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Br J Clin Pharmacol. 2017 Jan;83(1):129-139. doi: 10.1111/bcp.12913. Epub 2016 May 6.

It is rocket science - why dietary nitrate is hard to 'beet'! Part I: twists and turns in the realization of the nitrate-nitrite-NO pathway.

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King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas, Hospital, London, SE1 7EH, UK.
Department of Dietetics and Nutrition, Division of Diabetes and Nutritional Sciences, King's College London, London, SE1 0NH, UK.


Dietary nitrate (found in green leafy vegetables, such as rocket, and in beetroot) is now recognized to be an important source of nitric oxide (NO), via the nitrate-nitrite-NO pathway. Dietary nitrate confers several cardiovascular beneficial effects on blood pressure, platelets, endothelial function, mitochondrial efficiency and exercise. While this pathway may now seem obvious, its realization 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 1 of a two-part Review on the nitrate-nitrite-NO pathway 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 2.


blood pressure; dietary nitrate; endothelial function; ischaemia-reperfusion; nitrite; platelets

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