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

Fike CD, Aschner JL, Slaughter JC, Kaplowitz MR, Zhang Y, Pfister SL
Pediatr Res. 2011 70 (2): 136-41

PMID: 21516056 · PMCID: PMC3131458 · DOI:10.1203/PDR.0b013e3182207ce7

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.

MeSH Terms (18)

Animals Animals, Newborn Cyclooxygenase Inhibitors Cytochrome P-450 Enzyme System Enzyme-Linked Immunosorbent Assay Hypertension, Pulmonary Hypoxia Imidazoles Immunoblotting Indomethacin Intramolecular Oxidoreductases Prostaglandins Pulmonary Artery Reactive Oxygen Species Statistics, Nonparametric Sus scrofa Thromboxane-A Synthase Vasoconstriction

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