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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/H2516    most recent 01196.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Williams, J. G. Articles by Hintze, T. H. PubMed PubMed Citation Articles by Williams, J. G. Articles by Hintze, T. H.

Coronary nitric oxide production controls cardiac substrate metabolism during pregnancy in the dog

Department of Physiology, New York Medical College, Valhalla, New York

Submitted 15 October 2007 ; accepted in final form 14 April 2008

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 µmol/min) but greatly increased in response to L-NAME injection (to 19.9 ± 0.9 µmol/min, P < 0.05). Free fatty acid (FFA) oxidation was increased in P60 (from 5.3 ± 0.6 to 10.4 ± 0.5 µmol/min, P < 0.05) and decreased in response to L-NAME (to 4.5 ± 0.5 µmol/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.

free fatty acid oxidation; glucose metabolism; gene chip; no metabolic vasodilation