NO-synthase independent NO generation in mammals

Inorganic nitrate (NO3-) and nitrite (NO2-) are part of the nitrogen cycle in nature. To the general public these anions are generally known as undesired residues in the food chain with potentially carcinogenic effects. Among biologists, these inorganic anions have merely been viewed as inert oxidative end products of endogenous nitric oxide (NO) metabolism. However, recent studies surprisingly show that nitrate and nitrite can be metabolized in vivo to form nitric oxide (NO) and other bioactive nitrogen oxides. This represents an important alternative source of NO especially during hypoxia when the oxygen-dependent l-arginine–NO pathway can be altered. A picture is now emerging suggesting important biological functions of the nitrate–nitrite–NO pathway with profound implications in relation to the diet and cardiovascular homeostasis. Moreover, an increasing number of studies suggest a therapeutic potential for nitrate and nitrite in diseases such as myocardial infarction, stroke, hypertension, renal failure and gastric ulcers.