| Coronary endothelial function and vascular smooth muscle proliferation are programmed by early-gestation dexamethasone exposure in sheep. | |
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MedLine Citation:
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PMID: 20335378 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Exposure of the early-gestation ovine fetus to exogenous glucocorticoids induces changes in postnatal cardiovascular physiology. We sought to characterize coronary artery vascular function in this model by elucidating the contribution of nitric oxide and reactive oxygen species to altered coronary vascular reactivity and examining the proliferative potential of coronary artery vascular smooth muscle cells. Dexamethasone (dex, 0.28 mg x kg(-1) x day(-1) for 48 h) was administered to pregnant ewes at 27-28-day gestation (term 145 days). Coronary arteries were isolated from 1- to 2-wk-old dex-exposed offspring and aged-matched controls. Compared with controls, coronary arteries from dex-exposed lambs demonstrated enhanced vasoconstriction to endothelin-1 and ACh that was abolished by endothelial removal or preincubation with the nitric oxide synthase inhibitor L-NNA, membrane-permeable superoxide dismutase + catalase, or apamin + charybdotoxin, but not indomethacin. The rate of coronary vascular smooth muscle cell (VSMC) proliferation was also significantly greater in dex-exposed lambs. Protein levels of the proliferating cell nuclear antigen were increased and alpha-smooth muscle actin decreased in dex-exposed coronary VSMC, consistent with a proliferative state. Finally, expression of the NADPH oxidase Nox 4, but not Nox 1, mRNA was also decreased in coronary VSMC from dex-exposed lambs. These findings suggest an important interaction exists between early-gestation glucocorticoid exposure and reactive oxygen species that is associated with alterations in endothelial function and coronary VSMC proliferation. These changes in coronary physiology are consistent with those associated with the development of atherosclerosis and may provide an important link between an adverse intrauterine environment and increased risk for coronary artery disease. |
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Authors:
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Kenneth A Volk; Robert D Roghair; Felicia Jung; Thomas D Scholz; Fred S Lamb; Jeffrey L Segar |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-03-24 |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 298 ISSN: 1522-1490 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-25 Completed Date: 2010-06-15 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States |
Other Details:
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Languages: eng Pagination: R1607-14 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Catalase / metabolism Coronary Vessels / metabolism Dexamethasone / pharmacology* Endothelin-1 / pharmacology Endothelium / metabolism* Female Fetus / metabolism Glucocorticoids / pharmacology* Muscle, Smooth, Vascular / metabolism* Nitric Oxide / metabolism Nitric Oxide Synthase Type III Pregnancy Sheep / metabolism* Superoxide Dismutase / metabolism Vasoconstriction / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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ES 012268/ES/NIEHS NIH HHS; HD 050359/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Endothelin-1; 0/Glucocorticoids; 10102-43-9/Nitric Oxide; 50-02-2/Dexamethasone; EC 1.11.1.6/Catalase; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.15.1.1/Superoxide Dismutase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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