Dietary nitrite restores NO homeostasis and is cardioprotective in endothelial nitric oxide synthase-deficient mice

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 pr...

Full description

Saved in:
Bibliographic Details
Published in:Free radical biology & medicine 2008-08, Vol.45 (4), p.468-474
Main Authors: Bryan, Nathan S., Calvert, John W., Gundewar, Susheel, Lefer, David J.
Format: Article
Language:English
Subjects:
Animals
Diet
Homeostasis
Ischemia–reperfusion
Mice
Mice, Knockout
Myocardium - enzymology
Nitrate
Nitric oxide
Nitric Oxide - metabolism
Nitric Oxide Synthase Type III - genetics
Nitric Oxide Synthase Type III - physiology
Nitrite
Nitrite Reductases - metabolism
Nitrites - administration & dosage
Nitrites - pharmacology
Supplement
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2008.04.040