASMCs. Our data reveal that hypoxic vasoconstriction occurs in PAs, but not in mesenteric arteries (MAs)...
February 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29383676/regulation-signalling-and-functions-of-hormonal-peptides-in-pulmonary-vascular-remodelling-during-hypoxia
#5
REVIEW
Priya Gaur, Supriya Saini, Praveen Vats, Bhuvnesh Kumar
Hypoxic state affects organism primarily by decreasing the amount of oxygen reaching the cells and tissues. To adjust with changing environment organism undergoes mechanisms which are necessary for acclimatization to hypoxic stress. Pulmonary vascular remodelling is one such mechanism controlled by hormonal peptides present in blood circulation for acclimatization. Activation of peptides regulates constriction and relaxation of blood vessels of pulmonary and systemic circulation. Thus, understanding of vascular tone maintenance and hypoxic pulmonary vasoconstriction like pathophysiological condition during hypoxia is of prime importance...
January 30, 2018: Endocrine
https://www.readbyqxmd.com/read/29373219/cutaneous-vascular-responses-of-the-hands-and-feet-to-cooling-rewarming-and-hypoxia-in-humans
#6
Heather C Massey, James R House, Michael J Tipton
INTRODUCTION: This study investigated skin vasomotor responses in the fingers and toes during cooling and rewarming with and without normobaric hypoxia. METHODS: Fourteen volunteers (8 males and 6 females) were exposed to gradual air cooling (mean±SD: -0.4±0.1oC·min-1) followed by rewarming (+0.5±0.1oC·min-1) while breathing normoxic air (FIO2 0.21 at 761±3 mm Hg) or hypoxic gas (FIO2 0.12, at 761±3 mm Hg, equivalent to ~5000 m above sea level). Throughout the gradual cooling and rewarming phases, rectal temperature was measured, and skin temperatures and laser Doppler skin blood flow were measured on the thumb, little finger, and great and little toe pads...
January 16, 2018: Wilderness & Environmental Medicine
https://www.readbyqxmd.com/read/29364918/riociguat-versus-sildenafil-on-hypoxic-pulmonary-vasoconstriction-and-ventilation-perfusion-matching
#7
Virginia Chamorro, Daniel Morales-Cano, Javier Milara, Bianca Barreira, Laura Moreno, María Callejo, Gema Mondejar-Parreño, Sergio Esquivel-Ruiz, Julio Cortijo, Ángel Cogolludo, Joan A Barberá, Francisco Perez-Vizcaino
INTRODUCTION: Current treatment with vasodilators for pulmonary hypertension associated with respiratory diseases is limited by their inhibitory effect on hypoxic pulmonary vasoconstriction (HPV) and uncoupling effects on ventilation-perfusion (V'/Q'). Hypoxia is also a well-known modulator of the nitric oxide (NO) pathway, and may therefore differentially affect the responses to phosphodiesterase 5 (PDE5) inhibitors and soluble guanylyl cyclase (sGC) stimulators. So far, the effects of the sGC stimulator riociguat on HPV have been poorly characterized...
2018: PloS One
https://www.readbyqxmd.com/read/29363240/magnesium-attenuates-endothelin-1-induced-vasoreactivity-and-enhances-vasodilation-in-mouse-pulmonary-arteries-modulation-by-chronic-hypoxic-pulmonary-hypertension
#8
Yun-Ping Mu, Qiu-Hong Huang, Jie-Ling Zhu, Si-Yi Zheng, Fu-Rong Yan, Xiao-Ling Zhuang, James S K Sham, Mo-Jun Lin
Pulmonary hypertension (PH) is characterized by enhanced vasoreactivity and sustained pulmonary vasoconstriction, arising from the aberrant Ca2+ homeostasis in pulmonary arterial smooth muscle cells. In addition to Ca2+ , magnesium, the most abundant intracellular divalent cation, also plays critical roles in many cellular processes that regulate cardiovascular functions. Recent findings suggested that magnesium regulates vascular functions by altering the vascular responses to vasodilator and vasoactive agonists, and affects endothelial function by modulating endothelium-dependent vasodilation in hypertension...
January 23, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29334406/dasatinib-induced-pulmonary-arterial-hypertension
#9
REVIEW
Nurgül Özgür Yurttaş, Ahmet Emre Eşkazan
Drug-induced (Group 1) pulmonary hypertension (PH) is an important subgroup of PH involving dasatinib as a likely related agent, which is a second-generation tyrosine kinase inhibitor (TKI), that is used in the treatment of chronic myeloid leukemia (CML). The mechanism of dasatinib-induced pulmonary arterial hypertension (PAH) is unclear. However, the occurence of PAH at a late onset in CML patients suggests a chronic pathological mechanism with an insidious onset rather than an acute inflammatory or cardiac etiology...
