Journal article
Coronary Constriction to Angiotensin II Is Enhanced by Endothelial Superoxide Production in Sheep Programmed by Dexamethasone
Pediatric research, Vol.63(4), pp.370-374
04/2008
DOI: 10.1203/PDR.0b013e3181659bfa
PMCID: PMC3663587
PMID: 18356741
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 (AT
2
antagonist), but abolished by losartan (AT
1
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.
Details
- Title: Subtitle
- Coronary Constriction to Angiotensin II Is Enhanced by Endothelial Superoxide Production in Sheep Programmed by Dexamethasone
- Creators
- Robert D Roghair - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242Francis J Miller - Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242Thomas D Scholz - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242Fred S Lamb - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242Jeffrey L Segar - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Pediatric research, Vol.63(4), pp.370-374
- DOI
- 10.1203/PDR.0b013e3181659bfa
- PMID
- 18356741
- PMCID
- PMC3663587
- ISSN
- 0031-3998
- eISSN
- 1530-0447
- Grant note
- R01 HL081750-04 || HL / National Heart, Lung, and Blood Institute : NHLBI R21 ES012268-03 || ES / National Institute of Environmental Health Sciences : NIEHS R01 HL081750-02 || HL / National Heart, Lung, and Blood Institute : NHLBI R01 HL081750-03 || HL / National Heart, Lung, and Blood Institute : NHLBI R01 HL081750-01 || HL / National Heart, Lung, and Blood Institute : NHLBI
- Language
- English
- Date published
- 04/2008
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Child and Community Health; Neonatology
- Record Identifier
- 9984093213202771
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