Nitrate ion (NO3-)

Nitrate (NO3-) is an inorganic anion that serves as a vital component of the human nitrate-nitrite-nitric oxide (NO) pathway. While historically considered a stable and inert end-product of NO metabolism, nitrate is now recognized as a critical reservoir for the endogenous production of nitric oxide, particularly under conditions of hypoxia or acidosis where the oxygen-dependent L-arginine-NOS pathway is compromised. In humans, dietary nitrate from sources like green leafy vegetables is concentrated in the saliva, reduced to nitrite by oral commensal bacteria, and subsequently converted into bioactive nitric oxide in various tissues, where it promotes vasodilation and improves mitochondrial efficiency. Clinically, organic nitrates such as nitroglycerin and isosorbide mononitrate have been used for over a century as potent vasodilators for treating angina pectoris and heart failure. However, their therapeutic utility is often limited by the development of nitrate tolerance and significant safety risks, including severe hypotension when administered alongside phosphodiesterase-5 (PDE5) inhibitors.

Other names

Nitrate ionNO3-Nitrate(V)Nitrate anionAzotateInorganic nitrate

Nitrate is reduced to nitrite and subsequently to nitric oxide (NO) by enzymes such as xanthine oxidoreductase; NO then activates soluble guanylate cyclase (sGC) to increase intracellular cGMP, leading to smooth muscle relaxation and vasodilation.