January 15, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29330945/cyclosporine-a-induces-endothelin-converting-enzyme-ece-1-studies-in-vivo-and-in-vitro
#10
Samuel N Heyman, Zaid Abassi, Christian Rosenberger, Hiba Yaseen, Galia Skarjinski, Ahuva Shina, Susanne Mathia, Natalia Krits, Mogher Khamaisi
AIM: Cyclosporine A (CsA) induces renal vasoconstriction and hypoxia and enhances the expression of endothelin-1 (ET-1) pro-hormone (pre-pro ET-1), plausibly leading to a feed-forward loop of renal vasoconstriction, hypoxia, and enhanced synthesis of the potent vasoconstrictor ET-1. Endothelin converting enzyme (ECE)-1 cleaves big endothelin to generate endothelin (ET)-1 and is up-regulated by hypoxia via hypoxia-inducible factor (HIF). We hypothesized that in addition to the direct induction of ET-1 synthesis, CsA might also intensify renal ECE-1expression, thus contributing to enhanced ET-1 synthesis following CsA...
January 13, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29301601/role-of-ros-kv-hif-axis-in-the-development-of-hypoxia-induced-pulmonary-hypertension
#11
Wen Wu, Yan Li, Dun-Quan Xu
Hypoxic pulmonary hypertension (HPH) is a common complication in patients with chronic obstructive pulmonary disease (COPD), sleep-disordered breathing, or dwellers in high altitude. The exact mechanisms underlying the development of HPH still remain unclear. Reactive oxygen species (ROS), hypoxia inducible factors (HIF), and potassium channels (KV) are believed as the main factors during the development of HPH. We propose that the "ROS/Kv/HIF axis" may play an important initiating role in the development of HPH...
December 30, 2017: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
https://www.readbyqxmd.com/read/29298124/inhaled-budesonide-does-not-affect-hypoxic-pulmonary-vasoconstriction-at-4559-meter-of-altitude
#12
Marc Moritz Berger, Franziska Macholz, Peter Schmidt, Sebastian Fried, Tabea Perz, Daniel Dankl, Josef Niebauer, Peter Bärtsch, Heimo Mairbäurl, Mahdi Sareban
Berger, Marc Moritz, Franziska Macholz, Peter Schmidt, Sebastian Fried, Tabea Perz, Daniel Dankl, Josef Niebauer, Peter Bärtsch, Heimo Mairbäurl, and Mahdi Sareban. Inhaled budesonide does not affect hypoxic pulmonary vasoconstriction at 4559 m of altitude. High Alt Med Biol 00:000-000, 2017.-Oral intake of the corticosteroid dexamethasone has been shown to lower pulmonary artery pressure (PAP) and to prevent high-altitude pulmonary edema. This study tested whether inhalation of the corticosteroid budesonide attenuates PAP and right ventricular (RV) function after rapid ascent to 4559 m...
January 3, 2018: High Altitude Medicine & Biology
https://www.readbyqxmd.com/read/29200842/hemodynamic-and-gas-exchange-effects-of-inhaled-iloprost-in-patients-with-copd-and-pulmonary-hypertension
#13
Lan Wang, Yuan-Zhe Jin, Qin-Hua Zhao, Rong Jiang, Wen-Hui Wu, Su-Gang Gong, Jing He, Jin-Ming Liu, Zhi-Cheng Jing
Studies have shown that vasodilators such as iloprost can be useful for treating pulmonary hypertension (PH). However, in patients with COPD, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange. The efficacy and safety of iloprost inhalation was assessed in 67 patients with PH associated with COPD (COPD-PH), diagnosed by right heart catheterization. Of these, 37 patients had severe PH (mean pulmonary arterial pressure [mPAP] >35 mmHg or mPAP 25-35 mmHg with low cardiac index [<2...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29188077/orai1-2-3-and-stim1-promote-store-operated-calcium-entry-in-pulmonary-arterial-smooth-muscle-cells
#14
Jian Wang, Chuyi Xu, Qiuyu Zheng, Kai Yang, Ning Lai, Tao Wang, Haiyang Tang, Wenju Lu
Previous studies have demonstrated that besides the classic canonical transient receptor potential channel family, Orai family and stromal interaction molecule 1 (STIM1) might also be involved in the regulation of store-operated calcium channels (SOCCs). An increase in cytosolic free Ca2+ concentration promoted by store-operated Ca2+ entry (SOCE) in pulmonary arterial smooth muscle cells (PASMCs) is a major trigger for pulmonary vasoconstriction and proliferation and migration of PASMCs. In this study, our data revealed the following: (1) in both rat distal pulmonary arteries and PASMCs, chronic hypoxia exposure upregulated the expression of Orai1 and Orai2, without affecting Orai3 and STIM1; (2) either heterozygous knockout of HIF-1α in mice or knockdown of HIF-1α in PASMCs abolished the hypoxic upregulation of Orai2, but not Orai1, suggesting the hypoxic upregulation of Orai2 depends on HIF-1α; and (3) using small interference RNA knockdown strategies, Orai1, 2, 3 and STIM1 were all shown to mediate SOCE in hypoxic PASMCs...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/29167165/long-term-high-altitude-hypoxia-influences-pulmonary-arterial-l-type-calcium-channel-mediated-ca-2-signals-and-contraction-in-fetal-and-adult-sheep
#15
Christine Shen, Monica Romero, Alexander Brunelle, Craig Wolfe, Abigail Dobyns, Michael Francis, Mark S Taylor, Jose Puglisi, Lawrence D Longo, Lubo Zhang, Christopher G Wilson, Sean M Wilson
Long-term hypoxia (LTH) has a profound effect on pulmonary arterial vasoconstriction in the fetus and adult. Dysregulation in Ca(2+) signaling is important during the development of LTH induced pulmonary hypertension. In the present study we tested the hypothesis that L-type Ca(2+) channels, which are voltage-dependent and found in smooth, skeletal, and cardiac muscle, are important in the adaptation of pulmonary arterial contractions in post-natal maturation and in response to LTH. Pulmonary arteries were isolated from fetal or adult sheep maintained at low- or high-altitude (3,801 m) for >100 days...
