The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics

Nat Rev Drug Discov. 2008 Feb;7(2):156-67. doi: 10.1038/nrd2466.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diet
  • Drug Design
  • Humans
  • Nitrates* / metabolism
  • Nitrates* / pharmacology
  • Nitrates* / therapeutic use
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide* / biosynthesis
  • Nitric Oxide* / metabolism
  • Nitric Oxide* / physiology
  • Nitrites* / metabolism
  • Nitrites* / pharmacology
  • Nitrites* / therapeutic use
  • Vasodilation / drug effects


  • Nitrates
  • Nitrites
  • Nitric Oxide
  • Nitric Oxide Synthase