scholarly journals Prostanoid production and pulmonary arterial responses to reactive oxygen species (ROS) are altered in newborn piglets with chronic hypoxia‐induced pulmonary hypertension

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Candice Denise Fike ◽  
M R Kaplowitz ◽  
Yongmei Zhang ◽  
S L Pfister
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Hypertension ◽  
Chronic Hypoxia ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Newborn Piglets ◽  
Prostanoid Production ◽  
Pulmonary Arterial ◽  
Arterial Responses

scholarly journals Pulmonary Arterial Responses to Reactive Oxygen Species Are Altered in Newborn Piglets With Chronic Hypoxia-Induced Pulmonary Hypertension

2011 ◽  
Vol 70 (2) ◽  
pp. 136-141 ◽  
Author(s):  
Candice D Fike ◽  
Judy L Aschner ◽  
James C Slaughter ◽  
Mark R Kaplowitz ◽  
Yongmei Zhang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Hypertension ◽  
Chronic Hypoxia ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Newborn Piglets ◽  
Pulmonary Arterial ◽  
Arterial Responses

scholarly journals NADPH oxidases and reactive oxygen species at different stages of chronic hypoxia-induced pulmonary hypertension in newborn piglets

2009 ◽  
Vol 297 (4) ◽  
pp. L596-L607 ◽  
Author(s):  
Kathleen E. Dennis ◽  
J. L. Aschner ◽  
D. Milatovic ◽  
J. W. Schmidt ◽  
M. Aschner ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Hypertension ◽  
Chronic Hypoxia ◽  
Oxidant Stress ◽  
Reactive Oxygen ◽  
Gas Chromatography Mass Spectrometry ◽  
Oxygen Species ◽  
Resistance Arteries ◽  
Newborn Piglets ◽  
Air Control

Recently, we reported that reactive oxygen species (ROS) generated by NADPH oxidase (NOX) contribute to aberrant responses in pulmonary resistance arteries (PRAs) of piglets exposed to 3 days of hypoxia ( Am J Physiol Lung Cell Mol Physiol 295: L881–L888, 2008). An objective of the present study was to determine whether NOX-derived ROS also contribute to altered PRA responses at a more advanced stage of pulmonary hypertension, after 10 days of hypoxia. We further wished to advance knowledge about the specific NOX and antioxidant enzymes that are altered at early and later stages of pulmonary hypertension. Piglets were raised in room air (control) or hypoxia for 3 or 10 days. Using a cannulated artery technique, we found that treatments with agents that inhibit NOX (apocynin) or remove ROS [an SOD mimetic (M40403) + polyethylene glycol-catalase] diminished responses to ACh in PRAs from piglets exposed to 10 days of hypoxia. Western blot analysis showed an increase in expression of NOX1 and the membrane fraction of p67phox. Expression of NOX4, SOD2, and catalase were unchanged, whereas expression of SOD1 was reduced, in arteries from piglets raised in hypoxia for 3 or 10 days. Markers of oxidant stress, F2-isoprostanes, measured by gas chromatography-mass spectrometry, were increased in PRAs from piglets raised in hypoxia for 3 days, but not 10 days. We conclude that ROS derived from some, but not all, NOX family members, as well as alterations in the antioxidant enzyme SOD1, contribute to aberrant PRA responses at an early and a more progressive stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets.

scholarly journals Reactive Oxygen Species Production in the Early and Later Stage of Chronic Ventilatory Hypoxia

2012 ◽  
pp. 145-151 ◽  
Author(s):  
D. HODYC ◽  
E. JOHNSON ◽  
A. SKOUMALOVÁ ◽  
J. TKACZYK ◽  
H. MAXOVÁ ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Hypertension ◽  
Chronic Hypoxia ◽  
Reactive Oxygen ◽  
No Production ◽  
Oxygen Species ◽  
Air Plasma ◽  
Species Production ◽  
Specific Timing

Pulmonary hypertension resulting from chronic hypoxia is at least partly caused by the increased production of reactive oxygen species (ROS). The goal of the presented study was to investigate the dynamics and the site of production of ROS during chronic hypoxia. In our study Wistar rats were kept for 1, 4 and 21 days in an isobaric hypoxic chamber (FiO2=0.1), while controls stayed in normoxia. We compared NO production in expired air, plasma and perfusate drained from isolated rat lungs and measured superoxide concentration in the perfusate. We also detected the presence of superoxide products (hydrogen peroxide and peroxynitrite) and the level of ROS-induced damage expressed as the concentration of lipid peroxydation end products. We found that the production and release of ROS and NO during early phase of chronic hypoxia has specific timing and differs in various compartments, suggesting the crucial role of ROS interaction for development of hypoxic pulmonary hypertension.

scholarly journals PKCβ and reactive oxygen species mediate enhanced pulmonary vasoconstrictor reactivity following chronic hypoxia in neonatal rats