November 22, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29159668/new-pulmonary-hypertension-model-in-conscious-dogs-to-investigate-pulmonary-selectivity-of-acute-pharmacological-interventions
#16
Thomas Mondritzki, Philip Boehme, Lena Schramm, Julia Vogel, Ilka Mathar, Peter Ellinghaus, Peter Kolkhof, Erwin Bischoff, Jörg Hüser, Wilfried Dinh, Peter Sandner, Hubert Truebel
PURPOSE: Testing of investigational drugs in animal models is a critical step in drug development. Current models of pulmonary hypertension (PH) have limitations. The most relevant outcome parameters such as pulmonary artery pressure (PAP) are measured invasively which requires anesthesia of the animal. We developed a new canine PH model in which pulmonary vasodilators can be characterized in conscious dogs and lung selectivity can be assessed non-invasively. METHODS: Telemetry devices were implanted to measure relevant hemodynamic parameters in conscious dogs...
January 2018: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/29123389/alveolar-capillary-reserve-during-exercise-in-patients-with-chronic-obstructive-pulmonary-disease
#17
Mehrdad Behnia, Courtney M Wheatley, Alberto Avolio, Bruce D Johnson
Background: Factors limiting exercise in patients with COPD are complex. With evidence for accelerated pulmonary vascular aging, destruction of alveolar-capillary bed, and hypoxic pulmonary vasoconstriction, the ability to functionally expand surface area during exercise may become a primary limitation. Purpose: To quantify measures of alveolar-capillary recruitment during exercise and the relationship to exercise capacity in a cohort of COPD patients. Methods: Thirty-two subjects gave consent (53% male, with mean ± standard deviation age 66±9 years, smoking 35±29 pack-years, and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of 0-4: 2...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29092848/intrarenal-activation-of-endothelin-type-b-receptors-improves-kidney-oxygenation-in-type-1-diabetic-rats
#18
Stephanie Franzén, Liselotte Pihl, Angelica Fasching, Fredrik Palm
About one third of patients with type 1 diabetes develops kidney disease. The mechanism is largely unknown, but intrarenal hypoxia has been proposed as a unifying mechanism for chronic kidney disease including diabetic nephropathy. The endothelin system has recently been demonstrated to regulate oxygen availability in the diabetic kidney via a pathway involving endothelin type A receptors (ETA-R). These receptors mainly mediate vasoconstriction and tubular sodium retention, and inhibition of ETA-R improves intrarenal oxygenation in the diabetic kidney...
November 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29070491/rhoa-increases-asic1a-plasma-membrane-localization-and-calcium-influx-in-pulmonary-arterial-smooth-muscle-cells-following-chronic-hypoxia
#19
Lindsay M Herbert, Thomas C Resta, Nikki L Jernigan
Increases in pulmonary arterial smooth muscle cell (PASMC) intracellular Ca(2+) levels and enhanced RhoA/Rho kinase-dependent Ca(2+) sensitization are key determinants of PASMC contraction, migration, and proliferation accompanying the development of hypoxic pulmonary hypertension. We have previously shown acid sensing ion channel 1a (ASIC1a)-mediated Ca(2+) entry in PASMC is an important constituent of the active vasoconstriction, vascular remodeling, and right ventricular hypertrophy associated with hypoxic pulmonary hypertension...
October 25, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29047093/cross-talk-between-mitochondrial-reactive-oxygen-species-and-sarcoplasmic-reticulum-calcium-in-pulmonary-arterial-smooth-muscle-cells
#20
Tengyao Song, Yun-Min Zheng, Yong-Xiao Wang
Hypoxic pulmonary vasoconstriction (HPV) occurs during both fetal and postnatal development and plays a critical role in matching regional alveolar perfusion with ventilation in humans and animals. HPV also contributes significantly to the development of pulmonary hypertension. Although the molecular mechanisms of HPV and pulmonary hypertension remain incompletely understood, increasing evidence demonstrates that hypoxia induces an elevated intracellular reactive oxygen species concentration ([ROS]i) in pulmonary artery smooth muscle cells (PASMCs)...
2017: Advances in Experimental Medicine and Biology
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