Abstract

The inorganic anions nitrate (NO₃ ^-) and nitrite (NO₂ ^-) were previously thought to be inert end products of endogenous nitric oxide (NO) metabolism. However, recent studies show that these supposedly inert anions can be recycled in vivo to form NO, representing an important alternative source of NO to the classical l-arginine–NO-synthase pathway, in particular in hypoxic states. This Review discusses the emerging important biological functions of the nitrate–nitrite–NO pathway, and highlights studies that implicate the therapeutic potential of nitrate and nitrite in conditions such as myocardial infarction, stroke, systemic and pulmonary hypertension, and gastric ulceration.

Author affiliations

1. Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
   Email: jon.lundberg@ki.se
2. Section of Anesthesiology and Intensive Care, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm.
   Email: eddie.weitzberg@ki.se
3. Pulmonary and Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Heath, Bethesda, Maryland 20892, USA.
   Email: mgladwin@mail.nih.gov
4. Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda.

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