Pulmonary arterial responses to reactive oxygen species are altered in newborn piglets with chronic hypoxia-induced pulmonary hypertension

Candice D. Fike, Judy L. Aschner, James C. Slaughter, Mark R. Kaplowitz, Yongmei Zhang, Sandra L. Pfister

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)136-141
Number of pages6
JournalPediatric Research
Volume70
Issue number2
DOIs
StatePublished - Aug 2011
Externally publishedYes

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Pulmonary Hypertension
Pulmonary Artery
Reactive Oxygen Species
Thromboxanes
Lung
Blood Vessels
Xanthine Oxidase
Prostaglandins
Epoprostenol
Xanthine
Vasoconstrictor Agents
Prostaglandin-Endoperoxide Synthases
Hypoxia
Vasoconstriction
Constriction
Indomethacin

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Pulmonary arterial responses to reactive oxygen species are altered in newborn piglets with chronic hypoxia-induced pulmonary hypertension. / Fike, Candice D.; Aschner, Judy L.; Slaughter, James C.; Kaplowitz, Mark R.; Zhang, Yongmei; Pfister, Sandra L.

In: Pediatric Research, Vol. 70, No. 2, 08.2011, p. 136-141.

Research output: Contribution to journalArticle

Fike, Candice D. ; Aschner, Judy L. ; Slaughter, James C. ; Kaplowitz, Mark R. ; Zhang, Yongmei ; Pfister, Sandra L. / Pulmonary arterial responses to reactive oxygen species are altered in newborn piglets with chronic hypoxia-induced pulmonary hypertension. In: Pediatric Research. 2011 ; Vol. 70, No. 2. pp. 136-141.
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