Quantitative aspects of nitric oxide production from nitrate and nitrite

Nitric oxide (NO) is involved in many physiological and pathological processes in the human body. At least two major pathways produce NO: (1) the L-arginine-NO-oxidative pathway in which NO synthase (NOS) enzymes convert L-arginine to NO; (2) the nitrate-nitrite-NO reductive pathway in which NO is produced from the serial reduction of nitrate and nitrite. The deficiency of NO is involved in the pathophysiology of cardiometabolic disorders. Intervention with foods containing nitrate and nitrite can potentially prevent or treat some chronic diseases, including cardiovascular diseases and diabetes. A better understanding of the NO cycle would help develop effective strategies for preventing or treating the disorders in which NO homeostasis is disturbed. This review summarizes quantitative aspects of NO production, emphasizing the nitrate-nitrite-NO pathway. Available data indicates that total NO production by NOS-dependent L-arginine-NO pathway is about 1000 μmol.day^-1. Of about 1700 μmol.day^-1 ingested nitrate, ~25 % is extracted by the salivary glands and of which ~20 % is converted nitrite. It means that about 5 % of ingested nitrate is converted to nitrite in the oral cavity; assuming that all produced nitrite is reduced to NO in the stomach, it can be calculated that contribution of the nitrate-nitrite-NO pathway to the whole-body NO production is about 85 μmol.day^-1 (1700 ×0.05=85) or approximately 100 μmol.day^-1. The lower contribution of the nitrate-nitrite-NO pathway does not mean that this pathway has lower importance in the whole-body NO homeostasis. Even in the adequate L-arginine supply, NOS-dependent NO production is insufficient to meet all NO functions, and the nitrate-nitrite-NO pathway must provide the rest. In conclusion, the contribution of the nitrate-nitrite-NO pathway in the whole human body NO production is <10 %, and the nitrate-nitrite-NO pathway is complementary to the NOS-dependent NO production.