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Endothelial superoxide production is altered in sheep programmed by early gestation dexamethasone exposure. Neonatology 2008;93(1):19-27

Date

07/17/2007

Pubmed ID

17630494

DOI

10.1159/000105521

Scopus ID

2-s2.0-37249072735   18 Citations

Abstract

BACKGROUND: Animal models have demonstrated that maternal undernutrition or early gestation glucocorticoid exposure induces endothelial dysfunction in the offspring.

OBJECTIVES: We sought to determine whether early gestation dexamethasone (DEX) exposure is further associated with increased vascular superoxide anion production.

METHODS: DEX (0.28 mg/kg/day i.v. for 48 h) was administered to pregnant ewes at 27-28 days' gestation (term 145 days). Tissues were harvested from DEX-exposed and control lambs at 125 days' gestation (n = 6 for each group) and 4 months following delivery (n = 9 and 12, respectively).

RESULTS: By lucigenin-enhanced chemiluminescence, coronary and mesenteric arteries from DEX-exposed fetuses exhibited diminished basal superoxide production (both p < 0.01). Similarly, DEX-exposed carotid arteries from 4-month-old lambs had decreased superoxide production (p < 0.01) that localized to the endothelium by endothelial cell culture and dihydroethidium fluorescence. In contrast, DEX-exposed coronary arteries from the 4-month-old sheep had increased superoxide production (p < 0.05). Although early gestation DEX exposure did not alter lipid peroxidation, DEX exposure was associated with significantly increased renal and cerebral cortex aconitase activity (consistent with decreased protein oxidation). These changes occurred in the absence of alterations in renal cortex superoxide dismutase activity.

CONCLUSIONS: We conclude that in a DEX-exposure model of fetal programming, endothelial superoxide production and protein oxidation are decreased in the mesenteric and carotid circulation. This contrasts with the postnatal coronary artery-specific increase in superoxide production.

Author List

Roghair RD, Miller FJ Jr, Scholz TD, Lamb FS, Segar JL

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Carotid Arteries
Cerebral Cortex
Coronary Vessels
Dexamethasone
Endothelium, Vascular
Female
Fetal Development
Glucocorticoids
Heart Ventricles
Kidney Cortex
Lipid Peroxidation
Mesenteric Arteries
Oxidation-Reduction
Pregnancy
Prenatal Exposure Delayed Effects
Reactive Oxygen Species
Sheep
Superoxide Dismutase
Superoxides
Vasodilation
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0