2020 ◽  
Vol 318 (2) ◽  
pp. H470-H483 ◽  
Author(s):  
Joshua R. Sheak ◽  
Simin Yan ◽  
Laura Weise-Cross ◽  
Rosstin Ahmadian ◽  
Benjimen R. Walker ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Chronic Hypoxia ◽  
Primary Cultures ◽  
Pulmonary Arteries ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Neonatal Rats ◽  
Basal Tone

Reactive oxygen species (ROS), mitochondrial dysfunction, and excessive vasoconstriction are important contributors to chronic hypoxia (CH)-induced neonatal pulmonary hypertension. On the basis of evidence that PKCβ and mitochondrial oxidative stress are involved in several cardiovascular and metabolic disorders, we hypothesized that PKCβ and mitochondrial ROS (mitoROS) signaling contribute to enhanced pulmonary vasoconstriction in neonatal rats exposed to CH. To test this hypothesis, we examined effects of the PKCβ inhibitor LY-333,531, the ROS scavenger 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (TEMPOL), and the mitochondrial antioxidants mitoquinone mesylate (MitoQ) and (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (MitoTEMPO) on vasoconstrictor responses in saline -perfused lungs (in situ) or pressurized pulmonary arteries from 2-wk-old control and CH (12-day exposure, 0.5 atm) rats. Lungs from CH rats exhibited greater basal tone and vasoconstrictor sensitivity to 9,11-dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U-46619). LY-333,531 and TEMPOL attenuated these effects of CH, while having no effect in lungs from control animals. Basal tone was similarly elevated in isolated pulmonary arteries from neonatal CH rats compared with control rats, which was inhibited by both LY-333,531 and mitochondria-targeted antioxidants. Additional experiments assessing mitoROS generation with the mitochondria-targeted ROS indicator MitoSOX revealed that a PKCβ-mitochondrial oxidant signaling pathway can be pharmacologically stimulated by the PKC activator phorbol 12-myristate 13-acetate in primary cultures of pulmonary artery smooth muscle cells (PASMCs) from control neonates. Finally, we found that neonatal CH increased mitochondrially localized PKCβ in pulmonary arteries as assessed by Western blotting of subcellular fractions. We conclude that PKCβ activation leads to mitoROS production in PASMCs from neonatal rats. Furthermore, this signaling axis may account for enhanced pulmonary vasoconstrictor sensitivity following CH exposure. NEW & NOTEWORTHY This research demonstrates a novel contribution of PKCβ and mitochondrial reactive oxygen species signaling to increased pulmonary vasoconstrictor reactivity in chronically hypoxic neonates. The results provide a potential mechanism by which chronic hypoxia increases both basal and agonist-induced pulmonary arterial smooth muscle tone, which may contribute to neonatal pulmonary hypertension.

scholarly journals Reactive oxygen species from NADPH oxidase contribute to altered pulmonary vascular responses in piglets with chronic hypoxia-induced pulmonary hypertension

2008 ◽  
Vol 295 (5) ◽  
pp. L881-L888 ◽  
Author(s):  
Candice D. Fike ◽  
James C. Slaughter ◽  
Mark R. Kaplowitz ◽  
Yongmei Zhang ◽  
Judy L. Aschner
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Hypertension ◽  
Nadph Oxidase ◽  
Chronic Hypoxia ◽  
Reactive Oxygen ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Resistance Arteries ◽  
Vascular Responses ◽  
Air Control

Our main objective was to determine whether reactive oxygen species (ROS), such as superoxide (O2−) and hydrogen peroxide (H2O2), contribute to altered pulmonary vascular responses in piglets with chronic hypoxia-induced pulmonary hypertension. Piglets were raised in either room air (control) or hypoxia for 3 days. The effect of the cell-permeable superoxide dismutase mimetic (SOD; M40403) and/or PEG-catalase (PEG-CAT) on responses to acetylcholine (ACh) was measured in endothelium-intact and denuded pulmonary resistance arteries (PRAs; 90-to-300-μm diameter). To determine whether NADPH oxidase is an enzymatic source of ROS, PRA responses to ACh were measured in the presence and absence of a NADPH oxidase inhibitor, apocynin (APO). A Western blot technique was used to assess expression of the NADPH oxidase subunit, p67phox. A lucigenin-derived chemiluminescence technique was used to measure ROS production stimulated by the NADPH oxidase substrate, NADPH. ACh responses, which were dilation in intact control arteries but constriction in both intact and denuded hypoxic arteries, were diminished by M40403, PEG-CAT, the combination of M40403 plus PEG-CAT, as well as by APO. Although total amounts were not different, membrane-associated p67phox was greater in PRAs from hypoxic compared with control piglets. NADPH-stimulated lucigenin luminescence was nearly doubled in PRAs from hypoxic vs. control piglets. We conclude that ROS generated by NADPH oxidase contribute to the aberrant pulmonary arterial responses in piglets exposed to 3 days of hypoxia.

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