Document Detail

Dietary nitrite restores NO homeostasis and is cardioprotective in endothelial nitric oxide synthase-deficient mice.
MedLine Citation:
PMID:  18501719     Owner:  NLM     Status:  MEDLINE    
Endothelial production of nitric oxide (NO) is critical for vascular homeostasis. Nitrite and nitrate are formed endogenously by the stepwise oxidation of NO and have, for years, been regarded as inactive degradation products. As a result, both anions are routinely used as surrogate markers of NO production, with nitrite as a more sensitive marker. However, both nitrite and nitrate are derived from dietary sources. We sought to determine how exogenous nitrite affects steady-state concentrations of NO metabolites thought to originate from nitric oxide synthase (NOS)-derived NO as well as blood pressure and myocardial ischemia-reperfusion (I/R) injury. Mice deficient in endothelial nitric oxide synthase (eNOS-/-) demonstrated decreased blood and tissue nitrite, nitrate, and nitroso proteins, which were further reduced by low-nitrite (NOx) diet for 1 week. Nitrite supplementation (50 mg/L) in the drinking water for 1 week restored NO homeostasis in eNOS-/- mice and protected against I/R injury. Nitrite failed to alter heart rate or mean arterial blood pressure at the protective dose. These data demonstrate the significant influence of dietary nitrite intake on the maintenance of steady-state NO levels. Dietary nitrite and nitrate may serve as essential nutrients for optimal cardiovascular health and may provide a novel prevention/treatment modality for disease associated with NO insufficiency.
Nathan S Bryan; John W Calvert; Susheel Gundewar; David J Lefer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-05-05
Journal Detail:
Title:  Free radical biology & medicine     Volume:  45     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-14     Completed Date:  2008-09-30     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  468-74     Citation Subset:  IM    
The Brown Foundation Institute of Molecular Medicine, University of Texas-Houston Health Sciences Center, Houston, TX 77030, USA.
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MeSH Terms
Mice, Knockout
Myocardium / enzymology
Nitric Oxide / metabolism*
Nitric Oxide Synthase Type III / genetics,  physiology*
Nitrite Reductases / metabolism
Nitrites / administration & dosage,  pharmacology*
Grant Support
Reg. No./Substance:
0/Nitrites; 10102-43-9/Nitric Oxide; EC Oxide Synthase Type III; EC 1.7.-/Nitrite Reductases

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