Pulmonary arterial responses to reactive oxygen species are altered in newborn piglets with chronic hypoxia-induced pulmonary hypertension. Pediatr Res 2011 Aug;70(2):136-41
Date
04/26/2011Pubmed ID
21516056Pubmed Central ID
PMC3131458DOI
10.1203/PDR.0b013e3182207ce7Abstract
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.
Author List
Fike CD, Aschner JL, Slaughter JC, Kaplowitz MR, Zhang Y, Pfister SLAuthor
Sandra L. Pfister PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, 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
