About the Special Issue

Nitric oxide (NO), which is known as a bioactive substance, is produced in humans by the following two pathways and exhibits various pharmacological effects. (1) First, NO is produced by NO synthase (NOS) existing in cells using the amino acid arginine (Arg) as a substrate, and this pathway is called as the Arg-NOS-NO pathway. (2) Secondly, NO is produced by NO reductase (NOR) using NO metabolites (nitrite and nitrate) as sources, and this pathway is called as the nitrate-nitrite-NO pathway. These two paths have the following advantages and disadvantages. (1) The positive advantage of the Arg-NOS-NO pathway is that it acts directly and selectively. The fatal disadvantage of this pathway is that if the NOS is damaged, no more NO will be produced and the disease will result from a lack of NO. (2) The positive advantage of the nitrate-nitrite-NO pathway is that NO metabolites can be supplied as foods and that NOR is abundantly present in our body and/or cells, therefore suggesting that NOR damage does not occur and that the nitrate-nitrite-NO pathway is compensating for the disadvantages of the Arg-NOS-NO pathway. The negative disadvantage of this pathway is that NO metabolites must be continuously supplied. Thanks to two NO pathways, we now understand that NO is continuously produced everywhere and works on all tissues, including the brain. It is time to start to investigate and discuss the protective effects of NO and its metabolites (nitrite and nitrate) against neuronal damage.

Keywords: nitric oxide; nitrite; nitrate; diabetes; nitric oxide synthase; nitrite reductase; cardiovascular diseases; atherosclerosis; neurodegenerative diseases

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