Document Detail


Coronary nitric oxide production controls cardiac substrate metabolism during pregnancy in the dog.
MedLine Citation:
PMID:  18424630     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jeffrey G Williams; Caroline Ojaimi; Khaled Qanud; Suhua Zhang; Xiaobin Xu; Fabio A Recchia; Thomas H Hintze
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-04-18
Journal Detail:
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:
Created Date:  2008-06-09     Completed Date:  2008-08-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H2516-23     Citation Subset:  IM    
Affiliation:
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / 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:
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:
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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