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Coronary constriction to angiotensin II is enhanced by endothelial superoxide production in sheep programmed by dexamethasone. Pediatr Res 2008 Apr;63(4):370-4

Date

03/22/2008

Pubmed ID

18356741

Pubmed Central ID

PMC3663587

DOI

10.1203/PDR.0b013e3181659bfa

Scopus ID

2-s2.0-41349121008   8 Citations

Abstract

Early gestation dexamethasone (dex) administration is an ovine model of fetal programming associated with increased coronary reactivity to angiotensin II (Ang II). NADPH oxidase-dependent superoxide production plays an important role in both Ang II signaling and coronary disease. We sought to determine whether early gestation dex-exposure increases coronary reactivity to Ang II by enhancing endothelial NADPH oxidase-dependent superoxide production. Dex (0.28 mg/kg/d for 48 h) was administered to pregnant ewes at 27-28 d gestation. Dex-exposed and control offspring were studied at 4 mo of age. Coronary superoxide production was measured by lucigenin-enhanced chemiluminescence and dihydroethidium fluorescence. Coronary arteries from dex-exposed sheep had significantly enhanced vasoconstriction to Ang II, an effect abolished by either endothelial removal or preincubation with membrane-permeable superoxide dismutase and catalase. Ang II significantly increased endothelial superoxide production and NADPH oxidase activity in coronaries from dex-exposed offspring, but not controls. This programmed alteration in superoxide production was accentuated by PD123319 (AT2 antagonist), but abolished by losartan (AT1 antagonist). In conclusion, early gestation dex-exposure programs coronary reactivity to Ang II by enhancing Ang II-stimulated endothelial superoxide production. This programming effect may predispose to progressive coronary endothelial dysfunction and coronary artery disease.

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

Angiotensin II
Angiotensin II Type 1 Receptor Blockers
Angiotensin II Type 2 Receptor Blockers
Animals
Coronary Vessels
Dexamethasone
Endothelium, Vascular
Female
Glucocorticoids
Imidazoles
Losartan
NADP
Pregnancy
Prenatal Exposure Delayed Effects
Pyridines
Sheep
Superoxides
Vasoconstriction
Vasoconstrictor Agents
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00