Document Detail

Pulmonary arterial responses to reactive oxygen species are altered in newborn piglets with chronic hypoxia-induced pulmonary hypertension.
MedLine Citation:
PMID:  21516056     Owner:  NLM     Status:  MEDLINE    
Reactive oxygen species (ROS) have been implicated in the pathogenesis of pulmonary hypertension. ROS might mediate vascular responses, at least in part, by stimulating prostanoid production. Our goals were to determine whether the effect of ROS on vascular tone is altered in resistance pulmonary arteries (PRAs) of newborn piglets with chronic hypoxia-induced pulmonary hypertension and the role, if any, of prostanoids in ROS-mediated responses. In cannulated, pressurized PRA, ROS generated by xanthine (X) plus xanthine oxidase (XO) had minimal effect on vascular tone in control piglets but caused significant vasoconstriction in hypoxic piglets. Both cyclooxygenase inhibition with indomethacin and thromboxane synthase inhibition with dazoxiben significantly blunted constriction to X+XO in hypoxic PRA. X+XO increased prostacyclin production (70 ± 8%) by a greater degree than thromboxane production (50 ± 6%) in control PRA; this was not the case in hypoxic PRA where the increases in prostacyclin and thromboxane production were not statistically different (78 ± 13% versus 216 ± 93%, respectively). Thromboxane synthase expression was increased in PRA from hypoxic piglets, whereas prostacyclin synthase expression was similar in PRA from hypoxic and control piglets. Under conditions of chronic hypoxia, altered vascular responses to ROS may contribute to pulmonary hypertension by a mechanism that involves the prostanoid vasoconstrictor, thromboxane.
Candice D Fike; Judy L Aschner; James C Slaughter; Mark R Kaplowitz; Yongmei Zhang; Sandra L Pfister
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Pediatric research     Volume:  70     ISSN:  1530-0447     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-07     Completed Date:  2011-11-15     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  136-41     Citation Subset:  IM    
Department of Pediatrics, Vanderbilt University School of Medicine and Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee 37232, USA.
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MeSH Terms
Animals, Newborn
Anoxia / complications*
Cyclooxygenase Inhibitors / pharmacology
Cytochrome P-450 Enzyme System / metabolism
Enzyme-Linked Immunosorbent Assay
Hypertension, Pulmonary / etiology*,  metabolism*,  physiopathology
Imidazoles / pharmacology
Indomethacin / pharmacology
Intramolecular Oxidoreductases / metabolism
Prostaglandins / metabolism*
Pulmonary Artery / metabolism*
Reactive Oxygen Species / metabolism*
Statistics, Nonparametric
Sus scrofa
Thromboxane-A Synthase / antagonists & inhibitors,  metabolism
Vasoconstriction / drug effects,  physiology*
Grant Support
Reg. No./Substance:
0/Cyclooxygenase Inhibitors; 0/Imidazoles; 0/Prostaglandins; 0/Reactive Oxygen Species; 09ZFC7974Q/dazoxiben; 53-86-1/Indomethacin; 9035-51-2/Cytochrome P-450 Enzyme System; EC 5.3.-/Intramolecular Oxidoreductases; EC synthetase; EC Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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