It is Rocket Science – Why dietary nitrate is hard to beet! Part I: Twists and turns in the realisation of the nitrate-nitrite-NO pathway.

Dietary nitrate (found in green leafy vegetables such as rocket and in beetroot) is now recognised to be an important source of nitric oxide, via the nitrate-nitrite-NO pathway. Dietary nitrate confers several cardiovascular beneficial effects on blood pressure, platelets, endothelial function, mitochondrial efficiency and exercise. Whilst this pathway may now seem obvious, its realisation followed a rather tortuous course over two decades. Early steps included the discovery that nitrite was a source of NO in the ischaemic heart, but this appeared to have deleterious effects. In addition, nitrate-derived nitrite provided a gastric source of NO. However, residual nitrite was not thought to be absorbed systemically. Nitrite was also considered to be physiologically inert, but potentially carcinogenic, through N-nitrosamine formation. In Part I we describe key twists and turns in the elucidation of the pathway and the underlying mechanisms. This provides the critical foundation for the more recent developments in the nitrate-nitrite-NO pathway which are covered in Part II. This article is protected by copyright. All rights reserved.