| Coronary nitric oxide production controls cardiac substrate metabolism during pregnancy in the dog. | |
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MedLine Citation:
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PMID: 18424630 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The aim of this study was to examine the role of nitric oxide (NO) in the control of cardiac metabolism at 60 days of pregnancy (P60) in the dog. There was a basal increase in diastolic coronary blood flow during pregnancy and a statistically significant increase in cardiac output (55 +/- 4%) and in cardiac NOx production (44 +/- 4 to 59 +/- 3 nmol/min, P < 0.05). Immunohistochemistry of the left ventricle showed an increase in endothelial nitric oxide synthase staining in the endothelial cells at P60. NO-dependent coronary vasodilation (Bezold-Jarisch reflex) was increased by 20% and blocked by N(G)-nitro-l-arginine methyl ester (l-NAME). Isotopically labeled substrates were infused to measure oleate, glucose uptake, and oxidation. Glucose oxidation was not significantly different in P60 hearts (5.4 +/- 0.5 vs. 6.2 +/- 0.4 micromol/min) but greatly increased in response to l-NAME injection (to 19.9 +/- 0.9 micromol/min, P < 0.05). Free fatty acid (FFA) oxidation was increased in P60 (from 5.3 +/- 0.6 to 10.4 +/- 0.5 micromol/min, P < 0.05) and decreased in response to l-NAME (to 4.5 +/- 0.5 micromol/min, P < 0.05). There was an increased oxidation of FFA for ATP production but no change in the respiratory quotient during pregnancy. Genes associated with glucose and glycogen metabolism were downregulated, whereas genes involved in FFA oxidation were elevated. The acute inhibition of NO shifts the heart away from FFA and toward glucose metabolism despite the downregulation of the carbohydrate oxidative pathway. The increase in endothelium-derived NO during pregnancy results in a tonic inhibition of glucose oxidation and reliance on FFA uptake and oxidation to support ATP synthesis in conjunction with upregulation of FFA metabolic enzymes. |
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Authors:
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Jeffrey G Williams; Caroline Ojaimi; Khaled Qanud; Suhua Zhang; Xiaobin Xu; Fabio A Recchia; Thomas H Hintze |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-04-18 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 294 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-06-09 Completed Date: 2008-08-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H2516-23 Citation Subset: IM |
Affiliation:
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Department of Physiology, New York Medical College, Valhalla, NY 10595, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Animals Coronary Circulation* / drug effects Coronary Vessels / drug effects, enzymology, metabolism* Dogs Energy Metabolism* / drug effects, genetics Enzyme Inhibitors / pharmacology Fatty Acids, Nonesterified / metabolism Female Glucose / metabolism Hemodynamics Immunohistochemistry Lactic Acid / metabolism Myocardium / enzymology, metabolism* NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide / metabolism* Nitric Oxide Synthase Type III / antagonists & inhibitors, metabolism Oxidation-Reduction Pregnancy RNA, Messenger / metabolism Time Factors Up-Regulation Vasodilation* / drug effects Vasodilator Agents / pharmacology Veratrine / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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HL-50142/HL/NHLBI NIH HHS; HL-61290/HL/NHLBI NIH HHS; P0-1-HL-43023/HL/NHLBI NIH HHS; P01-HL-74237/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Fatty Acids, Nonesterified; 0/RNA, Messenger; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 50-21-5/Lactic Acid; 50-99-7/Glucose; 50903-99-6/NG-Nitroarginine Methyl Ester; 56-65-5/Adenosine Triphosphate; 62-59-9/Veratrine; EC 1.14.13.39/Nitric Oxide Synthase Type III |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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